Female Urology

FEMALE UROLOGY
CURRENT CLINICAL UROLOGY

Eric A. Klein, MD, SERIES EDITOR
Female Urology: A Practical Clinical Guide, edited by Howard Goldman and
Sandip P. Vasavada , 2007
Urinary Stone Disease: The Practical Guide to Medical and Surgical Management,
edited by Marshall L. Stoller and Maxwell V. Meng, 2007
Peyronie’s Disease: A Guide to Clinical Management, edited by Laurence A.
Levine, 2006
Male Sexual Function: A Guide to Clinical Management, Second Edition,
edited by John J. Mulcahy, 2006
Advanced Endourology: The Complete Clinical Guide, edited by Stephen
Y. Nakada and Margaret S. Pearle, 2005
Oral Pharmacotherapy of Male Sexual Dysfunction: A Guide to Clinical
Management, edited by Gregory A. Broderick, 2005
Urological Emergencies: A Practical Guide, edited by Hunter Wessells and Jack
W. McAninch, 2005
Management of Prostate Cancer, Second Edition, edited by Eric A. Klein, 2004
Essential Urology: A Guide to Clinical Practice, edited by Jeannette M. Potts,
2004
Management of Benign Prostatic Hypertrophy, edited by Kevin T. McVary, 2004
Pediatric Urology, edited by John P. Gearhart, 2003
Laparoscopic Urologic Oncology, edited by Jeffrey A. Cadeddu, 2004
Essential Urologic Laparoscopy: The Complete Clinical Guide, edited by Stephen
Y. Nakada, 2003
Urologic Prostheses: The Complete Practical Guide to Devices, Their Implantation,
and Patient Follow-Up, edited by Culley C. Carson, III, 2002
Male Sexual Function: A Guide to Clinical Management, edited by John J.
Mulcahy, 2001
Prostate Cancer Screening, edited by Ian M. Thompson, Martin I. Resnick, and
Eric A. Klein, 2001
Bladder Cancer: Current Diagnosis and Treatment, edited by Michael J. Droller,
2001
Office Urology: The Clinician’s Guide, edited by Elroy D. Kursh and James C.
Ulchaker, 2001
Voiding Dysfunction: Diagnosis and Treatment, edited by Rodney A. Appell, 2000
Management of Prostate Cancer, edited by Eric A. Klein, 2000
FEMALE UROLOGY
A PRACTICAL CLINICAL GUIDE
Edited by
HOWARD B. GOLDMAN, MD
Section of Female Urology and Voiding Dysfunction
The Glickman Urological Institute
The Cleveland Clinic
and
Department of Urology and Reproductive Biology
CASE School of Medicine
Cleveland, Ohio
SANDIP P. VASAVADA, MD
Section of Female Urology and Voiding Dysfunction
The Glickman Urological Institute
The Cleveland Clinic
Cleveland, Ohio
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Library of Congress Cataloging-in-Publication Data
Female urology : a practical clinical guide / edited by Howard B.

Goldman, Sandip P. Vasavada.
p. ; cm. — (Current clinical urology)
Includes bibliographical references and index.
ISBN 978-1-58829-701-3 (alk. paper)
1. Urogynecology. I. Goldman, Howard B. II. Vasavada,
Sandip P. III. Series.
[DNLM: 1. Genital Diseases, Female—Case Reports. 2. Urogenital
Diseases—Case Reports. 3. Pelvic Floor—physiopathology—Case
Reports. 4. Urinary Incontinence—Case Reports. 5. Urologic
Surgical Procedures—Case Reports. WJ 190 F32994 2007]
RG484.F464 2007
616.6—dc22
2006026761
Dedication
To my wife, Suri, and my children, Joshua, Ari, Michal, and Yonatan, for their
support, patience, and encouragement, and to my parents for their years of advice
and encouragement.
—HBG
***
To my wife, Pauravi, and my children, Samir, Sarinna, and Alisha, and my parents
for all your support, as you have all truly challenged and inspired me, and for that, I
am eternally grateful.
—SPV
v
Preface
The specialty of female pelvic medicine and reconstructive surgery is ever changing.
We have seen the evolution of procedures that have minimized the invasiveness of
surgery while continuously decreasing morbidity. We are now in an era where we are
using validated instruments instead of relying on physician only assessment and have
incorporated measures including quality of life instruments to get to the core question,
which is, “Have we really helped the patient with these interventions?”
To this end, we have developed Female Urology: A Practical Clinical Guide to incor-
porate some of the newer concepts in female pelvic medicine as they relate to anatomy,
bladder physiology, and urodynamics testing. However, perhaps the most exciting part
of this book is the case studies, in which noted experts from around the world comment
on complex cases common to urological practice. Hopefully, this section will allow the
reader to compare their own evaluation and treatment plans to that of the experts, and
potentially improve their ability to manage these types of patients.
We want to thank our authors for the time, dedication, and effort necessary to help us
produce such a multi-dimensional text and also thank you, the readers for your constant
quest for knowledge to enhance the goal of improved patient care.
Howard B. Goldman, MD
Sandip P. Vasavada, MD
vii
Contents
Dedication ...................................................................................................................... v
Preface ........................................................................................................................ vii
Contributors ............................................................................................................... xiii
List of Color Plates ................................................................................................... xvii
Part I. Evaluation
1. Anatomy of Pelvic Support .............................................................................................. 3
Melissa Fischer, Priya Padmanabhan, and Nirit Rosenblum
2. Neurophysiological Control of the Lower Urinary Tract .............................................. 19
Toby C. Chai and Todd J. Lehrfeld
3. Office Evaluation of Urinary Incontinence .................................................................... 35
Adonis Hijaz and Firouz Daneshgari
4. Urodynamic Evaluation of Female Stress Urinary Incontinence .................................. 41
Kelly M. Maxwell and J. Quentin Clemens
5. Urodynamic Assessment of Overactive Bladder: Neurogenic and Nonneurogenic ..... 51
Gary E. Lemack
Part II. Treatment
6. Conservative Therapy for Incontinence ......................................................................... 63
Diane K. Newman
Part A. Stress Urinary Incontinence
7. Pharmacological Therapy for Stress Urinary Incontinence ........................................... 83
Harriette M. Scarpero
8. Urethral Injectables for Stress Urinary Incontinence .................................................... 97
R. Duane Cespedes
9. Midurethral Slings ......................................................................................................... 111
Gregory T. Bales and Paula A. Fedunok
10. Bladder Neck Slings for Stress Urinary Incontinence ................................................. 131
O. Lenaine Westney
11. Complications of Sling Surgery ................................................................................... 159
Suzette E. Sutherland
Part B. Overactive Bladder
12. Pharmacological Therapy for Overactive Bladder ...................................................... 177
H. Mallory Reeves, Eric S. Rovner, and Alan J. Wein
13. Intravesical Treatments for Overactive Bladder .......................................................... 201
Craig B. Slotoroff, Dolores Shupp-Byrne, and Patrick J. Shenot
14. Urological Applications of Botulinum Toxin .............................................................. 213
Courtenay K. Moore and Howard B. Goldman
ix
x Contents
15. Nonsacral Neuromodulation ......................................................................................... 221

Richard C. Bennett, Andrew Bernstein, and Kenneth M. Peters
16. Sacral Neuromodulation for the Treatment of Overactive Bladder ............................ 237
Anurag K. Das
17. Augmentation Cystoplasty ............................................................................................ 251
Michael A. Aleman, Joseph B. Abdelmalak, and Raymond R. Rackley
18. Mixed Incontinence: Defining Symptoms, Management, and Outcomes .................... 261
Roger Dmochowski and Harriette M. Scarpero
Part C. Prolapse
19. Evaluation and Management of Anterior Vaginal Wall Prolapse ............................... 267
Sandip P. Vasavada and Matthew D. Barber
20. Treatment of Posterior Vaginal Wall Prolapse ............................................................ 281
David A. Ginsberg
21. Diagnosis and Mangement of Apical Prolapse ............................................................ 297
Daniel S. Elliott
Part D. Reconstruction
22. Evaluation and Management of Vesicovaginal Fistulas .............................................. 309
Matthew P. Rutnam, Donna Y. Deng, and Larissa V. Rodríguez
23. Female Urethral Diverticula ......................................................................................... 327
Erin Gibbons and Wendy W. Leng
Part III. Case Studies
1. Recurrent Stress Urinary Incontinence ........................................................................ 343
Jerry Blaivas
2. Recurrent Urinary Tract Infections and Pelvic Organ Prolapse .................................. 345
Jennifer Takacs and Philippe Zimmern
3. Mixed Incontinence ....................................................................................................... 351
Wachira Kochakarn and Gary E.Leach
4. Urinary Tract Infections and Pelvic Pain ..................................................................... 357
Suzette E. Sutherland
5. Multiple Sclerosis and Voiding Dysfunction ............................................................... 361
E. James Wright
6. De novo Overactive Bladder Symptoms After a Sling ................................................ 365
Victor W. Nitti, Carl G. Klutke, and Travis L. Bullock
7. Recurrent Pelvic Organ Prolapse .................................................................................. 371
Christopher C. Roth and J. Christian Winters
8. Recalcitrant Urinary Frequency and Urgency ............................................................. 375
Michael Chancellor and Gamal M. Ghoniem
9. Difficulty Voiding and Overactive Bladder Symptoms .............................................. 379
Michael J. Kennelly and Deborah Lightner
10. Post-Hysterectomy Incontinence .................................................................................. 385
Courtenay K. Moore
11. Severe Incontinence After Multiple Prior Procedures ................................................. 387
Roger Dmochowski
Contents xi
12. Urinary Frequency and Pelvic Pain .............................................................................. 391

E. Ann Gormley and Jeffery P. Weiss
13. Pelvic Organ Prolapse ................................................................................................... 397
Shlomo Raz, Matthew P. Rutman, and Kathleen C. Kobashi
14. Recurrent Pelvic Organ Prolapse After Colpocleisis ................................................... 405
Raymond Rackley
15. Stress Incontinence and Straining to Void ................................................................... 407
Steven Siegel
16. Male With Post-Prostatectomy Incontinence ............................................................... 411
Craig V. Comiter and Fred E. Govier
17. Mixed Incontinence in Elderly Woman ....................................................................... 417
Tomas L. Griebling
18. Male With Post-Prostatectomy Incontinence: Status Post-removal
of Eroded Artificial Sphincter ................................................................................. 421
Ajay Singla
Index .......................................................................................................................... 423
Contributors
JOSEPH B. ABDELMALAK, MD • Section of Female Pelvic Medicine and Reconstructive

Surgery, The Glickman Urological Institute, The Cleveland Clinic, Cleveland, OH
MICHALE A. ALEMAN, MD • Department of Urology, The University of Tennessee
Health Science Center, Memphis, TN
GREGORY T. BALES, MD • Section of Urology, University of Chicago Hospital,
Chicago, IL
MATTHEW BARBER, MD • Section of Urogynecology and Reconstructive Pelvic Surgery,
The Cleveland Clinic, Cleveland, OH
RICHARD C. BENNETT, MD • Department of Urology, William Beaumont Hospital,
Royal Oak, MI
ANDREW BERNSTEIN, MD • Department of Urology, William Beaumont Hospital,
Royal Oak, MI
JERRY G. BLAIVAS, MD • Department of Urology, Weill Medical College of Cornell
University, New York, NY
TRAVIS L. BULLOCK, MD • Department of Surgery, Division of Urology, Washington
University School of Medicine, St. Louis, MO
R. DUANE CESPEDES, MD • Director, Female Urology and Urodynamics, Department
of Urology (MCSU), Wilford Hall Medical Center, Lackland AFB, TX; Department
of Urology, University of Texas Health Sciences Center at San Antonio,
San Antonio, TX
TOBY C. CHAI, MD, FACS • University of Maryland, Baltimore, MD
MICHAEL CHANCELLOR, MD • Department of Urology and OBGYN, University of Pittsburgh
School of Medicine, Pittsburgh, PA
J. QUENTIN CLEMENS, MD • Section of Voiding Dysfunction and Female Urology,
Department of Urology, Northwestern University Feinberg School of Medicine,
Chicago, IL
CRAIG V. COMITER, MD • Department of Surgery/Urology, University of Arizona
Health Sciences Center, Tucson, AZ; Section of Urology, University of Arizona
Health Sciences Center, Tucson, AZ
FIROUZ DANESHGARI, MD • Center for Female Pelvic Medicine and Reconstructive
Surgery, The Glickman Urological Institute at The Cleveland Clinic, Cleveland, OH
ANURAG K. DAS, MD, FACS • Center for Neurourology and Continence, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, MA
DONNA Y. DENG, MD • Department of Urology, UCSF School of Medicine,
San Francisco, CA
ROGER DMOCHOWSKI, MD, FACS • Department of Urologic Surgery, Vanderbilt University
Medical Center, Nashville, TN
DANIEL S. ELLIOTT, MD • Department of Urology, Section of Female Urology
and Voiding Dysfunction, Mayo Clinic, Rochester, MN
PAULA A. FEDUNOK, PA-C • Section of Urology, University of Chicago Hospital,
Chicago, IL
xiii
xiv Contributors
MELISSA FISCHER, MD • Department of Female Urology, Urodynamics and Pelvic

Reconstructive Surgery, New York University School of Medicine, New York, NY
GAMAL M. GHONIEM, MD, FACS • Section of Voiding Dysfunction, Female Urology and
Reconstruction, The Cleveland Clinic; Department of Surgery/Urology NSU, OSU
and USF, The Cleveland Clinic; Chairman of Medical Student Education, The
Cleveland Clinic, Weston, FL
ERIN GIBBONS, MD • Department of Urology, University of Pittsburgh School of Medicine,
Pittsburgh, PA
DAVID A. GINSBERG, MD, FACS, USC • Department of Urology, USC Keck School of
Medicine, Los Angeles, CA; Department of Urology, Rancho Los Amigos National
Rehabilitation Center, Downey, CA
HOWARD B. GOLDMAN, MD • Section of Voiding Dysfunction and Female Urology, The
Glickman Urological Institute, The Cleveland Clinic, Cleveland, OH; Department
of Urology and Reproductive Biology, CASE School of Medicine, Cleveland, OH
E. ANN GORMLEY, MD • Department of Surgery, Section of Urology, Dartmouth-
Hitchcock Medical Center, Lebanan, NH
FRED E. GOVIER, MD • Department of Urology and Renal Transplantation, Virginia
Mason Medical Center, Seattle, WA
TOMAS L. GRIEBLING, MD, FACS, FGSA • Department of Urology, University of Kansas,
Lawrence, KS
ADONIS HIJAZ, MD • The Glickman Urological Institute at The Cleveland Clinic,
Cleveland, OH
MICHAEL J. KENNELLY, MD, FACS • Charlotte Continence Center, Charlotte Institute of
Rehabilitation, Carolinas Medical Center, Charlotte, NC; Department of Urology,
McKay Urology, Charlotte Institute of Rehabilitation, Carolinas Medical Center,
Charlotte, NC
CARL G. KLUTKE, MD • Department of Surgery, Division of Urology, Washington Uni-
versity School of Medicine, St. Louis, MO
KATHLEEN C. KOBASHI, MD • Continence Center at Virginia Mason Medical Center,
Seattle, WA; Section of Urology and Renal Transplant, University of Washington,
Virginia Mason Medical Center, Seattle, WA
WACHIRA KOCHAKARN, MD • Section of Urology, Department of Surgery, Ramathidbodi
Hospital, Mahidol University, Bangkok, Thailand; Faculty of Medicine FACS,
Ramathidbodi Hospital, Mahidol University, Bangkok, Thailand
GARY E. LEACH, MD • Tower Urology Institute for Continence, Cedars-Sinai Medical
Center, Los Angeles, CA; Center for Female Pelvic Health, Cedars-Sinai Medical
Center, Los Angeles, CA
GARY E. LEMACK, MD • Department of Urology, UT Southwestern Medical Center,
Dallas, TX
WENDY W. LENG, MD • Department of Urology, University of Pittsburgh School of
Medicine, Pittsburgh, PA
DEBORAH LIGHTNER, MD • Department of Urology, Mayo Clinic, Rochester, MN
KELLY M. MAXWELL, MD • Department of Urology, Northwestern University Feinberg
School of Medicine, Chicago, IL
COURTNEY MOORE, MD • Female Pelvic Medicine and Reconstructive Surgery, The
Glickman Urological Institute, The Cleveland Clinic, Cleveland, OH
DIANE K. NEWMAN, RNC, MSN, CRNP, FAAN • Division of Urology, Penn Center for Continence
and Pelvic Health, Philadelphia, PA
Contributors xv
VICTOR W. NITTI, MD, FACS • Department of Urology, New York University School
of Medicine, New York, NY
PRIYA PADMANABHAN, MD • Department of Urology, New York University School
KENNETH M. PETERS, MD • Department of Urology, William Beaumont Hospital, Royal
Oak, MI
RAYMOND RACKLEY, MD • Section of Female Pelvic Medicine and Reconstructive
Surgery, The Glickman Urological Institute, The Cleveland Clinic, Cleveland, OH
SHLOMO RAZ, MD • Department of Urology, Female Urology and Reconstructive
Surgery, UCLA School of Medicine, Los Angeles, CA; Department of Pelvic
Medicine, UCLA School of Medicine, Los Angeles, CA
LARISSA V. RODRÍGUEZ, MD • Department of Urology, David Geffen School of Medicine–
UCLA, Los Angeles, CA
NIRIT ROSENBLUM, MD • Department of Urology, New York University School of Medicine,
New York, NY
CHRISTOPHER C. ROTH, MD • Department of Urology, LSU/Ochsner Urology Program,
New Orleans, LA
ERIC S. ROVNER, MD • Department of Urology, Medical University of South Carolina,
Charleston, SC
MATTHEW P. RUTMAN, MD • Department of Urology, Columbia University School
HARRIETTE M. SCARPERO, MD • Department of Urologic Surgery, Vanderbilt University
Medical Center, Nashville, TN
PATRICK J. SHENOT, MD • Department of Urology, Jefferson Medical College, Department
of Urology, Philadelphia, PA
DOLORES SHUPP-BYRNE, PhD • Department of Urology, Jefferson Medical College,
Philadelphia, PA
STEVEN SIEGEL, MD • Metro Urology, Centers for Continence Care and Female
Urology, Minneapolis/St. Paul, MN
AJAY SINGLA, MD, FACS, FRCS, FICS • Department of Urology and Gynecology and
Department of Biomedical Engineering, Wayne State University, Detroit, MI; Vice
President and Urology Chair, International College of Surgeons-US Section
CRAIG B. SLOTOROFF, MD • Jefferson Medical College, Department of Urology,
Philadelphia, PA
SUZETTE SUTHERLAND, MD • Metro Urology, Centers for Continence Care and Female
Urology, Plymouth, MN
JENNIFER TAKACS • Department of Urology, UT Southwestern Medical Center, Dallas, TX
SANDIP VASAVADA, MD • Section of Female Urology and Voiding Dysfunction, The
Glickman Urological Institute, The Cleveland Clinic, Cleveland, OH
JEFFREY P. WEISS, MD • Department of Urology, The James Buchanan Brady
Department of Urology, The Joan and Sanford I. Weill Medical College of Cornell
University, New York, NY
O. LENAINE WESTNEY, MD • Division of Urology, University of Texas Medical School
at Houston, Houston, TX
J. CHRISTIAN WINTERS, MD • Department of Urology and Department of Female
Urology and Voiding Dysfunction, Ochsner Health Systems, New Orleans, LA
E. JAMES WRIGHT, MD • Department of Urology, Johns Hopkins Bayview Medical
Center, John Hopkins University, Baltimore, MD
PHILIPPE E. ZIMMERN, MD • Department of Urology, UT Southwestern Medical Center,
Dallas, TX
List of Color Plates
Color insert appears following p. 174
Color Plate 1. Fig. 1.4. See legend on p. 6 and discussion on p. 5.
Color Plate 5. Fig. 11.1. See legend and discussion on p. 161.
xvii



EVALUATION
I
1 Anatomy of Pelvic Support
Melissa Fischer, MD, Priya Padmanabhan, MD,

and Nirit Rosenblum, MD
CONTENTS
INTRODUCTION
BONY PELVIS
MUSCULATURE AND FASCIAE OF THE PELVIS
PELVIC CIRCULATION
FEMALE PELVIC VISCERA
PERINEUM
CONCLUSION
REFERENCES
INTRODUCTION
Female pelvic anatomy can be a conceptual challenge. To understand the function of
the pelvis, one must understand the basic anatomy and then the dynamic nature of the
structures that allow for urinary and bowel continence in a variety of circumstances. An
understanding of normal anatomy and function provides the clinician with a framework
for understanding the pathophysiology of pelvic organ prolapse and female urinary
incontinence. The evaluation of female urinary incontinence often involves the recognition
and treatment of concurrent pelvic abnormalities, such as cystocele, uterine prolapse,
enterocele, rectocele, or perineal laxity. The factors responsible for pelvic floor relaxation
rarely affect isolated anatomic areas. This chapter provides a detailed description of
normal female pelvic anatomy, and an emphasis is placed on key surgical landmarks for
reestablishing normal anatomy.
BONY PELVIS
The bony pelvis is comprised of the sacrum, coccyx, and two innominate bones,
formed by the fusion of the iliac, ischial, and pubic bones (Fig. 1) (1). An opening is
found between the pubic and ischial bones, medial to the acetabulum, known as the
obturator foramen. The ischiopubic ramus is the medial fusion of the pubic and ischial
bones. Transobturator devices used during antiincontinence procedures are passed
around the midpoint of this structure through the obturator foramen. The pectineal line
on the anteromedial aspect of the pubic bone is an important surgical landmark for
retropubic urethral suspensions (Fig. 2). The supporting sutures are often placed in
Cooper’s (pectineal) ligament, which overlies the pectineal line (1).
From: Current Clinical Urology: Female Urology: A Practical Clinical Guide

Edited by: H. B. Goldman and S. P. Vasavada © Humana Press Inc., Totowa, NJ
3
4 Part I / Evaluation
Fig. 1. The bones of the pelvis. (From ref. 13.)
Fig. 2. Surgical landmarks for retropubic urethral suspensions. (From ref. 14.)
The pelvic floor is diamond shaped, with the pubic symphysis anteriorly, the sacrum
posteriorly, and the ischial spines laterally as its apices. These structures provide the main
anchoring points for the supporting structures of the pelvic floor (2). The sacrospinous
ligaments (SSLs) span the posterior aspect of the pelvic floor from the ischial spines to
Chapter 1 / Anatomy of Pelvic Support 5
Fig. 3. Pelvic floor musculature and perineal body. (From ref. 15.)
the anterolateral aspect of the sacrum and coccyx, creating the greater and lesser sciatic
foramina (Fig. 1). The SSLs are instrumental in many prolapse repair techniques. Medially,
the SSL fuses with the sacrotuberous ligament, and together they serve to stabilize the
sacroiliac joint (3).
MUSCULATURE AND FASCIAE OF THE PELVIS

The striated musculature of the pelvic floor provides dynamic support for the visceral
contents of the abdominopelvic cavity. The pelvic floor consists of the pelvic diaphragm
and the perineal membrane, which are described separately (Fig. 3) (3). The pelvic dia-
phragm refers to the levator ani group (LAG), the coccygeus muscles, and the associated
fascia. The coccygeus muscle runs between the ischial spine and the lateral aspect of the
sacrum and coccyx, overlying the SSL. The LAG is comprised of the puborectalis,
pubococcygeus, and iliococcygeus, named according to their respective points of origin
(Fig. 4). These muscles form a shelf of support for the pelvic organs. The pelvic
diaphragm is innervated by proximal branches of the pudendal nerve and directly inner-
vated by S3 and S4 sacral nerve roots (4). The pudendal nerve is described in more
detail in the section on pelvic circulation.
Laterally, this broad sheet of muscle is attached to the pelvic sidewall by the arcus
tendinous fasciae pelvis (ATFP). The ATFP is a curvilinear condensation of the pelvic
fascia overlying the obturator internus muscle from the ischial spine to the lower aspect
of the pubic symphysis. The obturator internus is located on the pelvic sidewall and
passes through the lesser sciatic foramen to insert on the greater trochanter of the femur
(2). The ATFP provides support for the majority of the anterior pelvic diaphragm to the
bony pelvis and is often utilized for support during pelvic floor reconstruction.
Fig. 4. Levator ani group (LAG). PR, puborectalis; PC, pubococcygeus; IC, iliococcygeus; O, obturator
muscle; TA, tendinous arc of the obturator muscle.
Midline apertures in the LAG allow passage of the urethra, vagina, and rectum. These
apertures are collectively referred to as the levator hiatus. The dimensions of the hiatus
can vary depending on parity (Fig. 5). The LAG and associated fascial attachments
provide a dynamic hammock of support for these structures, contributing significantly
to urinary and fecal continence. The endopelvic fascia is a viscerofascial layer, superior
to the LAG, just beneath the peritoneum and covering adjacent organs (2). There are
several condensations of levator ani fascia that serve discrete functions. For example,
the medial edge of the LAG fascia corresponds anteriorly, around the bladder, to the
pubocervical fascia and posteriorly, around the cervix, to the cardinal and uterosacral
ligaments. The uterosacral and cardinal ligaments are important fascial condensations
involved in supporting the uterus and upper vagina and are discussed in the section on
genital structures.
The pubocervical fascia, also known as the vesicopelvic ligament, is a continuous
band of connective tissue from the pubic symphysis to the cervix (Fig. 6). The fascia is
a fusion of the superior layer of levator ani fascia (endopelvic fascia) and the posterior
layer. The fascia fuses anteriorly with the periurethral, perivesical, and anterior vaginal
wall fascia and posteriorly to the cardinal ligament complex. Attenuation of this fascial
support, either laterally from the ATFP or centrally, results in a cystocele. The pubo-
urethral ligaments support the urethra to the inferior pubis, just proximal to the striated
sphincter. The urethropelvic ligaments are derived from a fusion of the endopelvic and
periurethral fascia and are continuous with the pubocervical fascia laterally (Fig. 7).
These ligaments attach laterally to the ATFP on the pelvic sidewall, providing crucial
Fig. 5. Levator hiatus. (A) Normal levator floor and vaginal hiatus. (B) Attenuation and separation of
the levator fibers and widening of the posterior vaginal hiatus with parity. (From ref. 15.)
support to the urethra and anterior vaginal wall. An understanding of the supporting
structures of the pelvis is essential for successful reconstructive surgery.
PELVIC CIRCULATION
The arterial blood supply to the pelvis and perineum are briefly reviewed. Venous
drainage for the most part parallels the arterial vessels. The aorta bifurcates at the level
of the fourth lumbar vertebrae into the common iliac arteries (Fig. 8). The arteries run
anterior and lateral to the veins at this level (1). The common iliacs divide into the exter-
nal and internal iliac arteries at the level of the sacroiliac joint. The external iliac runs
along the medial aspect of the iliopsoas and exits the pelvis posterior to the inguinal
ligament as the femoral artery. In pelvic reconstructive surgery, the pertinent branches
Fig. 6. Anterior vaginal fascial support. (From ref. 15.)
Fig. 7. Schematic of urethral and anterior vaginal wall support.
of the femoral artery are the external pudendal artery to the labial fibrofatty pad and the
inferior epigastric artery, which supplies the rectus abdominus muscle. These relationships
are important during rotational flap techniques.
The internal iliac artery divides into an anterior and posterior trunk. The posterior
trunk gives off the superior gluteal, ascending lumbar, and lateral sacral arteries. The
anterior trunk has seven branches: superior vesical, middle rectal, inferior vesical,
uterine, internal pudendal, obturator, and inferior gluteal arteries (1). The course and
relationships of several of the branches are highlighted as they pertain to pelvic floor
surgery.
The obturator canal is an opening in the membrane overlying the obturator internus
through which the obturator vessels and nerve pass. The obturator nerve arises from the
Fig. 8. Pelvic circulation. (From ref. 16.)
L2 through S1 nerve roots and exits the pelvis through the obturator canal, where it
divides into anterior and posterior divisions to supply the muscles of the adductor
compartment. The obturator canal is nearly 5 cm superolateral to the midpoint of the
ischiopubic ramus. This relationship should be kept in mind when passing a device
around the ischiopubic ramus for a transobturator procedure (5).
The internal pudendal vessels and the pudendal nerve (S2–S4) exit the pelvis through
the greater sciatic foramen, wrapping around the ischial spine and SSL laterally (Fig. 9).
Care must be taken to avoid these structures when placing sutures in the SSL. The
pudendal nerve and vessels then pass through the lesser sciatic foramen and course
alongside the lateral aspect of the ischiorectal fossa to enter the pudendal canal (Alcock’s
canal) in the posterior perineum. The pudendal nerve branches into the inferior rectal,
perineal, and dorsal (clitoral) nerves (6).
Understanding lymphatic drainage is mainly significant in treating pelvic malignancy
but can be relevant in inflammatory states. The pattern of lymphatic drainage parallels
the venous circulation. The vulvar lymphatic vessels, including the distal urethra and
lower third of the vagina, drain into the inguinal lymph nodes. The bladder, proximal
urethra, uterus, and upper two-thirds of the vagina drain into the pelvic lymph nodes
(obturator, internal, and external iliac). The ovarian lymphatics follow the gonadal
vessels and drain into the para-aortic nodes (3).
Fig. 9. Nerves of the female perineum. (From ref. 16.)
FEMALE PELVIC VISCERA

Lower Urinary Tract
The bladder is comprised of the body and the trigone and normally serves to store
urine at low pressures and effectively contract to urinate (7). The bladder is composed
of an inner transitional epithelium, a multilayer muscular wall, and an outer serosal
covering. The exact dimensions and configuration of the bladder vary considerably
depending on degree of distention, prolapse, or other pathology. The bladder base and
urethra rest on the anterior vaginal wall (1). The bladder is an extraperitoneal organ
covered by peritoneum at the dome superiorly and posteriorly. The peritoneum then
reflects onto the anterior vagina and uterus, forming the vesicouterine pouch, and
continues over the posterior uterus and onto the rectum, creating the rectouterine space
or pouch of Douglas (Fig. 10) (3). The peritoneum in the rectouterine space may herniate
into the posterior vagina, resulting in an enterocele.
The ureter is a continuation of the renal collecting system and transports urine
from the kidney to the bladder (8). The ureter courses inferiorly and medially; below
the inferior border of the sacrum, the ureter is referred to as the lower, distal, or
pelvic ureter. The position of the distal ureter can be affected by bladder distention or
Fig. 10. Peritoneal cleavage planes. (From ref. 3.)
significant prolapse, and it is susceptible to injury during pelvic reconstruction. The

ureter crosses anterior to the common iliac vessels at the bifurcation medial to the
ovarian vessels. The course of the ureter is retroperitoneal and runs deep to the base
of the broad ligament before traveling through the cardinal ligament, where the ureter
passes underneath the uterine artery (Fig. 11) (3). The ureter is located in the anterior
vaginal wall before entering the bladder and is usually 1.5 cm superolateral to the
cervix (1).
The female urethra is approx 4 cm in length and extends from the bladder neck to the
external urethral meatus (1). As mentioned, the midportion of the urethra is attached
to the inferior pubis by the pubourethral ligaments. The ligaments divide the urethra
into proximal and distal halves; the external sphincter is just distal to the ligaments. The
urethra is typically divided into three portions: proximal, mid, and distal. The proximal
urethra is responsible for passive continence. The midportion, which contains the rhabdo-
sphincter, is responsible for passive and active continence. The distal one-third is
principally a conduit and, if damaged or resected, usually does not have an impact on
continence. The epithelium of the urethra varies proximal to distal, transitional to non-
keratinized squamous epithelium, respectively. Many small glands communicate with
the urethra and may be a source of urethral diverticula. The urethra is bordered laterally
by two small labia, which contain minor vestibular glands. The Skene ducts open on the
inner aspect of these labia and when inflamed can be palpated on the distal anterior
vaginal wall as a suburethral mass (3).
The mechanism of continence is multifactorial. Innate properties of the urethra provide
a measure of control. The urethral epithelium has many infoldings, which result in a
mucosal seal (Fig. 12). The surrounding vascular spongiosum and outer musculofascial
Fig. 11. Course of the ureter. (From ref. 3.)
layer provide additional compression of the urethra. The urethropelvic ligaments provide
passive and active support. They suspend the bladder neck and urethra in a higher retro-
pubic position than the more dependent bladder base, creating a valvular effect. During
increased activity of the LAG, the ligaments are drawn laterally, increasing compression
of the urethra and thereby augmenting continence. Finally, the urethral striated sphincter
provides resting tone, contributing to the closing forces of the urethra, and allows for
reflex and voluntary urinary control.
The ability to store urine safely and effectively and volitionally void at desired times
is a complex process involving the central nervous system and an intact spinal cord.
Innervation of the bladder and urethra is briefly reviewed as it is pertinent to urinary
continence (Fig. 13). The urinary system is regulated by autonomic and motor neurons.
The sympathetic nerves arise from the thoracolumbar region (T10–L2) and are carried
via the hypogastric nerve, which mediates storage. The parasympathetic nerves originate
from the sacral cord (S2–S4), are carried via the pelvic nerve, and facilitate detrusor
contraction and voiding. The pudendal nerve, as described in the section on pelvic circu-
lation, also originates from the sacral cord and innervates the urethral rhabdosphincter.
Afferent or sensory fibers, which are important during the storage phase, are carried via
the pelvic, hypogastric, and pudendal nerves (9).
Genital Structures
The uterus is a fibromuscular organ with dimensions and exact orientation that vary
considerably depending on hormonal status, age, and parity (3). It is comprised of two
Fig. 12. Urethral histology. E, urethral epithelium; S, surrounding vascular spongiosum; M, outer
musculofascial layer.
parts, an upper muscular corpus and a lower fibrous cervix. The uterus is lined by a
unique epithelium, the endometrium. The external cervical os is lined by squamous
epithelium and more proximally by columnar epithelium. The uterus and cervix are
supported by surrounding ligaments and fascia (Fig. 14). The cardinal ligaments are
dense, triangular condensations of pelvic fascia that originate from the pelvic sidewall
and insert into the lateral aspects of a fascial ring encircling the uterine cervix. The
cardinal ligaments support the uterus and vaginal apex and, as mentioned, fuse with
the pubocervical fascia, providing support for the bladder base (2). The cardinal liga-
ments fuse posteriorly with the uterosacral (sacrouterine) ligaments, which stabilize
the uterus, cervix, and upper vagina posteriorly to the sacrum. In addition, the broad
ligaments are fascial condensations covered by anterior and posterior sheets of perito-
neum, which provide lateral support for the more superior portion of the uterus. Many
important structures travel within the broad ligament, the fallopian tubes, the round and
ovarian ligaments, and the uterine and ovarian vessels. The uterine arteries enter near
the junction of the corpus and the cervix; however, this position varies considerably
(Fig. 11) (3).
The vagina is a hollow viscus with shape that is determined by the structures that
surround it. The vagina receives blood supply from downward branches of the uterine
artery and vaginal branches of the internal iliac (3). It is made up of an inner epithelium
layer, a stratified squamous epithelium, an inner muscular layer, and an outer fibrous
layer. The upper vagina is maintained in a nearly horizontal axis by fascial support and
inferiorly by the LAG shelf on which it is resting (Fig. 15). When this orientation is altered
postpartum or iatrogenically, vaginal prolapse may occur (2). Maintaining functional
depth and an adequate hiatus are important considerations in women who desire future
sexual activity.
Fig. 13. Bladder and urethral innervation and mechanism of continence. (From ref. 17.)
PERINEUM
The anatomic boundaries of the perineum are the pubis, thighs, and buttocks and can
be divided into an anterior urogenital and a posterior anal triangle by drawing a line
between the ischial tuberosities (Fig. 3) (7). The perineal body is a tendinous structure
in the midline of the perineum between the anus and the vaginal introitus, which
provides a central point of fixation for the superficial transverse perineal muscle, the
striated urogenital sphincter (formerly the deep transverse perineal muscle), the bulbo-
cavernosus muscles anteriorly, and the external anal sphincter posteriorly (3). The
perineal membrane, formerly the urogenital diaphragm, refers principally to the deep
transverse perineal muscles and associated superior and inferior fascia. This fibromus-
cular sheet is triangular shaped, with openings for the urethra and vagina, and supports
the anterior triangle. Voluntary contraction of the perineal membrane results in vaginal
compression and provides stability to the perineum during periods of increased intrab-
dominal pressure.
Fig. 14. Schematic diagram of normal uterine support. (From ref. 7.)
Fig. 15. Schematic diagram of normal vaginal support. (From ref. 7.)
Fig. 16. Schematic diagram of the rectovaginal septum. (From ref. 11.)
The clitoris is located at the apex of the urogenital triangle and is composed of
a glans, shaft, and crura. The shaft is anchored to the pubic bone by the suspensory
ligament. The crura run posterolaterally along the pubic rami. The urogenital triangle
is bordered laterally by the ischiocavernosus muscles, which originate from the
ischial tuberosities and the free posterior crura and insert onto the anterior crura and
the body of the clitoris (3). The bulbocavernosus muscles run on each side of the
vaginal vestibule beneath the labia majora from the pubis to the perineal body.
Beneath the bulbocavernosus muscles are the vestibular bulbs, which are highly vas-
cular erectile tissue. The Bartholin gland is found at the inferior aspect of the bulb;
therefore, care should be taken to minimize bleeding when dissecting in this area (3).
Of clinical significance, a fibrous fat pad lies just beneath the skin of the labia
majora, which can be used as a vascularized flap (Martius flap) when a multilayer
vaginal closure is necessary. The strength of the graft is derived from termination
of the round ligament into the fibrofatty tissue. The flap can be based inferiorly off
the inferior labial artery, a branch of the internal pudendal, or superiorly off the
superficial external pudendal artery (10).
The posterior triangle is described briefly as it relates to posterior vaginal wall prolapse.
The anatomy and function of the anal continence mechanism is complex and is outside
the scope of this text; however, defecatory, voiding, and sexual issues are all interrelated
and should be addressed during evaluation. The apex of the posterior or anal triangle is
the coccyx. The anus is located in the midline. An important space within the posterior
triangle is the posterior aspect of the ischiorectal fossa through which the pudendal
vessels and nerves traverse. This fossa is bordered by the LAG superomedially, the
obturator internus anterolaterally, and the skin inferiorly (3).
The rectovaginal septum is an extension of the peritoneal cul-de-sac between the
posterior vagina and the rectum to the perineal body, separating the urogenital and rectal
compartments (Fig. 16) (11). The septum is comprised of two distinct layers: the vaginal
Fig. 17. Schematic diagram of various breaks in the rectovaginal septum seen in patients with recto-
celes. (From ref. 11.)
wall fascia and the prerectal fascia. It is only distally, at the perineal body, that they fuse.
Proximally, the septum merges with the cardinal-uterosacral ligament complex, pro-
viding support for the posterior vaginal apex. Laterally, this fascial layer attaches to the
ischiococcygeus and pubococcygeus just below the ATFP (11). Furthermore, the pubo-
coccygeus muscle provides support for the proximal posterior vagina and intrapelvic
rectum. Transverse detachment of the rectovaginal septum from the perineal body may
result in a distal rectocele, or disruption of the prerectal fascia may result in a more
proximal rectocele (Fig. 17).
CONCLUSION
Each year in America an estimated 400,000 women undergo surgery for pelvic floor
dysfunction. Nearly 30% of the surgeries performed are reoperations (12). Clinicians
must have a clear understanding of functional anatomy and pathophysiology to accurately
diagnose and effectively treat disorders of the female pelvis. Successful pelvic floor
reconstruction requires consideration of the primary concern and any other often-
associated pelvic floor disorders.
REFERENCES
1. Brooks JD. Anatomy of the lower urinary tract and male genitalia. In: Campbell’s Urology, 8th ed.
(Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds.), Saunders, Philadelphia, 2002;41–80.
2. Klutke CG, Siegel CL. Functional female pelvic anatomy. Urol Clin North Am 1995;22:487–498.
3. De Lancey JO. Surgical anatomy of the female pelvis. In: Te Linde’s Operative Gynecology, 9th ed.
(Rock JA, Jones HW, eds.), Lippincott, Williams, and Wilkins, Philadelphia, 2003;63–93.
4. Strohbehn K. Normal pelvic floor anatomy. Obstet Gynecol Clin North Am 1998;25:683–705.
5. Whiteside JL, Walters MD. Anatomy of the obturator region: relations to a trans-obturator sling. Int
Urogynecol J 2004;15:223–226.
6. Bartsch G, Strasser H, Poisel S. Surgical anatomy of the genitourinary system. In: Adult and Pediatric
Urology, 4th ed. (Gillenwater JY, Grayhack JT, Howards SS, Mitchell ME, eds.), Lippincott, Williams,
and Wilkins, Philadelphia, 2002;3–46.
7. Wahle G, Young G, Raz S. Anatomy and pathophysiology of pelvic support. In: Female Urology,
2nd ed. (Raz S, ed.), Saunders, Philadelphia, 1996;57–72.
8. Kabalin J. Surgical anatomy of the retroperitoneum, kidneys and ureter. In: Campbell’s Urology,
8th ed. (Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds.), Saunders, Philadelphia, 2002;3–40.
9. Chancellor M, Yoshimura N. Physiology and pharmacology of the bladder and urethra. In: Campbell’s
Urology, 8th ed. (Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds.), Saunders, Philadelphia, 2002;
831–886.
10. Stothers L, Chopra A, Raz S. Vesicovaginal fistula. In: Female Urology, 2nd ed. (Raz S, ed.), Saunders,
Philadelphia, 1996;490–506.
11. Richardson AC. The rectovaginal septum revisited: its relationship to rectocele and its importance to
rectocele repair. Clin Obstet Gynecol 1993;36:976–983.
12. DeLancey JO. The hidden epidemic of pelvic floor dysfunction: achievable goals for improved
prevention and treatment. Am J Obstet Gynecol 2005;192:1488–1495.
13. Hinman F Jr. Atlas of Urosurgical Anatomy, Saunders, Philadelphia, 1993.
14. Paraiso MFR, Falcone T. Laparoscopic surgery for genuine stress incontinence and pelvic organ
prolapse. In: Urogynecology and Reconstructive Pelvic Surgery (Walters MD, Karram MM, eds.),
Mosby-Yearbook, St. Louis, MO, 1999, p. 199:213–226.
15. Raz S, Little NA, Juma S. Female urology. In: Campbell’s Urology, 6th ed. (Walsh PC, Retik AB,
Stamey TA, Vaughan ED Jr, eds.), Saunders, Philadelphia, 1992, p. 2783:2782–2828.
16. Netter FH. Atlas of Human Anatomy. Icon Learning Systems, Teterboro, NJ, 2003.
17. Benson JT, Walters MD. Neurophysiology of the lower urinary tract. In: Urogynecology and
Reconstructive Pelvic Surgery (Walters MD, Karram MM, eds.), Mosby-Yearbook, St. Louis, MO,
1999;31–43.
Neurophysiological Control
2 of Bladder Function
Toby C. Chai, MD, FACS and Todd J. Lehrfeld, MD

CONTENTS
INTRODUCTION
HIGHER LEVEL CENTRAL NERVOUS SYSTEM CONTROL
OF MICTURITION AND STORAGE
CONCLUSION
REFERENCES
INTRODUCTION
Normal bladder function is characterized by storage of adequate volumes of urine at
low pressures without leakage and without unwanted bladder sensations (urgency)
interspersed with short time periods of efficient unimpeded expulsion of urine. Tightly
regulated neural control of the bladder and outlet (urethral complex, i.e., internal and
external urethral sphincters) is required for the proper integration of urinary storage and
expulsion. The bladder and internal urethral sphincter are comprised of smooth muscle
fibers, whereas the external urethral sphincter is composed of skeletal striated muscle
fibers. Although we have learned much of bladder neurophysiology from studying
animal models, the actual pathological defects in bladder dysfunction frequently
encountered clinically, such as urinary incontinence (both stress and urge), nonneuro-
genic detrusor overactivity, hypersensitive bladder syndromes (e.g., overactive bladder
[OAB] and interstitial cystitis [IC]), and nonobstructive urinary retention, remain elusive.
Animal models have helped test etiological theories and define treatment modalities for
disorders of micturition and urinary continence. This review focuses on data obtained
from experiments performed with human tissues if available.
There is less published literature about neurophysiological control of urethral function
compared with that of the bladder. In addition, the functional framework of the urethral
complex is opposite that of the bladder: during storage, the urethra is contracted, and
the bladder is relaxed; during expulsion, the urethra is relaxed, and the bladder is con-
tracted. Therefore, treatments designed to reverse bladder dysfunction would require
opposite effects on the urethra.
The bladder is unique among autonomically innervated organs because of the high
degree of conscious or voluntary control that can be exerted on its function. This means
that well-established neural connections from higher neural centers (e.g., cerebral cortex)
to the bladder exist. Therefore, the neural control of bladder function is complex, and
a neurophysiological defect anywhere from the cerebral cortex to the bladder can result

19
in bladder dysfunction. This complexity in part explains our limited understanding of the
pathophysiology of bladder dysfunction and the limited treatments available for these
bladder problems. This chapter’s intent is to present a review of current literature on
bladder neurophysiology and its clinical relevance. Literature from experimental studies
utilizing humans or human bladder tissues is emphasized for maximal clinical relevance.
Bladder Efferent Pathway

PERIPHERAL EFFERENT NEURAL PATHWAYS
The motor pathway to the bladder is autonomic, meaning that there is at least one
synapse prior to the synapse at the motor neuromuscular junction (nerve terminal and
bladder smooth muscle fiber). The bladder efferent neuronal bodies originate from the
S2–S4 spinal cord within the sacral parasympathetic nucleus, which is situated between
the ventral and dorsal horn gray matter (Fig. 1, area 5). The preganglionic axons exit the
spinal cord in the ventral roots and merge into the periphery in the pelvic nerves. These
pelvic nerves synapse at ganglia within the periphery at the pelvic plexus or even within
the bladder wall (intravesical ganglia; Fig. 1B) (1,2). The postganglionic nerves then
synapse onto the bladder smooth muscle cells. The end effect of activation of the efferent
pathway is a coordinated, efficient bladder contraction that results in bladder emptying.
The sympathetic motor neuronal bodies reside in the thoracolumbar spinal cord. The
preganglionic motor fibers exit the spinal cord within the ventral nerve roots. The pre-
ganglionic fibers synapse on the postganglionic nerve at the paravertebral ganglia,
which lie close to the spinal cord. The postganglionic nerve becomes the hypogastric
nerve, closely following the hypogastric artery to innervate the bladder.
Although the role of the sympathetic motor innervation in normal bladder function is
not totally clear in the human, work in the cat suggests that it has a role in maintenance
of urinary continence. Activation of sympathetic outflow to the bladder via stimulation
of bladder afferents in anesthetized cats caused the bladder to relax and urethra to contract
(3,4). This vesicosympathetic pathway may have importance in maintaining continence
in humans. The relaxation of the bladder may be through inhibition of the parasympa-
thetic intravesical ganglia or through activation of G3-adrenergic receptor (G3-AR) on
the bladder. The human bladder smooth muscle has been found to have G3-AR, which
may mediate its relaxation (5). Therefore, the concept of using a G3-AR agonist for
detrusor overactivity is under active investigation.
DETRUSOR SMOOTH MUSCLE SIGNALING

The neurotransmitter released by the preganglionic parasympathetic nerves is acetyl-
choline. The postganglionic parasympathetic nerves also release acetylcholine, which
binds to muscarinic receptors (M2 and M3) on the bladder smooth muscle cells to initiate
the excitation-contraction event. Bladder smooth muscle contraction mechanisms have
been extensively studied because it is easy to obtain smooth muscle from animal models,
both in normal and experimentally induced diseased states (e.g., bladder outlet obstruc-
tion [BOO], diabetes, inflammation models). One must remember, however, that muscle
bath experiments are in vitro studies in which the bladder has been typically stripped of
the urothelium and neural input; thus, the findings from organ baths do not necessarily
reflect the complete in vivo picture.
In the normal human bladder, although M2 receptors predominate in quantity (70%
of total muscarinic receptors), it is actually the M3 receptors (30% of total) that are
Chapter 2 / Neurophysiological Control of the Bladder 21
Fig. 1. 1, medial preoptic (MPO) area; 2, periaqueductal gray (PAG) area; 3, pontine micturition center
(PMC), M region, or Barrington’s nucleus; 4, L region; 5, sacral parasympathetic nucleus; 6, Onuf’s
nucleus; A, dorsal root ganglia; B, intramural ganglia. See text for details.
responsible for contractions measured in an organ bath (6,7). However, M2 receptors,

not M3 receptors, mediate organ bath contractions in spinal cord-injured humans (8). It
was also shown that mRNA for M3 receptor decreased as a function of aging in the
human bladder (9), possibly explaining decreased contractility of the bladder in the
elderly. Another study suggested that unique variations in expression of M2 and M3
receptors could explain variable responses to antimuscarinics (10).
It has always been supposed that the mechanism of action of antimuscarinics in treating
patients with urinary urgency, frequency, and urge incontinence (OAB) is blockade of
presumed unwanted and “uninhibited” bladder smooth muscle contractions mediated
by either M2 or M3 receptors. Whether these presumed pathological detrusor smooth
muscle contractions are pathophysiological, whether there is an alteration in muscarinic
receptor phenotype distribution (M2:M3 ratio), or whether the primary pathology in
OAB is in the motor efferent pathway is not currently known. The physiological defect
in OAB may not lie completely in the bladder motor pathway and may also involve
the sensory pathway. It certainly would seem logical that urinary urgency is a sensory-
initiated phenomenon. Nevertheless, the efficacy of antimuscarinics for treatment of OAB
symptoms has been shown in multiple large clinical trials (11).
Muscarinic receptor activation can initiate various cascades of secondary messenger
events, which ultimately increases intracellular cytosolic calcium, the trigger for smooth
muscle contraction (Fig. 2). The prototypical smooth muscle contraction signaling
by increased cytosolic calcium is best explained by M3 receptor activation. M3 activa-
tion results in activation of phospholipase C, which hydrolyzes phosphoinositide-4,
5-biphosphate with subsequent release of inositol triphosphate (IP3) and diacylgycerol
(DAG) (12). DAG activates protein kinase C, which can increase cytosolic calcium through
release of intracellular stores. IP3 activates release of calcium from the sarcoplasmic
reticulum. These events ultimately result in increased cytosolic calcium. Surprisingly,
this prototypical sequence of events of phospholipase C activation and IP3 and DAG
release was not critical to M3-mediated human detrusor smooth muscle contraction (13),
demonstrating that there are species differences in secondary messenger events even if
M3 receptor activation is the upstream event. The contractions in human detrusor smooth
muscle were largely mediated by calcium influx through L-type, voltage-dependent
channels (Fig. 2) (nifedipine-sensitive channels).
The mechanism by which M2 receptors mediate detrusor smooth muscle contraction
is less direct than for M3 receptors, although increased cytosolic calcium is still the
ultimate event (Fig. 2) (14,15). It is important to understand downstream events of M2
receptor-mediated contractions as it has been shown that human bladders obtained from
spinal cord-injured patients have M2-mediated contractions (8). Activated M2 receptors
interact with the Gi unit of the G-family of signaling proteins. Gi then inhibits adenylyl
cyclase, resulting in decreased cytosolic adenosine monophosphate (cAMP). If cAMP
is decreased by M2 receptor activation, then cystosolic calcium will be increased, which
can lead to muscle contraction. Increased intracellular cAMP is also the key event
when the G-adrenergic receptor is activated, with resultant adenylyl cyclase activity
(Fig. 2). M2 receptor activation could induce smooth muscle contraction by counteracting
sympathetic effects on detrusor smooth muscle.
Receptors other than M3 may also mediate bladder contractions. This was based on
findings that bladder contractions in animals were resistant to both cholinergic and
adrenergic blockade (termed nonadrenergic, noncholinergic-mediated bladder contrac-
tions) (16). For example, in humans, it was shown that the purinergic agent adenosine
Fig. 2. Representation of a detrusor smooth muscle cell. See text for details.
triphosphate (ATP) can cause bladder smooth muscle contractions (17). These ATP-
mediated contractions occur through the P2X1 receptors on the bladder smooth muscle
(18). In disease states, bladder contractions could shift from muscarinic- to purinergic-
mediated mechanisms. In humans, it has been shown that bladder smooth muscle strips
obtained from patients with IC are much more responsive to ATP compared to control
human bladder strips (19). Also, in aging, the human detrusor has an increased purinergic
trigger as the basis for its contractions (20).
The excitation-coupling that occurs in the detrusor smooth muscle is triggered by
increased cytosolic calcium. Calcium binds to calmodulin and causes a conformal change
in calmodulin-exposing sites, which interact with myosin light-chain kinase. Myosin
light-chain kinase activation phosphorylates myosin light chain (MLC) protein, which
results in cycling of myosin crossbridges (heads) along actin filaments and the develop-
ment of tension (Fig. 2). Furthermore, phosphorylation of MLC activates myosin
adenosine triphosphatase ATPase, which hydrolyzes ATP to provide energy for detrusor
smooth muscle contraction. A secondary excitation-coupling mechanism that is calcium
independent can also occur via the rho-rho-kinase pathway. This pathway is dependent
on inhibition of MLC dephosphorylation (via inhibition of myosin phosphatase; 21).
The rho-rho-kinase pathway has been shown to mediate human detrusor smooth muscle
contractions (13,22). The rho-rho-kinase pathway may represent another therapeutic
target, assuming either it is pathologically altered in disease or it can be harnessed to
compensate for defects in the calcium-dependent excitation-coupling pathway.
One clinical condition that seems to be directly related to the efferent system is that of
idiopathic nonobstructive urinary retention. When patients present in urinary retention
without identifiable BOO, it is presumed that the detrusor smooth muscle is dysfunc-
tional in its ability to generate a contraction. However, treatment with oral urecholine, a
muscarinic agonist, has not proven to be uniformly useful clinically even though the first
description of its use was over half a century ago (23). Failure of the smooth muscle to
contract may be caused by a variety of reasons, including failure of the efferent nerves to
release acetylcholine, failure of the urethra or bladder outlet (pelvic floor) to relax, or
failure of excitation-contraction coupling at any point along the pathway from muscarinic
receptor activation to force generation. A synopsis of the complexities of smooth muscle
function in the lower urinary tract has been published (24).
CLINICAL MEASURES OF BLADDER EFFERENT PATHWAY
The clinical tool used to measure detrusor contraction is the cystometrogram. An
increase in intravesical pressure is measured during a detrusor contraction. When simul-
taneous uroflowmetry is obtained during the voiding phase of the cystometrogram, a
pressure-flow study (PFS) is created. The primary goal of analyzing components of the
PFS data (e.g., maximum detrusor pressure, maximum urinary flow rate) is to determine
whether there is an element of BOO. BOO should result in a high detrusor contraction
pressure with decreased maximal flow rate. Various mathematical constructs derived
from the PFS data have been proposed to help stratify patients into the obstructed vs
nonobstructed category (25,26).
Although the goal of the PFS is to determine the presence of BOO, using an occlusive
bladder catheter to measure isovolumetric bladder contraction pressure has been advo-
cated to measure detrusor contractile strength (27). Impaired detrusor contractility has
been underrecognized (28), especially if isovolumetric bladder contraction pressures
are not determined. Currently, the primary and most effective treatment of detrusor failure
remains intermittent clean catheterization.
Bladder Afferent Pathway

AFFERENT NEURAL PATHWAYS
Conventionally, the bladder afferent pathway begins with sensory nerve endings within
the bladder wall, which is responsive or triggered by stretch (29). Traditionally, it was
thought that the afferent fibers terminated in the lamina propria. However, recently sensory
afferent fibers were seen to extend into the rat bladder urothelium, intermingling with
urothelial cells (30). In humans, substance P-containing nerve terminals (a marker for
sensory fibers) have been found to be in close approximation to the urothelium (31).
These fibers are part of the bipolar sensory nerve with the neural soma (bodies) residing
in the dorsal root ganglia. The other end of the sensory nerve fiber terminates in the
dorsal horn of the gray matter in the spinal cord, where descending pathways can modulate
afferent input (32). Furthermore, afferent fibers can synapse onto the sacral parasympa-
thetic nuclei to modulate the efferent outflow to the bladder (33).
The bladder sensory nerves travel in the periphery within the pelvic, hypogastric,
and pudendal nerves. These sensory nerves are comprised of A-I myelinated fibers and
c-fiber unmyelinated. The A-I fibers respond to pressure and stretch and initiate the
micturition reflex (34). The c-fibers are normally silent, but in animal models with
experimentally injured states such as inflammation and spinal cord injury, these fibers
are activated (35,36). Patients with BOO (males and females) have been shown to have
a positive bladder ice-water test, which correlates with activation of the c-fibers (37).
C-fibers, in addition to responding to ice water, also respond to capsaicin, a neurotoxin
isolated from hot peppers. Capsaicin, and its derivatives such as resiniferatoxin, has been
proposed to be used to block activated c-fibers in disease states. It has been proposed
that IC results from activation of c-fibers, which can then transmit signals of pain and
burning. However, a large, multicenter, placebo-controlled clinical trial of intravesical
resiniferatoxin for IC symptoms showed no clinical benefit (38), arguing against c-fiber
activation as the cause of IC symptoms.
Studies of the human bladder sensory pathway have been difficult because of lack of
appropriate sensory measurement tools and inability to obtain dorsal root ganglia where
sensory nerve cells reside. Our understanding of human bladder neurophysiology has
traditionally focused on the efferent pathway primarily because of resources available
to study bladder smooth muscle physiology, with most resources borrowed from other
areas, such as vascular smooth muscle. However, advances in treatment for bladder
symptoms such as urinary frequency, urinary urgency, and bladder pain require better
understanding of how bladder sensory signals are processed. A review of bladder sensory
processing has been published (39).
The neurotransmitters responsible for sensation in the human bladder, whether in
normal or diseased states, is not completely known. Putative sensory neurotransmitters
derived from animal studies include substance P, calcitonin gene-related peptide (CGRP)
and corticotrophin releasing factor (CRF) (40,41). The importance of P2X3/P2X2
purinergic receptors to bladder sensory processing has been shown with knockout
animal models. P2X3 and P2X2 knockout mice have increased bladder capacity and
decreased voiding frequency consistent with decreased afferent signaling into the
micturition reflex (42).
UROTHELIAL AFFERENT SIGNALING

The bladder urothelium has been conventionally thought to function only as a barrier,
protecting the underlying stroma from potential urinary irritants. The bladder urothelial
cell has been shown to have neuronal-like properties (43). See Fig. 3 for the graphical
representation of urothelial cell signaling mechanisms. The urothelial cell can release
neurotransmitters such as ATP (44–46), nitric oxide (47), and acetylcholine (20). The
urothelial cell also expresses receptors that are typical signal transduction receptors
found on neurons, including muscarinic receptors (48), TRPV1 or “hot” receptors
(30,49), TRPM8 or “cool” receptors (49), and purinergic receptors P2X3 and P2X2
(50,51). The first work to suggest urothelial sensory ability was that by Ferguson et al.,
which showed that rabbit bladder urothelium releases ATP in response to stretching
(44). This finding has been reproduced in other species, including humans, and using
different experimental techniques to stretch the urothelium (45,46).
The importance of bladder urothelial cell in bladder sensory signaling has been
shown in the human condition of IC. Bladder urothelial cells from patients with IC have
increased ATP release in response to stretching (45). Increased ATP released by the
urothelial cells could bind to P2X3 receptors on sensory nerve endings within the
urothelium to transduce increased sensation during bladder filling, which is a common
symptomatic finding in IC. Furthermore, IC cells express more P2X3 and P2X3 receptors,
which suggests that the augmented ATP release by the IC urothelial cells could serve an
autocrine role (50,51).
CLINICAL MEASURES OF BLADDER AFFERENT ACTIVITY

The clinical measurement of bladder sensory signals traditionally has been based
on urodynamic measurement of three sensory thresholds: first sensation of filling, first
desire to void, and strong desire to void (52). Each of these sensations was easily
distinguishable from the others. These thresholds have clinical utility, for example, in
IC, in which the bladder capacity is significantly diminished because of pain with
bladder filling (53). This study also suggested that central processing of pain was altered
in patients with IC.
A constant current electrical stimulus was applied to the bladder urothelium via
an intravesical electrode to determine sensory thresholds (54). This methodology is
purported to provide reliable measures of spinal sensory and peripheral sensory nerve
function from the large and small myelinated and unmyelinated nerve fibers.
The intent of an ice-water test is to induce a reflex bladder contraction through rapid
infusion of ice water into the bladder and activation of the c-fibers, which ultimately
trigger bladder contraction. The clinical utility of this method of sensory testing in
routine practice has not been established. The high incidence of positive ice-water test
in a population of bladder-obstructed patients has been suggested to reflect bladder
neuroplasticity (37). The ice-water test is negative in control individuals without
voiding symptoms.
HIGHER LEVEL CENTRAL NERVOUS SYSTEM CONTROL

OF MICTURITION AND STORAGE
Bladder afferents transmit bladder sensory signals to the periaqueductal gray (PAG),
an area of the midbrain associated with nociception and emotion (Fig. 1, area 2). When
the bladder is sufficiently full, the PAG activates the pontine micturition center (PMC,
M region, or Barrington’s nucleus; Fig. 1, area 3). The neurons from the PMC synapse
on the parasympathetic nucleus in the sacral spinal cord (Fig. 1, area 5) to signal a bladder
contraction. Centers higher than the PAG may contribute to micturition, including the
medial preoptic area of the thalamus (Fig. 1, area 1). The L region of the pontine area
projects to Onuf’s nucleus (Fig. 1, area 4). Onuf’s nucleus is motoneurons that project
to the urethral sphincter and pelvic floor. There, activities of the M and L regions are
reciprocal. When the M region is activated, the L region must be inhibited (or deactivated)
to allow simultaneous bladder contractions and urethral relaxation (55,56).
The high degree of volitional control of bladder function is unique for the bladder
compared to other visceral organs. Investigators have studied the human brain using
either positron emission tomography or functional magnetic resonance imaging during
bladder storage and emptying and have found similar areas of activation, the PMC and
PAG, as compared to those found in animal models such as the cat and rat (57–59).
There are several other areas that have increased activity, which demonstrates a complex
visceral-sensory motor program is involved in continence and micturition. Functional
magnetic resonance imaging studies were performed on subjects without neurological
disease but with “poor bladder control” on urodynamics. These findings were compared
to control patients with normal bladder control (60). Patients with poor bladder control
had less activation of the orbitofrontal cortex during bladder filling. Therefore, activity
of the orbitofrontal cortex suppresses promicturition signals.
The descending pathways from the PMC to the sacral parasympathetic nucleus
respond to adrenergic receptor agonists/antagonists (61,62) in modulating the micturition
27
Fig. 3. Urothelial cells can function as both sensory and transducer cells by receiving and sending signals to neighboring urothelial cells, nerves, or detrusor
smooth muscle. See text for details.
reflex. Intrathecal adrenergic agonists augment the micturition reflex (promote bladder
emptying), whereas adrenergic antagonists inhibit the micturition reflex (promote bladder
storage). These findings are interesting in the context of F-blocker use in treatment of
benign prostatic hyperplasia and lower urinary tract symptoms (LUTS), such as urinary
frequency and urgency. The mechanism of action for F-blockers in treatment of benign
prostatic hyperplasia has traditionally been thought to be relaxation of prostatic smooth
muscle with subsequent decreased “dynamic” tone of the prostatic urethra (63). Another
effect on the prostate may be apoptosis of prostatic glandular cells (64). However, the
therapeutic effect of F-blockers in decreasing urinary frequency and urgency may also
target the central descending efferent pathways onto the sacral spinal cord and thereby
inhibit the micturition reflex. Furthermore, elevated catecholamine states such as hyper-
tension have been associated with increased LUTS in both animals and humans (65,66).
These findings suggest that the beneficial actions of F-blockers in LUTS may be more
complex than previously thought.
The association of depression and urge incontinence further highlights the complexity
of bladder control at supraspinal levels. Investigators have found a high association
between depression and idiopathic urinary incontinence (e.g., urge incontinence) (67,68).
As shown in a rat model, reduction of central nervous system serotonin by chlomi-
pramine induced bladder overactivity (69). Furthermore, the bladder overactivity in
serotonin-depleted animals could be reversed by treating the animals with the serotonin
reuptake inhibitor fluoxetine.
The importance of CRF, a stress-related neurotransmitter, to bladder function was
reviewed in ref. 70. The classical role of CRF, a 41-amino acid peptide released by
the paraventricular nucleus of the hypothalamus during stress, is stimulation of the
anterior pituitary to release adrenocorticotropic hormone. The adrenocorticotropic hor-
mone then stimulates stress steroid release from the adrenal cortex. This constitutes the
hypothalamus-pituitary-axis response to stress. However, CRF has also been implicated
as a neurotransmitter/neuromodulator in a variety of nonhypophyseal neuronal systems,
including the neural control of bladder function. The PMC is richly innervated with
CRF-containing neurons (71), demonstrating the importance of CRF in bladder control.
CRF-containing neurons have also been detected in areas such as the dorsal raphe
nucleus (associated with depression), amygdala (relay center for emotional stress and
visceral pain), and the hippocampus (associated with memory). These findings help
support an association among stress responses, depression, visceral pain, and micturi-
tional disturbances. However, it has not been determined whether a primary bladder
condition (such as IC or OAB) leads to depression or whether depression leads to
bladder symptoms.
Urethral Efferent Pathway
The urethra is a complex organ in that it is comprised of both smooth and striated
muscle. The smooth muscle component is autonomically innervated; whereas the striated
portion is somatically innervated. The striated portion of the urethra in both males and
females is called the rhabdosphincter or the external urethral sphincter. The motor
neuron for the rhabdosphincter arises from the S2–S4 spinal cord at Onuf’s nucleus,
which is more ventrally located than the sacral parasympathetic nucleus in the gray
matter. This nerve exits along with the parasympathetic motor nerves within the S2–S4
ventral nerve roots. However, the somatic motor innervation to the rhabdosphincter runs
in the pudendal nerve. The rhabdosphincter in the human is comprised of both slow- and
fast-fatigue fibers, possibly explaining the ability of this sphincter to maintain tone over
a long period of time (72).
The internal urethral sphincter is located proximal to the rhabdosphincter and is
primarily sympathetically innervated (73). The internal urethral sphincter is located in
direct proximity to the bladder neck. The sympathetic innervation of the internal urethral
sphincter in males allows for closure of this area during ejaculation, thus preventing
retrograde semen flow. Furthermore, the traditional mechanism of action of F-blockers
in treatment of LUTS secondary to benign prostatic hyperplasia was thought to be
relaxation of this internal urethral sphincter. However, as mentioned in the section on
bladder efferent pathways, F-blockers may also work at the level of the spinal cord,
modulating (inhibiting) descending influences on micturition pathways.
A review on the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor,
to modulate the contractility of the external urethral sphincter and bladder capacity
was published (74). Normally, descending pathways from higher centers promoting
urine storage (bladder relaxation and urethral contraction) synapse on Onuf’s motor
neurons, and the neurotransmitters involved at these synapses are norepinephrine and
serotonin. The proposed mechanism of action of duloxetine, then, is augmentation of
this urine storage reflex. Therefore, a blockade of reuptake of these neurotransmitters
would augment activity of motor neurons in Onuf’s nucleus with resultant increased
tone of the external urethral sphincter. The effectiveness of duloxetine in decreasing
stress urinary incontinence in females has been shown in a placebo-controlled clinical
trial (75).
Internal urethral dysfunction has been reported in young males (76–78). These
patients have BOO caused by presumed inappropriately high internal urethral tone.
Treatment with F-blockers and incision of the internal urethral sphincter and bladder
neck have been described as clinically effective.
The use of animal models to study urethral efferent function can result in different
findings in different species. The presence of a high-frequency oscillation of the rat
urethral sphincter is seen during electromyographic studies of the urethral muscular
function (79). The reason for the oscillations is unknown but probably reflects either
facilitation of bladder emptying or behavioral adaptation for marking territory. However,
these urethral oscillations were not seen in guinea pigs (80,81). Human urethral electro-
myographic measurements have not demonstrated this oscillatory urethral muscle activity
(82). These findings suggest that the guinea pig urethra is a better model for human
urethral function (81).
Urethral Afferent Pathway
The urethral sensory innervation schema is similar to that of the bladder in that
sensory nerves can travel along the pudendal, pelvic, and hypogastric nerves (83). The
sensory fibers synapse within the dorsal horn of the S2–S4 spinal cord (those that travel
in pudendal and pelvic nerves) and the thoracolumbar spinal cord (hypogastric nerve).
Fluid traversing the urethra activates the afferent pathway. These afferent fibers in
turn reinforce the bladder to contract more efficiently, probably through facilitatory
descending input. This urethrovesical reflex has been shown in humans (84,85). An
urethrovesical reflex that promotes urinary storage can also occur. It has been shown
that voluntary contraction of the external urethral sphincter can induce inhibition of
bladder contractions as well (86). This reflex may be the basis for how Kegel exercises
may induce bladder relaxation and prevent urge incontinent episodes.
CONCLUSION
The neural control of the bladder and the urethra is complex. Integrated knowledge
of the current peer-reviewed literature allows a framework in which to correlate clinical
bladder emptying and storage problems. A tenet is that findings from animal models
should be verified in the human to validate relevancy. Once the pathophysiology is iden-
tified and correlated in humans, targeted therapies can be developed. The continued
refinement of understanding of bladder/urethral neurophysiology is critical in advancing
the care of patients with bladder dysfunction.
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79. Streng T, Santti R, Andersson KE, Talo A. The role of the rhabdosphincter in female rat voiding. BJU
Int 2004;94:138–142.
80. Van Asselt E, Groen J, Van Mastrigt R. A comparative study of voiding in rat and guinea pig: simul-
taneous measurement of flow rate and pressure. Am J Physiol 1995;269:R98–R103.
81. Walters RD, McMurray G, Brading AF. Comparison of the urethral properties of the female guinea
pig and rat. Neurourol Urodyn 2006;25:62–69.
82. Mahajan ST, Fitzgerald MP, Kenton K, Shott S, Brubaker L. Concentric needle electrodes are
superior to perineal surface-patch electrodes for electromyographic documentation of urethral
sphincter relaxation during voiding. BJU Int 2006;97:117–120.
83. Russo A, Conte B. Afferent and efferent branching axons from the rat lumbo-sacral spinal cord
project both to the urinary bladder and the urethra as demonstrated by double retrograde neuronal
labeling. Neurosci Lett 1996;219:155–158.
84. Shafik A, Shafik AA, El-Sibai O, Ahmed I. Role of positive urethrovesical feedback in vesical evacuation.
The concept of a second micturition reflex: the urethrovesical reflex. World J Urol 2003;21:167–170.
85. Gustafson KJ, Creasey GH, Grill WM. A urethral afferent mediated excitatory bladder reflex exists in
humans. Neurosci Lett 2004;360:9–12.
86. Shafik A. A study of the continence mechanism of the external urethral sphincter with identification
of the voluntary urinary inhibition reflex. J Urol 1999;162:1967–1971.
3 Office Evaluation of Urinary
Incontinence
Adonis Hijaz, MD and Firouz Daneshgari, MD

CONTENTS
INTRODUCTION
HISTORY
FLUID INTAKE /VOIDING DIARY
PHYSICAL EXAMINATION
LABORATORY TESTS
MULTICHANNEL URODYNAMICS
REFERENCES
INTRODUCTION
The goals of the basic evaluation are to confirm urinary incontinence (UI) and to
identify factors that may be contributing to or resulting from UI. The general evaluation of
UI should include a history, fluid intake/voiding diary, physical examination, urinalysis,
urine culture, and measurement of postvoid residual urine. For selected patients, a blood
test (urea and creatinine), urodynamic evaluation, cystoscopy, and imaging studies of
the urinary tract or the central nervous system may be recommended.
HISTORY
A patient’s history should include the problem’s onset, duration, progression, evolution,
and precipitating factors (Valsalva maneuvers, change of position). A clear understanding
of the severity of the problem and its impact on quality of life should be sought. A patient’s
expectations from treatment should also be noted for it is often essential to make these
conform to realistic results. Important associated urinary symptoms such as pain, burning,
frequency, urgency, hesitancy, postvoid dribbling, nocturia, nocturnal enuresis, hematuria,
constipation, fecal incontinence, sexual dysfunction, dyspareunia, and prolapse symptoms
should also be recorded.
Structured condition-specific questionnaires may be used and may be administered
either by the clinician or self-administered. Questionnaires may facilitate disclosure of
embarrassing symptoms, ensure that symptoms are not omitted, and standardize infor-
mation, thereby aiding in follow-up of intervention and research.
A through review of the patient’s medical history is recommended to ascertain any
conditions that possibly interfere with urinary output, such as renal insufficiency, diabetes
mellitus, congestive heart failure, pelvic radiation therapy for treatment of cancer, or

35
neurological diseases such as multiple sclerosis, Parkinson’s disease, or stroke. Chronic

constipation, for example, has been associated with voiding difficulties, urgency, stress
incontinence, and increased bladder capacity. For certain patients, an assessment of
mobility and living environment is also important. All medications taken by the patient,
including antihypertensive drugs, diuretics, sedatives, hypnotics, analgesics, and anti-
depressants must be documented. Intake of caffeine should be determined because it is
also associated with overactive bladder symptoms. Finally, strong coughing associated
with chronic pulmonary disease can markedly worsen the symptoms of stress urinary
incontinence (SUI).
A review of the patient’s obstetric history is also important. This includes parity,
types of delivery, perineal repairs, and difficult deliveries.
Last, the surgical history should include all genitourinary surgical interventions for
treatment of incontinence or pelvic prolapse.
FLUID INTAKE/VOIDING DIARY

Patient histories regarding frequency and severity of urinary symptoms are often
inaccurate. A more reliable indicator of symptoms is a fluid intake/voiding diary, which
should be distributed to patients. They would be instructed to document in it the amount
and type of fluid consumed and the volume and time of voiding and leakage and to note
events associated with each incontinence episode.
PHYSICAL EXAMINATION
A complete physical examination is essential, and special emphasis should be given
to the abdominal, pelvic, genital, and neurological examinations.
• Abdomen: Inspect the abdomen for surgical scars and obesity and palpate for any
abdominal or retroperitoneal masses or bladder distension.
• Genitals: Inspect the external genitalia for any abnormalities (e.g., Bartholin’s cyst,
condyloma, adhesion, and scar formation) and for atrophy of the vaginal epithelium,
specifically shiny cell wall or loss of rugae. In addition, inspect for periurethral and
urethral lesions (e.g., mucosal prolapse, carbuncle, condyloma, Skein’s abscess, or
stenosis). Palpate for scarring, fibrosis, or tenderness, suggesting urethritis or urethral
diverticulum. And, with the patient placed in the lithotomy position, measure urethral
hypermobility by placing a Q-tip in the urethra to the level of the bladder neck. The
patient should be asked to cough and strain. A deflection of the Q-tip greater than 30°
suggests significant urethral hypermobility. Conversely, the absence of a hypermobile
urethra based on the Q-tip test suggests intrinsic sphincteric deficiency. Determine
postvoid residual urine by bladder ultrasound or straight catheterization. Inspect the
anterior, posterior, and apical aspects of the vaginal vault with the posterior blade of a
Grave’s speculum. With the patient at rest and after she strains, palpate the pelvic floor
muscles. Finally, ascertain the various components of prolapse (e.g., cystocele, rectocele,
enterocele, or uterine prolapse).
• Neurological examination: Examine the general neurological status, perineum, and
lower extremities for the presence of tremor, loss of cognitive function, weakness, or
gait abnormality. Examine the back for asymmetry of bone contours, for skin dimples
or scar. Evaluate the S2–S4 nerve roots by the bulbocavernosus reflex (contraction of
the external anal sphincter when pressure is applied to the clitoris). Evaluate lower
extremities by testing typical sensory patterns and evaluate deep-tendon and primitive
Chapter 3 / Office Evaluation of Urinary Incontinence 37
reflexes that may bear anatomic and etiologic significance. A stocking pattern of sensory
loss may be indicative of metabolic neuropathies such as diabetes or alcoholism. The
Babinski sign (primitive reflex) and ankle clonus suggest suprasacral cord lesions. Deep
tendon reflexes of the quadriceps (L4) and Achilles tendon (S1) can demonstrate
segmental spinal cord function as well as suprasegmental function.
• Provocation test/simple cystometrogram: A sterile catheter is inserted in the patient’s
bladder, residual urine is collected, and then a 50-cc syringe without its piston is
attached to the catheter and held above the bladder level. The patient is then asked to
sit or stand, and the bladder is filled with 50-cc aliquots of sterile water from the
syringe. Patient’s first sensation and maximum capacity are noted. The column of
water in the syringe is observed for any rise that can be caused detrusor overactivity.
The catheter is then removed and the patient is asked to cough in various positions
(supine, sitting, or standing). Loss of urine in spurts associated with the coughs suggests
the diagnosis of SUI.
LABORATORY TESTS
• Urinalysis is performed to exclude hematuria, pyuria, bacteriuria, glycosuria, and
proteinuria.
• A urine culture is obtained for evidence of bacteriuria or pyuria.
• Urine cytology is indicated to screen for bladder cancer if there is evidence of hema-
turia (2–5 red blood cells per high-power field) and frequency or urgency.
• Serum urea nitrogen (BUN) and serum creatinine level determinations are indicated in
patients with a history or findings of severe voiding dysfunction. Furthermore, excess
fluid intake may be reflected in an abnormally low serum urea nitrogen level.
• Vaginal swabs are used for culturing ureaplasma and chlamydia.
MULTICHANNEL URODYNAMICS
The workup described constitutes the basic office assessment (BOA) of UI; it is
generally accepted. However, the role of urodynamics in the evaluation of patients with
UI is controversial. This is because the true impact of urodynamics on clinical diagno-
sis, management plans, and patient’s outcome has not been studied in a well-designed
manner. As indicated by the Second International Consultation on Incontinence (ICI
2001): “In spite of the fundamental importance of urodynamics, the committee has
found that for each type of test the evidence for ability or inability of urodynamic
investigation to improve or at least predict the outcome of treatment of incontinence is
based either on case series (level 4 evidence) or expert opinion (level 5 evidence),” (1).
Nevertheless, they recommended urodynamic testing in the evaluation of UI under the
following conditions:
• Prior to invasive treatments.
• After treatment failures.
• As part of a long-term surveillance program in neurogenic lower urinary tract dys-
function.
• In complicated incontinence.
Complicated incontinence includes recurrent incontinence and incontinence asso-
ciated with the following: pain, hematuria, recurrent infection, voiding symptoms, pelvic
irradiation, radical pelvic surgery, and suspected fistula.
The Agency for Health Care Policy and Research recommended considering surgery
without referral for urodynamic testing for patients with symptoms of pure stress urinary
loss and with a voiding history and physical examination results suggestive of pure
hypermobility genuine stress incontinence (GSI), which includes the following (2):
1. Urine loss occurs only with physical exertion (history and stress test).
2. Voiding habits are normal (fewer than eight episodes per day and fewer than two
episodes per night).
3. There is no neurological history and no neurological findings.
4. Patient has no history of antiincontinence or radical pelvic surgery.
5. Pelvic examination documents hypermobility of the urethra and bladder neck, pliable
and compliant vaginal wall, and adequate vaginal capacity.
6. Postvoid residual volume is normal.
7. Patient is not pregnant.
Weidner et al. (3) reported that satisfying all Agency for Health Care Policy and
Research criteria would predict GSI with high C statistics of 0.807; however, the findings
applied to only 7.8% of the women seen in a tertiary care center. When Weber et al. (4)
conducted a cost-effectiveness analysis of preoperative testing (BOA vs urodynamics)
for SUI using a decision analysis model, they concluded that present findings suggest
that, in adult women with SUI symptoms, urodynamic testing provides only a modest
improvement in diagnostic accuracy compared to BOA. The effectiveness of therapy
was similar regardless of which type of preoperative evaluation was used. At a GSI
prevalence of 0.79 or less, urodynamic testing outweighed the BOA because it is both
less costly and more effective. However, at a GSI prevalence of 0.85 or above, the BOA
outweighed urodynamic testing. Thus, in this model, cost-effectiveness was essentially
related to the prevalence of GSI, which—at least in the Weidner et al. report—was
shown to be practice dependent.
The following procedures apply to selected patients with a history or physical findings
suggestive of underlying urologic disease, prolapse, hematuria, recurrent infection, or
recent history of an abdominal or pelvic procedure.
• Cystoscopy plays a limited role in the evaluation of patients with a straightforward,
isolated SUI (level B evidence). However, cystoscopy may be indicated in further
evaluation when the following conditions are present: sterile hematuria or pyuria (level B
recommendation); when urodynamics fails to duplicate symptoms (level C recommen-
dation); and in new onset of irritative voiding symptoms, bladder pain, recurrent cystitis,
or suspected foreign body (level B recommendation). Examination of the urethra may
reveal a diverticulum, fistula, stricture, or urethritis. The bladder is inspected for mucosal
or trigonal abnormalities, trabeculation, foreign bodies, and stones. Bladder-neck
hypermobility and intrinsic sphincteric deficiency may also be reassessed by having
the patient cough or strain with the scope in the midurethra.
• Urinary tract imaging plays a limited role in the evaluation of the uncomplicated case
of female incontinence. Intravenous pyelography, voiding cystourethrography (VCUG),
and ultrasound studies are commonly employed for evaluation of the upper and lower
urinary tract, but in the assessment of UI, these are never first-line studies.
• Intravenous pyelography is indicated if the patient’s history suggests the presence of an
ectopic ureter, hematuria, or recurrent urinary tract infections, and if hydrouretero-
nephrosis is found during ultrasound or computed tomography studies.
Chapter 3 / Office Evaluation of Urinary Incontinence 39
• Ultrasonography is useful for the evaluation of the upper urinary tract, particularly to
detect hydronephrosis caused by elevated bladder pressure in patients with neurogenic
bladder-sphincteric dysfunction. In addition to the analysis of pelvic pathology, ultra-
sound has been used to determine a postvoid residual volume and to detect urethral
diverticulum.
• VCUG is a simple, safe, and reliable examination that determines the integrity of the
female lower urinary tract when bladder or urethral pathology is suspected, such as
vesicovaginal or urethrovaginal fistulas, urethral diverticulum, or bladder prolapse. Now,
although urethral hypermobility may be detected on rest and strain views, the VCUG is
of limited reliability in providing conclusive evidence of intrinsic sphincteric deficiency
because bladder pressure is not recorded during the examination.
REFERENCES
1. Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence. Second International Consultation on
Incontinence, 2nd ed., Plymbridge Distributors, Plymouth, UK, 2002.
2. Agency for Health Care Policy and Research. Urinary Incontinence Clinical Practice Guidelines, US
Department of Health and Human Services, Agency for Health Care Policy and Research, Washington,
DC, 1996.
3. Weidner AC, Myers ER, Visco AG, Cundiff GW, Bump RC. Which women with stress incontinence
require urodynamic evaluation? Am J Obstet Gynecol 2001;184:20–26.
4. Weber AM, Taylor RJ, Wei JT, Lemack G, Piedmonte MR, Walters MD. The cost-effectiveness of
preoperative testing (basic office assessment vs urodynamics) for stress urinary incontinence in
women. BJU Int 2002;89:356–363.
4 Urodynamic Evaluation of Female
Stress Urinary Incontinence
Kelly M. Maxwell, MD,

and J. Quentin Clemens, MD, MSCI
CONTENTS
INTRODUCTION
LEAK-POINT PRESSURES
URETHRAL PRESURE PROFILOMETRY
URETHRAL RETRORESISTANCE PRESSURE
ROLE OF URODYNAMIC TESTNG IN THE ASSESSMENT OF FEMALE SUI
REFERENCES
INTRODUCTION
The American Urological Association has published guidelines for the surgical
management of female stress urinary incontinence (1). According to these guidelines,
the objective demonstration of stress urinary incontinence should be documented prior
to initiating surgical therapy. This can be accomplished with physical examination
(filling the bladder and observing stress incontinence with cough or Valsalva maneuver)
or with urodynamic testing. This chapter reviews the various urodynamic techniques
used to assess the presence and severity of female stress urinary incontinence.
LEAK-POINT PRESSURES
Leak-point pressures are an integral part of urodynamic testing. To understand the
utility of leak-point pressures (LPPs) in the evaluation and management of the stress
incontinent patient, it is critical to define our terms and the clinical situations to which
they apply. There is considerable confusion because there are two main LPPs, and they
are known by several names; in fact they are used in different clinical settings.
Detrusor Leak-Point Pressure
Detrusor leak-point pressure (DLPP), also referred to as bladder leak-point pressure,
is not a measure of stress urinary incontinence (SUI). However, it is often confused with
other LPP measurements used to assess SUI, so a brief review is pertinent. DLPP
refers to the lowest measured value of bladder pressure at which urine leakage is noted
without detrusor contraction or increases in abdominal pressure. In other words, DLPP
is the bladder pressure required to overcome fixed urethral resistance during passive
bladder filling in urodynamic testing, and it is marked by leakage.

41
DLPP was first described in a study of myelodysplastic children; it was noted that
children with higher DLPPs (>40 cm H2O) developed upper tract damage; those with
lower DLPPs did not (24). Ultimately, DLPP reflects urethral resistance and bladder
compliance (C = )V/)P). Whether a patient’s DLPP is high because of excess urethral
resistance or low compliance, the end result is a high-pressure system that is at risk for
upper tract damage as the increasing bladder pressure overcomes the ureteral expulsive
pressure and reflux ensues. DLPP is useful in the evaluation and management of neuro-
genic bladders in relation to the storage and compliance as a predictor of upper tract
health. However, it is not applicable for the assessment of SUI.
Abdominal Leak-Point Pressure (Valsalva Leak-Point Pressure)

Abdominal leak-point pressure is the lowest bladder pressure at which leakage
occurs with stress (Valsalva or cough) without detrusor contraction. This measurement
is commonly referred to as the Valsalva leak-point pressure (VLPP) but is also known
as stress leak-point pressure or cough leak-point pressure (CLPP) depending on the source
of increased intraabdominal pressure. For the purposes of this chapter, we use VLPP
because Valsalva is the most common source of stress in urodynamic testing.
Conceptually, VLPP is a dynamic test that reflects the urethral resistance by measuring
the intraabdominal pressure that is sufficient to drive urine across the urethral unit.
Stratification of severity and type of stress incontinence based on VLPP measurements
are described in the section on interpretation.
Techniques
The initial description of the VLPP measurement by McGuire et al. utilized a 10-French
triple-lumen pressure-transducing catheter to fill the bladder with contrast to 150 cc
with the patient in the upright position. A Valsalva maneuver was performed, and the
leak point was defined as the pressure at which contrast was seen to pass through the
bladder neck on fluoroscopy (Fig. 1) (2). Numerous subsequent studies have been pub-
lished using variations of this technique, which has led to difficulty in interpretation of
the VLPP measurements and clinical application across studies.
In general, there are six components of VLPP testing that affect the outcome: patient
position, catheter size, transducer zeroing, bladder volume, method of leakage observation,
and type of stress used to generate increased intraabdominal pressure. It is important to
recognize that using absolute numbers for diagnosis is problematic, and caution must be
taken to recognize the parameters that are used for interpretation.
PATIENT POSITION
VLPP was originally described with patients in the upright position, although several
authors have used the sitting position. One study reported that CLPP measurements
were not affected by patient positioning, and the authors recommended utilizing the
positioning that best fits the equipment and patient preference (3).
CATHETER SIZE
VLPP has been described with 3-, 8-, and 10-French catheters. It has been demons-
trated that larger catheter size results in higher VLPP, possibly because of mild obstruction
from the larger catheters (4). At present, there is no standardized catheter size, and the
choice is based on practitioner preference.
Chapter 4 / Urodynamic Evaluation of Female Stress Urinary Incontinence 43
Fig. 1. (A; top) and (B; bottom) correspond to the indicated locations on the urodynamic tracing in
Figure 2. With Valsalva maneuver, contrast is seen to pass through the bladder neck (bottom image).
Fig. 2. Multichannel urodynamic study demonstrating stress urinary incontinence.
TRANSDUCER ZEROING
VLPP measurements can be zeroed to the patient or to atmospheric pressure. The
original description of VLPP measurements to diagnose the types of stress incontinence
was zeroed to atmospheric pressure.
BLADDER VOLUME
McGuire et al. first described VLPP at a bladder volume of 150 mL (2). Later studies
used 250-mL volumes; others have recommended utilizing near-capacity or capacity
volumes by data obtained from voiding diaries. Notably, larger volumes have been asso-
ciated with lower VLPP measurements. Therefore, if leakage is not observed at lower
volumes, the bladder can be filled to near capacity, and repeat testing can be performed
to see if leakage can be provoked.
METHOD OF OBSERVATION OF LEAKAGE

Leakage can be observed via patient report, direct observation, or fluoroscopy.
Fluoroscopy is the most definitive way to measure leakage objectively, although it adds
expense to the exam and is not always readily available. When possible, it should be part
of the urodynamic assessment.
TYPE OF STRESS
Stress may be induced by Valsalva or cough. There is discussion in the literature
regarding the different effects of the two mechanisms on intra-abdominal pressure.
Some authors have noted that CLPPs are higher than VLPPs. This is thought to be
because of reflex contraction of the urethral mechanism during the transient cough,
which is not observed during the slow progressive stress of a Valsalva maneuver.
Most urodynamicists would start with VLPP measurement and if negative proceed to
CLPP measurements.
Interpretation
The utility of VLPP lies in its potential to quantify the severity of stress incontinence.
Studies have shown that VLPP above 120 cm H2O are typically consistent with type I
stress incontinence (urethral hypermobility <2.0 cm); VLPPs between 60 and 120 cm
H2O are found with type II stress incontinence (urethral hypermobility >2.0 cm), and
those patients with VLPPs below 60 cm H2O commonly demonstrated type III stress
incontinence (intrinsic sphincter deficiency). Although this is an attractive algorithm
and would apparently lend itself to the determination of appropriate treatment (suspen-
sion vs sling vs bulking agents), the variations in technique have a great impact on the
results of a given VLPP measurement. Therefore, comparison is difficult across centers
and even practitioners.
At present, measurement of the VLPP is useful in characterizing a specific patient’s
urethral resistance. If a practitioner utilizes the same techniques with every patient,
the practitioner may use the experience to help stratify patients and determine the best
treatment option. It is not possible to generalize the measurements of VLPP across
patients in different study conditions; therefore, unless universal techniques are adopted
and carefully studied, the primary usefulness of VLPP will remain in the hands of
individual urologists to interpret.
URETHRAL PRESSURE PROFILOMETRY

Historically, the first urodynamic parameter measured to characterize stress inconti-
nence was the resting urethral pressure profile (UPP), which was based on the idea that
continence is maintained as long as urethral pressure exceeds intravesical pressure. It
was thought that measuring the pressure exerted by the urethra in relation to the intra-
vesical pressure would predict both presence and severity of stress incontinence.
Although this is conceptually reasonable, the pressure measurements of both sympto-
matic incontinent patients and controls overlap so widely that no conclusions can be
made by the absolute measurements. Furthermore, the measured values vary widely
depending on the study conditions. Despite numerous efforts to derive additional
urodynamic parameters based on UPP measurements, none of these have been demon-
strated to correlate reliably with the presence of stress incontinence. In the following
sections, we outline the components of urethral pressure profilometry and discuss the
techniques and limitations of these measurements.
Relationship Between UPP and Urethral Anatomy

Multiple studies of the structural and functional composition of the female urethra
have been performed. Both the intrinsic urethral components and surrounding structures
have been identified as contributors to urethral continence. The current understanding
of urethral function is complex but essentially reflects a combination of sphincteric
components and structural support of the bladder neck and urethra. Components of
urethral closure have been described by Rud et al. in a systematic study of the effects
of muscular and vascular contributions to UPP (5). The conclusion of this work was
that approximately one-third of the urethral closure is dependent on striated sphincter
and pelvic floor musculature, one-third is caused by blood flow, and the final one-third
is related to periurethral and connective tissues. Ultimately, the exact anatomy and
function of the female urethra has yet to be fully elucidated, and measurements of urethral
pressure must be considered a summation of a number of complex interactions.
UPP and Urethral Closure Pressure Profile

The UPP is the direct measurement of urethral pressure at rest. Urethral pressure
measurement was first described by Bonney in 1923 as the pressure required to infuse
fluid retrograde into the urethra as measured by an external manometer (6). Although
the measurement techniques have evolved significantly from fluid perfusion catheters
to membrane, microtip, and fiber-optic catheters, the underlying concept remains
unchanged; the static urethral pressure is measured throughout its length, and a topo-
graphical pressure curve is generated. Several parameters can be measured from this
curve; the International Continence Society has recommended a standard nomenclature
(7). Maximum urethral closure pressure (MUCP) is the difference of maximum urethral
pressure (MUP) and bladder pressure (MUCP = MUP Pves) and correlates to the
junction of the striated and smooth muscle sphincters. Functional profile length is
the total length at which urethral pressure exceeds bladder pressure and represents the
total length of urethra that contributes to continence.
The urethral closure pressure profile (UCPP) involves the same techniques of
urethral pressure measurement but further delineates intra-abdominal and detrusor
pressures. A total of six measurements is required: perineal electromyography, intra-
vesical pressure Pves, intra-abdominal pressure Pabd, intraurethral pressure Pura, true
detrusor pressure Pdet, and urethral closure pressure (UCP). Many of the parameters
measured in the UCPP have been studied regarding both prediction of stress inconti-
nence and the response to surgical intervention, without reliable results. Whether
measuring MUCP or total functional length, the overlap of continent and incontinent
subjects precludes using these parameters to stratify patients in the workup for stress
incontinence. The only parameter that has been shown to correlate with operative result
is an MUCP less than 20 cm H2O, which is considered to be indicative of intrinsic
sphincter deficiency.
Weber reviewed the published literature on UPP and female SUI in 2001 and con-
cluded that, although the terms of UPP are consistently defined, the techniques used to
measure UPP are not standardized, and results are therefore variable. In addition,
patients with an MUCP less than 20 cm H2O have been shown to have higher failure
rates after suspension procedures, but as Weber pointed out, these are based on retro-
spective studies only (8).
Dynamic UPP: Cough and Valsalva

Similar to the VLPP, dynamic UCPPs are an attempt to measure the urethral
response to stress. This is thought to more appropriately characterize the presence and
severity of stress incontinence than the static measurement of resting UPP and MUCP.
There are two types of dynamic UPP: Valsalva and cough. Valsalva UPP is measured
by manually withdrawing the urethral pressure transducing catheter while the patient
sustains maximum Valsalva effort. Cough UPP is measured with the patient coughing
every 2–3 s while the catheter is manually withdrawn. During both tests, the urethral
meatus is monitored for leakage. The pressure is measured in the same way as static
UPPs are obtained.
Pressure Transmission Ratio

More recently, the pressure transmission ratio (PTR) has been described (9). In this
measurement, the functional urethral length is divided into quarters, and the PTR is
calculated for each quarter using the equation ()Pura/)Pves) × 100%. Lower PTRs are
consistent with SUI, although significant overlap exists between continent and incon-
tinent patients, and no set cutoff has been determined.
Techniques of Profile Measurement
Whether measuring resting UPP, UCP, or dynamic UPP, the study conditions are
similar. Patients are typically studied while seated with a full bladder in a urodynamic
chair. A specialized catheter (most commonly a microtip catheter) is inserted intravesi-
cally with a transducer measuring the intravesical pressure and an additional transducer
located 6 cm more proximally measuring the urethral pressure. An additional pressure
probe is inserted either intravaginally or rectally to measure Pabd, and external electrodes
are applied to record electromyographic activity. Similar to VLPP measurement, there
are many variables that affect the results of a UPP study. The following discussion is a
summary of the important variables.
CATHETER CHOICE
UPP was first described using perfusion catheters in which the pressure measured
reflected the pressure required to lift the urethral wall from the catheter side holes.
Membrane catheters function by the same mechanism, but the catheter tip is surrounded
by a balloon or membrane to prevent loss of infusion fluid during measurement, a short-
coming that was identified in the perfusion catheters. Microtip catheters are the most
commonly used at present, and pressure is measured by a pressure-sensitive transducer
that allows for dynamic pressure measurement. Finally, fiber-optic catheters similarly
measure the urethral pressure in a direct manner. As described in the evaluation of LPPs,
the catheter size has been shown to affect the results of UPP measurements, with larger-
bore catheters resulting in higher UPP pressure measurements.
PATIENT POSITION
The UPP can be measured with the patient in the supine, seated, or standing position.
At present, the only conclusion obtained from many studies comparing UPP measure-
ments in different patient positions is that position affects the results of the UPP in some
patients but not in a predictable or reproducible manner. From supine to seated to stand-
ing measurements, some studies have reported increasing, decreasing, or no change,
respectively, in UPP measurement (8).
CATHETER WITHDRAWAL SPEED AND ORIENTATION
Commonly, the withdrawal speed used is 1–2 mm/s. Orientation of the catheter trans-
ducer can change the results of the test. With the transducer at the 12 o’clock position,
the pressure recorded will be elevated, whereas at the 6 o’clock position it will be
decreased. Therefore, the UPP is measured with the transducer oriented at a lateral
position (6 or 9 o’clock).
ZEROING OF PRESSURE SENSORS
As with LPP measurement, the pressure recorded will depend on whether the
transducer is zeroed to the patient or to the atmosphere. It is important to consider
the starting point for accurate interpretation.
Interpretation
Interpreting UPP measurements for stress-incontinent patients is problematic. Lack
of standardization in technique and the number of measurement variables contribute
to the significant overlap of measurements in stress-incontinent patients and controls.
Stratification of severity and type of incontinence has only been described for the
low-pressure urethra with a MUCP less than 20 cm H2O, which has been related to
type III or intrinsic sphincter deficiency. At present, despite wide usage and much
effort to describe derivations of urethral pressure profilometry, it is not a standardized,
reproducible, or predictive test of SUI. The main utility of this test may be to follow
individual patient outcomes throughout treatment.
URETHRAL RETRORESISTANCE PRESSURE

A new urodynamic measurement system for urethral retroresistance pressure (URP)
has been described. URP is defined as the pressure required to achieve and maintain
an open urethral sphincter and is measured by occluding the urethral meatus with a
cone-tipped plug placed 5 mm in the urethra. Sterile fluid is then infused retrograde at
a rate of 1 mm/s while the required pressure is measured on a pressure vs time plot,
and the plateau of the asymptotic curve represents the URP (10,11).
In a randomized, multicenter trial of 258 symptomatic females, URP, LPP, and MUCP
were measured after assessment of incontinence severity by validated questionnaires.
The authors concluded that URP has a consistent relationship to incontinence severity,
whereas MUCP and LPP were not reliably decreased in patients with increased degrees of
incontinence (10). In a second study, 61 asymptomatic females underwent URP measure-
ment after confirming a negative standing stress test; the goal was to characterize the
distribution and reproducibility of URPs in asymptomatic women (11). The URP measure-
ments in this population exhibited a normal distribution, and in 32 females who underwent
retesting 3–7 d later, there was no statistically significant difference between test and
retest URP measurements. Furthermore, when comparing the symptomatic and asymp-
tomatic premenopausal patients, the mean URP was significantly different.
This work represents an attempt to define and characterize a novel approach to
measuring urethral function with the goal of finding a parameter that is reproducible,
accurately identifies stress incontinent patients, and predicts treatment outcome. Although
initial investigations of URP are promising, it remains investigational and will require
further evaluation before its clinical utility can be determined.
ROLE OF URODYNAMIC TESTING IN THE ASSESSMENT

OF FEMALE SUI
Although urodynamic testing is frequently performed as part of the evaluation of SUI,
the benefits obtained by performing such testing have not been well defined. Advocates
of a “minimalist” approach argue that direct observation of stress incontinence on phys-
ical examination is sufficient to allow the treating physician to proceed with surgery
in the majority of patients. Some studies have indicated that routine performance of
urodynamics in the evaluation of female stress incontinence is not cost-effective (12,13).
This opinion has perhaps become more prevalent with the advent of minimally invasive
midurethral sling procedures, which have yielded good continence results in large,
heterogeneous patient samples. Advocates for urodynamic testing argue that important
information about concomitant bladder dysfunction (detrusor overactivity, compliance

abnormalities, poor detrusor contractile function) may significantly alter the treatment
approach in certain patients. Furthermore, identification of urodynamic intrinsic sphincter
deficiency does appear to significantly reduce the stress incontinence cure rate for
midurethral slings (14,15).
Currently, it is not known if routine urodynamic assessment improves outcomes prior
to stress incontinence surgery. Therefore, the decision to perform this testing is indivi-
dualized based on the availability of the testing equipment, the expertise of the treating
physician, and the complexity of the patient. The utility of preoperative urodynamic
testing will continue to be controversial until definitive studies are carried out to examine
the issue. Ideally, these would be multicenter, prospective, randomized trials involving
women who have undergone standardized urodynamic testing, with the treating physician
blinded to the urodynamic outcomes in one group and aware of the outcomes in the other.
REFERENCES
1. Leach GE, Dmochowski RR, Appell RA, et al. Female Stress Urinary Incontinence Clinical Guidelines
Panel summary report on surgical management of female stress urinary incontinence. J Urol 1997;158:
875–880.
2. McGuire EJ, Fitzpatrick CC, Wan J, et al. Clinical assessment of urethral sphincter function. J Urol
1993;150(5 pt 1):1452–1454.
3. Stiltberg H, Larsson G, Victor A. Reproducibility of a new method to determine cough-induced
leak-point pressure in women with stress urinary incontinence. Int Urogynecol J 1996;7:13–19.
4. Bump RC, Elser DM, McClish DK. Valsalva leak point pressures in adult women with genuine stress
urinary incontinence: reproducibility, effect of catheter caliber, and correlations with passive urethral
pressure profilometry. Neurourol Urodyn 1993;12:307–308.
5. Rud T, Andersson KE, Asmussen M, Hunting A, Ulmsten U. Factors maintaining the intraurethral
pressure in women. Invest Urol 1980;17:343–347.
6. Bonney V. On diurnal incontinence of urine in women. J Obstet Gynaecol Br Emp 1923;30:358–365.
7. Lose G, Griffiths D, Hosker G, et al. Standardisation of urethral pressure measurement: report from
the Standardisation Sub-Committee of the International Continence Society. Neurourol Urodyn
2002;21:258–260.
8. Weber AM. Is urethral pressure profilometry a useful diagnostic test for stress urinary incontinence?
Obstet Gynecol Surv 2001;56:720–735.
9. Bump RC, Copeland WE, Jr, Hurt WG, Fantl JA. Dynamic urethral pressure/profilometry pressure
transmission ratio determinations in stress-incontinent and stress continent subjects. Am J Obstet Gynecol
1988;159:749–755.
10. Slack M, Culligan P, Tracey M, Hunsicker K, Patel B, Sumeray M. Relationship of urethral retro-
resistance pressure to urodynamic measurements and incontinence severity. Neurourol Urodyn 2004;
23:109–114.
11. Slack M, Tracey M, Hunsicker K, Godwin A, Patel B, Sumeray M. Urethral retro-resistance pressure:
a new clinical measure of urethral function. Neurourol Urodyn 2004;23:656–661.
12. Diokno AC, Dimaculangan RR, Lim EU, Steinert BW. Office based criteria for predicting type II
stress incontinence without further evaluation studies. J Urol 1991;161:1263–1267.
13. Weber AM, Taylor RJ, Wei JT, Lemack G, Piedmonte MR, Walters MD. The cost-effectiveness of
preoperative testing (basic office assessment vs urodynamics) for stress urinary incontinence in women.
BJU Int 2002;89:356–363.
14. Liapis A, Bakas P, Salamalekis E, Botsis D, Creatsas G. Tension-free vaginal tape (TVT) in women
with low urethral closure pressure. Eur J Obstet Gynecol Reprod Biol 2004;116:67–70.
15. Paick JS, Ku JH, Shin JW, Son H, Oh S, Kim SW. Tension-free vaginal tape procedure for urinary
incontinence with low Valsalva leak point pressure. J Urol 2004;172:1370–1373.
5 Urodynamic Assessment
of Overactive Bladder
Neurogenic and Nonneurogenic
Gary E. Lemack, MD
CONTENTS
INTRODUCTION
WHO REQUIRES URODYNAMICS?
KEY COMPONENTS IN URODYNAMIC TESTING
OF OVERACTIVE BLADDER
FINDINGS IN NONNEUROGENIC OVERACTIVE BLADDER
FINDINGS IN NEUROGENIC OAB
CONCLUSION
REFERENCES
INTRODUCTION
Urodynamic studies (UDS) generate information about bladder function that,
currently, no other testing can provide. Though clearly not necessary to evaluate all lower
urinary tract symptoms (LUTS), UDS can be useful when confronted with situations in
which the normal noninvasive parameters used to assess LUTS, such as questionnaires,
flow rates, and postvoid residual testing, are not helpful. There are a few keys to devel-
oping a successful urodynamic laboratory and to conducting studies that can be readily
interpreted and utilized for clinical planning. Perhaps the foremost among these are the
ability to re-create the LUTS in question during the UDS and training capable techni-
cians who understand the equipment and the patients so that they are able to accomplish
this task. Having the clinician present or readily available during the study is essential
to generating interpretable data. A poorly conducted UDS test will tell you nothing
about the symptom or problem in question, may only serve to further muddy the clinical
picture, and may dissuade the patient from further care. On the other hand, a properly
conducted test will give insight into the pathophysiology underlying the clinical condition,
may provide some type of assessment of risk to the patient of leaving the condition
untreated, and will clearly help guide management.
This chapter discusses the role of UDS in assessing patients with overactive bladder
(OAB), both neurogenic and idiopathic, and the common findings seen in each of these
conditions are reviewed.

51
WHO REQUIRES URODYNAMICS?
The issue of the optimal evaluation for OAB remains contentious. Although few
would argue that patients with known neurological conditions and bladder dysfunction
merit a thorough urodynamic evaluation to establish risk assessment and determine
appropriate therapy, the same cannot be universally said of patients with OAB symptoms
and no known neurological condition.
It seems clear that, in most patients with classic urinary symptoms of urinary urgency,
frequency with or without urge urinary incontinence, a thorough history, physical exam-
ination, and urinalysis should be carried out prior to instituting any type of medical therapy
for OAB. It is further clear that validated urinary questionnaires and voiding diaries, at
least 48–72 h in duration, can provide additional information about severity of frequency
and incontinence, functional bladder capacity, overall urine production, and degree of
nocturia, which may be difficult to ascertain otherwise (1). Each of these assessments
can provide insight into the proper treatment. Measuring postvoid residual in women
without prolapse, previous incontinence, or prolapse surgery; no history of recurrent
bladder infections; and without voiding symptomatology (straining, hesitancy, staccato
voiding) is generally considered unnecessary in most patients with OAB symptoms
because overall the prevalence of elevated residuals is low (2).
The controversy surrounding the use of urodynamic testing in OAB involves three basic
principles. The first principle is that many women with no specific bladder complaints will
be found to have “abnormal” findings on urodynamic testing. Indeed, idiopathic detrusor
overactivity may be found in up to 69% of asymptomatic patients undergoing ambulatory
UDS (3). Advocates of ambulatory urodynamic studies note that these outpatient studies
may establish a diagnosis in as many as 56% of patients in whom conventional studies were
unable to do so (4). Still, although some contend that urodynamically diagnosed bladder
dysfunction may merit treatment in women with LUTS who do not specifically complain
of OAB-type symptoms (5), more often than not it is unclear that findings noted only
during urodynamics require treatment.
Indeed, the inability of UDS to correlate closely with LUTS is the second principle
surrounding the controversy of UD usefulness. Because conventional in-office studies take
place over a short window of time, it is not uncommon for them to inadequately demonstrate
the cause of LUTS, particularly in the case of urgency and urge incontinence. In general,
about 18–23% of patient with OAB-type symptoms and incontinence may have normal
urodynamic findings (6,7). Furthermore, a meta-analysis of studies investigating the ability
of UD testing to diagnose bladder dysfunction accurately noted a sensitivity of only
45–72% for OAB/urge incontinence, with somewhat higher figures noted for stress
incontinence (8). We found that utilizing the Urogenital Distress Inventory Questionnaire
allowed us to improve the sensitivity of diagnosing detrusor overactivity in patients with
either urinary frequency or urge incontinence to 75–83%, although the questionnaire was
inadequate at predicting voiding disturbances (9).
Last, it is unclear, even if one can accurately diagnose OAB in patients with LUTS
highly suggestive of this condition, that urodynamic findings will allow us to predict
optimal treatment based on UD findings. For example, it has not been conclusively
demonstrated that particular anticholinergic medications are superior based on indices
of bladder function obtained during cystometry (such as capacity, threshold volume
for detrusor contractions, or amplitude of detrusor contractions) or that overall treat-
ment response to any anticholinergic medication is predictable based on UD findings.
Chapter 5 / Urodynamic Assessment of Overactive Bladder 53
A crossover study of tolterodine and oxybutynin noted no difference in treatment effi-

cacy based on severity of OAB as defined urodynamically, although there was the
suggestion that patients with high-amplitude contractions did not fare as well on either
medication (10). Other studies have noted no influence of urodynamic parameters on
efficacy of medical treatment, local estrogen, or bladder training (11,12).
Therefore, the decision to perform urodynamics remains controversial and, in many
cases, experientially based. Among the most commonly accepted reasons to perform
urodynamic testing in nonneurogenic female patients with OAB symptoms include
failure to respond adequately to pharmacological management, the presence of voiding
symptoms, history of incontinence or prolapse surgery, recurrent urinary tract infections,
and concurrent pelvic prolapse. Male patients, many of who are commonly treated with
α-blockers or 5α-reductase inhibitors, may require urodynamics if medical management
does not improve symptoms, particularly if surgery for presumed outlet obstruction is
under consideration.
KEY COMPONENTS IN URODYNAMIC TESTING

OF OVERACTIVE BLADDER
After the decision is made to proceed with urodynamic testing, the next consideration
is the type of testing to be conducted. Most current urodynamic machines offer only
multiple-channel testing because single-channel testing is prone to considerable arti-
facts. In general, because it is difficult to predict for the presence of specific voiding
dysfunction in women based on urinary symptoms alone (9), it is good urodynamic
practice always to perform a pressure flow study at the end of filling to assess for
voiding disturbance. Although controversial, the use of patch or needle electromyo-
graphic perineal electrodes can assess for lack of pelvic floor relaxation or external
sphincter dyssynergia in patients at risk. The addition of simultaneous cystourethro-
graphy (videourodynamics), although clearly not always mandated, does allow further
evaluation of the outlet during voiding, which can aid in determining the level of
obstruction and evaluating the bladder for foreign bodies, vesicoureteral reflux, and
diverticula. Although it may not be universally available, the addition of imaging of
the lower urinary tract during urodynamic testing may be most useful when evaluating
patients with known neurological conditions, young men with severe LUTS, and women
with possible pelvic floor dysfunction.
Typically, a 6- or 7-French dual-lumen urethral urodynamic catheter is used, along
with either a rectal or vaginal catheter to assess extravesical pressure fluctuations.
Patients are typically standing for the study, particularly if they are also complaining
of stress incontinence, or they sit in a urodynamics chair. Fluid (room temperature
sterile water or radiographic contrast) is instilled at 25–100 mL/min, keeping in mind
that OAB contractions can be elicited by more rapid rates of filling, by utilizing a cold
filling solution, and by performing certain provocative maneuvers during filling (such
as heel bouncing). The threshold volume for OAB contractions should be noted in
addition to the amplitude of the overactive contraction because there are some data to
suggest that the severity of the contraction may correlate with the nature of the disease
process responsible for detrusor overactivity (DO) (13). Many patients will attempt to
suppress leakage that may accompany the contraction, and if leakage still ensues, it
should be recorded, as should the maximum bladder capacity. Compliance should also
be assessed because altered compliance may be responsible for upper tract deterioration,
particularly in neuropathic bladders. Although widely accepted cutoff values for outlet
obstruction in women are still lacking, a number of strategies have been proposed
(14–16), and a properly conducted voiding study (adjust transducers as the patient sits
to void) is imperative after the conclusion of filling.
FINDINGS IN NONNEUROGENIC OVERACTIVE BLADDER

Although no clear criteria exist for differentiating neurogenic from idiopathic DO, it
has been suggested that unstable bladder contractions occurring as a result of neuro-
logical disease may be more likely to result in urge incontinence (17) and have a greater
amplitude. Regardless, perhaps the most common urodynamic pattern seen in patients
with idiopathic OAB is symptomatic urgency reported during filling without the finding
of DO (so-called sensory urgency). It is well established that, in up to 74% of patients
with frequency or urgency symptoms and in as many as half of patients with urge UI, DO
may not be seen during urodynamic testing (18). Interestingly, data suggest that, of the
four symptoms most commonly associated with OAB (frequency, urgency, nocturia, and
urge incontinence), it is the specific complaint of frequency that may be most readily
linked to the urodynamic finding of DO (19). Frequency and urgency symptoms and urge
incontinence all appear to be associated with earlier first sensation during UDS.
In general, nonphasic low-grade overactive contractions during voiding appear to be
the most common pattern seen with idiopathic detrusor overactivity. In general, these
contractions are associated with urgency. Frequently, simultaneous electromyographic
activity associated with a conscious contraction of the pelvic floor to avoid leakage is
also seen (Fig. 1).
Idiopathic detrusor overactivity need not always be completely benign, however.
Even patients without a clear neurological basis for their overactivity may experience
intense detrusor spasms resulting in significant incontinence. Presumed bladder wall
damage from other processes, such as radiation, may induce changes in bladder wall
compliance (Fig. 2), resulting in severe frequency and OAB symptoms. Radiation can
also induce high-grade bladder overactivity even several years out from the time of
treatment, as seen in the urodynamics obtained from a woman who was over two decades
out from radiation treatment for uterine cancer who suffered from intense urinary
urgency and extreme frequency (Fig. 3).
Stress-induced OAB contractions have also been described. Although the precise
etiology is not proven, it is believed that coughing or other maneuvers that induce urine
to be deposited beyond the bladder neck into the proximal urethra can induce bladder
overactivity. Typically, leakage associated with stress-induced overactivity is difficult to
differentiate based on history or physical examination alone, and UDS are the most
effective means of determining the true cause of incontinence, which often is a result
of both sphincteric weakness and abnormal detrusor instability (Fig. 4).
Terminal detrusor overactivity, which occurs at the end of filling, can develop in the
absence of any definable intrinsic bladder or bladder outlet abnormality and may be
associated with urge incontinence when the bladder contraction cannot be suppressed
(Fig. 5). In an analysis of urodynamic characteristics of DO, Defreitas and colleagues
noted that men with BOO-induced DO were more likely to have terminal DO only
in comparison with men with DO secondary to Parkinson’s disease (PD), in whom
the DO occurred throughout filling (17). In many cases, the urge to void can be tempo-
rarily suppressed, and the bladder contraction itself can subside if filling is terminated.
Fig. 1. Nonphasic detrusor overactivity. Note simultaneous low-grade detrusor contractions (closed
arrows) and increased sphincteric activity (open arrows).
Fig. 2. Loss of compliance in patient with OAB symptoms.

Fig. 3. Intense periodic overactive detrusor contractions in patient treated with radiation treatment for
uterine cancer over two decades prior to study.
Fig. 4. Stress-induced detrusor overactivity. Note detrusor contraction (closed arrow) induced by cough
and Valsalva. Patient leaks with both cough/Valsalva and at time of detrusor overactive contraction.
Fig. 5. Terminal detrusor overactivity. Note detrusor contraction occurs prior to terminating filling and
is associated with urgency. Patient was not instructed to suppress voiding. Note sphincteric relaxation.
If terminal DO occurs after a normal fill volume, then typically this urodynamic pattern
would be associated with urgency and potential urge incontinence episodes in the
absence of severe frequency.
FINDINGS IN NEUROGENIC OAB

Patients with neurogenic OAB tend to have severe symptoms that are more difficult
to treat pharmacologically. It is not immediately clear that the overactive contractions
experienced by patients with neurological conditions are necessarily of greater amplitude
or occur earlier during filling, although there is some indirect evidence to support this
contention (13). Phasic detrusor contractions that crescendo and result in urge-related
urine leakage appear to be more commonplace in patients with neurogenic overactivity,
for example, in patients with multiple sclerosis (MS) (Fig. 6). Voiding dysfunction,
either with or without DO, also appears to be common in patients with MS. True detrusor
external sphincter dyssynergia may be present in many as 40% of patients with LUTS sec-
ondary to MS (20); the incidence of bladder neck dyssynergia independent of detrusor
overactivity may be even higher.
Patients with movement disorders also appear largely to suffer from DO on uro-
dynamic testing. One unique finding among patients with movement disorders involves
external sphincteric testing. Incompetent external sphincteric function resulting from
denervation secondary to neuronal cell loss in the anterior horn of Onuf’s nucleus is
present in the majority of patients with multiple system atrophy and can lead to debilitating
urinary incontinence (21). Both sphincteric deficiency and sphincteric bradykinesia
(failure to relax) have been described in patients with PD, making surgical endeavors
Fig. 6. Phasic detrusor overactivity (closed arrows) resulting in urinary leakage (open arrows) in
patient with multiple sclerosis and urge incontinence.
to treat BOO presumed secondary to prostatic obstruction treacherous because inconti-

nence rates following transurethral prostatectomy among patients with PD have historically
ranged as high as 20%. It is unclear whether this dismal rate of success will be improved
with other heat-based prostatic treatments.
Patients with interruptions of the spino-bulbo-spinal pathway, typically as a result of
spinal cord injury, may have debilitating urinary incontinence in addition to severely
impaired bladder emptying secondary to detrusor external sphincter dyssynergia (Fig. 7).
In these instances, detrusor pressures may remain elevated because of the sustained
detrusor contraction (particularly true in spinal cord injury) in the absence of external
sphincter, and frequently bladder neck, relaxation. Concurrent fluoroscopic monitoring
can be useful to evaluate for bladder wall abnormalities or vesicoureteral reflux and
further evaluate sphincteric function. In patients with severe or detrusor dysfunction,
bladder diverticula can develop (Fig. 8), which can ultimately result in further impair-
ment of bladder drainage and create a haven for the development of bladder stones and
malignant bladder lesions.
CONCLUSION
Urodynamic testing remains an integral part of the complete evaluation of patients
with OAB symptoms, particularly those who fail to respond to conventional manage-
ment strategies, those with specific complaints of voiding dysfunction, and those with
Fig. 7. Detrusor sphincter dyssynergia in patient with T5 spinal cord injury. Note sustained intra-
vesical pressure elevation (closed arrow) and simultaneous sphincteric activity (open arrow).
Fig. 8. Video picture during voiding attempt in patient with detrusor sphincter dyssynergia. Note
ballooning of proximal urethra (closed arrow) and left-sided diverticulum (open arrow).
neurogenic bladder disease. Although the urological community continues to search

for less-invasive means of monitoring bladder function, at the present time multichannel
urodynamic testing is the most accurate and reliable assessment tool, and it provides a
means of directing appropriate therapeutic strategies, determining treatment response,
and monitoring for disease progression.
REFERENCES
1. Klovning A, Hunskaar S, Eriksen BC. Validity of a scored urological history in detecting detrusor
instability in female urinary incontinence. Acta Obstet Gynecol Scand 1996;75:941–945.
2. Bonde HV, Sejr T, Erdmann L, et al. Residual urine in 75-year-old men and women. A normative
population study. Scand J Urol Nephrol 1996;30:89–91.
3. van Waalwijk van Doorn ES, Meier AH, Ambergen AW, Janknegt RA. Ambulatory urodynamics:
extramural testing of the lower and upper urinary tract by Holter monitoring of cystometrogram,
uroflowmetry, and renal pelvic pressures. Urol Clin North Am 1996;23:345–371.
4. Swithinbank LV, James M, Shepherd A, et al. Role of ambulatory urodynamics monitoring in clinical
urological practice. Neurourol Urodyn 1999;20:249–257.
5. Digesu GA, Khullar V, Cardozo L, Salvatore S. Overactive bladder symptoms: Do we need urodynamics?
Neurourol Urodyn 2003;22:105–108.
6. Sand PK, Hill RC, Ostergard DR. Incontinence history as a predictor of detrusor instability. Obstet
Gynecol 1988;71:257–260.
7. De Muylder X, Clae H, Neven P, De Jaegher K. Usefulness of urodynamic investigation in female
incontinence. Eur J Obstet Gynecol Reprod Biol 1992;44:205–208.
8. Colli E, Artibani W, Goka J, Parazzini F, Wein A. Are urodynamic tests useful tools for the initial
conservative management of non-neurogenic urinary incontinence? A review of the literature. Eur
Urol 2003;43:63–69.
9. Lemack GE, Zimmern PE. Predictability of urodynamic findings based on the Urogenital Distress
Inventory Questionnaire. Urology 1999;54:461–466.
10. Giannitsas K, Perimenis P, Athanasopoulos A, Gyftopoulos K, Nikiforidis G, Barbalias G.
Comparison of the efficacy of tolterodine and oxybutynin in different severity grades of idiopathic
detrusor overactivity. Eur Urol 2004;46:776–783.
11. Wagg A, Bayliss M, Ingham NJ, Arnold K, Malone-Lee J. Urodynamic variables cannot be used to
classify the severity of detrusor instability. BJU 1998;82:499–502.
12. Holtedahl K, Verelst M, Schiefloe A, Hunskaar S. Usefulness of urodynamic examination in female
urinary incontinence—lessons from a population-based, randomized, controlled study of conservative
treatment. Scand J Urol Nephrol 2000;34:169–174.
13. Lemack GE, Zimmern PE, Frohman E, Hawker K, Ramnarayan P. Urodynamic distinctions between
idiopathic detrusor overactivity and detrusor overactivity secondary to multiple sclerosis. Urology 2006;
67:960–964.
14. Lemack GE, Zimmern PE. Pressure flow analysis may aid in identifying women with outflow obstruc-
tion. J Urol 2000;163:1823–1828.
15. Nitti VW, Tu LM, Gitlin J. Diagnosing bladder outlet obstruction in women. J Urol 1999;161: 1535–1540.
16. Blaivas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract
symptomatology. Neurourol Urodyn 2000;19:553–564.
17. Defreitas GA, Lemack GE, Zimmern PE, Roehrborn CG, Dewey RB. A urodynamic comparison of
patients with Parkinson’s disease and males with lower urinary tract symptoms: distinguishing neuro-
genic from non-neurogenic detrusor overactivity. J Urol 2003;169:1506–1509.
18. Fitzgerald MP, Brubaker L. Urinary incontinence symptom scores and urodynamic diagnoses.
19. Van Brummen HJ, Heintz APM, van der Vaart CH. The association between overactive bladder
symptoms and objective parameters from the bladder diary and filling cystometry. Neurourol Urodyn
2004;23:38–42.
20. Araki I, Matsui M, Ozawa K, Takeda M, Kuno S. Relationship of bladder dysfunction to lesion site
in multiple sclerosis. J Urol 2003;169:1384–1387.
21. Kirby RS, Fowler CJ, Gosling J, et al. Urethro-vesical dysfunction in progressive autonomic failure in
multiple systems atrophy. J Neurol Neurosurg Psychiatry 1986;49:554–562.
6 Conservative Therapy for Incontinence
Diane K. Newman, RNC, MSN, CRNP, FAAN

CONTENTS
INTRODUCTION
LIFESTYLE CHANGES/BEHAVIOR MODIFICATION
TOILETING PROGRAMS
PELVIC FLOOR MUSCLE REHABILITATION OR TRAINING
CONCLUSION
REFERENCES
APPENDIX
INTRODUCTION
Conservative therapy is an accepted treatment option for persons with urinary
incontinence (UI) and overactive bladder (OAB). These interventions improve symp-
toms through identification of lifestyle habits (e.g., smoking, excess weight, dietary
bladder irritants, inadequate fluid intake, bowel habits, physical activities and exercises)
and changing a person’s behavior, environment, or activity that are contributing factors
or triggers (Newman, 2005). Interventions such as bladder retraining (BT) and pelvic
floor muscle (PFM) rehabilitation or training (PFMT) attempt to decrease incontinence
and OAB symptoms through increasing awareness of the function and coordination of
the PFM to gain muscle identification, control, and strength and to decrease bladder
overactivity. These interventions are referred to as behavioral treatments as they
involve learning new skills and altering behavior through extensive one-on-one patient
instruction. Toileting programs (e.g., habit training and prompted voiding [PV]) are
used for more care-dependent persons. The International Consultation on Incontinence
has published recommendations from evidence-based research for conservative treatments.
These are outlined in Table 1. This chapter discusses the use of conservative therapy
in clinical practice.
LIFESTYLE CHANGES/BEHAVIOR MODIFICATION

In many instances, lifestyle practices can contribute to or cause urinary tract
symptoms of UI, urgency, and frequency. Patients can improve symptoms by lifestyle
modifications incorporated into their overall treatment program (Nygaard et al., 2002).
Clinicians in all care settings can teach these techniques through easy patient education
material as outlined in the Patient Guide (Newman, 2004, 2007). There are five key
components to lifestyle modification:

63
64 Part II / Treatment
Table 1
Recommendations for Conservative Therapy
The following are recommendations concerning specific conservative therapies by committees
for the International Consultation on Incontinence (Fonda et al., 2005; Newman et al., 2005;
Wilson et al., 2005). The following levels of evidence were used:
Grade A: Good-quality randomized controlled trials
Grade B: Good quality prospective “cohort” studies, case-control studies, or case series studies
Grade C: Expert opinion
• Nursing home residents should receive adequate oral hydration to increase voided volume.
Grade C
• Conflicting evidence on whether caffeine intake is associated with UI. Grade B
• Decreased caffeine intake should be considered for frail elderly. Grade C
• Chronic straining caused by constipation may be a risk factor for pelvic organ prolapse and UI;
no intervention trials have examined the impact of resolving constipation on UI. Grade B/C
• Obesity is an independent risk factor for urinary incontinence, and weight morbidly obese
women may decrease incontinence. Grade B
• No data have been reported examining whether smoking cessation resolves incontinence.
Grade B/C
• Prompted voiding should be offered to decrease daytime UI in nursing home residents and
homebound older adults if caregivers comply with the protocol. Grade A
• Bladder training and PFMT might be similarly effective for women with SUI, urge UI,
or mixed UI. Grade B
• PFMT should be a standard component of prenatal and postpartum care. Grade B
• Primiparous women should be offered a sufficiently intensive and supervised antenatal
PFMT program to prevent postnatal UI. Grade B
• Supervised PFMT is more effective than standard care for the treatment of UI at
3 mo postpartum. Grade B
• PFMT and vaginal cones might have similar effectiveness for women with SUI. Grade B
• Further investigation is warranted to assess the efficacy of PFMT and bladder training
for primary prevention of UI in older adults. Grade B
• For women with SUI or mixed UI, a combination of bladder training/PFMT
may be more effective than PFMT alone in the short term (3 mo), but any
additional benefit may not be maintained longer term (6 mo). Grade B
• Clinicians should provide the most intensively supervised PFMT program possible
within service constraints. Grade B
• There does not appear to be any posttreatment benefit of biofeedback-
(home or clinic) assisted PFMT over PFMT alone. Grade B
• PFMT might be better than electrical stimulation for women with SUI. Grade B
• PFMT might be better than oxybutynin for women with detrusor overactivity or
detrusor overactivity and urodynamic SUI. Grade B
• PFMT might be less effective than surgery for women with urodynamically
proven SUI. Grade B
1. Altering fluid intake (decreasing to reduce incontinence and frequency, increasing to

improve urine concentration).
2. Modifying the diet to eliminate possible bladder irritants (e.g., reducing caffeine, alcohol,
and carbonated beverages).
3. Regulating bowel function to avoid constipation and straining during bowel movement.
Chapter 6 / Conservative Therapy for Incontinence 65
4. Quitting smoking.
5. Reducing weight.
Fluid Management
Individuals may subscribe to either restrictive or excessive fluid intake behavior.
Adequate fluid intake is needed to eliminate irritants from the bladder. Underhydration
may play a role in the development of urinary tract infections (UTIs) and decreases the
functional capacity of the bladder (Dowd, 1996). Excessive fluid intake can trigger
incontinence and OAB. Surveys of community-residing elders reported self-care
practices to include self-imposed restrictions of fluids as they fear UI, urinary urgency,
and frequency (Engberg et al., 1995; Johnson et al., 2000). Adequate fluid intake is
important for older adults, who already have a decrease in their total body weight and
are at increased risk for dehydration. Fluid intake should be regulated to 6- to 8-oz
glasses or 30 cc/kg body weight per day with a 1500 mL/d minimum at designated times
unless contraindicated by a medical condition.
However, the research showing the relationship of quantity of fluid intake to urinary
symptoms is inconclusive. Certain professionals who drank less while working to decrease
their voiding frequency were at higher risk of UTI (Nygaard and Linder, 1997). In a
geriatric population, there appears to be a strong relationship among evening fluid
intake, nocturia, and nocturnal voided volume. Aging causes an increase in nocturia,
defined as the number of voids recorded from the time the individual goes to bed with
the intention of going to sleep to the time the individual wakes with the intention of
rising. Nocturia is an average of less than two nocturnal voids per night. Nocturia can
be diagnosed as nocturnal polyuria, which causes the largest amount of urine production
to occur at rest while the person is supine. Chronic medical conditions such as congestive
heart failure, venous stasis with peripheral edema, hypoglycemia and excess urine output,
obstructive sleep apnea, and diuretics as well as evening/nighttime fluid consumption
are causes of nocturnal polyuria. Patients who develop edema of the lower extremities
should be advised to elevate their lower extremities on a stool or recliner during the day
or to lie in bed for a nap before lunch to stimulate natural diuresis and reduce the amount
of voiding during the night. To decrease nocturia precipitated by drinking fluids primarily
in the evening or with dinner, the patient should be instructed to reduce fluid intake after
6 PM and shift intake toward the morning and afternoon.
Influence of Bladder Irritants

Common dietary staples can cause diuresis or bladder irritability, contributing to OAB
and incontinence symptoms. Caffeine is an ingredient found in certain beverages, foods,
and medications and is felt to have an impact on urinary symptoms by causing a significant
rise in detrusor pressure and an excitatory effect on detrusor contraction.
The consumption of caffeinated beverages, foods, and medications should not be
underestimated. In the United States, over 80% of the adult population consumes
caffeine in the form of coffee, tea, or soft drinks on a daily basis. In addition, the US
Food and Drug Administration has listed that more than 300 drugs bought off the shelf
in pharmacies and retail drug stores contain caffeine (Newman, 2004, 2005).
In addition to caffeine, alcohol is felt to have a diuretic effect that can lead to
increased frequency. Alcohol with dinner or consumed during evening hours may be
a contributing factor for nocturia. Anecdotal evidence suggests that eliminating
dietary factors such as artificial sweeteners (aspartame) and certain foods (e.g., highly
spiced foods, citrus juices, and tomato-based products) may play a role in continence
(Newman, 2007).
Working women surveyed reported fluid intake limitations and avoidance of caffei-
nated beverages as strategies to avoid urinary symptoms (Fitzgerald et al., 2000).
Research has shown that urine leakage can be decreased when caffeine consumption is
reduced (Arya et al., 2000; Tomlinson et al., 1999). Therefore, clinicians believe that
OAB symptoms of urgency, frequency, and urge UI have been shown to improve when
women practice BT and caffeine reduction. Assessment of daily caffeine intake on all
patients with UI and OAB and instructions on the correlation between symptoms and
caffeine intake are integral to clinical practice. It is recommended that patients with
incontinence and OAB avoid excessive caffeine intake (e.g., no more than 200 mg/d,
2 cups). The patient should be instructed to eliminate the identified product on a
“one-by-one” basis to see if symptoms decrease or resolve.
Regularity of Bowel Function
Chronic constipation (defined as having fewer than three stools per week) and straining
during defecation can contribute to UI and OAB. The close proximity of the bladder and
urethra to the rectum and their similar nerve innervations make it likely that there are
reciprocal effects between them (Dohil et al., 1994). Studies of severely constipated
women who over a prolonged period have strained during defecation have demonstrated
changes in pelvic floor neurological function (Snooks et al., 1985).
Lubowski et al. (1988) reported that denervation of the external anal sphincter and
PFM may occur in association with a history of excessive straining on defecation. Many
believe that if these are lifetime habits, then they may have a cumulative effect on pelvic
floor and bladder function. Self-care practices that promote bowel regularity should be
an integral part of any treatment care plan. Suggestions to reduce constipation include
the addition of fiber to the diet, increased fluid intake, regular exercise, external stimu-
lation, and establishment of a routine defecation schedule. High fiber intake must be
accompanied by sufficient fluid intake. Improved bowel function can also be achieved
by determining a timetable for bowel evacuation so that the patient can take advantage
of the urge to defecate.
Smoking
Conditions exist in which increased intraabdominal pressure may promote the
development of UI and urinary urgency, particularly in women. These conditions
include pulmonary diseases such as asthma, emphysema, and chronic cough such as
seen in persons who smoke. Smoking increases the risk of developing all forms of UI,
and stress UI (SUI) in particular, depending on the number of cigarettes smoked (Bump
and McClish, 1992, 1994). Causes appear to be related to more frequent and violent
coughing, which causes downward pressure on the pelvic floor, causing repeated stretch
injury to the pudendal and pelvic nerves. Nicotine may contribute to detrusor contrac-
tions, and tobacco products may have antiestrogenic hormonal effects that may have an
impact on the collagen synthesis. No data have been reported examining whether
smoking cessation in women resolves incontinence. However, in clinical practice,
women who smoke are educated on the relationship between smoking and UI, and
strategies designed to discourage women from smoking are often suggested; however,
no evidence supports their effectiveness.
Obesity
Obesity has been identified as an independent risk factor for the development of SUI
and mixed UI in women (Wilson et al., 2005). The SUI seen in obesity may be secondary
to increases in intraabdominal pressure on the bladder and greater urethral mobility.
Also, obesity may impair blood flow or nerve innervation to the bladder. Weight loss is
an acceptable treatment option for morbidly obese women. Research has shown that
SUI symptoms decrease in morbidly obese women who undergo extreme weight loss
after gastric bypass surgery (Bump et al., 1992). At this time, weight loss may resolve
incontinence in women who are moderately obese (Subak et al., 2005).
TOILETING PROGRAMS
The Cochrane Collaboration has published systematic reviews for toileting programs
that include habit training, timed or scheduled voiding, and PV (Eustice et al., 2002;
Ostaszkiewicz et al., 2002a, 2002b). These programs are reviewed in Table 2. These
programs can be utilized to improve continence, especially in frail elders who are home-
bound or reside in an institution (Lekan-Rutledge and Colling, 2003). Excluded from
these programs are residents with mobility impairment necessitating a mechanical or
multiple person transfer; those terminally ill, comatose, or severely behaviorally disturbed
residents are excluded from a PV trial. However, the frequency of toileting assists by
nursing staff in nursing homes in the United States is inadequate to maintain continence.
Therefore, there is a need to combine toileting programs with interventions geared to
nursing staff.
Scheduled toileting and habit training are toileting a person on fixed schedules
whether or not a sensation to void is present. The goal is to toilet or have the person void
prior to involuntary urine loss, thus maintaining continence but not modifying bladder
function. Prefixed times such as every 2–3 h have been adopted for toileting programs
in institutions such as nursing homes. A more realistic schedule may be developed
around certain daily routines, such as on awakening, before or after meals, and at bedtime,
or based on patterns identified in a voiding record. Regular voiding prevents chronic
bladder distension and its sequelae (e.g., compromised detrusor contractility caused by
overstretching of the muscle fibers); UTI (because of urine stasis and a poorly perfused
bladder wall); and urine leakage with activity (caused by elevated intravesical pressures).
PV is a type of scheduled toileting program that employs behavior modification to
reinforce both appropriate toileting behaviors and the individual’s desire to stay dry. PV
has been shown to reduce UI episodes by up to 33% in nursing home residents regardless
of their type of UI or cognitive deficit (Ouslander et al., 1995). Requirements for inclusion
in this program are ability to
• Respond appropriately.
• State one’s name.
• Reliably point to one of two objects.
There are five major steps of a prompted voiding program: (1) scheduled checking
to allow the patient to request toileting; (2) discussing with the patient the incontinence
problem; (3) prompting the patient to void; (4) providing positive reinforcement to the
patient for making an effort to use the toilet; and (5) if incontinent, then indicate to
the patient that the expectation is that they stay dry (Engberg et al., 2002; Newman, 2007;
Ouslander et al., 1995).
Table 2
Types of Bladder Programs
Changes in intervoid
intervals (times
Program Other terms between voiding) Patient profile Approach
Scheduled or Scheduled voiding Unchanged Spinal cord injury causing Fixed voiding regimen (e.g., every 2 or 3 h)
timed Timed toileting neurogenic bladder Techniques to facilitate or “trigger” voiding may
voiding Cognitively impaired, be helpful (e.g., crede maneuver, running water
available and compliant at the sink, placing hands in a basin of warm water,
caregiver drinking warm fluids, pouring warm water on
the perineum)
Habit Habit training Increased or Spinal cord injury Assigned toileting schedule (every 2–3 h); schedule
(including decreased Cognitively impaired, should be determined by voiding pattern determined
patterned available and compliant from a voiding diary; encourage delaying toileting until
urge response) caregiver the set times unless urge is unbearable
Bladder drill
68
Prompted Bladder training Prompting Cognition requires that the Prior to implementing a PV program, a trial
voiding schedule patient be able to state should be done for 3 consecutive days; predictors
name and reliably point of a good response include those residents who
to one of two objects Respond to prompts when toileting
Available and compliant Void a high maximum volume of urine (>150 mL)
caregiver Have appropriate number of voids (voids at least 50%
of the time into a toileting receptacle)
Have incontinence frequencies <4 episodes in 12 h
(baseline incontinence rate)
Have normal PVR urine volume (<150–120 mL)
Bladder Bladder training Increased Cognitively and neurologically Patients are instructed to void during specific intervals
retraining Bladder reeducation intact persons who are (e.g., every 30 min or 1 h); if urge occurs during the
Behavioral training motivated to change interval, distraction or relaxation techniques or
Urge suppression or symptoms self-affirming statements are used to decrease urgency;
inhibition over time, voiding interval increased at comfortable
intervals until a maximum of every 3–4 h is reached
BT helps to restore normal bladder function by gradually increasing the intervals

between voiding in an attempt to correct urinary frequency and eventually diminish
urgency. Mechanisms of action are not well understood, but it is felt that BT improves
cortical inhibition over detrusor contractions, facilitates cortical ability over ure-
thral closure during bladder filling, strengthens pelvic striated muscles, and alters
behaviors that affect continence (e.g., frequent response to urgency). The patient is
provided information about normal bladder control and given methods called urge
suppression strategies to control the urgency. The main outcomes for a BT program
are to (1) improve bladder overactivity by controlling urgency and decreasing fre-
quency; (2) increase bladder capacity; and (3) reduce urge incontinence episodes
(Newman, 2005). BT is most appropriate for patients with all types of UI and OAB,
are motivated and can comprehend, and who can read and follow instructions (Roe
et al., 2002).
The most common BT protocol is provided in an outpatient or office practice
program supervised by a knowledgeable clinician. The patient is assigned an initial
voiding interval, typically beginning every 30–60 min during waking hours (Wilson
et al., 2005; Wyman, 2003). The voiding intervals are based on the baseline micturition
frequency as determined by the bladder diary. Initially, it is important for the patient
with urgency to schedule short voiding intervals as the shorter intervals will decrease or
eliminate these symptoms (Newman, 2005). The goal is for the patient to void “before”
the urge sensation of bladder fullness. The patient is taught methods to resist or inhibit
the urge sensation so an expanded voiding interval can be adopted. Improving the
ability to suppress the urge sensation and eventually diminish urgency will enable
the patient to adopt a more normal voiding pattern. There are several strategies or tech-
niques used to control and inhibit the urge sensation, including slow, deep breathing to
consciously relax the bladder to combat a stressful rush to the toilet or performing five
or six rapid, deliberate, and intense pelvic muscle contractions of 2–3 s long. The
scheduled intervals between voiding are increased by 15–30 min each week depending
on the tolerance of the schedule (e.g., fewer incontinence episodes, less frequency) until
a voiding interval of 3–4 h or longer is achieved. The use of reminders such as a kitchen
timer or stopwatch can be beneficial in helping the patient keep on a schedule
(Newman, 2005). Self-monitoring through the use of bladder diaries is essential to
evaluate adherence and to determine the next weekly voiding interval.
As with most behavioral interventions, the relationship between the clinician and
patient is important to the success of the retraining. The clinician must monitor the
patient’s progress and provide praise and encouragement if appropriate.
It is felt by most experts that, in patients with OAB symptoms, combining behavioral
interventions with treatments such as drug therapy is the most efficacious (Burgio et al.,
2002; Mattiasson et al., 2003).
PELVIC FLOOR MUSCLE REHABILITATION OR TRAINING

The primary technique of conservative therapy is PFMT with or without biofeedback.
The rationale for this is that mastering a voluntary contraction of the PFM will help to
increase pressure in the urethra, inhibit detrusor contractions, and control leakage of
urine. It is a skill that patients seldom master on their first try, but with repeated
training, it can be used successfully and provide significant improvement in reducing
incontinence episodes.
Pelvic Floor Muscle Exercises

Pelvic floor muscle exercises (PFMEs) were introduced in the 1940s by Dr. Arnold
Kegel and have been referred to as Kegel exercises. Research on exercising the pelvic
floor most recently has centered on specific PFME or PFMT, and data have accumu-
lated concerning the efficacy of these exercises in decreasing all types of incontinence
and OAB symptoms of urgency and frequency in cognitively intact, motivated, and
neurologically intact patients (Wilson et al., 2005).
The proposed mechanisms of action for PMEs include (1) urethral closure through
increases in urethral pressure; (2) mechanical pressure rise that causes lifting of the
endopelvic fascia, which presses it upward toward the pubic symphysis; and (3) a pelvic
muscle “reflex” contraction that precedes increased bladder pressure and may inhibit
bladder overactivity (Newman, 2005).
The PFM is under voluntary control, and exercises of this striated skeletal muscle
consists of contractions of two types of muscle fibers: type I, slow-twitch muscle fibers;
and type II, fast-twitch muscle fibers. Type I (80%) muscle fibers produce less force on
contraction and assist in improving muscle endurance by generating a slower, more
sustained but less-intense contraction to maintain a general level of pelvic support and
urethral closure pressure. Type II or fast-twitch fibers cause strong and forceful muscle
contractions, build pelvic muscle strength, and are most helpful during sudden increases
in intraabdominal pressure by contributing to urethral closure. The use of pictures or
diagrams of the PFM and its support for the pelvic organs are helpful when educating
patients (see Fig. 1 A, female; B, male).
Clinicians should provide specific instructions on location and isolation of the PFM.
The following instructions can be used when asking the patient to contract or tighten the
pelvic muscle:
• Without tensing the muscles of the legs, buttocks, or abdomen, imagine trying to con-
trol the passing of gas or pinching off a stool by tightening the ring of muscles around
the anus. A closing-and-lifting sensation should be felt.
• For men, ask them to imagine moving the penis up and down without moving any other
part of the body.
Patients should be cautioned not to perform these exercises during voiding and not to
stop and start urine flow as a form of exercising. This exercise has good face validity
for effectiveness because many patients initially report an inability to stop the urine flow
when it begins. However, there is some controversy over this practice because it is non-
physiological and can be harmful. Also, patients should not overexercise the PFM as
women can develop levator ani myalgia by performing excessive exercises (DeLancey
et al., 1993).
Once the patient is able to identify the muscle, he or she is instructed to perform a
series of “quick flicks” or 2-s contractions followed by sustained (endurance) contrac-
tions of 5 s and longer as part of a daily exercise regimen. It is equally important to
control both muscle tightening and relaxing, to relax for the same amount of time the
muscle is contracted, and to relax completely between each muscle contraction. The
patient is encouraged to aim for a high level of concentrated effort with each PFM con-
traction as greater contraction intensity is associated with improvement in PFM
strength (Bo and Talseth, 1996; Newman, 2005). Patients are given the following
instructions about positions to use when performing these exercises:
Fig. 1. Side vew of female (A) and male (B) anatomy depicting the position of the pelvic floor muscle.
Copyright Diane K. Newman.
• Sit upright in a straight-back chair, knees slightly apart, and feet flat on the floor or legs
stretched out in front and crossed at the ankles.
• Stand by a chair; keep back straight and knees slightly bent with feet shoulder-width
apart and toes slightly pointed outward.
• Lie on the back flat or with head slightly elevated, knees bent, and feet slightly apart.
A minimum of 30–45 PMEs per day is recommended. A gradual increase in number
of contractions over a period of PME practice has been shown to increase muscle
strength significantly and decrease urine loss. An exercise prescription as shown in
Table 3 can be used in clinical practice when recommending PFMT.
The patient should also be taught a preventive PFM contraction referred to as the
knack (Miller et al., 2001). The knack is the skill of consciously timing an intentional
contraction of the PFM just before and throughout the activity that causes an increase
in intraabdominal pressure (Miller et al., 1996). This technique is an acquired motor
skill that requires the patient to anticipate urine leakage. Contracting the PFM before
sneezing, coughing, lifting, standing, or swinging a golf club can prevent SUI from
occurring. The muscle also can be contracted when a strong urge to void occurs.
Repeated correct contractions of the pelvic floor, strengthening the PFM in a regular,
intensive, and long-lasting training program, are essential for effective improvement
through PFMT. Results may not occur until after 6–8 wk of exercise, and optimal results
usually take longer. For muscle contractility to improve, five principles of muscle training
must be considered (Newman, 2003):
1. Strength: maximum force or contraction that a muscle can generate.
2. Power: referred to as quick flicks or the ability for the muscle to contract-relax as
quickly and strongly as possible.
3. Endurance: muscle is timed until it fatigues, up to 10 s.
4. Repetitions: number of times (up to 10) a muscle contraction of equal force that can be
repeated. Use at least a 5-s muscle relaxation between each contraction (easily fatigable
Table 3
Exercise Prescription Sample
Please complete the following exercises:
1. Short quick exercise: Contract the muscle for 2 s and immediately relax.
2. Long sustained exercise: Contract the muscle and hold the contraction for a count of 10,
then immediately relax for a count of 10.
Exercise session
Lying Down Do 10 exercises holding for 2 s
Do 10 exercises holding for 10 s
Sitting Do 10 exercises holding for 2 s
Standing Do 10 exercises holding for 2 s
3. Be sure to rest your muscle after each muscle contraction for the same length of the contrac-
tion or longer. Do two exercise sessions per day for a total of 60 exercises every day.
4. When you have completed both types of exercises in all three positions, you will have com-
pleted one session.
Special tips
• Always empty your bladder prior to beginning your exercise session.
• Count out loud with sustained or long exercises; remember to keep breathing.
• Keep your stomach, leg, and buttock muscles relaxed. Rest your hand on your stomach,
which should not move or tense.
• If it helps, take a deep breath between each exercise to help keep other muscles relaxed.
© 2000 Diane K. Newman.
muscles need a chance to recover) without permitting excessive rest periods for strong
muscles.
5. Fatigue: failure to maintain the required or expected force of the pelvic muscle contraction
for more than one or two times in succession.
The tone of the PFM is also important. Low muscle tone is the impaired ability to
isolate and contract the PFM in the presence of weakness and atropy. High muscle tone
refers to the clinical condition of hypertonic, spastic PFM with resultant impairment of
muscle isolation, contraction, and relaxation. A high resting baseline with high variability
and occasional spasms may be seen in patients with chronic pelvic pain syndromes
(e.g., painful bladder syndrome) (Fletcher, 2005). Rehabilitating the PFM can be central
in resolving pain when muscle spasm is present. Using PMEs on patients with high tone
to enhance muscle relaxation is referred to as down training. Teaching a muscle to relax
is often more difficult than teaching it how to contract (up training) as the feeling of
relaxation is small.
Most clinicians in this field have relied on the use of verbal and written instructions
for patients to use for home practice of PMEs. Self-monitoring practice through the use
of a calendar record, audio- and videotaped material that review the exercises can
improve protocol compliance (Newman, 2007).
Research in the area of PMEs is extensive, but long-term results have been reported
only rarely (Bo and Talseth, 1996). Cure rates for PFMT range from 16 to 27% and
improvement rates from 48 to 80.7%. However, the most critical variables in PFMT are
isolation of the PFM and adherence to a prescribed exercise regimen.
Use of Biofeedback Therapy
The basic debate regarding efficacy of PFMT involves the added benefit of adjunct
techniques such as biofeedback using electromyography (EMG) or other methods.
Biofeedback is the technique by which information regarding physiologic processes,
in this case PFM contractions and relaxations, is displayed in a form understandable
to the patient to permit self-regulation of these events. Biofeedback therapy uses
either EMG or manometric pressure. EMG measures electrical activity of a muscle in
microvolts. The advantage of EMG over manometric pressure is that, provided the
machinery is sufficiently sophisticated with adequate filtering, EMG apparatus can
engage the use of the newer types of electrodes that are lightweight and designed to
stay in place, hence allowing more functional positions during assessment and treat-
ment (Newman, 2003). Also, EMG can be multichannel, which allows the simultaneous
reinforcement of contractions of the PFM and inhibition of accessory muscles (e.g.,
abdominal muscle contractions). A common error in contracting the PFM is to con-
tract the abdominal, gluteal, or adductor muscles simultaneously. This may mask the
strength of the PFM contraction. Abdominal contraction increases intra-abdominal
pressure, which mechanically elevates bladder pressure, so it is important to measure
concurrent use of abdominal contraction (Sapsford and Hodges, 2001). When an addi-
tional muscle group is contracting at the same time as the pelvic floor, it is called
recruitment. Monitoring for accessory muscle recruitment during initial EMG and
subsequent visits are necessary until recruitment stops and should be considered for
all patients.
Four methods of EMG measurements have been used in the investigation of lower
urinary tract dysfunction (Workman et al., 1993):
• Vaginal sensor.
• Anal sensor or plug electrode.
• Surface skin electrodes.
• Needle electrodes.
Vaginal and anal sensors are internal probes designed to provide accurate detection
of EMG muscle activity. The accuracy of longitudinal sensing electrodes has been
shown to be virtually identical to the gold standard of inserted needle electrodes.
However, the use of vaginal or rectal sensors is limited in patients with severe pelvic
pain, for whom insertion of the sensor causes discomfort; pregnancy; recent pelvic or
rectal surgery; and atrophic vaginitis. Skin electrodes are relatively noninvasive and
well tolerated and provide quantitative information about muscle activity. Needle
electrodes are primarily used during urodynamic testing. The EMG data are measured
in microvolts. The actual threshold of PFM required for maintaining continence is
unknown at this time, as are the normal values for PFM strength.
The baseline and all follow-up EMG recordings should include two sets of measure-
ments of maximum or short/quick muscle contractions of 2-s duration with an equal
amount of resting muscle activity and sustained or long muscle contractions (5, 10, or
30 s) with resting muscle activity for the same length of time as muscle contraction. The
ability to relax one’s pelvic muscle following a contraction is most important if one is
to gain control and coordination of these muscles.
Manometry is the use of an instrument to detect, assess, and record pressure. A pres-
sure perineometer first described by Kegel consists of a vaginal or rectal probe with a
connector tube to a manometer. The pressure changes can be measured in centimeters
of water (cm H2O) or millimeters of mercury (mmHg) (Theofrastous et al., 2002).
Although manometers and pressure sensors are available with certain clinical systems
and have been used in several clinical trials, they are primarily used for treatment of
rectal dysfunction.
Different biofeedback methods can be used in PFMT (Newman, 2007), including
proprioception and verbal encouragement:
• Digital (e.g., vaginal or rectal) PFM assessment of the levator ani muscle is a form of
biofeedback and is an important component of teaching correct pelvic muscle contrac-
tion and muscle awareness (Bo and Finckenhagen, 2001). Appropriate treatment with
PFMT should always include an assessment of PFM contraction and relaxation
because the effect of PFMT is dependent on whether the contractions and relaxations
are performed correctly.
• Verbal feedback of a voluntary contraction can also encourage and assist in enhancing
patient effort. The levator ani can be palpated in the 4 and 8 o’clock positions, just
superior to the hymenal ring. Pain or discomfort during palpation may indicate high-tone
pelvic muscle.
• Manometric and EMG biofeedback not only helps in PFMT awareness, but also pro-
vides interest, challenge, and reward for effort, a greater feeling of control, and progress
monitoring.
Research, in both men and women, is extensive in detailing the efficacy of the use
of biofeedback-assisted behavioral therapy for PFMT. However, there is debate over
the use of adjuncts such as biofeedback therapy (Wilson et al., 2005). The consensus
is that conservative therapy combining lifestyle changes, toileting or BT programs, and
PFMT with or without biofeedback is most effective when provided by a clinician who
specializes in the area of pelvic floor dysfunction. Clinician-supervised PFMT with
biofeedback is felt to provide the most favorable long-term results, and many multi-
disciplinary pelvic floor dysfunction or “continence” centers provide these services
(Newman, 2007). Augmenting drug therapy with a supervised bladder training pro-
gram is felt to yield the best outcomes in the treatment of urge incontinence and OAB
(Burgio et al., 2002).
Use of Vaginal Weights

Vaginal weights are another example of an adjunct technique that can be used in
PFMT. They have been most successful as part of a structured resistive pelvic exercise
program in woman with SUI. The weights are made of plastic and shaped like a tampon.
All weights are identical in size but have increasing weight. The idea is that the stronger
the PFM becomes, the higher the weight of a cone must be to stimulate the PFM to hold
the weight inside the vagina. The user is instructed to insert the lightest weight into the
vagina in the position of a tampon. The user then walks around for up to 15 min con-
tracting the PFM to prevent the weight from slipping out. If the weight is easily retained
during this time, then the next-heaviest weight is introduced, and the procedure is
repeated until a weight of a certain heaviness slips out. To increase the exercise value of
these weights, the woman is instructed to practice retaining the weight during coughing,
jumping, or any stress-provoking act that causes incontinence. Theoretically, when the
weight is placed in the vagina it provides sensory feedback and prompts a PFM contrac-
tion to keep it from slipping out. The perceived advantages of vaginal weight training
are that it involves less teaching time, can be self-taught, may be motivational, and can be
used with minimal supervision. The weights can be purchased at www.seekwellness.com.
Weighted vaginal cones are better than no active treatment, but on the other hand,
they add no benefit to a PFMT program (Herbison et al., 2002). Although vaginal
weight training may take less instructional time in terms of office practice, it may be less
acceptable to some women than PFME alone, as noted by higher attrition rates in some
clinical trials (Cammu and Van Nylen, 1998). Reasons given for their nonuse were aesthetic
dislike, unpleasantness, discomfort, difficulty in insertion, or bleeding (Wyman, 2003).
Pelvic Floor Electrical Stimulation

Pelvic floor electrical stimulation (PFES) is the application of low-grade electrical
stimulation to the PFM to stimulate the muscle to contract. PFES has a twofold action:
contraction of PFM and inhibition of unwanted detrusor contractions. PFES for SUI is
the result of stimulation of afferent fibers of the pudendal nerve activating both the
pelvic floor and periurethral muscles. For urge UI and OAB, bladder inhibition occurs
through pudendal- (afferent) to-pelvic (efferent) nerve reflex and a pudendal-to-hypo-
gastric reflex.
Electrical stimulation can be performed in the clinician’s office and is prescribed as
a home program using a battery-operated home unit. The delivery of the electrical cur-
rent to the tissues is via a sensor with vaginal or rectal sensors preferred. There are many
differences in clinical application that have not yet been investigated. For example, some
clinicians suggest that active electrical stimulation (i.e., the patient voluntarily contracts
the PFM during stimulation) is better than passive electrical stimulation, but the effect of
these two approaches has not yet been evaluated. Equally, it may be that some popula-
tions or subgroups of patients benefit from electrical stimulation more than others.
The home program consists of using the stimulator for 15 min twice a day for several
weeks to months, although the length of time and number of treatments are highly variable.
The patient is instructed to use the maximum tolerable level during stimulation.
However, with the wide variations in stimulation parameters, including time, intensity,
and frequency of sessions, it is difficult to make comparisons across studies. Given the
equivocal results, the benefit of electrical stimulation in SUI, urge, and mixed UI in
women remains controversial (Wilson et al., 2005).
CONCLUSION
Conservative therapy is considered front-line treatment for persons with SUI, urge,
or mixed UI and for those with OAB. These treatments, especially lifestyle interven-
tions, can be offered to patients in the primary care setting before or with medication
therapy. Clinicians need to become familiar with the different conservative therapies to
maximize improvement in these chronic conditions.
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APPENDIX
Patient Guide: Controlling Your Bladder Symptoms
Common bladder symptoms include
Urinary urgency: sudden and strong sensation to urinate immediately
Frequency: urinating often, usually more than eight times in a day
Urinary incontinence: accidental leakage of urine
Special exercises and medications are available to reduce common bladder symptoms.
In addition, many people find that specific diet and lifestyle changes may help reduce
bladder problems.
Pelvic Floor Muscle Exercises

Bladder control depends on muscles working together when the bladder is filling:
The bladder muscle should be relaxed, and the muscle around the urethra (the tube that
urine passes through), called the pelvic floor muscle, should be tight. Exercises that
strengthen the pelvic floor muscle can help hold urine inside the bladder, preventing
leakage. These are commonly called pelvic floor muscle exercises or Kegel exercises,
named after the doctor who developed them. To perform a pelvic floor muscle exercise,
imagine that you are trying to control the passing of gas or pinching off a stool. Or,
imagine you are in an elevator full of people, and you feel the urge to pass gas. What do
you do? You tighten or pull in the ring of muscle around your rectum, your pelvic floor
muscle. Women will feel a lifting sensation in the area around the vagina or pulling in
of the rectum. Men may see their penis lift or feel a pulling in of the rectum. One exercise
consists of both tightening and relaxing the muscle. Start by tightening the muscle for
5 s and build until you can hold the tightening for 10 s. Be sure to relax completely
between each muscle tightening.
Bladder Retraining
Bladder control can be improved by scheduling bathroom trips. The schedule is
changed over a period of weeks or months to gradually increase the time between trips.
For example, a person who normally goes to the bathroom every hour could plan to go
every hour and 15 min. After maintaining the new schedule for a few days, the time
could be increased to every hour and 30 min. The goal is to void no more than every
3–4 h. If you get the urge to void and it is not yet your scheduled voiding time, then
stop all activity and sit down if possible. Then, try one of these techniques to help you
lessen the urge, which will cause the bladder to relax and give you more time to get to
the bathroom:
• Take some slow, deep breaths through your mouth, concentrating on your breathing; or,
concentrate on an activity, such as taking a vacation, visiting a friend, counting back-
ward from 100, or reciting the words of a favorite song or nursery rhyme.
• Tighten your pelvic floor muscle quickly several times in a row.
Monitor Your Diet and Medications

Certain foods and beverages can irritate the bladder and make symptoms worse.
These include alcoholic beverages; caffeinated foods or carbonated beverages (soft
drinks, coffee or tea, chocolate); tomato-based products; citrus fruits and juices; spicy
foods; and artificial sweeteners (e.g., Equal). Also, some over-the-counter medications
and prescription drugs (e.g., Excedrin, Midol, Anacin, Dristan, Sinarest) can worsen
bladder problems. Do not stop taking prescription drugs without talking to your health
care provider first.
Maintain Bowel Regularity

Keeping healthy bowel habits may lessen bladder symptoms. Some suggestions
include (1) increase such fiber-rich foods as beans, pasta, oatmeal, bran cereal, whole
wheat bread, and fresh fruits and vegetables in your diet; (2) exercise to maintain regular
bowel movements; (3) drink plenty of nonirritating fluids (water); (4) see your doctor if
you have bowel problems.
Maintain a Healthy Weight

Being overweight can put pressure on your bladder, which may cause leakage of
urine when you laugh or cough. If you are overweight, then weight loss can reduce pres-
sure on your bladder.
Stop Smoking
Cigarette smoking is irritating to the bladder muscle. It can also lead to coughing
spasms, which can cause urinary leakage.
7 Pharmacological Therapy for Stress
Urinary Incontinence
Harriette M. Scarpero, MD
CONTENTS
ANATOMIC AND FUNCTIONAL INFLUENCES ON CONTINENCE
HORMONE REPLACEMENT THERAPY
IMIPRAMINE
F-ADRENERGIC AGONISTS
G2-ADRENOCEPTOR AGONISTS AND ABTAGONISTS
SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS
CONCLUSION
REFERENCES
Stress urinary incontinence (SUI) is the involuntary loss of urine with activities that
increase intra-abdominal pressure, such as coughing, sneezing, and walking. Treatment
options vary and include behavioral modifications, pelvic floor muscle exercises
(PFMEs), barrier methods, bulking agents, and surgery. No drug approved by the Food
and Drug Administration (FDA) exists for SUI. A few agents are occasionally used off
label for SUI, but randomized controlled trials proving their efficacy and safety for this
indication are lacking.
Urinary incontinence (UI) of any type is an important health concern that often has a
substantial effect on an individual’s perception of well-being, body image, and quality of
life (QOL). It is estimated that 13 million people in the United States, of which 11 million
are women, suffer from UI (1). The actual prevalence of UI in women is not known.
Most women who experience UI never seek or receive treatment (2,3). A limitation of
existing national databases is that they capture only the minority of incontinent women
who are treated for incontinence.
The economic impact of UI is better understood and formidable. According to the
recently published Urologic Diseases in America Project, UI in women was the
chief reason for more than 1 million office visits in the year 2000 at a cost of $452
million (4). Despite the public’s recognition of the disorder, embarrassment and fear
that surgery is the only treatment option can still inhibit a woman from discussing
incontinence with her physician. A prodigious growth of information and treatment
options for UI has developed, but SUI remains without an effective pharmacological
treatment.

83
84 Part IIA / Stress Urinary Incontinence
ANATOMIC AND FUNCTIONAL INFLUENCES ON CONTINENCE
Female continence is maintained by the interplay of several anatomic and functional

mechanisms. With increases in intraabdominal pressure, the abdominal pressure is
passively transmitted to the proximal urethra, followed by active contraction of the
striated external sphincter. The suburethral supportive layer of periurethral fascia, ante-
rior vaginal wall, and levator ani muscles act as a backboard of support against which
the urethra is compressed during increases in intraabdominal pressure so that leakage
does not occur. Also contributing to continence is reflex contraction of the levator muscles
that directly increases midurethral pressure. Addition of voluntary contractions of levator
and obturator muscles to increase tension on the urethropelvic ligaments does the same.
Alteration or damage to any of these anatomic structures may result in SUI, and anti-
incontinence surgery attempts to restore the anatomic deficits contributing to leakage.
However, prevailing theories of continence hold that the etiology of SUI is not purely
anatomic. Functional factors such as the intrinsic urethral function are responsible as well,
a concept illustrated by the observation that not all women with hypermobility of the
urethrovesical unit leak. The intrinsic function of the urethra is related to its makeup of
smooth and striated muscle, connective tissue, vascular plexus, and mucosa, which together
provide inwardly directed forces that help coaptation and, ultimately, continence.
Nervous system control of the lower urinary tract is another integral part of its
physiology and the pathophysiology of incontinence. It plays a crucial role in deter-
mining the detrusor capacity and compliance as well as urethral competence necessary
to maintain or restore continence. Extrinsic efferent innervation of the lower urinary
tract includes three major nerves carrying the three principal divisions of the peripheral
nervous system: sympathetic, parasympathetic, and somatic. Activity of the detrusor
smooth muscle, bladder neck muscles, and internal sphincter are autonomically controlled,
whereas the striated muscle of the external sphincter is controlled by the somatic branch
of the peripheral nervous system (5).
The autonomic nervous system predominates in the lower urinary tract. The hypogastric
nerve carries sympathetic input responsible for bladder relaxation and exerts its effect
through G-adrenergic receptors (G3) at the detrusor and F1- (F1) receptors in the bladder neck
and proximal urethra. The pelvic nerve carries parasympathetic input for bladder contrac-
tion via acetylcholine stimulation of muscarinic receptors (M3) in the body of the detrusor.
The distribution of autonomic receptors in the lower urinary tract varies. Numerous types
of postsynaptic nerve receptors exist: F-adrenergic, G-adrenergic, cholinergic, histaminic,
and serotonergic. In general, G-adrenergic stimulation produces smooth muscle relaxation,
and F-adrenergic and cholinergic stimulation cause muscle contraction.
Specific receptor functions at specific lower urinary tract sites are still incompletely
understood. The detrusor is predominantly supplied with postganglionic parasympathetic
cholinergic nerve terminals. Few noradrenergic nerves targeting G-adrenergic receptors
are found at the trigone and none in the detrusor. The G-adrenergic receptors in the
detrusor facilitate relaxation and bladder filling. Cholinergic receptors in the dome are
responsible for detrusor contraction during micturition. The F-adrenergic receptors of
the F1-subtype are found in low density in the detrusor, and other F-adrenoceptors are
absent. Newly recognized serotonin (5-HT) receptors within the detrusor appear to
facilitate neuromuscular cholinergic transmission (6). H1 histamine receptors have also
been identified in the detrusor, but currently no role for histamine as a neurotransmitter
in the lower urinary tract has been discovered (7).
Chapter 7 / Pharmacological Therapy for Stress Urinary Incontinence 85
Fig. 1. Peripheral nervous system.
Neural control of the urethral muscle itself is supplied by all three divisions of the
peripheral nervous system (Fig. 1). Sympathetic preganglionic neurons in the upper
lumbar spinal cord give rise to preganglionic axons, which are carried along the inferior
splanchnic nerves. Some axons synapse with sympathetic postganglionic nerves within
the inferior mesenteric ganglion and project along the hypogastric nerve; other pregang-
lionic axons pass through the ganglion and continue along the hypogastric nerve to
innervate postganglionic sympathetic neurons in the pelvic plexus (8). Sympathetic
postganglionic fibers are primarily noradrenergic and innervate longitudinal and circular
smooth muscle in the urethra (8).
Parasympathetic innervation from parasympathetic preganglionic neurons in the
sacral spinal cord begets preganglionic axons, which are carried on the pelvic nerve to
connect with parasympathetic postganglionic neurons in the pelvic nerve, which connect
with parasympathetic postganglionic neurons in the pelvic plexus. Most parasympathetic
postganglionic neurons are primarily cholinergic and innervate longitudinal and circular
smooth muscle (9).
Somatic innervation arising from urethral sphincter motor neurons in the ventral horn
of the sacral spinal cord, in a region known as Onuf’s nucleus, are cholinergic motor
axons. They are carried along the pudendal nerve and make direct synaptic connections
with the striated sphincter (Fig. 2) (10). Reflex control of the urethral innervation is
through a series of spinal and supraspinal reflexes. The primary transmitter for these
reflexes is glutamate, and 5-HT and norepinephrine (NE) exert some neuromodulatory
control (10).
Newer investigation into the pharmacological treatment of UI has targeted the central
nervous system (CNS) and peripheral innervation of the lower urinary tract. Several
CNS transmitter systems have been found to modulate voiding, and two important ones
are the serotonergic and noradrenergic systems of the brainstem. Neuroanatomical
Fig. 2. Cholinergic motor axons making synaptic connections with the striated sphincter.
studies demonstrate high densities of serotonergic and noradrenergic terminals in areas

of the spinal cord associated with lower urinary tract reflex pathways, such as Onuf’s
nucleus (10). The most promising new investigational agent for SUI is directed at these
neurotransmitters for the purpose of increasing neural activity to the external sphincter.
HORMONE REPLACEMENT THERAPY

The female genital tract and urinary tract are intimately connected from early develop-
ment, both embryologically derived from the urogenital sinus. Estrogen receptors have
been located within the vagina, urethra, bladder, and pelvic floor muscles, indicating
the estrogens have a significant effect on the anatomic and functional roles of the
urogenital organs (11). Many women notice that their urinary symptoms, including UI,
may be affected by their menstrual cycle, and these changes have been demonstrated
urodynamically (12,13). The influence of hormonal fluctuations in estrogen and prog-
esterone is also noted in the increased incidence of urgency, frequency, and detrusor
overactivity in pregnancy. The urogenital effect of estrogen variations becomes even
more noticeable after menopause. As estrogenization of the vaginal tissues wanes after
menopause, women often experience irritative vaginal and lower urinary tract symp-
toms. The increased incidence of bothersome lower urinary tract symptoms and vaginal
atrophy after menopause has led to the use of hormone replacement therapy (HRT) for
their treatment. The presumed benefits of HRT to the urogenital tract have been far
reaching, although without much rigorous medical substantiation by large randomized
and placebo-controlled trials.
Although rarely used as primary therapy for SUI, HRT has been advocated commonly
for its treatment. The rationale behind its use stems from several theories of the role
of estrogen in the lower urinary tract. Estrogens may have an impact on continence
by increasing urethral resistance, raising the sensory threshold of the bladder, increasing
F-adrenoreceptor sensitivity in the urethral smooth muscle, or promoting G3-adreno-
receptor-mediated relaxation of the detrusor muscle (14,15). HRT is also thought to increase
the number of epithelial cells lining the bladder and urethra, improve the thickness
and quality of the subepithelial vascular plexus, and thus improve the coaptation of
urethral walls and urethral resistance (16). Overall, many claims have been made
regarding the benefit of estrogens for lower urinary tract symptoms. Data from several
large studies described in this section have finally elucidated the effect of conjugated
estrogens on the condition of SUI.
The role of estrogens for the treatment of SUI is at best controversial. Until recently,
the majority of studies examining the use of estrogen for UI were observational series
examining a wide range of different preparations, dosages, and routes of administration.
In addition, the inconsistent use of progestogens for endometrial protection was a
confounding factor in several studies (17). Older studies document an increase in the
maximum urethral pressure and symptomatic improvement in 65–70% of stress
incontinent women using oral estrogens (18). Several reviews and meta-analyses of the
literature on this subject demonstrated the limitations of many of the available studies:
small numbers, lack of randomization, and lack of placebo control (19–21). Results
vary, pointing out the limitations of meta-analysis as well and that conclusions can
really only be made from a well-designed randomized clinical trial with an adequate
control. According to the Cochrane Database of Systemic Reviews, 28 trials including
2926 women reported using estrogens in a variety of combinations, dosages, routes of
administration, and duration of therapy for UI (22). The consensus of these trials was
that the rate of subjective improvement and cure of both stress and urge incontinence
were statistically higher in women receiving estrogens as compared to women receiving
placebo. A meta-analysis of 87 articles on the use of estrogens for SUI revealed that
estrogens were not effective treatment for SUI, although they may provide improvement
in the symptoms of urgency and the prevention of recurrent urinary tract infections in
the postmenopausal woman when administered topically (23).
Two relatively small randomized and placebo-controlled trials of HRT for the treatment
of postmenopausal SUI were conducted with similar results. In 83 women with urody-
namic evidence of SUI or detrusor overactivity, conjugated equine estrogens (CEEs)
and medroxyprogesterone given orally for 3 mo produced no significant change in the
number of incontinence episodes after treatment, no change in the QOL measures, or no
change in patient perception of improvement (20). A similar double-blind, placebo-
controlled randomized trial of 67 women with genuine SUI not treated with HRT found
no significant effect over placebo of 2 mg estradiol valerate given for 6 mo (24). Neither
study addressed the use of HRT for prevention or as adjunctive treatment.
The Heart and Estrogen/Progestin Replacement Study was designed as a randomized
controlled trial to evaluate daily oral conjugated estrogen plus medroxyprogesterone
acetate (MPA) therapy for the prevention of coronary heart disease events in post-
menopausal women with known coronary disease (25). As a separate evaluation in this
population, 1525 (55%) of the 2763 women who had at least weekly UI at the initiation
of the study were evaluated for change in the severity of incontinence. Women were
randomly assigned to HRT or placebo and followed for 4.1 yr. Incontinence improved
in 26% of the placebo group as compared to 21% in the HRT group. Conversely, 27%
of the placebo group and 39% of the HRT group realized a worsening of symptoms,
which was a statistically significant difference. Furthermore, the incidence of inconti-
nence episodes per week increased by an average of 0.7 in the HRT group and decreased
by 0.1 in the placebo group, also a statistically significant difference.
Findings of the Women’s Health Initiative support a higher risk of UI in women
receiving CEE alone and CEE with MPA (26). This multicenter, double-blind,
placebo-controlled, randomized trial of HRT in 27,347 postmenopausal women sought

to assess the effect of HRT on the incidence and severity of symptoms of stress, urge,
and mixed incontinence. Results revealed that HRT (both CEE alone and CEE with
MPA) increased the incidence of all types of UI at 1 yr among women who were con-
tinent before HRT. Furthermore, the risk of developing SUI was the highest. HRT also
worsened preexisting UI at 1 yr.
A reasonable conclusion from the more recent clinical trials is that conjugated
estrogens with or without MPA have no place in the treatment of SUI. Less is known
about topical local hormone replacement for the treatment of UI.
IMIPRAMINE
The tricyclic antidepressant imipramine is indicated for nocturnal enuresis and
is often used off label for SUI, mixed incontinence, and urinary urgency incontinence.
Imipramine has several effects in both the central and peripheral nervous system.
Despite its long-time use for UI, the exact mechanism of action most responsible
for action on the lower urinary tract has not always been clear because it has so
many pharmacological actions. It has a systemic anticholinergic effect but none on
the bladder itself. It has a sedative and antihistamine effect. It directly stimulates
F-adrenergic receptors in the bladder neck and urethra (27). Imipramine also inhibits
the reuptake of NE and 5-HT in the adrenergic nerve endings in the urethra. The
increased presence of NE allows for greater stimulation of urethral smooth muscle. In
addition, through its inhibition of the reuptake of NE and 5-HT, increased striated
sphincter tone by action at the spinal cord level (Onuf’s nucleus) is possible. In all,
imipramine potentially has three therapeutic modalities in incontinence therapy: CNS
activity modulation, modulation of bladder and urethral activity, and modulation of
urine output (28).
In the CNS, imipramine has shown affinity for adrenergic F1-, 5-HT2-, H1-, and
muscarinic receptors and no affinity for adrenergic F2-, 5-HT1-, and H2-receptors (28).
Imipramine is a potent inhibitor of NE reuptake in the rat brain and with weaker inhibi-
tion of 5-HT reuptake. The increased availability of neurotransmitter at the postsynaptic
membrane caused by reuptake inhibition seems acutely to facilitate storage of urine
through centrally decreased detrusor activity. After prolonged administration, this effect
tends to disappear. Activity in Onuf’s nucleus of the sacral cord, which controls activity
of the external urethral sphincter, is influenced by noradrenergic and serotonergic inner-
vation projections of supra- and intraspinal origins. The effect at Onuf’s nucleus is to
stabilize the urethral sphincter.
At the level of peripheral nerves, imipramine inhibits NE reuptake, which enhances
detrusor muscle relaxation through G-adrenergic receptors (29). Evidence of a direct
smooth muscle relaxing effect that contributes to larger storage function exists, but the
peripheral anticholinergic activity of imipramine is not considered significant (30).
Debate continues, however, regarding whether the observed functional alteration in
external sphincter tone is a central or peripheral mechanism.
Another interesting action of imipramine in the urinary tract is its effect on the
excretion of antidiuretic hormone (31). Imipramine induces an antidiuresis secondary to
an antidiuretic hormone-independent renal mechanism that conserves fluid by decreasing
solute excretion. This action is most evident in nocturnal polyuric patients and is the
rationale behind its indication for nocturnal enuresis.
Imipramine also has been used for the treatment of SUI for its F-stimulating effect at
the urethra, which can increase the urethral closure pressure and functional urethral
length. Available data on the use of imipramine are largely anecdotal. No randomized
controlled studies of imipramine for SUI have been done. In small, uncontrolled studies,
cure rates of 35–70% have been reported (32,33).
Side effects are numerous and related to its anticholinergic properties of dry mouth,
weakness, fatigue, sedation or mania, parkinsonian effects, orthostatic hypotension,
sweating, arrhythmia, and sexual dysfunction, which may preclude the use of the drug
(34). The usual starting dose of imipramine is 25 mg daily, but this may be slowly titrated
up by 25- to 50-mg increments each week to a total maximum daily dosage of 150 mg.
Patients must be cautioned against the abrupt cessation of the drug after prolonged use
and instead should taper off the drug. Imipramine is toxic in high doses, and overdose
can produce lethal cardiac dysrhythmia or conduction blocks (35). It is prudent to
consider a pretreatment electrocardiogram before initiating imipramine therapy.
Although studies demonstrating myriad actions by imipramine on the lower urinary
tract exist, there are few clinical data showing a significant positive effect for SUI.
Ultimately, data in support of imipramine for the treatment of SUI are scarce, and larger
randomized controlled studies are necessary to validate its use.
F-ADRENERGIC AGONISTS
Increased outlet resistance theoretically should be able to be achieved by the use of
F-adrenergic agonists to stimulate the large number of F1-receptors at the proximal
urethra and sphincter. Contraction of the F-receptors in the proximal urethra leads to an
increase in the maximum urethral pressure and maximum urethral closure pressure.
However, currently available agents are nonselective and produce significant adverse
side effects, including blood pressure elevation, anxiety, insomnia, headache, tremor,
weakness, palpitations, cardiac arrhythmias, and respiratory difficulties. These drugs
must be used with caution in women with hypertension, cardiovascular disease, or
hyperthyroidism. Side effects have been so prevalent and dangerous that in November
2000 the FDA issued a public health advisory concerning phenylpropanolamine (PPA).
The FDA requested that all drug companies discontinue marketing products containing
PPA, and PPA has now been removed from the market. Results of several small clinical
studies using PPA for the treatment of SUI are now only of historical interest and therefore
are not addressed in this chapter.
Ephedrine and its stereoisomer pseudoephedrine are sympathomimetic agents that
increase the release of NE from sympathetic neurons and stimulate F- and G-adrenergic
receptors. Few studies exist to support the use of ephedrine. In a small study of 38 patients
with sphincteric incontinence, 27 achieved a “good-to-excellent” result with ephedrine
sulfate (36). Continence was improved mostly in the patients who experienced mild SUI.
With either agent, tachyphylaxis may develop after prolonged use, perhaps because of
depletion of NE stores. Although pseudoephedrine is available in the United States with-
out a prescription in the form of Sudafed, access to this compound is limited in many parts
of the country because it is a key ingredient in the making of methamphetamine.
Several pharmacological studies revealed that the F1A-subtype is the predominant
F-adrenoceptor subtype in the human lower urinary tract, and the F1L-adrenoceptor is
the receptor subtype primarily involved in NE-induced contraction of the lower urinary
tract. In theory, an adrenoceptor agonist selective for the F1L-subtype may produce fewer
side effects. Several agents with F1A/1L-adrenoceptor selectivity have been identified:
methoxamine and NS-49 are two such F-adrenoceptor agonists with known ability to
induce contractions in the male and female urethra (37–39).
A clinical trial of another selective F1A/1L-adrenoceptor partial agonist, Ro 115–1240,
was undertaken in women with mild-to-moderate SUI (40). There were 37 women who
received 1.5 mg of the drug twice a day or matching placebo for 2–4 wk. For those
completing the study, the drug produced a 53% reduction in incontinence episode
frequency (IEF) compared to a 34% reduction in IEF produced by placebo. Overall, the
drug provided a 19% improvement over placebo (41). Adverse events were mild and
transient: headache, chills, piloerection, and pruritus. No significant cardiovascular
effect was seen. Neither drug nor placebo produced a significant difference in mean
systolic blood pressure or diastolic blood pressure. Scalp tingling was the only adverse
event responsible for discontinuation of the drug in one patient.
In general, currently available F-adrenergic agonists provide moderate improvement
in a subset of patients with mild SUI. The potential adverse side effects have greatly
diminished their utility and are responsible for the removal of PPA from the market.
Given the perceived lack of safety associated with PPA, it is reasonable to assume that
other agents in this group could potentially be unsafe, and therefore risk far outweighs
benefit with this class of drug at this time. The F1A/1L-subtype selective F-agonists may
have potential in the treatment of SUI with remarkably fewer side effects, but larger
randomized controlled trials are necessary.
G2-ADRENOCEPTOR AGONISTS AND ANTAGONISTS

Clenbuterol is a G2-adrenoceptor agonist available in Japan for the treatment of SUI.
In a small clinical study examining the effect of clenbuterol on frequency of inconti-
nence episodes, amount of leak, and patient impression of improvement, results showed
73% clinical efficacy, defined as any degree of improvement in outcome measures,
compared to 55% response in women receiving placebo (42). This effect may be because
of relaxation of the detrusor and facilitation of storage more than an effect at the outlet
because stimulation of G-adrenoreceptors would be expected to contribute to relaxation
rather than contraction of urethral smooth muscle.
A second trial that compared clenbuterol to PFMEs showed a 76.9% improvement
in IEF, amount of leakage, and patient impression of improvement during 12 wk of
treatment. PFME alone provided a 52.6% improvement, and PFME with clenbuterol
produced an 89.5% improvement (43).
Propranolol, a G-adrenergic antagonist, has been studied for the treatment of SUI,
but no drug in this class has been approved for SUI or has been tested in randomized
controlled trials (44,45).
SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS

Duloxetine, a centrally acting agent, affects SUI by blocking the reuptake of 5-HT
and NE in Onuf’s nucleus, where the pudendal motor neurons are located in the spinal
cord. When higher levels of 5-HT and NE exist, there is increased activity on more
postsynaptic receptors, greater activation of pudendal nerve motor neurons, and increased
urethral sphincter tone. Duloxetine has shown little or no inhibition of dopamine reuptake
or affinity for histaminergic, dopaminergic, adrenergic, or cholinergic receptors; therefore,
potentially it may produce few side effects.
In the anesthetized cat model, under conditions of bladder irritation from the infusion
of acetic acid, duloxetine reduced the bladder activity and increased periurethral striated
sphincter activity eightfold (46). This effect was primarily central because the drug had
no effect on bladder contractions evoked by direct electrical stimulation of efferent
fibers in the pelvic nerve. Interestingly, the sphincter activity was not increased during
bladder contraction in micturition. The difference is glutamate. During filling and storage,
glutamate, a stimulatory neurotransmitter, is activated and increases tone in the sphincter.
Glutamate is deactivated during voiding, allowing relaxation of the sphincter. Duloxetine
does not appear to affect urethral activity when glutamate is deactivated; therefore, it
does not affect voiding.
In human studies, duloxetine was found to be safe and well tolerated in healthy
adults. A large phase II trial from 48 US study centers, evaluated the efficacy and safety
in women with SUI (47). The 533 women enrolled experienced at least four incontinent
episodes per week, had normal bladder capacity, and had no prior continence surgery;
86 women underwent urodynamic studies testing, and 92% had urodynamic evidence
of SUI. Women were randomized to 12 wk of treatment with placebo or duloxetine at
one of three doses: 20, 40, or 80 mg/d. Duloxetine at all doses performed better than
placebo, and response was dose dependent. Results showed that 80 mg/d provided
better results in all end points measured: IEF, Patient Global Impression of Improvement
(PGI-I) scale, and Incontinence Quality of Life (I-QOL) questionnaire. The median
IEF decrease was 64% for duloxetine 80 mg/d compared with 41% with placebo. A total
of 18.7% of patients receiving 80 mg/d duloxetine experienced complete elimination of
their incontinence on the voiding diary, yet, remarkably, so did 15.2% of women receiving
placebo (47).
Improvements in IEF were significant by 4 wk after treatment, and a concurrent
increase in the average voiding interval in duloxetine groups was also observed. In a
specific subset of 163 patients with more severe SUI, defined as at least 14 incontinent
episodes per week, duloxetine produced a 49–64% reduction in IEF compared to 30%
with placebo. Adverse events with the use of duloxetine were generally mild. Nausea
was the most common adverse event that led to discontinuation. Nausea (that was dose
related) occurred in 13% of women taking 80 mg/d duloxetine and in 2% taking placebo.
Phase III studies, enrolling 683 women, were undertaken in North America to
confirm efficacy and safety (48). These women with predominant SUI had at least seven
weekly episodes of SUI. They were randomly assigned to either 80 mg/d duloxetine or
placebo for 12 wk. Women receiving duloxetine showed statistically significant reduc-
tions of IEF vs placebo (50 vs 27%, p < 0.001). Even women with severe or high-grade
SUI showed equivalent improvement, indicating that duloxetine was effective in SUI of
all degrees. Improvements in QOL were statistically significant in the total population
of women with severe SUI (+11 vs +6.8, p < 0.001). Improvements were associated
with significant increases in voiding intervals, indicating that the response was not to
voiding more frequently. A full 10.5% of duloxetine-treated patients and 5.9% of placebo-
treated patients had no incontinent episodes (p < 0.05).
In 436 patients with more than 14 incontinent episodes per week or severe SUI,
improvements in IEF and I-QOL were similar. Of particular clinical importance,
duloxetine patients had statistically significant improvements compared with placebo
in three I-QOL domains: avoidance and limiting behavior, social embarrassment, and
psychosocial impact. Based on the PGI-I, 62% of patients receiving duloxetine con-
sidered their incontinence to be better compared with 39.6% of patients receiving
placebo (p < 0.001). An extension trial was initiated and completed in this study, with
approx 90% of patients who completed the duloxetine arm going on to the extension.
Nausea, reported by 22.7% of patients, was the most common cause of discontinuation
of the study. Of patients experiencing nausea, 91% developed the symptom within the
first 4 wk of treatment and most within the first 2 d. The nausea was considered mild
to moderately severe in 78 patients (87%), and 58 (74%) of these completed the study.
A phase III trial conducted in Europe and Canada of 494 women with SUI
demonstrated similar results (49). Duloxetine achieved a 50% median decrease in
IEF compared to 29% for the placebo treatment (p = 0.002). Comparable results
were found in women with severe SUI. Of women receiving duloxetine, 52% demons-
trated a 50–100% reduction in IEF compared to 34% of women taking placebo
(p < 0.001). The duloxetine group also showed significantly greater improvement in
I-QOL scores (7.3 vs 4.3, p = 0.008) Millard et al. conducted a similar study across
four continents in 458 women with predominant SUI. Participants were randomly
assigned to either 80 mg/d duloxetine or placebo. Results were in keeping with the
other phase III trials (50).
Another phase III, double-blind, placebo-controlled trial investigated the efficacy and
safety of duloxetine in women with severe SUI symptoms (>14 incontinence episodes
per week) and urodynamically confirmed pure SUI who were awaiting surgery for SUI
(51). In 14 centers, 109 female participants were randomly assigned to placebo or
duloxetine for 8 wk. Doses for the first 4 wk were 80 mg/d, and they were 120 mg/d for
the last 4 wk. In addition to the usual efficacy variables (IEF, I-QOL, and PGI-I), the
continence pad usage and willingness of patients to proceed with surgery were also
assessed. Response was defined as decreased weekly IEF of 50% or more. Response
was significantly greater with duloxetine than placebo in patients with and without
intrinsic sphincter deficiency. Response was also rapid: 61% responded within 3 d, 75%
within 5 d, and 100% within 2 wk. Significant decreases were seen in pad usage (–34.5
vs –4.8%, p = 0.008). More patients receiving duloxetine perceived their incontinence
as much or very much better (33.3 vs 7.7%, p = 0.003). At the conclusion of the study,
20% of patients receiving duloxetine indicated that they were no longer interested in
surgery as compared to 0% in the placebo group. The increased dose of 120 mg/d did
increase efficacy, but the change did not differ statistically from the 80 mg/d dose.
Ghoniem et al. compared the effectiveness of combined pelvic floor muscle training
(PFMT) and duloxetine with sham PFMT and placebo for 12 wk (52). In addition, the
effectiveness of combined treatment vs single treatment, single treatment vs other single
treatment, and single treatment vs no treatment was evaluated. In a double-blind,
randomized, controlled trial, 201 women with SUI (v2 incontinence episodes per day)
from 17 centers in the United States and Europe were enrolled. Women were randomly
assigned to one of four combinations: 80 mg/d duloxetine with sham PFMT, placebo
and drug, drug and PFMT, and placebo with sham PFMT. Efficacy measures were IEF,
number of continence pads used, and I-QOL. Duloxetine with or without PFMT showed
superior reduction in IEF over no treatment or PFMT alone. Analysis of the number of
continence pads used and I-QOL scores demonstrated greater improvement with com-
bined treatment rather than single treatment. Overall, data supported improved efficacy
of combined PFMT and duloxetine. In this study, as in other phase III clinical trails,
more duloxetine-treated patients than placebo-treated patients discontinued because of
adverse events. Nausea was the prevailing cause for discontinuation, but 83% of those
who experienced nausea (33 of 40) completed the study.
CONCLUSION
SUI is a medical condition rarely treated pharmacologically. Currently, no FDA-
approved drug exists for SUI, and the medications commonly used to treat it are used
off label. Factors that influence treatment choice are the nature of the UI, the amount of
bother it causes, whether prior treatment has been instituted, and how successful any
prior treatment was. Most important, a woman should be given all of her options, the
risks of therapy, and the percentage likelihood of cure/improvement with each so that
she may make a truly informed decision. Currently available pharmacological agents
lack proven efficacy and have a high incidence of bothersome side effects.
Imipramine, F-adrenergic agonists, and estrogens have been tried with anecdotal
success. Important new data about estrogens calls their use into question. Investigation
into the use of G-adrenergic antagonists, G-adrenergic agonists, and combined 5-HT and
NE reuptake inhibitors is ongoing. Duloxetine is a balanced dual 5-HT and NE reuptake
inhibitor that is currently FDA approved for depression and diabetic neuropathy
(Cymbalta) and has been investigated for SUI indication. It is the most exciting new
development in the pharmacotherapy of SUI in recent decades, but the manufacturer
withdrew its application to the FDA. In open-label extensions of controlled studies of
Cymbalta for SUI in adult women, a higher-than-expected rate of suicide attempts was
observed that was not seen in controlled trials of Cymbalta for treatment of depression
or diabetic neuropathic pain (53). Currently, duloxetine is not approved for the treatment
of SUI, and the FDA is evaluating additional data. Effective and well-tolerated medical
therapy for SUI remains elusive.
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Menopause and Postmenopausal Years (Campbell S, ed.), MTP, Carnforth, UK. 1976, pp. 291–298.
17. Robinson D, Cardozo L. Oestrogens and the lower urinary tract. BJOG 2004;111:10–14.
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19. Zullo MA, Oliva C, Falconi G, et al. Efficacy of oestrogen therapy in urinary incontinence. A meta-
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20. Fantl JA, Bump RC, Robinson D, et al. Efficacy of oestrogen supplementation in the treatment of
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21. Sultana CJ, Walters MD. Oestrogen and urinary incontinence in women. Maturitas 1995;20:129–138.
22. Moerher B, Hextall A, Jackson S. Oestrogens for urinary incontinence in women. Cochrane Database
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23. Hextall A. Oestrogens and lower urinary tract functions. Maturitas 2002;36:83–87.
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incontinence. Int Urogynecol J 1993;4:146–151.
43. Ishiko O, Ushiroyama T, Saji F, et al. G2-Adrenergic agonists and pelvic floor exercises for female
stress incontinence. Int J Gynaecol Obstet 2000;71:39–44.
44. Gleason DM, Reilly RJ, Bottacini MR, et al. The urethral continence zone and its relation to stress
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default.htm.
TREATMENT
II
PART A: STRESS URINARY INCONTINENCE
II
PART B: OVERACTIVE BLADDER
II
PART C: PROLAPSE
II
PART D: RECONSTRUCTION
II
8 Urethral Injectables for Stress Urinary
Incontinence
R. Duane Cespedes, MD
CONTENTS
HISTORICAL PERSPECTIVE
PATIENT SELECTION
SURGICAL TECHNIQUE
RESULTS
COMPLICATIONS
OTHER FDA-APPROVED INJECTABLE AGENTS
CONCLUSION
REFERENCES
HISTORICAL PERSPECTIVE
The use of bulking agents dates to 1938, when Murless injected sodium morrhuate,
a sclerosing agent, into the anterior vaginal wall of 20 incontinent women (1). The
inflammatory response compressed the urethra, providing improved continence in 17
women; however, complications precluded further use of the agent. In 1955, Quackels
successfully treated two patients with periurethral paraffin injections (2). Sachshe
utilized Dondren, a sclerosing agent, in 1963; however, pulmonary emboli complicated
the procedure (3).
The modern era of bulking agents began when Berg and later Politano and associates
popularized the use of polytetrafluoroethylene (PTFE; Teflon, Polytef, and Urethrin) in the
early 1970s (4,5). This agent is a thick paste, with most of the particles ranging in size
from 4 to 100 Rm. PTFE was extensively used until 1984, when animal studies demon-
strated particle migration and granuloma formation in the brain, liver, spleen, and lungs,
dampening enthusiasm for this agent. PTFE is not currently approved by the Food and
Drug Administration (FDA) as a bulking agent.
In 1989, autologous fat was first described as an injectable bulking agent by
Gonzales-Garibay and colleagues (6). A report by Santarosa and Blaivas on 15 patients
noted that 5 patients were cured and 5 significantly improved with 11-mo follow-up
(7). In contrast, others have reported high reabsorption rates and poor long-term results
(8). In addition, one fatal case of pulmonary fat embolism has been reported (9).
Because of the labor-intensive nature of fat harvesting, poor long-term results, and
potential complications, autologous fat injection is not commonly used in the treatment
of incontinence.

97
In 1993, the FDA approved the usage of bovine collagen as a new, minimally invasive
treatment for stress incontinence. Glutaraldehyde crosslinked (GAX) collagen (Contigen,
CR Bard Co., Covington, GA) is a highly purified bovine dermal collagen crosslinked
with glutaraldehyde and suspended in a phosphate base. GAX collagen contains 3.5%
collagen by volume and contains approx 95% type 1 collagen and 1–5% type 3 collagen.
It is prepared by selective hydrolysis of the nonhelical amino terminal and carboxyl
terminal segments (telopeptides) of the collagen molecules. Because the telopeptides
are the antigenic markers for collagen, GAX collagen has less antigenicity. The glutar-
aldehyde crosslinking also reduces hydrolysis by fibroblast-secreted collagenases. As a
result, GAX collagen is reabsorbed much slower than previous collagen compounds
used in cosmetic surgery (10). GAX collagen is biocompatible and does not cause foreign
body reaction, and particle migration has not been demonstrated. A mild inflammatory
reaction does occur, which appears to result in replacement of the bovine collagen by
the patient’s own collagen (11). Last, GAX collagen is easily injected through a small
needle, allowing precise placement of the collagen using standard equipment and local
anesthesia. Because GAX collagen remains the most commonly used injectable agent in
the treatment of stress urinary incontinence (SUI) in females and many of the principles
apply to other injectables, this chapter focuses on its use.
PATIENT SELECTION
There are two general etiologies for urinary incontinence: dysfunction of the bladder
or of the urethral sphincter. Bladder conditions that can produce incontinence include
detrusor instability and poor detrusor compliance. Detrusor instability (also called an
overactive bladder) is common in elderly patients and is manifested by a sudden urge to
void that cannot be inhibited. If severe, then urgency may result in urge incontinence.
Poor detrusor compliance is characterized by an abnormal increase in detrusor pressure
as a result of filling (12). This condition is most commonly seen in patients with neuro-
genic bladders and after pelvic irradiation. It is important to distinguish these forms of
incontinence from SUI as neither overactive bladder nor poor compliance is treatable
with injectable agents.
The classification of patients with SUI has undergone many changes (13). An
analysis of abdominal (or Valsalva) leak-point pressure (ALPP) data using fluoro-
scopic imaging in a prospective study of females with stress incontinence found three
relatively distinct groups of patients (14). Some incontinent patients demonstrated high
abdominal leak-point pressures (>100 cm H2O); another group demonstrated very low
leak point pressures (<60 cm H2O); last, a smaller group of patients was in the gray
zone (ALPP between 60 and 100 cm H2O) (15). Type III stress incontinence, more
recently called intrinsic sphincter deficiency (ISD), is characterized by a low ALPP
(<60 cm H2O) and little or no urethral mobility with straining (Fig. 1). It is well estab-
lished that patients with ISD are at increased risk of failing a suspension procedure,
and treatment with one of the sling procedures or an injectable agent is recommended
(16–20). As ISD is most often associated with prior failure of a surgical procedure or
with elderly females, collagen injections provide a minimally invasive method of
attaining continence. Early studies demonstrated that patients successfully treated with
collagen injections had an average increase in the ALPP of 31 cm H2O; however, there
was little change in the voiding pressure because muscular relaxation allowed the
bladder neck to open widely (21).
Chapter 8 / Urethral Injectables for SUI 99
Fig. 1. Intrinsic sphincter deficiency in a 63-yr-old female previously treated with a retropubic
suspension. During a Valsalva maneuver, the bladder neck opened at a low leak-point pressure
with minimal mobility of the bladder neck with resulting incontinence.
Type II stress incontinence is associated with urethral hypermobility, and incontinence

occurs at higher ALPPs, usually greater than 100 cm H2O (Fig. 2). On physical exami-
nation, the urethra is mobile in conjunction with prolapse of the adjacent vaginal wall.
All incontinence procedures that provide support and immobilize the urethra work
reasonably well. Although collagen has shown good efficacy in treating patients with
hypermobility, it is rarely used because sling procedures are associated with better
long-term results in this younger group of patients.
As with any procedure, proper patient selection is the key to therapeutic success
and patient satisfaction. The ideal candidate for collagen injections is one with ISD,
minimal urethral mobility, and normal detrusor function. Clinically, these female
patients are often elderly and have some degree of detrusor instability. Detrusor insta-
bility that coexists with SUI is not a contraindication for collagen injection; however,
it is prudent to treat the instability medically before continuing to collagen injections.
The patient must also know that multiple injections 4–6 wk apart will be required, and
that transient urinary retention requiring intermittent catheterization may occur in rare
circumstances. In most cases, only two or three total injections will be required to
achieve dryness. In addition, as collagen is slowly reabsorbed and replaced by the
patient’s own collagen, some patients will require reinjection in the future even if they
are continent for many years. If the patient is unwilling to undergo a minimum of two
injections and perform transient self-catheterization if retention occurs, then other
therapies should be discussed with the patient.
The only absolute contraindications to collagen injections are an untreated urinary
tract infection and hypersensitivity to the material. Therefore, all patients are skin tested
using 0.1 mL of the more immunogenic noncrosslinked collagen 30 d before collagen
treatments are started. The overall hypersensitivity rate has been reported as between
2 and 5% (22). Extra caution should be used in immunocompromised patients and
patients on steroids because they may not react to the skin test even if they are allergic
to bovine collagen. Last, collagen injections have not been well studied in pregnant
women, and other alternatives should be considered.
Fig. 2. Fluorourodynamic study demonstrating incontinence secondary to urethral hypermobility. During

a Valsalva maneuver, the bladder neck (at the arrows) rotates posteriorly, and incontinence occurs.
SURGICAL TECHNIQUE
Collagen may be injected using either a periurethral or a transurethral approach
(Fig. 3). The initial studies were performed using the periurethral approach; however,
now that specialized transurethral instrumentation exists, the transurethral approach
has become more popular (23). The endoscopic injection procedure can be performed
with minimal patient discomfort in the outpatient setting using a local anesthetic. If
performed in the operating room, then sedation or general anesthesia is usually favored
as spinal anesthesia may cause prolonged urinary retention. The patient normally takes
a single dose of a fluoroquinolone antibiotic preinjection and an additional dose the next
day. The patient is then placed in the lithotomy position, and the perineum and vagina
are prepped and draped. We use the Wolf 21-French panendoscope, which has a Nesbit-
type working element and rigid 23-gage needle (Richard Wolf Instruments, Vernon
Hills, IL).
The key to obtaining good results with collagen is the precise placement of the
transurethral needle, ensuring accurate placement of the collagen. In addition, less
collagen is wasted, improving cost-effectiveness. Collagen injections in females usually
require only two injection sites as the collagen usually dissects circumferentially around
the bladder neck if the proper plane is found. Normally, the 4 and 8 o’clock positions
are selected at the bladder neck. A small amount (0.2–0.5 mL) of 1% plain lidocaine
is injected first to decrease pain and to help in dissecting the appropriate plane for the
collagen to fill. Without withdrawal of the needle, the collagen syringe is attached,
and the collagen is injected slowly. It usually takes at least 2–3 min to inject each
syringe. Collagen will fill the submucosal plane and effectively “close off” the bladder
neck (Fig. 4). Resist the temptation to overinject as the mucosa will rupture, and all
the collagen will be lost. The injection of collagen requires tissue “expansion” and as
such must be done slowly over a relatively long period of time to decrease the chances
of tissue rupture.
Certain technical aspects of the injection are important to understand. If the needle
is placed too deep, then collagen is wasted, and the desired bulging of the urethral
mucosa does not occur. Generally, only 1–2 mL need to be injected before this bulging
Fig. 3. A syringe of GAX collagen (Bard, Covington, GA) shown with both the periurethal and
transurethral injection needles.
Fig. 4. In this series of intraoperative photographs, the open bladder neck is sequentially closed by the
injection of collagen: (A) preoperative view; (B) the needle has been inserted into the right side of the
bladder neck, with bulging of the mucosa to the midline seen. (C) The left side of the bladder neck is
closed with collagen; (D) the final result. Normally, only two injection sites are needed in female
patients, and only one or two syringes of collagen are injected per visit.
Table 1
Results Using GAX Collagen for Incontinence in Females
Mean (cc)
No. Mean follow- cumulative Significantly
Authors of pts up (mo) volume Cured (%) improved (%) Failed (%)
O’Connell (18) 44 N/A 9.1 45 18 12
Monga (19) 29 24 10.8 48 20 N/A
Cross (28) 139 18 N/A 74 N/A 5
(dry +
significantly
improved)
Appell (31) 149 12 19.2 80.8 N/A N/A
Hershorn (20) 31 8.4 12.7 48 41 9
Stricker (38) 50 11 14.4 42 40 14
Kieswetter (39) 16 4.5 N/A 43 50 18
Richardson (40) 42 46 28.3 40 43 17
N/A, not available.
is evident. Conversely, if the needle depth is too shallow, then a small amount of
collagen will cause a mucosal bleb, identified by the lack of blood vessels in the lining
of the tissue. This bleb will eventually rupture, creating a defect and loss of all collagen
injected.
Ideally, the collagen should be injected slowly using the fewest injection sites possible.
Avoid injecting directly into the external sphincter as this may result in dysuria and perineal
pain. Usually, one syringe (2.5 mL) or occasionally two syringes are used per session
depending on the degree of coaptation achieved. The end point of the procedure is visual
closure of the bladder neck without leakage of urine in response to increased intra-
abdominal pressure. To test the efficacy of the injection, leave the bladder half full,
remove the scope, and have the patient cough. If leakage occurs, more collagen can be
given but keep in mind that if more than two syringes are required to close the bladder
neck completely, then the injection is likely in the wrong plane.
Postoperatively, an indwelling catheter should be avoided as collagen may be
“squeezed out” through the injection sites or the collagen may be molded around the
catheter, reducing efficacy. All patients must be able to void prior to leaving the clinic
or be taught clean intermittent catheterization using a 10- to 14-French catheter.
RESULTS
Multiple studies have reported good results using collagen in selected patients
(Table 1). In 1990, the initial studies using collagen reported that 78% of females
became dry, and overall 93% were significantly improved (24). Dryness was achieved
in 88% using three or fewer injections, and 58% required only one injection. At 2 yr,
of patients rendered initially dry, 78% remained dry, demonstrating the durability of
collagen injections in females.
Monga and colleagues reported a 68% subjective cure rate and 48% objective cure
rate at 24 mo postcollagen injection (19). This group was also the first to report a sustained
decrease in the symptoms of urge incontinence; although unexpected, this may greatly
benefit these hard-to-treat patients.
Steele and colleagues compared the results of using collagen in patients with and
without urethral hypermobility (25). Of 40 patients, 9 were diagnosed with hypermobility.
They reported a subjective dry rate of 76% in the hypermobile group compared to 46%
of the nonmobile group. It is clear that many patients with hypermobility can be treated
successfully using collagen; however, it is important to remember that patients in this
group are typically younger and usually have pelvic prolapse in other areas. Therefore,
a sling procedure and prolapse repair should be considered in this group.
In a review of a small urban practice, Tschopp and colleagues examined the durability
of collagen injection in 99 women (26). A success rate of 56% with a follow-up of 9 mo
was reported. They concluded that collagen injection has minimal morbidity with good
success in appropriate patients.
In 1995, O’Connell et al. reported their results using collagen injections. Patient
response to treatment was evaluated by the change in the number of pads required to
effect significant improvement. Cure was achieved for 63%, with four patients having
previously used greater than 10 pads per day prior to injection. No major complications
were noted (18).
Moore et al. provided an objective report of collagen injections using exams, pad
tests, and urodynamic evaluation in postoperative follow-ups (27). They found signi-
ficant decreases in pad number and weight from baseline, with no difference in residual
volume, voided volume, or flow rate. Interestingly, two women reported only “improve-
ment” yet were objectively cured; conversely, one patient felt she was cured, yet leaked
11 g urine on pad testing. Two patients developed cystitis; however, no patients experienced
urinary retention.
Cross et al. reported their long-term follow-up of patients treated with collagen
injections over a period of 36 mo (28). Through telephone interviews and chart review,
they reported an overall 74% dry or improved rate, with 72% achieving continence after
two or fewer injections. Reinjections were required in 11 patients to regain dryness in
this series.
It is important to note that the results of collagen injection therapy cannot be directly
compared to other modalities used to treat ISD because it is a biodegradable bulking
agent (29). In some cases of so-called treatment failure, the procedures were in fact not
failures but incomplete treatments. Simply injecting once or twice to “see what happens”
is inappropriate, and all patients should receive at least three injections and 10 mL
collagen before being declared a treatment failure and another therapy is initiated. In
addition, a patient who is dry for 2 yr and then begins to leak again is a cure and not a
treatment failure. The patient simply needs another injection—a feature known and
understood when using injectable agents. Therefore, in reviewing the results of injectable
agent studies, these caveats should be kept in mind.
COMPLICATIONS
Overall, collagen injection has few side effects, and most are minor. The risk of
postoperative urinary tract infection probably varies depending on whether preoperative
antibiotics are given; however, this has not been proven in controlled trials. The risk of
urinary tract infections appears to vary between 1.4 and 6% (22,24,30). A periurethral
abscess has been reported, but these are fortunately rare (30). Symptomatic hematuria
(even in patients on anticoagulants) or prolonged perineal pain is uncommon and
self-limited (22).
Fig. 5. A syringe of Durasphere and the required specialized needle are seen on the left side of the
photograph. On the right side, a close-up view of the Durasphere particles and carrier is shown.
Transient postinjection urinary retention requiring intermittent catheterization was

reported in 4% by Cross et al.; permanent retention in the nonneurologic patient has
been reported in only one patient (28,31).
The fear of particle migration has concerned users of injectable materials since the
initial reports by Malizia; however, there have been no such reports using GAX collagen
as an injectable agent (32). The immunogenicity of GAX collagen has also been exten-
sively evaluated. In 1998, Leonard found that 3 of 10 children developed antibodies to
the bovine collagen, but there was no seroconversion to antibodies that crossreacted
with human collagen (33). Hypersensitivity has previously been shown to be in the
range of 2 to 5%; however, Stothers and Goldenberg reported three cases of delayed
patient hypersensitivity to the agent (34). Despite initial negative skin tests, each of
these patients developed distinct induration at the forearm test site after they received
the first transurethral injection 4 wk later. Two of the three reported arthralgias, and all
responded to conservative management.
OTHER FDA-APPROVED INJECTABLE AGENTS

Carbon-Coated Beads (Durasphere)
Durasphere (Boston Scientific, Natick, MA) is a relatively new nonantigenic
injectable agent (no skin test required) composed of nonabsorbable, pyrolytic, carbon-
coated zirconium oxide beads suspended in a 2.8% glucan carrier gel (35) (Fig. 5).
Table 2 provides a list of the injectable agents currently available or in development.
The majority of Durasphere particles are in the 251- to 300-Rm range, more than
three times larger than the 80-Rm threshold for particle migration, minimizing the
potential for migration. From 1996 to 1998, there were 355 women enrolled in a
Table 2
Injectable Agents Currently in Use or in Development
Compound Name Company FDA approved?
Bovine collagen Contigen® CR Bard Yes
GAX crosslinked Durasphere EXP® Boston Scientific Yes
carbon-coated beads
DMSO and ethylene Tegress® CR Bard Yes
vinyl alcohol copolymer
Adjustable volume ACT® Uromedia No
balloons
Calcium Coaptite® Bioform No
hydroxylapatite
Hyaluronic acid Zuidex® Q-Med No
and dextranomer
microspheres
Crosslinked Hylagel® Biomatrix No
hyaluronic acid
Silicone polymer Macroplastique® Uroplasty No
copolymer/DMSO
Implantable Urovive® American Medical No
microballoons Systems
randomized, controlled, double-blind study to compare the safety and efficacy of this
material with GAX collagen (35). At 12 mo, the investigators found that 66.1% of
Durasphere patients were dry or significantly improved compared to 65.8% of collagen
patients. At 1 yr after the last injection, 80.3% of the Durasphere patients were dry or
significantly improved compared to 69.1% in the collagen group. The number of injec-
tions given was similar in both groups (1.6), but a significantly smaller volume was
required in the Durasphere group. A long-term follow-up comparison between collagen
and Durasphere revealed no significant difference in efficacy (36). Adverse events were
similar in the two groups except for a slightly higher urgency/retention rate in the
Durasphere arm. The theoretical advantages of this agent are improved durability compared
to GAX collagen, room temperature storage, and the ability to treat immediately as skin
testing is not required. Unfortunately, injection requires a larger, 18-gage needle, and
the radio-opaque beads can separate from the viscous glucan carrier, requiring specialized
injection techniques and making it more difficult to inject than collagen.
In a small study, Pannek and colleagues also demonstrated bead migration in 2 asymp-
tomatic patients (37). A modified version, called Durasphere EXP, was introduced. The
radiolucent, pyrolytic, carbon-coated beads are suspended in a water-based carrier,
allowing for easier injection than the previous version. Long-term clinical results are not
yet available, but theoretically these should be similar to the original compound.
Ethylene Vinyl Alcohol Copolymer (Tegress)

Tegress (C. R. Bard, Murray Hill, NJ) is the newest injectable agent approved by the
FDA (Fig. 6). Tegress is composed of ethylene vinyl alcohol copolymer suspended in
dimethyl sulfoxide (DMSO). Tegress can be injected through a 25-gage needle because
of its low viscosity but solidifies after injection. On injection and when exposed to
Fig. 6. Tegress is a clear liquid prior to injection (upper image) but becomes a gelatinous compound
when injected into the urethra, as seen in the lower image.
any aqueous solution, the DMSO diffuses out of the compound, causing the injected
liquid to change into a gelatinous mass. This phase transformation takes place rapidly,
usually within 60 s of injection. Like Durasphere, Tegress does not require skin testing
and has no known immediate or delayed antigenic properties. Refrigeration is also
not required for Tegress. The volume of Tegress remains essentially unchanged after
injection—basically, “what you see is what you get.” Of note, volume loss to absorption
of the aqueous carrier when using collagen has previously been overcome by simply
overinjecting. At 1 yr postinjection, results from the multicenter trial comparing collagen

to Tegress revealed 39 vs 55% dry, respectively, and a mean pad weight 30% better
than collagen. The complication rates were similar in both groups.
The injection of Tegress is more complex than for collagen as the needle must be
carefully primed with material, and the injection is placed closer to the midurethra and
into a slightly deeper plane. Approximately 1 mL is typically injected into each side of
the urethra over a 1-min time frame. After injecting, the needle should be left in place
for 1 min to minimize extravasation of material into the urethra. The needle is then
slowly twisted as it is removed so that no material “tails” are left in the urethra. If this
does occur, then the stringlike tails can simply be knocked off with the scope.
Editor’s note: Tegress is no longer marketed by the manufacturers HB6.
CONCLUSION
As with any procedure, the results obtained with injectable agents greatly depend
on patient selection, expertise in performing the procedure, and the use of specialized
equipment. Patient satisfaction depends on understanding the treatment options and,
if collagen or another injectable is selected, knowing that multiple injections will be
necessary, with periodic reinjections after dryness is achieved to restore continence.
In addition, when performed in the clinic using local anesthesia, injectable agents
give patients who are poor surgical candidates or are on anticoagulant therapy the
opportunity to achieve continence. Overall, injection therapy for stress incontinence
is easy to perform, minimally morbid, and convenient for the patient and remains
cost-effective, especially when performed in the outpatient office setting. The addi-
tion of Tegress to the list of injectable agents may make the ongoing search for an
inexpensive, nonantigenic, easily injected, and durable injectable agent a reality, but
further study will be needed.
ACKNOWLEDGMENT
The opinions contained herein are those of the author and are not to be construed as
reflecting the views of the Air Force or the Department of Defense.
REFERENCES
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521–524.
2. Quackels R. Deux incontineces après adenoectomic queries par injection de paraffine dans le perinee.
Acta Urol Belg 1955;23:259–262.
3. Sachse H. Treatment of urinary incontinence with sclerosing solutions. Indications, results, complica-
tions. Urol Int 1963;15:225–229.
4. Berg SL. Polytef augmentation urethroplasty. Correction of surgically incurable urinary incontinence
by injection technique. Arch Surg 1973;107:379–381.
5. Politano VA, Small MP, Harper JM. Periurethral Teflon injection for urinary incontinence. J Urol
1974;111:180–183.
6. Gonzales-Garibay S, Jimeno C, York M, et al. Endoscopic autotransplantation of fat tissue in the
treatment of urinary incontinence in the female. J Urol (Paris) 1989;95:363–366.
7. Santarosa RP, Blaivas JG. Periurethral injection of autologous fate for the treatment of sphincter
8. Trockman BA, Leach GE. Surgical treatment of intrinsic urethral dysfunction. Injectables (fat). Urol
Clin North Am 1995;22:665–671.
9. Currie L, Drutz HP, Oxorn D. Adipose tissue and lipid drop embolism following periurethral injection
of autologous fat. case report and review of the literature. Int Urogyn J 1997;8:923–926.
10. Stegman SJ, Chu S, Bensch K. A light and electron microscopic evaluation of Zyderm collagen and
Zyplast implants in aging human facial skin. Arch Dermatol 1987;123:1644–1649.
11. Canning D, Peters C, Gearhart J, et al. Local tissue response to glutaraldehyde crosslinked collagen in
the rabbit bladder. J Urol 1988;139:258–259.
12. Cespedes RD, McGuire EJ. Proper diagnosis. A must before surgery for stress incontinence. J Endourol
1996;10:201–205.
13. Blaivas JG, Olsson CA. Stress incontinence. Classification and surgical approach. J Urol 1988;139:
737–741.
14. McGuire EJ, Fitzpatrick CC, Wan JH, et al. Clinical assessment of urethral sphincter function. J Urol
1993;150:1452–1455.
15. Cespedes RD, McGuire EJ. Leak Point Pressures. In: Practical Urodynamics (Nitti V, ed.), Saunders,
Philadelphia, 1998, pp. 94–107.
16. McGuire EJ, O’Connell HE. Surgical treatment of intrinsic sphincter dysfunction. Slings. Urol Clin
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17. Blaivas JG, Jacobs BZ. Pubovaginal fascial sling for the treatment of complicated stress urinary
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1995;154:1463–1465.
19. Monga AK, Robinson D, Stanton SL. Periurethral collagen injections for genuine stress incontinence.
A 2 yr follow-up. Br J Urol 1995;76:156–160.
20. Herschorn S, Steele D, Radomski S. Long term follow-up of intraurethral collagen for female stress
incontinence. J Urol 1995;153:433A. Abstract 818.
21. Appell R. Periurethral collagen injection for female incontinence. Problems in urology
1991;5:134–140.
22. Winters JC, Appell R. Periurethral injection of collagen in the treatment of intrinsic sphincter deficiency
in the female patient. Urol Clin North Am 1995;22:673–678.
23. McGuire EJ, English SF. Periurethral collagen injection for male and female sphincteric incontinence:
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24. CR Bard Company. PMAA submission to US FDA for IDE G850010, 1990.
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26. Tschopp PJ, Wesley-James T, Spekkens T, Lohfeld L. Collagen injections for urinary stress inconti-
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1999;162:779–782.
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9 Midurethral Slings
Gregory T. Bales, MD, and Paula A. Fedunok, PA-C

CONTENTS
INTRODUCTION
HISTORY AND BACKGROUND
PATIENT SELECTION
ANESTHETIC REQUIREMENTS
TECHNIQUES
MATERIALS
OUTCOMES
COMPLICATIONS
SUMMARY
REFERENCES
INTRODUCTION
An evolution in sling procedures has occurred, from bladder neck slings to slings
located at the midurethral level, making midurethral slings the cornerstone of antiincon-
tinence surgery. This is mostly because these midurethral procedures have proved durable,
reproducible, and highly effective. This chapter focuses on the attributes of midurethral
slings that make them so efficacious. Based on review of pertinent literature, the
midurethral sling techniques and corresponding postoperative outcomes are discussed.
In addition, a current compilation of complications and related problems with these pro-
cedures is reviewed. Finally, a historical perspective on the genesis of the midurethral
approach is included.
HISTORY AND BACKGROUND

Literature on sling procedures for the treatment of female incontinence can be found
as far back as 1910 in a report by Goebell (1). He described a pubovaginal sling (PVS)
fashioned from pyramidalis muscle. Other reports were described in subsequent years
as surgeons experimented with different materials and sling placement techniques (2,3).
As slings evolved, autologous, cadaveric, and synthetic materials were all utilized for
placement at the bladder neck and proximal urethra. These materials were tensioned via
suture suspension and generally secured to the overlying rectus fascia. This practice
lifted the bladder neck, restoring the anatomic position of the urethra and creating a
partial obstruction necessary to prevent leakage with stress activities. Unfortunately,
applying the correct tension was difficult and patient specific, and these slings also

111
caused difficulty voiding and other symptoms of urinary dysfunction, such as de novo
urgency (4,5).
In the later part of the 20th century, these vaginal sling procedures were also still
competing with abdominal anti-incontinence procedures such as the Marshall-Marchetti-
Krantz and Burch procedures (6,7). Neither of these abdominal procedures provided
satisfactory long-term durability, and both required a hospital stay of several days and
often caused other associated perioperative morbidities (8,9). As a result, sling proce-
dures gradually regained popularity as refinements in technique allowed these cases to
be undertaken on an outpatient basis as well as with reduced morbidity and decreased
hospital stays (10).
In 1995, Ulstem and coworkers first described the intravaginal slingplasty, a minimally
invasive sling procedure that focused on a more distal midurethral sling placement
(11,12). Originally trialed in Sweden and Australia, it was determined that, unlike the
more proximal bladder neck slings, the midurethral sling caused less interference with
bladder neck funneling and potentially less voiding dysfunction. The slings were also
not placed under tension, and their effect was the result of a backboard-type support
immobilizing the urethra and keeping the urethra from opening during Valsalva and other
exertional activities. In addition to their distal and tensionless placement, the procedure
was generally reproducible from patient to patient.
Based on Ulmsten’s original midurethral sling model, the tension-free vaginal tape
(TVT) was introduced in 1998 in a commercially available kit as the first midurethral
procedure (13). The actual TVT sling comprised a slender strip of polypropylene
housed in a plastic sleeve and attached on either end to a trocar. The sling was devel-
oped as a vaginally placed procedure by which the trocars would be directed from the
vagina under the pubic bone and the mesh pulled out retropubically through the abdom-
inal wall on both sides (Fig. 1). Since 1998, the trocars have been modified and are now
thinner in profile than the originally introduced product. In addition, the tape itself is
now dyed a bluish-purple so it can be more easily visualized after placement. However,
the integrity of the concept has not changed since introduction of the product.
As expected, the midurethral sling has undergone multiple modifications to both
the surgical technique and the sling material in an effort to appeal to the full spectrum
of pelvic surgeons. The suprapubic arc (SPARC) technique was the first top-down
retropubic sling manufactured. Comprised of a polypropylene mesh with characteris-
tics similar to the TVT, the top-down approach allows the surgeon to insert the trocar
from above through the abdominal wall first, directing it out a vaginal incision. To
accommodate practitioners who felt more comfortable with the SPARC, the manufac-
turers of TVT have modified their kit to include an attachment that can be connected
to the standard trocars also to allow a top-down approach. Although the TVT and
SPARC represent two of the most common approaches to placing the retropubic
midurethral sling, numerous sling products are now available from various manufac-
turers (Table 1).
A more recent refinement in technique allows surgeons to utilize the obturator
foramen rather than the retropubic space as a means to situate the sling under the ure-
thra. Figures 1 and 2 show schematics of how both the retropubic and obturator slings
are anatomically situated. For many practitioners, the transobturator route has become
the preferred access to placing the midurethral slings because of the uniformity of the
anatomy and a perception that this approach poses less risk for bladder injury and
Chapter 9 / Midurethral Slings 113
Fig. 1. Schematic representation of TVT.
Table 1
Retropubic and Obturator Sling Products
Product Manufacturer Synthetic Weave type Procedure
Retropubic
Advantage Boston Polypropylene Monofilament Bottom to top
Scientific
IVS Tunneler US Surgical Polypropylene Multifilament Bottom to top
Suprapubic arc American Polypropylene Monofilament Top to bottom
sling (SPARC) Medical Systems
Transvaginal Ethicon Inc. Polypropylene Monofilament Bottom to top
tape (TVT) monofilaments
Transobturator
Monarc American Polypropylene Monofilament Out to in
Subfascial Medical Systems
Hammock
(Monarc)
ObTape Porges-Mentor Polypropylene Monofilament Out to in
ObTryx Boston Scientific Polypropylene Monofilament Out to in
TVT-Obturator Ethicon Inc. Polypropylene Monofilament In to out
UraTape Porges-Mentor Polypropylene Monofilament Out to in
Fig. 2. Schematic representation of TVT-obturator.
bowel perforation. The various transobturator products currently available are depicted
in Table 1.
Variability can also be seen in the sling materials regarding the weave, filament size,
and mono- or multifilament nature of the product (14). Furthermore, the different
manufacturers employ different methods of connecting the mesh to the trocars. Finally,
the various trocars each have their own shape and other unique characteristics. Many
practitioners find one device with which they are most comfortable after a period of
trial and error with the assorted sling products.
PATIENT SELECTION
In general, all patients with stress urinary incontinence (SUI) are candidates for
midurethral slings. Patients with mixed incontinence still can benefit from a sling as this
addresses one component of the pathology (15). Within the elderly population, it is
thought that the minimal dissection requirements and shorter operative times required
for midurethral slings may make this procedure ideal. A study by Walsh et al. found that
TVT patients exceeding 70 yr of age experienced minimal morbidity as well as signi-
ficant improvement in both incontinence and quality-of-life scores (16). In addition,
several groups specifically investigated the impact of body mass index (BMI) on the
success of the TVT procedure, and each found no BMI-related differences in either
efficacy or morbidity between groups with normal vs elevated BMIs (17–19). These two
subgroups of patients, the elderly and obese, are therefore excellent candidates for
midurethral procedures.
ANESTHETIC REQUIREMENTS
One of the proposed benefits to midurethral sling surgery is the minimal amount of
anesthetic requirements. Both the Marshall-Marchetti-Krantz and the Burch procedures
are performed through abdominal incisions; thus, patients require either spinal or general
anesthesia. Today, there are a number of investigators who perform the midurethral
procedures with local anesthesia or intravenous sedation (20,21). This further underscores
the simplicity of these procedures and improves patient acceptance.
Niemczyk et al. were early proponents of performing TVT procedures under a local
anesthetic with minimal sedation (22). In their series, 100 patients undergoing TVT
were evaluated prospectively with history and pelvic examinations, urodynamics, and
outcome and satisfaction questionnaires. Of the patients, 97 then had the procedure
performed under local anesthesia with intravenous sedation. The surgical time averaged
35.5 min, and within 24 h after the procedure, 95% of patients were able to void success-
fully. Using postoperative questionnaires for data collection, Niemczyk’s group concluded
that the TVT procedure performed under a local anesthetic may prove to be the operation
of choice to treat SUI for many women.
Lo et al. conducted a review of surgical outcomes following use of local and intra-
venous anesthesia in a group of 45 elderly women undergoing TVT for SUI (23). Per
report, their mean operating time was 21 min (range 18 to 35), and mean postoperative
hospital stay was 24.2 h (range 12 to 72). These physicians summarized by saying that
the TVT procedure can be performed under local/intravenous anesthesia with safe and
effective results in patients over 65 yr of age.
TECHNIQUES
Because all midurethral slings are situated under the middle portion of the urethra in
a tensionless fashion, the routes taken in putting the sling at this location may vary.
Slings can be placed either retropubically or via a transobturator approach. It should be
noted that great care should always be taken to cover the sling with full-thickness vaginal
wall regardless of the placement technique used.
Retropubic
The retropubic slings, which include the TVT and SPARC, require blind passage of
trocars and mesh through the retropubic space. This may be accomplished both by
beginning vaginally and advancing out to the suprapubic area and by starting supra-
pubically and working down into the vagina. Physicians may frequently refer to these
options as inside-out or in-to-out vs a top-down or out-to-in approach, respectively. The
original and best-studied TVT sling uses an in-to-out approach by which a small (2–3 cm)
incision is made in the vagina midurethrally, and the trocars are directed from the
midurethral location up behind the pubic bone and out the abdominal wall. This is done
bilaterally and allows the hammock-type sling to be well positioned at the location of
the midurethral incision under the vaginal wall (Fig. 1).
The alternative top-down approach, which is employed in the SPARC system as well
as others, again involves making an initial midurethral vaginal incision and dissecting
superolaterally toward the endopelvic fascia. These approaches differ from the original
TVT, however, because bilateral abdominal stab incisions are then made, and the
accompanying trocars are directed from above, behind the pubic bone and inferomedially
onto the surgeon’s fingertip within the vagina. The fingertip guidance allows the correct
placement of the trocar into the midurethral position.
Regardless of the approach, cystoscopy is essential to confirm that the bladder has not
been perforated prior to completing the procedure. If the trocar has violated the bladder
or urethral epithelium, then the trocar can be repositioned to avoid placing the sling in an
aberrant location. In general, a bladder laceration will not cause significant morbidity as
long as the injury is identified and corrected during the procedure. Most physicians will
leave a catheter transiently postoperatively when a bladder laceration has occurred.
Transobturator
The retropubic midurethral slings have been well studied, and their efficacy is
clear, but it is also understood that blind trocar passage via this route can jeopardize
the bowel (24). In an attempt to minimize the risk of bowel injury, Delorme intro-
duced a novel transobturator approach to sling placement that would allow surgeons
to avoid passing trocars through the retropubic space (25). In 2003, his system was
approved by the Food and Drug Administration in the United States and became com-
mercially available as the ObTape transobturator sling. In this approach, a midurethral
incision is again made, but trocars are inserted lateral to the labia, perforate through
the obturator membrane bilaterally, and are then brought in through the previously
made vaginal incision.
Like the aforementioned retropubic midurethral slings, the transobturator approach
has been modified by various manufacturers, and currently the obturator positioning can
be accessed with either a vaginal-to-obturator (in-to-out) or an obturator-to-vaginal
(out-to-in) approach, depending on surgeon preference. The efficacy and complications
do not appear to differ between the in-to-out or out-to-in procedures. It should be stressed
that the final midurethral location of these slings will be the same regardless of the
placement technique, and this is why outcomes appear similar.
Since their introduction, these newer transobturator slings have evolved and currently
have been well accepted in the urologic and urogynecologic communities (Table 1). The
anatomic concerns involved in directing the slings through the obturator foramen
chiefly center on avoiding the obturator nerve and vessels, which are located supero-
laterally in the obturator foramen. Great care must be taken to stay medial alongside
the inferior pubic ramus when directing the trocars in obturator sling placement. The
newer obturator approaches do not have as lengthy a follow-up as the retropubic slings,
although the use of the obturator route likely will continue to expand as more surgeons
are introduced to this technique.
Percutaneous
Because the majority of surgeons avail themselves of the manufactured midurethral
sling kits, several investigators have explored cutting and tailoring a piece of prepack-
aged “off-the-shelf” mesh and using it to perform a midurethral sling procedure (46,47).
The primary objective with this technique is still to achieve a tensionless synthetic
material under the midurethra while minimizing the costs associated with the packaged
sling kits. The operative technique is performed by utilizing Stamey needles as the carrier
to place the sling material at the level of the midurethra. Much like the kit procedures,
great care is taken to ensure that the sling is not placed under tension, and cystoscopy
should be performed intraoperatively to rule out any bladder or urethral violations.
Table 2
Commercially Available Meshes and Grafts
Basic component Trade name Type/processing
Synthetic meshes
Polypropylene Marlex (CR Bard) Monofilament
Prolene (Ethicon) Monofilament
Atrium (Atrium) Monofilament
Polytetrafluoroethylene (PTFE) Teflon (CR Bard) Monofilament
Expanded PTFE Gore-Tex (WL Gore) Multifilament
Polyethylene terephthalate Mersilene (Ethicon) Multifilament
Polyglycolic acid Dexon (Davis & Geck) Multifilament
Polyglactin 910 Vicryl (Ethicon) Multifilament
Natural grafts
Human dermis Repliform (Boston Scientific) Freeze-dried/chemical
Duraderm (CR Bard) Freeze-dried
Duraderm (CR Bard) Freeze-dried/irradiated
Human fascia lata Tutoplast (Mentor) Tutoplast process
Porcine small intestinal submucosa Stratasis (Cook) Freeze-dried
MATERIALS
As the midurethral sling procedures have grown in popularity after the original
success with the TVT, manufacturers have developed various products that employ
similar technology. One way in which the products differ is by including different
synthetic or natural substances as the sling product itself. Although a comprehensive
overview of the biology of how synthetics and natural substances are incorporated
into host tissues is beyond the scope of this chapter, this section briefly reviews some of
the properties of the different materials utilized in the competing sling technologies
(Table 2).
As mentioned, there are two subgroups of materials employed for the midurethral
slings: synthetics and naturally occurring substances. Loosely defined, any natural or
synthetic substance that incorporates or integrates into a patient’s tissues during the
treatment is defined as a biomaterial (26). The ideal (graft) compound would be inert,
sterile, noncarcinogenic, and mechanically durable. Furthermore, the foreign body should
cause no inflammatory or immune reaction, must withstand modification by body tissues,
and should be inexpensive, convenient, and easy to use (27).
Synthetics can be absorbable or nonabsorbable. Absorbable meshes have generally
fallen into disfavor because of poor tensile strength and poor scar formation, leading to
high recurrence rates (28). Nonabsorbable meshes, like the Prolene used in the TVT,
have enjoyed much greater success. The unique properties of nonabsorbable synthetics
are the pore size and filament type. In general, acceptable pore sizes are greater than
75–100 Rm because they allow access to fibroblasts and collagen and allow immune
cells to scavenge for bacteria (29). The Prolene mesh used in the TVT, as well as others
commonly utilized in pelvic reconstructive surgery, has a pore size greater than 75 Rm.
Smaller pore sizes allow passage only to histiocytes, and adhesion to host tissue is therefore
unstable (27).
The filament type also contributes to overall mesh function. Polypropylene, which is
commercially packaged as Marlex and Prolene, is a monofilament. By contrast, several
competing meshes, such as Gortex, Mersilene, Dexon, and Vicryl, are multifilament.
Multifilaments have small interstices that may prevent access to key immune cells and
contribute to higher infectious complications, which can lead to erosion. Mersilene
mesh use, for example, is now discouraged because of the high erosion and fistula rates
with bowel (30). With Prolene and other monofilament large-pore meshes, erosions as
well as infectious complications are uncommon.
The natural materials used in slings can be classified as autologous, allografts, or
xenografts. The autologous slings utilized historically enjoyed good success except for
the obvious disadvantage of increased morbidity, risk of wound infections, and longer
recovery times associated with the additional incision at the tissue harvest site (21).
Allografts save the added step of tissue harvest, but concerns have arisen with allograft
stability. Several different processes are employed to prepare the allografts, including
irradiation, freeze-drying, or solvent dehydration (31). Fitzgerald et al. found a high rate
of failure with allografts owing to dissolution of the cadaveric fascia (32). In addition,
some reports have demonstrated DNA fragments in the allografts, and a potential for
HIV transmission exists (33,34). Prion transmission has also been cited as a potential
risk as prions are resistant to L-irradiation and autoclaving (35).
Xenografts have been described as a useful sling material for correcting SUI. The
greatest experience has been with porcine small intestine submucosa (SIS) and dermis.
SIS maintains strong tensile strength, is biocompatible, and minimizes inflammatory
reaction (36). One report with SIS revealed a 4-yr cure rate of 93% for SUI with no
infections or graft erosions (37). Overall, natural materials will continue to be studied
in sling and pelvic floor procedures but likely will never demonstrate the consistent
durability of the synthetics.
OUTCOMES
Retropubic
There have been multiple studies that have addressed outcomes after midurethral
slings. One of the difficulties inherent in interpreting the results of these investigations
is the variety of outcome measures utilized. Also, the cohort of patients treated in many
centers is heterogeneous, which affects outcomes. In addition, there is significant vari-
ation in the length of follow-up performed. As a result, it can be difficult to make
meaningful comparisons between the types of midurethral slings employed. Never-
theless, this section attempts to provide a general overview of the results seen with
these sling procedures.
Several French investigators were early proponents of midurethral repairs. Villet et al.
looked at 124 consecutive patients treated for SUI with a TVT (38). Preoperatively, all
patients completed a urodynamic assessment and exhibited urine leak with a stress test.
Of the women, 54 (44%) also had some clinical signs of urgency. Outcomes were
assessed by patient satisfaction questionnaires. With a mean follow-up of 32.5 mo, this
group found that 110 (88.7%) patients became totally continent, 10 (8%) improved, and
4 (3.3%) failed the procedure. Overall, 117 patients (94.3%) were subjectively satisfied.
In addition, urgency resolved in 38 of the 54 patients (70%). This group of investigators
concluded the TVT technique was valuable because of the good outcomes and repro-
ducibility of the procedure.
Another European group evaluated outcomes in 191 patients who underwent a TVT
sling (39). Preoperatively, 127 women (66%) had SUI alone; 64 (34%) had mixed
incontinence, although none of the patients underwent urodynamic assessment. Thirty-
four women (18%) underwent a concomitant surgical procedure, and the group utilized
both local and spinal anesthesia. All together, 164 (86%) of patients were completely
cured, and 23 patients (12%) experienced no improvement. Sixty percent had less urge
incontinence. A further breakdown of their results revealed cure rates were as follows:
97% among SUI patients vs 69% among mixed incontinence patients. There was no
difference seen in outcomes between local or spinal anesthesia groups or when comparing
TVT alone vs TVT in combination with other surgery. They concluded that TVT was
an acceptable choice for patients with either SUI or mixed incontinence, but that lower
success is seen with TVT performed for patients with mixed incontinence.
The midurethral slings can be combined with other surgical repairs without compro-
mising success. This has been demonstrated in multiple studies, such as the Laurikanine
and Kiillholma study (39). In another investigation, Groutz et al. studied the efficacy
and safety of the TVT procedure in 100 consecutive women with significant genitouri-
nary prolapse and occult SUI (40). Interestingly, none of the women complained of
SUI preoperatively; however, all had urodynamically confirmed occult SUI after repo-
sitioning of the prolapse. Surgical intervention comprised transvaginal prolapse repair
and prophylactic TVT procedure. At a mean follow-up of 27 mo, only two patients had
developed SUI. However, postoperative urodynamic studies revealed asymptomatic
sphincteric incontinence in 15 (15%) other patients. Furthermore, 13 (72%) of 18 patients
with preoperative urge incontinence had postoperative persistent urge incontinence.
These physicians concluded that the TVT procedure is effective and safe when used for
occult SUI in patients undergoing prolapse repair.
Although the above reports dealing with midurethral sling outcomes primarily looked
at TVT, other articles have evaluated results with other midurethral approaches. The
safety and efficacy of the suburethral polypropylene (SPARC) procedure was reported by
Deval et al. in a prospective multicenter trial of the suprapubic approach of SPARC taping
for the treatment of genuine SUI (41). One hundred four consecutive women underwent
SPARC at three centers. All women had urethral hypermobility preoperatively, and detrusor
instability was ruled out by cystometry. Subjective and objective cure rates were evalu-
ated by questionnaires as well as clinical and urodynamic examination. Objective cure
rate was 90.4%, and this group found no difference in improvement between patients
with preoperative genuine SUI and those with mixed incontinence. Interestingly, the
subjective cure rate was 72%. These authors found a higher bladder injury rate in women
with previous incontinence surgery (36.3 vs. 7.5%). Also, 12% of women developed
de novo urge symptoms. Overall, these investigators concluded the SPARC procedure is
safe and effective despite a relatively high incidence of de novo urgency.
Several comparative trials have been performed analyzing midurethral sling outcomes
compared to more traditional antiincontinence procedures. Chung and Chung retro-
spectively evaluated outcomes in 91 cases of TVT alone or in combination with other
procedures compared to outcomes in 51 cases of laparoscopic Burch procedure (42).
They also divided the patients into groups based on BMI. Results between the groups
demonstrated comparable symptom improvement and cure rates. Operative time for
TVT ranged from 18 to 40 min; the laparoscopic Burch procedures took over 1 hr.
In addition, these physicians concluded that the TVT was safer and more minimally
invasive for patients regardless of their BMI.
Another comparative evaluation was performed by Paraiso et al. (9). In this study,
72 women were randomly assigned to receive either laparoscopic Burch colposuspen-
sion or TVT. The mean operative time was significantly greater in the laparoscopic
Burch group. Furthermore, postoperative urodynamic studies revealed a higher rate of
SUI in the laparoscopic Burch group at 1-yr follow-up, 18.8 vs 3.2% in the TVT
patients. The investigators concluded that the TVT procedure results in greater objective
and subjective cure rates for SUI then does laparoscopic Burch colposuspension.
In an effort to better define long-term results, Nilsson et al. prospectively evaluated
and followed 90 consecutive patients who had a TVT operation (43). Their median follow-
up was an impressive 56 mo, with some patients assessed nearly 7 yr after surgery. In
this group, 72 of 85 evaluated patients (84.7%) were both objectively and subjectively
cured. Another 9 patients (10.6%) were significantly improved, and 4 (4.7%) were regarded
as failures. Furthermore, no patient complained of long-term voiding difficulties, and no
tapes eroded or extruded. In addition, 14 of 25 patients (56%) with preoperative com-
plaints of urgency saw their symptoms relieved. This article was one of the first to
conclude that TVT fulfilled the high expectations of long-term cure, as suggested by
previous short-term reports.
Transobturator
Short-term data regarding the efficacy and complications associated with the newer
transobturator slings suggest that these products perform as well as their retropubic
counterparts and may perhaps cause fewer complications. Ansyer et al. retrospectively
analyzed two groups of patients with similar characteristics except that one group (n = 25)
had received a retropubic and the other (n = 24) a transobturator sling procedure (44).
Two bladder injuries occurred with the retropubic approach, whereas none occurred
with the transobturator approach. Overall, however, these investigators found similar
continence results and concluded that the obturator approach achieves comparable efficacy
to the retropubic technique.
Another group of doctors from Lyon, France also compared the obturator route with
the TVT (45). In their retrospective study, one 18-mo period of 94 tension-free obturator
tape cases was compared to an 18-mo period of 99 TVT procedures. The TVT surgeries
had immediately preceded the change in approach to the obturator route. All operations
were performed by the same surgeon using the same Prolene mesh, and no concomitant
procedures were added. Their outcome analysis showed that the obturator sling cure
rates were identical to those seen with the classic retropubic TVT approach. Further
analysis showed bladder injuries were more frequent in the TVT group (10 vs 0%), as
were hemorrhagic complications (10 vs 2%), although the differences were not statisti-
cally significant. These investigators determined that, because of the simplicity and safety
of the procedure along with the excellent continence results, the obturator approach
represents the best method of suburethral tape insertion.
Percutaneous
In a controlled trial, Hung et al. prospectively analyzed two groups of patients under-
going treatment of SUI, one group undergoing a standard TVT procedure (n = 23) and the
other group, for financial reasons, electing polypropylene mesh off the shelf placed in a
conventional pubovaginal fashion using Stamey needles (n = 57) (46). Eighty women
were therefore included, and the mean follow-up was 23 mo for the TVT technique and
20 mo for the PVS procedure. Postoperatively, SUI (91.3 vs 93.0%), concomitant urge
symptoms (85.0 vs 85.3%), and the negative impact of incontinence and urogenital
distress on patients’ quality of life (79.8 vs 77.8% and 77.4 vs 68.8%, respectively) had
improved markedly. These physicians concluded that both techniques were effective
treatment modalities for female SUI. However, interestingly, the TVT was not as
effective in this series in treating overweight or obese women as the PVS procedure.
In a review article, Rackley et al. compared the percutaneous vaginal tape (PVT)
sling experience with that of the TVT (47). PVT procedural steps were analogous to the
TVT insofar as both procedures use sling material composed of polypropylene mesh,
and both require placement of the material at the midurethral level using a retropubic
approach. In the case of the PVT, the mesh is placed in an antegrade fashion using a
percutaneous ligature carrier, and in the case of the TVT, a typical retrograde technique
using vaginal trocars is employed. It was found that both techniques are reproducible,
easy to master, and minimally invasive with respect to tissue handling. In addition, a
cost savings was realized when the PVT was employed. Most important, reported out-
comes with the PVT were comparable to the TVT experience, and both repairs appeared
durable over several years of surveillance.
COMPLICATIONS
Since the introduction of the TVT in 1998, the synthetic midurethral tension-free
slings have revolutionized the treatment of female stress incontinence. A big reason for
their appeal to both patients and surgeons has been reduced operative and anesthetic
times and excellent efficacy. However, another significant advantage is the safety profile
of these techniques. Studies now clearly demonstrate that fewer complications occur
when midurethral slings are compared to other antiincontinence procedures, particularly
those requiring an abdominal incision (48). Although data have consistently supported
the favorable safety reputation of the midurethral sling, it is important to recall that
these slings use a heterogeneous group of procedures. Variability in patient selection,
mesh type, sling placement technique, surgeon experience, and patient follow-up make
analysis of the literature difficult. Within these limitations, synthetic midurethral sling
studies with short- and medium-term follow-up can be found abundantly in the litera-
ture, and the various complications and their management strategies are outlined next.
Intraoperative Complications
The most prevalent intraoperative midurethral sling complications are urethral, bladder,
and bowel injuries; vascular injuries; bleeding; and hematoma formation. To date, these
have been primarily described in patients undergoing retropubic slings, procedures that
require blind passage of mesh through the retropubic space using trocars or needles to
perforate the endopelvic fascia. The retropubic midurethral sling can be placed in either
an antegrade or a retrograde fashion, and several studies have sought to establish the
superior safety of one approach over the other.
The largest body of data exists for the TVT, a sling that is traditionally placed in an
in-to-out, retrograde fashion. Studies support its excellent safety profile. In a survey
investigation by Agonstini et al., input was received from 21 urologists and 71 gyneco-
logists, who reported a combined experience of 12,280 TVT procedures (49). Although
urethral injuries were not mentioned, 901 bladder injuries (7.34%), 26 vaginal healing
defects (0.21%), 3 bowel perforations (0.02%), and 39 (0.32%) retropubic or vulvovaginal
hematomas were reported.
The TVT can be performed either alone or in combination with other surgical procedures,
such as a hysterectomy or prolapse repair, with no significant increase in complications.
In their cohort of 313 TVT patients receiving such combination surgeries, Levin et al.
reported a 5.1% bladder injury rate (16 patients), but no other complications (50). In
Karram’s series of 350 TVT patients, some undergoing multiple procedures, the group
noted a 4.9% bladder perforation rate, no urethral injuries, and a 1% significant bleeding
rate (51). Similarly, Debodinance et al. found that when 256 patients underwent TVT
either alone or in combination with other vaginal surgeries, bladder perforation
occurred at a rate of 5.5%, and urethral injury and retropubic hematoma both had rates
of 0.4% (52).
The SPARC procedure, which is newer than the TVT, is placed via a descending
rather than an ascending retropubic approach. Despite this difference, studies thus far have
failed to establish the superior safety of one over the other. Andonian et al. found that
when 84 women were randomly assigned to receive either a SPARC (n = 41) or a TVT
(n = 41), bladder perforation rates were high in both groups (24 vs 23%, respectively),
but patients in the SPARC cohort experienced additional complications, including one
tape erosion and one infected pelvic hematoma (53). When Tseng et al. evenly randomized
62 patients to receive either a SPARC or a TVT procedure, the authors clinically noted
differences between the group outcomes, but no statistically significant differences were
seen (54). These researchers reported four (12.9%) and zero respective bladder injuries,
and as determined by postoperative pelvic ultrasound, three (9.7%) and five (16.1%)
respective retropubic hematomas greater than 5 cm. Despite the hematomas, no patients
experienced significant bleeding according to the authors.
The possibility of blood vessel injury and significant bleeding is a concerning
although infrequent complication of the retropubic sling procedures. In a retrospective
chart review series by Kobashi and Govier, 140 patients underwent placement of a
SPARC sling and spent one night in the hospital for observation (24). Six patients (4.3%)
experienced perioperative complications, including one bowel perforation and five
significant bleeding episodes (3.6%), with four patients requiring transfusion and one
requiring percutaneous drainage of a hematoma. Although it is unclear whether the afflicted
patients were symptomatic with these bleeds, the authors, who used a postoperative day
1 hematocrit to assess each patient, found an overall mean drop in hematocrit levels
of 7.1% secondary to SPARC surgery. Their group proposes that the incidence of bleeding
with these procedures may be more significant than many surgeons realize.
With either approach, knowledge of the neurovascular anatomy is critical, and
patients with prior vaginal or abdominopelvic surgeries may present an increased surgical
risk due to both altered anatomy and fibrotic tissue. Ultrasonagraphy can be used to
identify interceding bowel prior to introducing trocars. For the most part, case reports
of serious bleeding are mentioned infrequently throughout the literature, and the preva-
lence of this complication appears less than 1% (49). Per report, most intraoperative
bleeding is mild to moderate and can be managed conservatively with compression (55).
A recent modification to the midurethral sling procedure involves a transobturator
approach. The benefits of this approach seem to be fewer intraoperative bowel and
bladder injuries because the retropubic space is not crossed. Although no large studies
compare the intraoperative complications of the retropubic to the transobturator approach,
trends appear to favor the transobturator in smaller series. Ansquer et al., in a non-
randomized trial comparing the retropubic (n = 25) and obturator (n = 24) approaches
found similar rates of cure and symptom improvement, but noted two vs zero bladder
injuries, respectively (44). Similarly, in a randomized trial by deTayrac et al. in which

31 patients received a TVT and 30 patients received a TVT-obturator, bladder injuries
were 0 and 3 (9.7%), respectively (56). The safety record of the transobturator approach
was reinforced by two separate series of 80 and 150 patients, each receiving the trans-
obturator UraTape for stress incontinence. No intraoperative complications were reported
by either set of investigators (57,58).
Because of the perceived safety of the transobturator technique, many surgeons
report no need for intraoperative cystoscopy, a procedure that can diagnose bladder
perforation during midurethral sling surgery. Accounts of bladder laceration during
transobturator sling placement can be found in the literature, although infrequently, and
routine cystoscopic surveillance must still be recommended (59,60). Intravesical injuries
may be discovered in a delayed fashion (61). In one transobturator sling series by Levin
et al., two injuries were detected at 3 and 15 mo postoperatively (50).
Postoperative Complications
EROSION AND INFECTION
Included in the list of early postoperative complications are vaginal and urethral
erosions; infections of mesh, soft tissue, and bone; fistulas; and transient postoperative
urinary retention. With the exception of urinary retention, it is thought that the type of
synthetic mesh used and patient factors such as wound healing play into the development
of these complications. Arguably, synthetic mesh has added a durability to incontinence
repairs that has not been seen with prior surgical techniques. However, mesh has also
contributed to the development of postoperative complications requiring novel manage-
ment strategies.
Erosions, which are thought to be caused in part by an immunologic response to the
foreign body mesh, are a relatively rare sling complication (0.26–1.8%) when poly-
propylene material is used (49,62–64). As a result, this synthetic is currently incorporated
into most sling kits and used off the shelf in many “homemade” slings (65–67). Vaginal
erosions most commonly present with palpable mesh and vaginal discharge, although
vaginal pain, dyspareunia, and partner discomfort during intercourse may also be pre-
senting symptoms (63,68,69). Urethral erosions may cause urinary retention, urethral
bleeding, or pain, or they may present as recurrent stress incontinence (63,68,70). It is
important to note that 35% of vaginal erosions and 89% of urethral erosions may be
completely asymptomatic and may be discovered incidentally on exam or cystoscopy
(63). With either complication, delayed presentation is a consideration.
In small slings series utilizing other than polypropylene mesh, increased incidences
of erosion can be seen. In a prospective study of 10 patients receiving 2 × 10 cm silicone-
coated polyester slings secured with bone anchors, 2 patients (20%) experienced erosion
at 6 and 10 mo postoperatively and underwent subsequent mesh removal (71). Kato et al.
had similar results with the Vesica system, which utilizes a bovine collagen-injected
woven polyester with bone anchors (72). In their series of 19 patients, 4 (21%) deve-
loped vaginal erosion and required total (n = 3) or partial (n = 1) mesh removal. When
Mersilene mesh was used in a series of 176 sling patients, a 4% (n = 8) erosion rate was
reported (73). In a series of 141 patients, use of Gortex as a sling material resulted in
5 patients (3.6%) developing granulation tissue and requiring mesh removal (74). In a
study using UraTape, which is a transobturator sling made of silicone-coated
polypropylene, Cindolo et al. reported only 1 erosion in an 80-patient series (57).
Management of sling erosions usually begins conservatively. Kobashi and Govier

reported spontaneous vaginal healing of SPARC sling erosions in four women when
vaginal rest was prescribed for 3 mo (69). Investigators also reported use of estrogen
cream intravaginally to promote spontaneous resolution of vaginal erosions (73).
When conservative measures fail or vaginal nonhealing is a result of a refractory
infection, partial or complete mesh removal must be performed. One minimally invasive
surgical management strategy involves trimming exposed mesh and granulation tissue
and reclosing the vagina in two layers. Myers and LaSala reported complete resolution
of erosion of Mersilene mesh in all seven patients undergoing this procedure (75).
Frequently, removal of the exposed mesh will not jeopardize continence, and after com-
plete healing, many investigators agree that a second sling can be replaced with minimal
complication (76).
Persistent vaginal infections, although likely underreported, are a risk related to
synthetic use (48). With use of monofilament polypropylene mesh, the infection rate is
low, ranging between 0.4 and 2% (77,78). Other synthetics are associated with higher
infection rates. For instance, when polyfilament polypropylene mesh slings were placed
by Bafghi et al. in a series of 149 women, 11 patients (7.5%) experienced vaginal infection,
with 6 patients requiring unilateral and 4 requiring bilateral mesh removal (79).
Reports suggested that bone anchors have also been associated with infections,
including osteomyelitis, which may commonly be unresponsive to conservative manage-
ment (80). However, when using bone anchors to secure either a polyethylene mesh
In-Taca sling (15 patients) or a fascia lata sling (46 patients), Schulte-Baukloh et al.
concluded that the sling material used rather than the bone anchors were the cause of
infection (81). They found that 33% of patients with polyethylene and 15% of patients
with fascia lata developed infections. Shah et al., in a 5-yr follow-up of 58 patients
receiving a polypropylene sling secured with bone anchors, reported no infections,
nonhealing, or erosion of the slings (82).
Infections, because of their heterogeneous nature, must be managed on a case-by-case
basis. Although most surgeons agree that a trial with topical anesthetics, such as intra-
vaginal betadyne, and systemic antibiotics is worth trying, many patients will require
complete or partial mesh removal (79). Both retropubic and transobturator slings can
harbor infection across the entire mesh surface, and necrotizing surgical site infections,
abscesses, fistulas, and other unique presentations have been described in case reports
(83–86). Fistulas are not reported often in conjunction with midurethral sling place-
ment, but Glavind and Larsen reported 1 fistula complication in a series of 31 patients
receiving TVT slings (87). This patient had a prior Kelly plication.
VOIDING AND SEXUAL DYSFUNCTION

Late complications consist primarily of voiding dysfunction and include urinary
retention and obstructive symptoms; irritative symptoms such as urgency, frequency,
de novo detrusor instability, and urge incontinence; as well as return of stress incontinence.
Sexual dysfunction following sling surgery has also been reported.
During the immediate postoperative period, transient voiding difficulties and
increased postvoid residuals are not uncommon. Because midurethral slings are not
placed under tension, the etiology of this syndrome is poorly understood. Expectant
management strategies include teaching double-voiding, self-intermittent catheteri-
zation, and placing prophylactic suprapubic cystostomy tubes or indwelling urethral
Foley catheters at the time of sling surgery. In an attempt to define which strategy
helps patients recover normal voiding more quickly, Gandhi et al. performed a retro-
spective analysis of 161 TVT patients who had used either intermittent catheterization
or continuous Foley drainage following surgery (88). Their group determined that
normal voiding returned significantly faster (8 d vs 12 d, respectively) in the Foley
drainage group.
Many studies have been conducted to assess the long-term urodynamic and sympto-
matic voiding changes that can accompany midurethral sling placement. Although most
patients are satisfied with these slings, those dissatisfied complain of symptoms that
include hesitancy, straining, or sensation of incomplete emptying, often caused by inad-
vertent persistent urethral obstruction. In one retrospective series of 600 patients receiving
TVT slings, Klutke et al. noted a 2.8% incidence (17 patients) of bothersome obstructive
symptoms requiring transvaginal sling release (20). In their series, all patients experienced
resolution of symptoms with this procedure, although one patient experienced return of
stress incontinence.
Prospective studies using urodynamics to evaluate pre- and post-TVT voiding
parameters are common, and although studies agree that both subjective and objective
changes occur after a sling is placed, they disagree on the significance of these changes.
Lukacz et al., analyzing data from 65 patients undergoing TVT, found that although
TVT does significantly reduce flow rates, patient detrusor pressures, and residual
urine measurements, subjective voiding symptoms are not clinically impaired (89). In
a similar study with 1-yr follow-up of 45 patients who underwent TVT, a significant
reduction in flow rate, increase in postvoid residuals, and changes in pressure flow data
were noted, although only 1 patient was considered urodynamically obstructed (90).
Another TVT study that followed 145 TVT patients at yearly intervals found that
although there were initial changes in obstructive parameters, the flow rates, postvoid
residuals, and subjective symptoms seemed to normalize in the interval between 1 and
2 yr postoperatively (91).
Postoperative voiding dysfunction may correlate with low preoperative flow rates,
preoperative vault prolapse, or concomitant vault suspension surgery (92). The incidence
of prolonged voiding dysfunction following TVT ranges between 1.9 and 2.8% (20,93).
In a large series of 1,175 patients who underwent a TVT midurethral sling procedure,
1.9% (23 women) required surgical intervention for voiding dysfunction refractory to
conservative management (93). In this series, Rardin et al. performed sling release
on 23 women (1.9%) an average of 17.3 wk from sling placement (93). After release,
all patients experienced resolution of incomplete emptying and irritative voiding symp-
toms over a 6-wk period; however, three patients (13%) reported complete recurrence
of stress incontinence equal to or worse than their baseline leakage.
When patients are unequivocally obstructed, surgical sling release is always necessary.
Ozel et al. found that when obstruction was identified early in two transobturator
patients, the anterior vaginal incision could be opened and the sling loosened without
transecting or removing the mesh (94). This procedure, however, will likely be impossible
in the late postoperative period when tissue ingrowth has occurred around the sling.
Other investigators described a sling release procedure that entails either transecting or
segmentally excising a portion of the suburethral mesh (92,95). Should a patient have
recurrent stress incontinence, placement of a second midurethral sling remains a curative
option (20,96).
De novo overactive bladder symptoms are another reported complication of slings;
again, this has been studied most rigorously in the TVT population. Interestingly, typical
results demonstrate that midurethral slings contribute more to resolution of frequency,

urgency, and urge incontinence than they do to the cause of these symptoms.
A review was performed on 98 patient charts following TVT surgery, and it was
revealed that only 8.7% of 98 patients started taking anticholinergic medications after
sling placement, whereas 57.7% of patients who used this class of medications prior to
surgery no longer needed them following surgery (97). In another series of 256 TVT
placements, 12% of patients experienced de novo urinary urgency, but again, it was noted
that 50% of patients with preoperative urgency experienced resolution of this symptom
after the operation (52).
Obviously, outright sling failures as well as subjective or objective return of SUI may
occur postoperatively. By all accounts, a second sling procedure may correct the stress
incontinence without significant operative complications (98). Prior to placing another
sling, however, a thorough examination, including urodynamics, should focus on excluding
alternate causes for incontinence, such as a fistula and de novo urge incontinence.
The topic of patient and partner sexual satisfaction following synthetic midurethral
slings has not received much attention in the literature. In a retrospective study utilizing
65 responses in mailed questionnaires from women who had undergone TVT, 17 women
(26%) described intercourse as better after surgery, 47 women (73%) said it was
unchanged, and 1 woman reported a worse experience because of worsening inconti-
nence (99). Two European studies that also used self-administered mailed questionnaires
to collect data found greater prevalence of sexual dissatisfaction following TVT surgery.
Of the 55 TVT patients who completed questionnaires, 8 (14.5%) reported dyspareunia
after surgery, and 3 (5.4%) reported loss of libido (100). In the United Kingdom, of the
43 sexually active patients surveyed, most reported no change in sexual function (72%),
2 patients (4.7%) reported improvement, and 6 (14%) reported worsening function
because of loss of libido (101). Overall, researchers have generally concluded that the
TVT procedure has little effect on sexual function.
SUMMARY
Midurethral slings have taken their place as a first-line simple reproducible procedure
for incontinence. A wealth of studies has now confirmed the efficacy of these proce-
dures. Although not entirely complication free, multiple investigators have determined
that the overall complication rate is low and acceptable. Easily learned, the midurethral
slings have rapidly become first line antiincontinence procedures for many physicians.
Continued refinements in technique in achieving midurethral tensionless positioning
should further improve what is already a technically sound and successful operation.
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10 Bladder Neck Slings for Stress Urinary
Incontinence
O. Lenaine Westney, MD
CONTENTS
INTRODUCTION
HISTORY
PATIENT SELECTION
SURGICAL TECHNIQUE AND VARIATIONS
MATERIAL, EQUIPMENT, AND TECHNICAL VARIATIONS
REFERENCES
INTRODUCTION
The title of this chapter reflects the need to specify anatomical placement when
discussing slings. A decade ago, such a distinction was unnecessary as bladder neck
positioning was standard. The birth, continued evolution, and success of the midurethral
sling have altered the role of the bladder neck sling. This chapter discusses the history,
applications, patient selection, technique, materials success rates, and complications of
the bladder neck sling.
HISTORY
The concept of suburethral support to treat urinary incontinence dates to the
early 1900s. Giordano was the first to describe utilization of the gracilis muscle to
partially encircle the urethra in 1907 (1). Goebell adapted the approach to treat
two myelodysplastic children using the pyramidalis muscle in lieu of gracilis (2).
The pyramidalis sling was sutured underneath the urethra at the urethrovesical junc-
tion. Stoeckel modified the Goebell technique by adding a plication of the vesical
neck (3). The introduction of fascial material was proposed by Frangenheim, who
reported the use of rectus abdominis muscle and fascia (4). Millin, Aldridge, and
Studdiford followed with varying techniques using rectus abdominis fascia to support
the urethra (5–7).
Other native materials, such as levator ani (8), bulbocavernosus muscle (9), palmaris
longis fascia (10), lyophilized dura mater (11), fascia lata (12,13), and vaginal wall
(14,15), have been used for slings (16). Xenograft materials, including porcine dermis
and small intestine submucosa (SIS), have been processed as alternative biologics.
Synthetic materials have also been used for suburethral compression.

131
Historically, although the continence rates with these materials have been good, the
complications—vaginal wall erosions and urethral transection/sloughing—requiring
sling removal have been dismal (17). The more severe complications seem to be sling
tension and infectious related. In the absence of excessive tension, the practice of aseptic
technique, and in the presence of good blood supply, nontension synthetic slings have had
fewer such problems (18). In addition, attention has been given to the importance of
structural characteristics and host reaction to synthetic materials in adverse events (19).
Despite introduction in the early 20th century, Wharton and TeLinde noted that the
perception of technical difficulty and complications prevented the pubovaginal sling
from becoming a popular procedure in the mid-1900s (20). In their technical report, little
morbidity was noted. The initial indication for a sling procedure for stress urinary
incontinence (SUI) was failure of a more conventional procedure (i.e., anterior colporrha-
phy). Jeffcoate used the Aldridge technique in 40 women whom he determined required
more than an anterior repair (21).
Several independent investigators in the 1970s reported the existence of stress incon-
tinence in the absence of urethral hypermobility. Robertson identified the “stovepipe”
urethra, which was characterized by poor closure (22). Green and Hodgkinson separately
described the radiological appearance of a urethra—immobile and incompetent—leaking
fluid easily with increasing abdominal pressure (23,24).
The urodynamic era brought the classification of intrinsic sphincter deficiency (ISD)
or type III SUI as a definable entity, identifying the ideal group for treatment with a
pubovaginal sling (25). Slings have been used successfully for ISD secondary to myelo-
dysplasia (26), urethral erosion secondary to a long-term indwelling Foley catheter (27),
urethral trauma (28), or associated with a urethral diverticulum (29). Still, however, the
sling technique did not gain widespread use until reintroduction by McGuire and
Lytton in 1978 (30). In this technical description, the fascial strip was left in continuity
with the abdominal rectus muscle sheath. Blaivas is credited with the transition to free
autologous graft segments anchored by suture and tied over the rectus fascia (31).
In the mid-to-late 1990s, there were many reports of the application of pubovaginal sling
for all types of SUI (32–34). The pubovaginal sling became the treatment of choice—
primary and secondary—for stress incontinence attributed to urethral hypermobility or
ISD. In support of this progression, the American Urological Association Stress
Incontinence Guidelines Treatment Panel confirmed that sling procedures and retropubic
suspension were superior to needle suspensions and anterior colporrhaphy for surgical
treatment of female urinary incontinence (35).
PATIENT SELECTION
Increasingly, suitability for a bladder neck sling is based on the inability for a less-
invasive procedure to confer sufficient urethral coaptation to restore continence or after
multiple failures of alternate techniques. The history of prior anti-incontinence procedures
in itself predisposes toward the presence of ISD. McGuire previously demonstrated that
women are more likely to have type III SUI after a prior anticontinence procedure (36).
Evaluation should include a complete history and physical examination, stress test, 3-d
voiding diary, 24-h pad test, validated urinary symptom disease-specific questionnaire, and
urodynamic evaluation.
Valsalva leak-point pressure (VLPP) is a functional measure of the coaptation
and closure capabilities of the proximal urethra to withstand intraabdominal pressure
Chapter 10 / Bladder Neck Slings for SUI 133
fluctuations. This value is recorded in centimeters of water pressure. The upper limit
for ISD has not been well defined; however, readings below 60 cm H2O are accepted as
true ISD. The growing perception is that varying amounts of dysfunction are present in
all degrees of urinary incontinence. The low-pressure urethra has also been described
using maximal urethral closure pressure (MUCP) less than 20 cm H2O. Sand et al.
initially identified low MUCP in a group of women who failed retropubic suspension
(37). The measurement is not active and therefore may reflect a different aspect of the
same condition. This may explain why the correlation between VLPP and MUCP has
ranged between 50 and 65% (38–40). The presence of both, however, is reflective of
poor urethral function. Urodynamic technique is reviewed in Chapter 4.
Patients with urethral tissue loss in the area of the bladder neck secondary to trauma
or fistulas will require reconstruction of the bladder neck mechanism (i.e., coaptation).
This situation obviates the need for a pubovaginal sling composed of autologous material.
Similarly, in patients with a urethral diverticulum complicated by incontinence prior
to excision or in whom an extensive resection in the bladder neck area is projected,
supplementation of the bladder neck support with an autologous or allograft sling is
indicated. In both cases, biologics are suggested because of the requisite tension and
reduction of erosion/urethral transection of compromised tissue (41).
SURGICAL TECHNIQUE AND VARIATIONS

The bladder neck sling has been subject to multiple variations of every aspect of the
procedure. With the exception of sling material, few of these alternations have been
prospectively compared. Therefore, the majority of these permutations are surgeon pre-
ference. The following technique is a basic description of a 6- to 8-cm autologous rectus
fascial sling.
Pubovaginal Sling (Autologous Rectus Fascia)

For the autologous rectus fascia sling, general or spinal anesthesia is administered.
The patient is placed in modified dorsal lithotomy position with the legs elevated in
Yellowfin stirrups (Allen Medical Systems, Acton, MA) positioned to avoid pressure on
the calf. The legs are flexed gently at the hip to allow free simultaneous access to the
suprapubic area and vagina. A 16-French Foley catheter is placed, and the balloon is
inflated with 10 cc saline to facilitate palpation of the bladder neck and urethra. In lieu of
placing the catheter to drainage, it is clamped with a Kelly and released after passing the
sling sutures to evaluate for hematuria. A weighted vaginal retractor (Scherback retractor,
Aesculap Co., San Francisco) is placed. The labia majora may be sewn laterally or a Gelpi
retractor used (Miltex Inc., York, PA), if necessary. Alternatively, a Gen II Lonestar
(Lone Star Medical Products, Stafford, TX) retractor may be utilized for retraction.
The suprapubic incision and dissection are performed first to minimize bleeding time
from the well-vascularized vaginal wall. An 8-cm Pfannenstiel incision is made about
2–3 cm superior to the pubis. The rectus fascia is identified and exposed for the entire
length of the wound. The fascia is incised transversely for 6–8 cm, 3–4 cm superior to
the pubis. The underlying rectus muscle is dissected from the fascia to ease in sling harvest
and fascial closure. In addition, the lateral border of the rectus muscle should be exposed
for sling suture passage.
Usually, the sling is harvested from the lower fascial leaf (Fig. 1). The sling dimensions
should be 6–8 cm long and 1–1.5 cm in the midline, tapering to 1–0.8 cm at the ends.
Fig. 1. Rectus fascial sling harvest. (From ref. 131 with permission.)
Zero Vicryl (polyglactin 910, Ethicon Inc., Somerville, NJ) sling sutures are placed
perpendicular to the direction of the fibers approx 0.5 cm from the ends, incorporating
the full width of the sling. Permanent suture is unnecessary based on the fixation of the
sling at the level of the endopelvic fascia by 3 wk postoperatively. Permanent suture
may represent a source of discomfort, especially in patients with little subcutaneous
fat. From above, entry into the retropubic space is obtained by bluntly piercing the
transversalis fascia lateral to the rectus muscle and advancing the index finger along
the posterior surface of the pubis. In patients who have had a prior retropubic or needle
suspension, this may be difficult. It may be necessary to place the tips of a Metzenbaum
scissors on the posterior surface of the pubis and advance slowly into the retropubic
space.
The vaginal portion of the procedure is initiated by placing an Allis clamp on the
anterior vagina wall midway between the urethral meatus and bladder neck for superior
traction. Injectable saline or local anesthetic may be infiltrated to aid in dissection prior
to the incision. An inverted U or midline incision is made over the proximal urethra
(Fig. 2). The mucosa is dissected from the white periurethral fascia. If the periurethral
fascia is breached, then profuse bleeding from the corpora spongiosum may result.
Once the appropriate level of dissection is identified, bleeding can be controlled by
reapproximating the periurethral fascia over the spongiosal tissue with an absorbable
figure-of-eight suture.
Dissection is initiated using a Church scissors, which are helpful in atrophic or
scarred vaginal tissue. When the correct plane has been identified, Metzenbaum scissors
are used. The retropubic space is entered by perforating the endopelvic fascia with
Metzenbaum scissors pointed slightly superiorly and laterally (Fig. 3). After the endopelvic
fascia has been opened, the scissors are spread to accommodate the sling width.
Simultaneous palpation of the retropubic dissection from the vaginal and suprapubic
Fig. 2. Vertical vaginal wall incision centered over the bladder neck.
approaches is performed manually to confirm that the bladder is safely medial, and the
passage is ready for sling suture transfer.
A Crawford or Sarot clamp is placed from above lateral to the rectus muscle and
directed into the vaginal incision. The clamp should be in contact with the pubic peri-
osteum and the index finger of the vaginal operator at all times (Fig. 4). The Foley is
unclamped, and the bladder is partially drained to evaluate for hematuria after each
clamp is passed. When the bladder is densely adherent to the pubis, Stamey (Cook
Urological, Spencer, IN) ligature carriers may be utilized to transfer the sling sutures.
Both ligature carriers should be passed, then cystoscopy performed with a 70° lens to
ensure that bladder perforation has not occurred. Injuries occur at the 11 and 1 o’clock
positions, near the dome of the bladder. Detrusor injury with Stamey or Raz ligature
carriers may be missed if not evaluated cystoscopically.
Conversely, perforation of the bladder with larger and more blunt clamps is usually
heralded by gross hematuria (Fig. 5). The sling is centered, positioned at the level of
the bladder neck, and secured by suturing the sling to the periurethral fascia with a 3-0
Vicryl suture (Fig. 6). The ends of the sling are seated in the retropubic space. The
vaginal mucosa is closed with 2-0 absorbable suture in an interrupted or running locking
fashion.
Fig. 3. Entrance into the retropubic space (vaginal approach). Scissors are oriented parallel to the per-
ineum. (From ref. 131.)
The sling sutures are passed though the inferior leaf of rectus fascia using a sharp
right angle clamp. The rectus fascia is closed with zero polyglactin in a running fashion.
The vaginal retractor is removed; the sling sutures are pulled up to remove any slack.
The sutures are tied over the rectus fascia with the least amount of tension required to
prevent urethral motion (Fig. 7). This roughly corresponds to one or two fingers
between the knot and the rectus fascia. In addition, preoperative assessment of the
abdominal leak-point pressure and the amount of urethral mobility are helpful in making
this decision. Inject 10 mL 0.25% bupivicaine in the subcutaneous tissue. Scarpa’s fascia
is approximated with interrupted absorbable suture. The skin is closed with absorbable
suture (4-0 monocryl or polydioxanone) in a subcuticular running fashion. The Foley
catheter is placed to straight drainage. A betadine-soaked or estrogen cream-laced gauze
is packed within the vaginal vault. The average operative time with a suprapubic and
vaginal operator is 30 min.
Fig. 4. Passage of the Sarot or Crawford clamp through retropubic tunnel with guidance from the
vaginal operator. (From ref. 131 with permission.)
Pubovaginal Slings in the Repair of Urethral Diverticula

For pubovaginal slings in the repair of a urethral diverticum, the diverticulum should be
completely dissected circumferentially and excised from the urethra at the intersection
with the ostium. As much periurethral fascia as possible should be preserved. The urethral
opening is closed in two layers—simple interrupted, then Lembert sutures—with 4-0
polyglactin suture. The urethral muscularis is approximated over the suture line with 3-0
polyglactin suture. The sling is fashioned and positioned in a manner such that the fascial
defect and the bladder neck are appropriately addressed. In cases of recurrent diverticulum
with compromised appearing periurethral tissue, the addition of a Martius flap may be
indicated. If stress incontinence is not present or the dissection is extensive, then a fascial
defect may be directly patched with the autologous rectus fascia secured laterally to the
periurethral fascia (Fig. 8A, B) The vaginal mucosa is closed in the standard fashion.
Postoperative Care
The vaginal pack is removed on postoperative d 1. The Foley catheter is removed on
postoperative day 1 or 2 depending on how well the patient is ambulating. If urethral
diverticulectomy is performed, then the catheter is removed in the clinic at 2–3 wk
postoperatively with a voiding cystourethrogram. After catheter removal, the patient
receives intermittent catheterization instruction and catheterizes for postvoid residuals
Fig. 5. The sling sutures are passed to the suprapubic incision. (From ref. 131 with permission.)
every 4 h and as needed. The patient may cease catheterizing when the postvoid
residuals are 60 mL or less for 24 h. Patients are instructed not to engage in any vigorous
physical activities, primarily bending over and lifting, for 4–6 wk. Intercourse may be
resumed at 3 wk. Postoperative antibiotics are not routinely given except in cases of
urethral diverticulectomy. The patient returns for postoperative follow-up in the clinic
about 3 wk after the procedure.
MATERIAL, EQUIPMENT, AND TECHNICAL VARIATIONS

Sling Material Selection
The most desirable sling material (Table 1) would combine effectiveness, nonreactivity,
and durability at a reasonable cost. Autologous rectus fascia and fascia lata meet these
criteria at the cost of discomfort at the harvest sites. The use of allograft, xenograft, and
synthetic materials has the advantages of decreased patient pain and disability. However,
the individual host response to some materials is unpredictable.
Fig. 6. Fascial sling positioned at the bladder neck.
AUTOLOGOUS MATERIAL
Rectus Fascia. The long-term success rates for autologous rectus fascial slings
have ranged from 73 to 92% (33,34,42). Rectus fascia has been the most widely utilized
autologous sling material. The primary drawbacks are (1) the need for harvest, particularly
in the case of full-length slings, and (2) increased suprapubic discomfort. The history
and surgical technique have been reviewed previously.
Fascia Lata. Fascia lata gained popularity secondary to the ability to obtain longer
fascial strips even in the presence of multiple prior abdominal incisions. This remains,
however, at the theoretical cost of additional incisions, pain, and repositioning for
the patient. Success rates with fascia lata have been demonstrated to be equal to those
for rectus fascia, although not in a randomized fashion (13,43,44). The complications
Fig. 7. Completed pubovaginal fascial sling after suprapubic sutures are tied.
directly attributable to the harvest are hematoma (1%), seroma (3%), thigh cellulitis
(7%), tendonitis, and hernia (45). There are multiple minor variations; however, the
standard technique is reviewed.
Fascia Lata Harvest Technique. For fascia lata harvest, the patient is positioned in
the full lateral position. The lateral thigh is fully prepped from the iliac crest to below
the knee. The greater trochanter and lateral malleolus are identified with a surgical
marker. Parallel horizontal incisions spaced 2–3 cm apart are placed along the course of
the fascia lata. The number of incisions is dependent on the desired length of fascia.
Metzenbaum scissors and manual dissection are utilized to connect the incisions sub-
cutaneously. The fascia is transected at the inferior and superior limits of the dissection.
The incisions are reapproximated, and a pressure dressing is applied to the thigh (43).
In lieu of manual sharp and manual dissection, use of a fascial stripper has been described
eliminating the need for multiple incisions (46).
Vaginal Wall. The vaginal wall sling was first introduced by Raz in 1989 (14). A
brief description of the technique follows. The anterior wall of the vagina is infiltrated
with saline. A rectangular portion of vaginal wall centered at the bladder neck is dissected
Fig. 8. (A) Fascial sling placed under the periurethral fascial defect and bladder neck. (B) Autologous
or cadaveric fascial patch positioned under periurethral fascial defect only.
free from its ligamentous attachments. A 1-0 polypropylene suture is run along the
lateral edges of the sling. A small suprapubic incision is made to accommodate passage
of Peyrera needles for sling suture passage. The sutures are tied together over the rectus
fascia. The vaginal mucosa is closed, burying the vaginal wall sling. Stress incontinence
cure rates for this procedure have ranged from 71 to 97% with variable lengths of follow-
up (47–49). Some evidence suggests that the efficacy is significantly lower in patients
with severe ISD (50). The utilization of buried epithelialized vaginal wall mucosa
generates a complication specific to this type of sling: the vaginal wall inclusion cyst.
Reports of this unusual occurrence have been sporadic and are notably absent in larger
series (51,52). Stothers described a variation of the procedure in which the vaginal
mucosa is not covered (53).
Table 1
Sling Technique Variations
Accrual Sling Suture Sling dimensions Suture Anchoring Method of
Reference years n evaluable material material (cm) passage mechanism tension
33 Approx 251 ARF 2-0 2 × 15 Long Debakey Suture Tied loosely
82–97 nonabsorbable clamp
42 NS 128 ARF 2-0 2 × 15 Long Debakey Suture NS
nonabsorbable clamp
34 93–96 247 ARF Zero PG 1–1.5 × 6–8 Sarot clamp Suture 1–2 fingers
between knot
and RF
142
32 NS 60 ARF 1-0 PP 2 × 6–8 Long Debakey Suture Elimination of
or Sarot clamp mobiity; 2
finger breadths
130 95–98 134/140 ARF (49) 2-0 PP 2 × 12 Long Debakey Suture Minimal
AFL (22) or Sarot clamp
CFL (63)
13 94–95 30/32 AFL 2-0 PP 2.5 × 24–28 Kelly clamp Sling to 1 finger between
sling sling and
rectus
15 90–96 42/52 VWS Zero PP 2- to 3-cm Stamey needle Suture Light tension;
vaginal flap cysto
49 93–99 373 VWS No. 1 PP NS Peyrera needle Suture 1–2 fingers
between knot
and RF
60 96–99 91/104 CFL 1-0 PP 2 × 15 Double-pronged Suture Without tension
Peryera
106 98–99 145/154 CFL No. 1 PP 4 × 7 folded None TV bone Without undue
anchor tension
69 NS 25 CD Zero PG 2 × 12 Sarot or Kelly Suture Minimal
68 98–03 234/253 CD PP 2×4 None TV bone Cystoscope @
anchor 45°
111 NS 74 PD No. 1 PG 2 × 10–12 15° Stamey needle Suture Minimal; stress
test
78 99–02 152 SIS No. 1 PP 2 × 10 None TV bone None
anchor
131 NS 48 ARF (32); 3-0 PG × 4 1.5 × 12 NS Suture Leak point
Gortex (16)
17 86–91 108 PTFE None .8–1.5 × 20 Sling to Q-tip angle:
rectus fascia -5–10°
86 89–94 90/141 PTFE patch 2.0 PTFE 1.5 × 3.5 cm NS Suture NS
87 89–98 72/84 PTFE patch No. 2 nylon 1.5 × 3.0 “Needle” Suture Bladder neck
US
143
90 86–92 88 Marlex None 2 × NS Clamp Material to Midretropubic
Cooper’s position
ligament
97 90–00 136/176 Mersilene None 1–3 × 30 None Material to No tension
fascia
92 NS 64 Prolene None 2 × 30 Curved Kelly clamp Mesh to Cystoscopy;
mesh mesh stress test
NS, nonspecified; ARF, autologous rectus fascia; AFL, autologous fascia lata; CFL, cadaveric fascia lata; VWS, vaginal wall sling; CD, cadaveric dermis; PD, porcine
dermis; SIS, small intestinal submucosa; PTFE, polytetrafluoroethylene; PP, polypropylene; PG, polyglactin; TV, transvaginal; RF, rectus fascia; US, ultrasound.
Allograft
CADAVERIC FASCIA LATA
Handa et al. reported the first use of cadaveric fascia lata for female urinary incontinence
(54). Surgical series evaluating the success rate of the cadaveric fascia lata sling have
had variable results. Clarification of the true efficacy of a sling consisting of this material
has been hampered by heterogeneous material sources with different proprietary
processing techniques (L-irradiation, freezing, solvent dehydration, and so on) and the
failure to compare the sling directly to autologous fascia lata in a randomized fashion.
There is insufficient information to determine the individual contributions of the tissue-
processing and host-vs-graft factors to the outcome. However, there have been several reports
revealing histological evidence of poor incorporation of the graft into the surrounding
host tissue to complete degradation (55,56).
Bent et al. compared autologous and cadaveric fascia lata sling groups in a nonran-
domized fashion and noted similar stress incontinence cure rates at 42.4 and 35.2 mo,
respectively. However, the cadaveric fascia group had a significantly higher incidence
of de novo urge incontinence (57). Repeatedly, early reports of good results are not
supported with longer term reports verifying the results.
In contrast, Brown and Govier reported a comparative study between cadaveric and
autologous fascia lata. Patients (121) received cadaveric fascia lata slings sourced as fresh
frozen from a single local tissue bank. Of 104 evaluable patients at a mean follow-up of
12 mo, the early failure (>3 pads/d postoperatively) rate was 7% (58). In a follow-up
report in 2002, there were eight additional failures occurring between 4 and 13 mo. Of
8 patients, 5 underwent postfailure urodynamics, demonstrating a mean leak-point
pressure of 33.5 cm H2O. Similarities in these patients included prior antiincontinence
surgeries, and three of eight had neurological diagnoses (59). In comparison, at a mean
follow-up of 19.4 mo, Amundsen et al. reported an 84% cure and improved rate post-
cadaveric fascia lata sling from a single tissue source. The processing technique utilized
for the material, however, was solvent dehydration (60).
CADAVERIC DERMIS/ACELLULAR COLLAGEN MATRIX

Since the early 1990s, decellularized cadaveric dermis has been utilized in the treatment
of burns. Its usage has been extended to a wide range of plastic and reconstructive
applications, including abdominal wall and pelvic reconstruction, tympanoplasty,
rhinoplasty, and cleft palate repair (61–64). There are comparatively few published data
on the use of cadaveric dermis for pubovaginal slings. Cadaveric dermis has been proven
safe, but with variable results linked to the quality and processing of the tissue and the
subsequent host reaction.
Several studies have demonstrated revascularization of decellularized human dermis
in animal models (65,66). One perceived advantage of dermis is the ability to attain a
consistent thickness facilitated by dermatome harvest. In addition, the possibility for
suture pull through is theoretically reduced because of the lack of striations in the tissue.
Improved strength in comparison with cadaveric fascia lata was proven by Choe et al.
Tensile strength was analyzed in full-length and patch slings composed of dermis
(autologous and decellularized), rectus fascia, cadaveric fascia lata (freeze-dried, L-irra-
diated), Gore-Tex® (W. L. Gore & Associates Inc., Flagstaff, AZ), and polypropylene.
The greatest tensile strength was possessed by the full-length synthetic and dermis
(autologous and decellularized) slings (67).
Two surgical series reported the use of cadaveric human dermis for slings. Crivellaro et al.
presented a mean 18-mo follow-up of 234 of 253 patients who underwent placement of
a transvaginal sling composed of Repliform™ cadaveric human dermal allograft
(LifeCell Corp., The Woodlands, TX) with bone anchor fixation (68). Subjective outcomes
were determined using UDI-6 and IIQ-7 questionnaires. Based on patients’ responses,
the cure and improvement from SUI symptoms was 78%. In comparison, Owens and
Winters reported on 14 patients with a mean-follow-up of 14.8 mo (8–23 mo) (69). The
sling was composed of a 2 × 12 Duraderm™ (C. R. Bard, Covington, GA) human
dermis graft with suture fixation. Between 6 and 12 mo, the dry and improved rates
changed from 68 to 32% and 24 to 36%, respectively. This reflects a significant down-
ward migration in efficacy during that time period. Of note, in one patient who underwent
repeat autologous pubovaginal sling, no remnants of the dermal graft material could be
identified intraoperatively.
Xenograft
PORCINE DERMIS MATRIX
Similar to human dermis, porcine dermis is deepithelialized, lyophilized, and sterilized.
Reports of slings composed of porcine dermis began to appear in the literature in the late
1980s (70,71). Material processing during that time included glutaraldehyde crosslinking,
which not only protected the material from degradation but also potentiated graft
mineralization. Currently available porcine dermis is crosslinked with hexamethylene-
diisocyanate and L-irradiated. Early success rates with the porcine dermis sling appear
to be similar to other biologics.
Barrington et al. reported on a group of 40 patients who received a porcine dermis
sling. At a mean follow-up of 12 mo (6–18 mo) with no patient loss, the cure rate was
85% (72). The material, however, does not appear exempt from failure caused by unpre-
dictable host response. Gandhi et al. performed histopathological examination of tissue
from women who underwent reoperation after porcine dermis sling for urinary retention
or recurrent stress incontinence. Pathological evaluation demonstrated limited collagen
remodeling, with evidence of foreign body reaction in some specimens. The light
microscopic appearance was highly variable between patients with the same surgical
indications (73).
PORCINE SMALL INTESTINAL SUBMUCOSA

Porcine SIS (Cook Urologic, Spencer, IN) is processed via a proprietary technique
that converts porcine jejunum into a collagen matrix, with endogenous growth factors
stimulating host neovasculzarization and cell proliferation. Animal studies have demon-
strated complete replacement of SIS with host tissue within 90 d from implantation
(74). In humans, Wiedemann and Otto examined the tissue of patients who required
reoperation because of recurrent SUI. In contrast to the similar study of porcine dermis
slings by Gandhi et al., there was no evidence of inflammatory reaction (75).
The material is supplied in differing thicknesses (one, four, and eight ply) depending
on whether the intended use is reconstructive or for incontinence (bladder neck or
tension-free midurethral) (76). Bladder neck slings utilizing four-ply SIS have
demonstrated good results in the pediatric neurogenic and female nonneurogenic
populations. Missieri et al. (77) reported a 75% dry rate for a group of 26 neuropathic
patients with leak-point pressures of 25 cm H2O or less. Similarly, Rutner et al. reviewed
a mean 2.3-yr follow-up of 152 patients who underwent SIS sling with bone anchor
fixation. They reported a 93.4% dry rate with seven failures, two of which were clearly
bone anchor related (78).
Regarding strength, Kubricht et al. analyzed tensile strength of SIS and cadaveric fascia
lata via a pull-through analysis using polypropylene and polyglactin suture (79).
Although the load could be improved based on the technique used for folding the graft
ends and suture placement, the cadaveric fascia lata demonstrated more tensile strength
than the SIS. It should be noted, however, that single-ply SIS was utilized in this study.
Synthetic Materials
The availability and use of synthetic material pre-dates allografts. However, the initial
studies for the application of female incontinence were complicated by high erosion and
infection rates. More contemporary data suggest that shorter operative times, antibiotic
prophylaxis, and vaginal preparation have combined to decrease the complication
rates (80,81). Synthetic meshes are categorized based on their filamentous composition
(mono or multi) and pore size (macro or micro). Interstices less than 75 nm are not suffi-
cient for the passage of inflammatory agents and completion of the process of fibrous
and neovascular ingrowth (82). In the microporous category, those with pores less than
10 Rm allow for the possibility of bacterial entrance and proliferation without the threat
of a neutrophil and macrophage response.
POLYTETRAFLUOROETHLYENE
The use of polytetrafluoroethylene (PTFE; Gore-Tex) in general and vascular surgery
pre-dates its introduction to stress incontinence procedures by over a decade (83,84). Both
full-length (20- to 30-cm) and patch-type (30- to 35-mm) slings have been utilized
(85–87). In lieu of simple suspension of the expanded PTFE patch, the periurethral fascia
and pubourethral ligaments are integrated into the bladder neck support. High rates of
sling removal related to vaginal erosion, sinus tract formation, and abdominal wound
abscess reported separately by Weinberger and Bent in the early 1990s decreased
markedly by later in the decade (88).
POLYPROPYLENE MESHES
Marlex (C. R. Bard/Davol, Cranston, RI) and Prolene (Ethicon) are both composed
of monofilament polypropylene mesh but differ in porosity and stiffness (41,89).
Marlex. The largest series discussing the utilization of Marlex slings has been
reported by Morgan et al. in Toronto in Canada. These selection criteria focused on
patients with recurrent SUI after retropubic or other suspension procedures (90). One
unique technical element was the attachment of the sling material to Cooper’s ligament.
Prolene. As initially described by Ulmsten et al., the majority of available distal
urethral slings are composed of Prolene (91). However, there are series utilizing the
mesh as a bladder neck sling. Kuo reported the long-term results of 108 patients treated
with a polypropylene mesh sling for varying types of stress incontinence. The cure and
improvement rate was 85.2%, with a patient satisfaction level of 89.8% (92).
Silicone Elastomer. For silicone elastomer (Silastic, Dow Corning Corp., Midland,
MI), Stanton et al. introduced the usage of a sling composed of a 1 × 19 cm Silastic
strip anchored to the ileopectineal ligament in 1985 (93). Despite a follow-up report
demonstrating a durable success rate of 71% at 5 yr, the material has not been widely
utilized because of high erosions and de novo detrusor instability rates (94).
POLYESTER MESHES
Polyethylene Terephthalate. Mersilene (Ethicon) is a polyethylene terephthalate
multifilamented polyester mesh. Williams and TeLinde introduced the use of Mersilene
tape slings in 1962 (95). Initially, the narrow tape had unacceptable erosion rates.
Moir revised the technique by devising the “gauze hammock” variation (96). In contem-
porary series, the complication rate has been decreased markedly by increasing the
suburethral portion of the tape to 3 cm (97,98). In the recent past, a sling composed of
polyester with various additional preparations has been linked to complications reminiscent
of early synthetic slings.
Bovine Collagen-Injected Polyester. Kobashi et al. reported on 34 women from
five centers who received slings made from polyester pressure injected with bovine
collagen (ProteGen®, Boston Scientific, Natick, MA) and required removal of the
slings for erosion, infection, or pain (99). Although the report was limited to patients
with complications only, the number of women and their time to erosion represented a
significantly higher rate and earlier presentation than for other currently used synthetic
materials. The product was recalled in January 1999, citing a higher-than-acceptable
overall rate of complications.
Silicone-Coated Polyester. Govier et al. reported the results of a premarket study of
bone-anchored slings using a polyester coated with silicone (American Medical Systems,
Minnetonka, MN) (100). Of the patients, 31 experienced vaginal extrusion of the material.
Attempts to excise portions of the mesh combined with repeat closure were failures. The
investigators theorized the formation of a biofilm similar to that associated with an
artificial urinary sphincter prevented salvage of the sling procedures.
Suture Selection
After the description of detached sling material by Blaivas, the need for suspension
suture material arose. In this description, 2-0 polyester suture was selected as the material.
Since that time, Prolene suture has been the more common choice. However, Cespedes
et al. proposed a transition from polypropylene suture to polyglactin suture (101). The
rationale behind the change was twofold: (1) the belief that permanent sling fixation
occurs where the material traverses the endopelvic fascia, and (2) knotted prolene suture
could be uncomfortable in the thin patient and a source for suture granuloma.
There have been no randomized studies with suspension suture as the single variable
under examination. However, in an in vitro comparison between cadaveric fascia lata
and small intestinal submucosa by Kubricht et al., polypropylene and polylactin were
compared (79). In suture pull analysis measured by a tensiometer, the mean suture
breaking load (in pounds) of 1-0 and 2-0 polyglactin was greater than 1-0 polypropy-
lene. The strength of the suture is unlikely to persist after degradation of in vivo
polyglactin initiates.
Method of Suspension
SUTURE
For the majority of pubovaginal sling series, the mechanism of suspension is via
sutures. Various techniques have been utilized to tie the suture over the rectus fascia. The
sides are tied to each other across the midline or with the assistance of a two-pronged
needle passer, tied over a fascial bridge. When the material is of sufficient length, the
material can be sutured to itself or directly to the fascia. Sling suspension methods have
not been examined in a randomized fashion; therefore, surgeon preference or patient

diagnosis is the primary basis for selection.
BONE ANCHOR
Leach and subsequently Benderev reported the use of percutaneous suprabically
placed bone anchors in needle suspension (102,103). Appell et al. combined this fixation
method with a 2 × 6 cm piece of polypropylene mesh (Vesica™, Microvasive/Boston
Scientific Corp., Natick, MA). Short-term results have the typical high continence rates
(104). However, Reid and Parys reported 5-yr follow-up of 40 patients that demon-
strated a dramatic decline in efficacy, from 85 at 6 mo to 31% at 5 yr (105). Reoperation
of failed procedures demonstrated fraying of the suspension suture at the level of the
bone anchor.
Madjar et al. were the first to report utilization of a transvaginal placement of titanium
bone anchors in the symphysis utilizing an angled disposable drill (106). Full-length
sutures or a suture loop are swedged on the anchor to permit for attachment to the
material of the surgeon’s choice. The results of bone-anchored slings are highly variable,
possibly secondary to the wide variety of sling materials utilized in different reports.
Carbone et al. reported a series of 200 patients who underwent procedures with
cadaveric fascia lata anchored with transvaginal bone anchors. The early failure rate
was exceedingly high at 31% (107). When the material and suspension method are both
novel, assignment of culpability is difficult. Although the bone anchors appeared to be
intact at operation and the sling material was degraded or absent in many cases, it
should be noted that neither fascial source nor preparation was uniform. Complications
specific to bone anchors—osteitis pubis and osteomyelitis—are discussed at the end of
the chapter.
Incisions
The presence and size of a suprapubic incision depend on the need for rectus fascial
harvest and the method of suspension, including the suture-passing instruments. In the
absence of the need to obtain material, the suprapubic incision need only be of sufficient
size to accommodate the passing instruments. The standard pubovaginal sling with rec-
tus fascia harvest is performed via a suprapubic incision measuring at least 6–8 cm.
When cadaveric or xenograft material is used, a single 2-cm central incision or use of
two separate lateral incisions is adequate.
Sling Tension
One of the most debated components of the bladder neck sling technique is the ideal
amount of tension applied to the bladder neck by the sling. Insufficient tension results
in clinical failure—immediate or delayed. Conversely, excessive tension may be heralded
by de novo irritative voiding symptoms (urgency, frequency, and urge incontinence)
or urinary retention. Subjective descriptions such as “without tension” or “loosely,” or
variables such as “two fingers between the rectus fascia and the knot” as in the prior
operative description are prevalent (108).
In the interest of devising more objective measures, cystoscopic deflection during
tying (109), intraoperative Q-tip test (110), stress test (111) spacers, and intraopera-
tive ultrasound (112) are used. Multiple attempts have been made to standardize the
Table 2
Series Outcome Measures
Mean months
Accrual Sling follow-up Outcome Post-op
Reference years n evaluable material (range or SD) measurement Questionnaire pad test
33 Approx 82–97 251 ARF 36 (12–180) Blaivas category Validated Yes
42 NS 128 ARF 44.9 Outpatient follow-up None No
34 93–96 247 ARF 51 (22–68) Questionnaire UDI-6 No
32 NS 60 ARF 25.1 (11–34) Outpatient follow-up None No
130 95–98 134/140 ARF (49) 29 ± 3 (autograft) phone questionnaire Self-designed No
AFL (22)
CFL (63) 44 ± 7 (allograft)
13 94–95 30/32 AFL 14 (3–33) Telephone questionnaire Self-designed No
15 90–96 42/52 VWS 31 (5–67) Telephone questionnaire Self-designed No
49 93–99 373 VWS 39.8 (±11.4) F/U Self-designed No
60 96–99 91/104 CFL 19.4 (± 10.3) Questionnaire UDI-6, IIQ-7 No
106 98–99 145/154 CFL 10.6 (6–16) Questionnaire Self-designed No
149
69 NS 25 CD 14.8 (8–23) Phone questionnaire Self-designed No
68 98–03 234/253 CD 18 (6–54) Questionnaire UDI-6, IIQ-7 No
110 NS 74 PD 12 (6–24) Stress test; Self-designed No
mail questionnaire
78 99–02 152 SIS 27.6 (4–48) F/U and questionnaires Not stated No
131 NS 48 ARF (32) 30–38 Urodynamics None No
Gortex (16)
17 86–91 108 PTFE 10 (2–39) Urodynamics None No
86 89–94 90/141 PTFE patch 51 (27–84) Mail questionnaire MESAAQ No
87 89–98 72/84 PTFE patch 75 ± 37 (type II) Questionnaire Self-designed No
50 ± 28 (type III)
90 86–92 88 Marlex 49.7 (1–84) Questionnaire Self-designed No
97 90–00 136/176 Mersilene 30 (5–107) Stress test; urodynamics None No
92 NS 64 Prolene mesh 24 (6–41) Blaivas category None Yes
NS, nonspecified; ARF, autologous rectus fascia; AFL, autologous fascia lata; CFL, cadaveric fascia lata; VWS, vaginal wall sling; CD, cadaveric dermis; PD, porcine
dermis; SIS, small intestinal submucosa; PTFE, polytetrafluoroethylene; PP, polypropylene; PG, polyglactin; TV, transvaginal; RF, rectus fascia; US, ultrasound;
UDI-6, Urogenital Distress Inventory-6; IIQ-7, Incontinence Impact Questionnaire-7.
Table 3
Sling Results and Complications
Vaginal
erosion/
sinus Supra-
Blad- tract, pubic Urethro-
n De der granu- wound lysis/
Accrual Evalu- Sling novo Late per- Urethral lation infec- sling
Ref. years able material Dry Improved Failure Retention urge failure foration erosion tissue Pain tion removal
150
33 Approx 251 ARF 73% 19% 8% 2% 3% 0.60% 0% 0% 0.30% 0% 2%
82–97
42 NS 128 ARF 73.40% 20.20% 6.30% 11.10% 10% 13.30% 3.70% 0% 0% 0.8 42% 0%
34 93–96 247 ARF 88.00% 8.80% 3.20% 2.00% 7.00% 8.00% 0% 0% 0% NS NS 2.00%
32 NS 80 ARF 95% 5% 0% 5% 0% 0% 0% 5% 0% 0%
130 95–98 134/140 ARF (49) ARF/AFL ARF, ARF, ARF, AFL ARF/AFL 1.40% 0% 0% 0% 5.6% 1.4%
AFL (22) 77% AFL 13% AFL 10% 4.2% 28% (auto- (auto-
CFL (63) CFL CFL CFL CFL CFL graft) graft)
71% 13% 16% 1.5% 5%
13 94–95 30/32 AFL 70% 20% 10% 6% 9% 0% 0% 0% 3% 0% 3%
15 90–96 42/52 VWS 55% 19% 26% 12% 9% 0% 0% 0% 7% 2% 0%
49 93–99 373 VWS 96% 1% 8% 0% 2% 2% NS 3% 0%
(suture)
60 96–99 91/104 CFL 63% 21% 16% 1% 15% 0% 0% 0% 0% 0% 1%
106 98–99 145/154 CFL 60% 9% 31% 0% 3% 0% 0% 0% 17% 0% 0%
69 NS 25 CD 32% 36% 32% 12% 0% 24% NS 0% 0% NS NS 0%
68 98–03 234/253 CD 56% 40% 4% 2% 5% 2% 0% 0% 5% 0% 0%
110 NS 74 PD 89.20% 2.70% 8.10% 8.10% 6% 0% 0% 0% 1.4 0% 6.80%
78 99–02 152 SIS 93.40% 2% 4.60% 0.70% 7% 1.30% 0% 0% 0% minimal 0% 0.70%
131 NS 48 ARF (32) 81.2% 18.8% 12.5% 15.5% 0% 12.5% NS NS NS 12.50%
Gore-Tex (ARF) (ARF) (Gore- (ARF) (Gore-
(16) 100% Tex) Ttex)
(Gore-Tex)
17 86–91 108 PTFE 61% 39% 8% 33% NS 0% 25.50% 1% 12% 22.40%
86 89–94 90/141 PTFE 89% 11% 8% 9.6% 0% 0% 5% 0% 0% 2.20%
patch
87 89–98 72/84 PTFE 78% 14% 8% NS 15% 0% 0.90% 0% 11% NS 0.90%
patch
90 86–92 88 Marlex 85.20% 9.10% 5.70% 2.30% 6.80% 0% 0% 0% 0% 2.20% 0% 0%
97 90–00 136/176 Mersilene 95% 5% 5.00% 8.80% 4% 0.50% 0.50% 4% 1% 0% 2.00%
92 NS 64 Prolene 81%* 16%* 3% 5% 5% 2% NS 0% 0% 17% 0% 3%
mesh
151
NS, nonspecified, ARF, autologous rectus fascia; AFL, autologous fascia lata; CFL, cadaveric fascia lata; VWS, vaginal wall sling; CD, cadaveric dermis; PD, porcine
dermis; SIS, small intestinal submucosa; PTFE, polytetrafluoroethylene; PP, polypropylene; PG, polyglactin; TV, transvaginal; RF, rectus fascia; US, ultrasound.
tension utilizing either a sound or cystoscope in the urethra. Rovner et al. (109) described
tying the sling sutures while positioning a cystoscope sheath in the urethra at 20–30° to
the horizontal plane. Nguyen et al. (110) performed a Q-tip test while tying the sus-
pension sutures to simultaneously measure the urethrovesical junction angle. In a
group of 160 patients who underwent vaginal wall sling, utilization of this technique
resulted in no unexpected urinary retention and a recurrent SUI rate of 6.8%. Finally,
there have been formulas based on patient anteroposterior dimensions and body
weight that dictate the amount of suture exposed above the level of the rectus abdominus
fascia (113,114).
The need for postoperative adjustment has been addressed by several investigators.
Choe and Palma et al. reported “tightening” slings by extending the previously tied
suspension sutures using a loop technique (115,116). The initial suture material must
be nonabsorbable to utilize this option in a delayed fashion. In addition, there are
several adjustable sling systems that allow changes in tension postoperatively (117). As
utilization of the sling transitions to patients with severe ISD, tension may be varied
directly with preoperative VLLP.
Outcome Measurements and Results

The outcome measurements and results for multiple pubovaginal sling series are
detailed in Tables 2 and 3. The comparison of results for different studies are compli-
cated by nonstandardized outcome measures. In addition, objective measures such as
postoperative pad test, stress test, or urodynamics are often absent from reports.
Finally, length of follow-up is often insufficient to determine the efficacy of the proce-
dure. Results should be interpreted based on an intent-to-treat analysis. Success rates
calculated from patients available for follow-up may underestimate failure rates. If
clinical follow-up is unavailable, then mail or telephone completion of a standardized
questionnaire is reasonable for determination of patient perception and satisfaction
with the procedure.
Complications
BLADDER INJURY
Bladder injuries are most frequently encountered when passing instruments to the
vaginal incision for sling transfer (Table 3). Patients with prior bladder neck sling
procedures, retropubic suspensions, or pelvic surgery are at higher risk for this compli-
cation because of adhesions of the space of Retzius. Suspicion should be heightened
when instrument passage is difficult. The Foley catheter should be evaluated to check
for blood-tinged urine. In the event of any questions, cystoscopy is the best option to
check for bladder perforation. Recognized injuries are treated with Foley catheter
drainage for 5–7 d.
URINARY RETENTION
The incidence of prolonged urinary retention in large series ranges from 0 to 12%.
As stated by Webster (118), the temporal relationship between the surgery and the onset
of urinary retention should indicate an obstructive etiology. Transvaginal urethrolysis is
the treatment for retention secondary to outlet obstruction. Urethrolysis may consist of
dividing the sling, removal of a small suburethral segment, or sharp dissection of the tissue
underneath the urethra to the level of the endopelvic fascia bilaterally (118–120).
DE NOVO URGENCY/URGE INCONTINENCE

The reported incidence of postoperative new onset urgency is 0–33% The differenti-
ation between isolated de novo urgency/urge incontinence and partial outlet obstruction
is difficult. Urodynamics are necessary to identify those patients requiring relief of
partial bladder outlet obstruction.
VAGINAL EROSION
Erosion of sling material may be heralded by bloody or profuse vaginal discharge or
uncomfortable intercourse for the male partner. In some cases, local therapy with vaginal
estrogen preparations results in successful reepithelialization of the mucosal defect.
Small defects (<5 mm) may be treated conservatively with abstinence, metronidazole
gel, and vaginal estrogen. In cases of larger areas of exposed mesh or failure of conser-
vative management, outpatient excision with elevation of mucosal flaps is generally
successful (121–123).
URETHRAL EROSION/TRANSECTION
Although most urethral erosion and transactions are linked to the use of synthetic
material, this complication has been reported with autologous fascia (124). Tension in
combination with poorly vascularized tissue can produce this complication. Generally,
it may be heralded by obstructive voiding symptoms and urinary tract infections.
OSTEITIS PUBIS/OSTEOMYELITIS
Bony complications may result after suture or anchor placement in the periosteum or
bony cortex, respectively (125,126). Transabdominally placed anchors predated trans-
vaginal ones; therefore, the information reflecting the incidence of complications is
more mature. Goldberg et al. reported a 1.3% incidence of bony-related infections
in suprapubically placed bone anchors (127). Frederick et al. performed a literature
review of 1228 transvaginal bone anchor sling procedures, including 440 from the
authors. The resulting rates of osteitis pubis and osteomyelitis were 0.16 and 0.8%,
respectively (128).
Symptoms consist of pelvic pain, which may be accompanied by a draining vaginal
sinus tract, and vaginal granulation tissue (129). Diagnosis is based on the combined
findings on imaging studies, which may include plain films, magnetic resonance imaging,
computed tomography, and bone scans. Osteitis pubis is managed conservatively with
activity restriction and nonsteroidal antiinflammatory medication. In osteomyelitis, intra-
venous antibiotics are combined with surgical extraction of the anchors and associated
synthetic suture. Usually, destruction of the bone facilitates the removal of the anchors.
When the bony structure remains intact, fluoroscopy and orthopedic instruments are
necessary to facilitate removal.
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11 Complications of Sling Surgery
Suzette E. Sutherland, MD
CONTENTS
INTRODUCTION
INTRAOPERATIVE COMPLICATIONS
POSTOPERATVE COMPLICATIONS
CONCLUSION
REFERENCES
INTRODUCTION
Until recently, abdominal Burch colposuspension was considered the gold standard
for the surgical treatment of stress urinary incontinence (SUI) (1,2). However, the intro-
duction of vaginal sling surgery has been met with great enthusiasm because of comparable
efficacy, but with lower surgical morbidity (3). With the advent of minimally invasive,
tension-free, midurethral vaginal slings (4), colposuspension has been replaced as the
most frequently performed procedure for SUI associated with urethral hypermobility
with or without concomitant intrinsic sphincter deficiency (5). Although the incidence
of significant complications has been low, the learning curve for vaginal sling surgery
still needs to be respected.
With respect to bladder neck slings, autologous fascia (rectus fascia or fascia lata of
the thigh) has been the most commonly used material. Although success rates have been
high (6), potential disadvantages include graft harvest site incision size and morbidity,
inconsistent graft strength, and unavailability of satisfactory fascia. Cadaveric and porcine
materials have been tried but are associated with higher-than-expected intermediate
failures (7–9) because of rapid loss of tensile strength and stiffness over time (10).
Commercially processed cadaveric allografts have been shown to retain intact genetic
material and antigenicity, with associated concerns for potential virus or prion transmis-
sion and tissue rejection (11,12). A variety of synthetic materials have been tried with
pubovaginal sling techniques, many of which have been associated with increased
postoperative voiding dysfunction and tissue erosion rates compared to autologous
fascia. Prevalent functional problems include postoperative voiding dysfunction
(2–37%), urinary retention or incomplete bladder emptying requiring long-term Foley
or self-catheterization (2–8%), persistent urge incontinence (3–30%), and de novo urge
incontinence (7%) (13–15).
Complications associated with the loosely placed, tension-free midurethral slings
appear to be less severe and possibly less common, especially regarding significant
postoperative obstruction and voiding dysfunction (0.9–5%) requiring subsequent

159
sling revision (1.9–5%). Although rare, other reported complications include bleeding
(0.9%), intraoperative bladder perforation (4.9–9%), recurrent urinary tract infection
(1–10.9%), vaginal or urethral mesh erosion (0.9–1%), and nerve injury (0.9–3%)
(16–19).
Bleeding/Hematoma Formation
According to the Food and Drug Administration’s MAUDE (Manufacturer and
User Facility Device Experience) database (20), life-threatening bleeding associated
with 33 major vessel injuries has resulted in two known deaths following retropubic
tension-free vaginal tape (TVT) procedures. Other self-reported vascular complications
during TVT trocar passage include injuries to the inferior epigastric, obturator, external
iliac, and femoral vessels. A few case reports described retropubic hematomas requir-
ing blood transfusions and catastrophic bleeding requiring surgical intervention
(21–23).
It has been suggested that the technique associated with the TVT procedure, specifi-
cally passage of the retropubic trocars in a down-up motion from the vaginal incision to
the suprapubic incision, provides only a small zone of surgical safety and potentially
less control within that zone during needle passage as compared to its sling predecessors,
which utilize a finger-guided up-down retropubic needle passage for sling placement.
Detailed anatomical cadaveric dissections demonstrate the effect within the retropubic
space of small deviations laterally or cephalad during upward passage of the trocar. The
vulnerable vessels (the obturator, inferior epigastric, superficial epigastric, and external
iliac) were reported to be 3.2, 3.9, 3.9, and 4.9 cm from the path of ideal trocar passage,
respectively (24).
Regardless of the technique utilized for trocar passage, instrument control during
blind retropubic passage is of utmost importance to prevent such iatrogenic injuries.
Nevertheless, the overall incidence of such bleeding complications is still low. In a
large cohort of 1455 TVT patients, Kuuva and Nilsson reported 0.1% incidence of
major vessel injuries (25). In other large series, the incidence of significant retroperi-
toneal bleeding was between 0.9 and 2.5% (18,26), with urgent surgical intervention for
hemostasis performed in 0.5% (27). The incidence of significant hematoma formation
requiring subsequent surgical evacuation was 0.7% (17,18,25).
Although similar retroperitoneal bleeding during other sling procedures can still
occur, more serious large-vessel injuries have yet to be described. This may be partly
due to the overall smaller number of non-TVT retropubic slings performed as they
were introduced significantly later to the surgical market. In one retrospective review
of 140 suprapubic arc (SPARC) cases, a mean reduction in hematocrit of 7.1%
(range 1 to 14%) was seen on postoperative day 1. Despite a reported mean intra-
operative blood loss of 170 cc (range 50 to 700 cc), 6 (4.3%) patients required some
degree of immediate resuscitative care, with 4 (2.8%) of these requiring blood trans-
fusion (2–6 U packed red blood cells). Retropubic hematoma formation requiring
percutaneous drainage for symptomatic relief was also noted in 1 patient (28). In
another larger review of 445 SPARC slings, only one case of significant retroperi-
toneal hematoma requiring blood transfusion was described. Only one other patient
required postoperative blood replacement, but underwent a concomitant cystocele
repair (29).
Chapter 11 / Complications of Sling Surgery 161
Fig. 1. TVT mesh embedded in mucosa. (Courtesy of Dr. Howard B. Goldman, Cleveland Clinic
Foundation, Cleveland, OH.)
Visceral Injuries
BLADDER PERFORATION
Although reported rates of bladder perforation during retropubic midurethral sling
procedures reach 25%, more recent large, multicenter trials observed much smaller rates
of 3.8–6.7% (17,25,26,29). Increasing the risk for such intraoperative injury is prior anti-
incontinence or pelvic surgery. In a study involving more than 2500 patients, Tamussino
et al. reported a twofold increase in bladder injury rates in patients with a previous
history of incontinence surgery as compared to surgically naive patients (4.4 vs 2%)
(30). When recognized and corrected at the time of trocar perforation, conservative
management with short-term (3–5 d) catheterization can avoid potential long-term
sequelae (31). Careful inspection with cystoscopy must be performed intraoperatively so
an inadvertent bladder perforation is not missed. The need for familiarity and expertise
with cystoscopy must be emphasized.
With the newer transobturator approaches to midurethral sling placement, the theo-
retical risk of visceral perforation is eliminated by remaining below the endopelvic fascia
with needle trocar passage. In a review of 107 inside-out transobturator tape procedures,
no such bladder injuries were reported (32). A review of the experience within my insti-
tution of over 300 outside-in transobutrator Monarc procedures revealed the same (33).
Missed bladder perforations with subsequent intravesical placement of mesh present
a problem (Fig. 1). Although few, various examples have been reported. Missed bilat-
eral bladder perforation with the Sabre (bioreabsorbable) pubovaginal sling was found
10 mo after placement and associated with chronic intractable pelvic pain and SUI (34).
Volkmer et al. reported two intravesical slings following TVT placement (35). Complete
sling removal by an open suprapubic approach has generally been advocated. However,
Hodroff et al. took a minimally invasive transurethral approach to intravesical sling
removal with the use of the holmium laser. In three cases, the laser was used to ablate
Fig. 2. Holmium laser of mesh puncture site at bladder neck. (Courtesy of Dr. Andrew Portis, Metro
Urology, St. Paul, MN.)
the mesh at a point slightly deeper than mucosa to allow the mucosa to grow over the
puncture sites (Figs. 2 and 3). The excised mesh tape was then removed from the bladder
transurethrally with a flexible grasper (Fig. 4). There were no bladder perforations
during the laser intervention, and complete reepithelialization was seen cystoscopically
in all cases at 1 mo (36).
BOWEL PERFORATION
Although few reports of bowel perforation during sling surgery have appeared in the
literature (27–29,37,38), the potential seriousness of such an iatrogenic injury cannot be
overlooked. According to the US Food and Drug Administration’s MAUDE database
(20), six deaths have occurred as a result of unrecognized bowel injury following min-
imally invasive retropubic sling procedures. Such complications indicate the importance
of proper patient selection as well as the need for vigilant postoperative monitoring of
side effects. Previous pelvic transperitoneal procedures may result in bowel adhesions
within the retropubic space, increasing the risk of inadvertent visceral injury during
“blind passage” of the trocars. Keeping the location of the trocars snug along the posterior
aspect of the pubic symphysis during passage may help to reduce this risk. Any symptoms
of pelvic or abdominal pain, bowel obstruction, fever, or certainly suspicious drainage
from the suprapubic puncture sites should be investigated promptly. Computed tomographic
imaging may prove helpful, but with a high index of suspicion, emergent exploratory
laparotomy is recommended for complete mesh removal and repair.
POSTOPERATIVE COMPLICATIONS
Postoperative Voiding Dysfunction
URINARY RETENTION
The incidence of urethral obstruction after vaginal sling placement is reportedly
1.9–5% (19,39). It is most often identified by postoperative changes in voiding and type of
Fig. 3. Puncture site in bladder after mesh removed and holmium laser treatment of mucosa. (Courtesy
of Dr. Andrew Portis, Metro Urology, St. Paul, MN.)
Fig. 4. Excised mesh freely floating in the bladder. Remnant removed transurethrally with flexible
grasper. (Courtesy of Dr. Andrew Portis, Metro Urology, St. Paul, MN.)
incontinence. The diagnosis is usually obvious in a patient with prolonged postoperative

urinary retention or with incomplete bladder emptying in whom unobstructed voiding
was experienced preoperatively. De novo urge incontinence with postural voiding (leaning
forward to void) is the more common presentation. In addition, cystoscopy can play a
vital role by revealing fixed retropubic urethral angulation or by visually confirming
urethral obstruction.
Fig. 5. Obstructing mesh placed too distally. Scapel indicates appropriate midurethral position.
(Courtesy of Dr. Oscar Aguirre, Urogynecology Associates of Colorado, Denver, CO.)
To avoid long-term complications, vigilant observation for signs of obstruction is

needed. When recognized early within the first few postoperative weeks, a simple sling
adjustment can be made by loosening the sling via the midurethral incision. As significant
tissue ingrowth of the mesh would not have yet occurred, the sling is still movable within
the tissues. Following full tissue incorporation of the mesh, however, loosening is no longer
an option, but a simple suburethral sling incision has been described with good results.
In the majority of cases, this maneuver provides relief of obstruction from excess sling
tension under the urethra without return of SUI (19,39). More significant and complex
obstruction may require formal urethrolysis (vaginal, suprameatal, or retropubic approach)
with or without tissue interposition (i.e., Martius fat pad) to reduce the risk of recurrence.
Following referral for postoperative obstructive voiding after TVT placement, a few
cases were associated with an unusual complaint of a retrograde trajectory of the uri-
nary stream causing buttock cheek wetting during voiding. In these cases, the sling was
tightly located under the distal quarter of the urethra rather than in the midurethral posi-
tion (Fig. 5). Following sling incision, one patient underwent subsequent abdominal
paravaginal repair and repeat TVT for treatment of prolapse and recurrent severe
incontinence. At the time of retropubic dissection, no mesh was located in the space of
Retzius. Further exploration found that the prior tape had been passed anterior to the
symphysis (O. Aguirre, Director, Urogynecology Associates of Colorado, Denver,
personal correspondence).
DE NOVO URGENCY, FREQUENCY, URGE INCONTINENCE
De novo overactive bladder (OAB) symptoms and urge incontinence are known risks
of anti-incontinence procedures, with a reported incidence of 3–24% after bladder neck
sling procedures and 6.1–12.5% following retropubic midurethral sling procedures
(TVT/SPARC) (25,29,40– 43). This compares to a 5–32% rate of de novo bladder
overactivity following the previous gold standard, the retropubic colposuspension.
It has been suggested that, because the TVT is placed without tension at the level of
the midurethra, it should result in a lower rate of voiding dysfunction, de novo urge
incontinence, and OAB symptoms. Appropriate intraoperative sling tensioning, however,

is key. Albeit less frequent, postoperative voiding dysfunction and de novo bladder over-
activity can still be experienced after retropubic midurethral slings (4.3–10% and 6–15%,
respectively) (18,44–46).
Even fewer postoperative voiding difficulties have been described with the newer
transobturator slings. In a retrospective comparison of retropubic vs transobturator
slings, Ansquer et al. noted an overall 40% rate of postoperative voiding difficulties
following retropubic slings, with only 8% extending longer than 1 wk; this compared
to 8% overall and 0% beyond 1 wk for their transobturator slings (47). Although the
U-shaped placement of retropubic approaches can cause kinking of the urethra, the
relative horizontal positioning through transobturator placement decreases this risk of
overcorrection. It has also been hypothesized that mesh in the retropubic space may
cause direct compression and irritation on the lateral bladder walls during filling,
thereby leading to de novo symptoms of bladder overactivity. The possibility of this is
eliminated with the transobturator method, by which both trocar passage and mesh
placement remain below the endopelvic fascia.
Resolution of Overactive Bladder Symptoms/Urge Incontinence

Previous studies have shown that 50–74% of patients with mixed incontinence are
cured of their urge incontinence after appropriate surgical support of the bladder neck
(48–51). In addition, as many as 57% of patients with preoperative OAB symptoms
have experienced complete resolution of these symptoms following a midurethral TVT
and no longer required anticholinergic therapy (44,52). Theoretically, a severely weak
urethral sphincter mechanism associated with intrinsic sphincter deficiency results in
funneling of the proximal urethra. When bladder filling occurs, or when intraabdominal
pressure increases, urine enters the proximal urethra through the weak, open sphincter,
producing sensory stimulation through a urethral-bladder reflex, which leads to reflex
contractions of the bladder. Eliminating the initial unwanted leak of urine into the prox-
imal urethra through improved suburethral support may abolish such reflex-initiated
symptoms of OAB and urge incontinence (50,53,54).
Vaginal and Urethral Erosion

Historically, the concern associated with the use of synthetic materials has been that
of postsurgical infection and tissue erosion. Clearly, with the use of “traditional” tight
sling techniques, the risk of urinary tract erosion increases when synthetic materials are
used. Urethral erosion, defined as sling material entering the urethral lumen, is most
commonly thought to be caused by excess sling tension under the urethra. Another possi-
bility, however, can be technical error, such as inadvertent urethral entry or dissection in
a plane too close to the urethra. Compromising the thickness of the suburethral tissue
may result in urethral devascularization.
Patient factors, such as urethral atrophy with a compromised blood supply because
of prior radiation therapy or estrogen deficiency may also be implicated. Iatrogenic factors,
such as traumatic urethral catheterization or forceful urethral dilation and sagittal rotation
in attempts to loosen a sling, have also been reported as possible contributors to sling
erosion (55,56). A few cases have been known to occur by inadvertent passage of the
trocars through the urethra at the time of surgery. In cases of urethral erosion, complete
sling excision has been advocated.
The hypothesis, however, surrounding the potential generation of a synthetic-induced

foreign body inflammatory reaction, subsequently resulting in higher risk of infection,
erosion, and perhaps fistula formation, has yet to be proven in a comparative trial
with nonsynthetic materials. To date, there are few series reported in the literature of
urethral or vaginal mesh erosion. A meta-analysis performed by the American Urological
Association Clinical Guidelines Panel of the literature on surgical management of
female SUI using synthetic slings identified a 2.7% rate of urethral erosion and a 0.7%
rate of vaginal extrusion (42). The conditions, however, may be underidentified or
underreported as others have reported such mesh erosion rates of various synthetic sling
materials at up to 23% (57–64). Differences in erosion rates, clinical characteristics, and
appropriate management are clearly related to surgical technique and the material of
synthetic mesh utilized. With the introduction of loosely woven, monofilament mesh
into the world of anti-incontinence sling surgery, healing-related complications have
decreased considerably. The large pore (>75 R) polypropylene slings provide improved
tissue ingrowth, resulting in better integration of the sling with the host tissue, and limited
secondary inflammation, infection, or erosion (65).
The first synthetic slings made of woven polyester and other tightly woven material
were known to erode 15 times more often than nonsynthetic slings (autologous, allograft,
and xenograft slings). In one multicenter series, 34 women with woven polyester slings
treated with pressure-injected bovine collagen (ProteGen) were referred for problems
with erosion, infection, or pain at a mean of 8 mo following sling placement. In this
cohort of 34 patients, 7 (21%) had isolated urethral erosion, 17 (50%) had vaginal
extrusion, and 6 (18%) were associated with urethrovaginal fistulas. All slings required
removal (66). Owing to this high complication rate, ProteGen was recalled in 1999 and
is no longer available in the United States.
Silicone-coated polyester slings have not performed any better, with a 20% vaginal
exposure rate noted at 6 and 10 mo in a single series (57). Another study looking at the
use of silicone slings (silicone rubber reinforced with woven polyethylene) was halted
early as five of the seven slings resulted in erosion, infection, and sinus tract formation
(67). A fusion-welded, thermally bonded, nonwoven, nonknitted polypropylene mesh
(Uratape/Obtape, Mentor-Porges, Le Plessis-Robinson, France) experienced a 13.8%
rate of vaginal mesh exposure (68). The poor incorporation of the sling was thought to be
associated with unique characteristics of the mesh. Specific modifications to this mesh
caused a shrinkage of the pore size (50 R), leaving it smaller than the minimal 75 R
recommended to ensure adequate macrophage and leukocyte infiltration as well as
vascular and tissue ingrowth (69).
An interesting case of simultaneous urethral erosion of a ProteGen bladder neck sling
and midurethral TVT with intervening urethrovaginal fistula has also been described
(70) (Figs. 6 and 7). The TVT was placed after the bladder neck ProteGen sling in an
attempt to treat persistent SUI. Removal of all mesh and repair of the urethrovaginal
fistula were successfully performed transvaginally. A new pubovaginal sling of auto-
logous rectus fascia was placed over a Martius fat pad, with successful results reported
at 3-mo follow-up.
Vaginal mesh exposure, or extrusion, is most commonly detected by the patient’s
sexual partner during intercourse (scratching sensation) or thorough vaginal inspection
during postoperative physical examinations. Many women with small areas of vaginal
mesh extrusion are asymptomatic, but some extrusions have been associated with
symptoms of minimal, yet persistent, vaginal discharge or spotting, vaginal or pelvic
Fig. 6. Eroded ProteGen sling at bladder neck (background) and eroded polypropylene sling at
midurethra (foreground). (Courtesy of Dr. Howard B. Goldman, Cleveland Clinic Foundation,
Cleveland, OH.)
Fig. 7. Exposed vaginal mesh with urethrovaginal fistula seen on vaginoscopy. (Courtesy of Dr.
Howard B. Goldman, Cleveland Clinic Foundation, Cleveland, OH.)
discomfort, recurrent urinary tract infection, or, in the case of concomitant infection,
symptoms of fever or malaise (66).
In the past, recommendations were made to completely remove any eroded synthetic
material. This is appropriate when the erosion involves the bladder or urethra (67,71, 72).
However, in cases limited to extrusion of loosely woven polypropylene mesh within the
vagina, conservative management or observation may prove successful. Such was
reported in four SPARC cases of small (<1 cm) polypropylene mesh extrusion, with com-
plete spontaneous reepithelialization over the mesh following 3 mo of observation (73).
The large interstices associated with loosely woven polypropylene mesh allow for tissue
ingrowth and integration of the graft into the surrounding tissues. Some recommend the
addition of local estrogen therapy to augment the healing process. This conservative
management may also prove successful with autologous and allograft materials. However,
other, more tightly woven, synthetic materials, such as polyester and silicone slings,
should be removed entirely, even in cases of vaginal extrusion, because it is unlikely that
epithelialization over these materials will occur (58,61, 63–67). In the case of larger or
nonhealing, uninfected extrusion, there is no need for entire mesh removal. Simple
exposed mesh excision and covering with a healthy vaginal flap is recommended.
With respect to the cause of vaginal mesh extrusion, one theory suggests that sub-
clinical infection of sling material impedes wound healing, thereby resulting in wound
separation, presenting as erosion (66). With this in mind, the routine use of perioperative
prophylactic antibiotics and a thorough preoperative vaginal scrub was advocated,
with a significant reduction in subsequent vaginal mesh extrusion appreciated (74).
Tightly woven meshes have been associated with a higher incidence of vaginal extrusion,
possibly because of incomplete incorporation and subsequent rubbing against the host
tissue, causing undue friction and chronic mechanical irritation to the tissues (67,68).
Another problem may be related to surgical technique (75). Excessive thinning of the
vaginal mucosa, resulting in devascularization during dissection, will likely increase the
risk of subsequent mesh exposure. Appropriate thickness of the vaginal wall flap must
be maintained to ensure tissue viability and ensure proper healing.
Infection/Abscess
An interesting case of bladder wall abscess following intravaginal slingoplasty (IVS)
midurethral sling placement was reported that was diagnosed at 8 mo after evaluation
for persistent unilateral lower abdominal pain (76). In a series of over 1500 midurethral
sling procedures using different types of synthetic mesh (TVT, SPARC, IVS, Uretex,
Monarc), only four cases of abscess formation were reported, and all were seen with the
IVS mesh (77). Bafghi et al. noted a 7.4% rate of retropubic space abscess formation
following IVS mesh use and suggested small mesh pore size associated with the IVS
product impedes effective host immune activity (78). Similarly, in an in vivo comparison
study of three different polypropylene mesh slings (Monarc-type I mesh, pore size 1 mm2;
Obtape-type II mesh, pore size < 75 R; IVS-type III mesh, pore size < 75 R), Slack et al.
noted increasingly greater inflammation and less fibrous tissue ingrowth and mesh
incorporation with both the Obtape and IVS because of their closely spaced filaments and
smaller pore size (65). Other in vivo studies with similar findings have likewise supported
the utilization of large-pore (>75 R), type I mesh for surgical implantation (79,80).
A review of infectious complications unique to the transobturator approach included
an infected hematoma near the obturator foramen (81), a small thigh abscess with associated
superficial thrombophlebitis (32), and a large thigh abscess tracking from the obturator
Fig. 8. Large left thigh abscess (see air within tissue) following transobturator sling procedure.
(Courtesy of Dr. Howard B. Goldman, Cleveland Clinic Foundation, Cleveland, OH.)
externus distally along the gracilis and adductor magnus muscles halfway to the knee
(Fig. 8) (82). All responded to surgical drainage, debridement, and appropriate anti-
microbial therapy.
Bone Anchors
The use of bone anchors in an attempt to stabilize the mesh to the pubic bone does
not seem to result in improved efficacy over existing nonanchoring techniques but carries
with it a risk of osteomyelitis. Cases of both osteomyelitis and retropubic abscesses have
been reported following bone-anchoring sling procedures (83,84). A 10-yr review of the
literature done in 2001 yielded 6 cases of osteomyelitis in 1018 bone anchor procedures,
for an overall incidence of 0.6% (85). However, in a more recent multicenter study
involving major referral centers in the United States, a higher osteomyelitis incidence
of 1.3% was reported following bone-anchored bladder neck suspension (87). Although
the most common offending organism in such infections has been Staphylococcus
epidermis (83), a more serious case of pelvic actinomycosis following placement of a
bone-anchored sling has been reported (87). Appropriate treatment of actinomycosis
infection requires prolonged antibiotic for 6 –12 mo. In spite of the rare incidence of
postoperative osteomylitis, each case incurs substantial morbidity and requires aggres-
sive multimodal medical and surgical treatment to include exploratory laparotomy,
anchor removal, bony debridement, and prolonged parenteral antibiotics (83).
CONCLUSION
The tension-free midurethral sling has rapidly become the most frequently performed
anti-incontinence procedure for women, having surpassed the traditional abdominal
Burch colposuspension. The advent of synthetic slings brought specific advantages,
such as eliminating the need for fascial graft harvest, decreased morbidity, ease of use,
and comparable efficacy to other anti-incontinence procedures. Loosely woven mono-
filament material such as polypropylene has gained popularity by demonstrating good
tissue ingrowth with limited inflammatory reaction, thereby reducing postoperative
healing complications.
Despite these advantages, significant complications associated with bleeding, visceral
perforation, postoperative voiding dysfunction, and mesh erosion have occurred following
minimally invasive sling surgery. However, the incidence of these complications seems
to be on the decline according to more recent reports from larger series. This may be
due to the development of improved surgical techniques, advances in synthetic materials,
and/or the learning curve of the procedure. Nevertheless, such complications can result
in devastating consequences and underscore the importance of proper patient selection,
surgical precision, and vigilant postoperative care.
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12 Pharmacological Therapy
for Overactive Bladder
H. Mallory Reeves, MD, Eric S. Rovner, MD,

and Alan J. Wein, MD
CONTENTS
INTRODUCTION
UROSELECTIVITY
SPECIFIC AGENTS
CONCLUSION
REFERENCES
INTRODUCTION
Multiple classes of drugs, drug therapies, and other pharmacological agents are
potentially useful to decrease bladder contractility or decrease sensation and thereby
treat overactive bladder (OAB) (see Table 1), but few have been utilized clinically (1).
Antimuscarinic agents are the only oral class of drugs that have demonstrated proof of
concept in managing this disorder and remain the most commonly prescribed treatment.
Since Diokno and Lapides described the properties and application of oxybutynin
chloride in the therapy of urinary dysfunction, antimuscarinic therapy has remained the
mainstay of therapy for detrusor overactivity and, more recently, the symptom complex
known as OAB (2,3). According to the International Continence Society (ICS), OAB is
classified as a symptom syndrome and is characterized by urgency, with or without
incontinence and sometimes with frequency and nocturia (4). These symptoms are
suggestive of detrusor overactivity (that is, urodynamically demonstrable IVCs) but can
be attributed to other forms of voiding or urinary dysfunction as well.
Despite years of basic science and clinical research, the optimal pharmacotherapy
for OAB has not yet been identified. The ideal or optimal pharmacological treatment for
OAB would be universally efficacious in relieving or curing the symptoms of OAB
completely without side effects, adverse events, effects on other organs, or interactions
with other drugs; would have no contraindications; and finally, could be administered
conveniently, easily, and inexpensively. Unfortunately, none of the existing or currently
emerging agents meet all of these criteria. Advancements in the understanding of the
pathophysiology of OAB and the multiple, nonautonomic mechanisms that may respon-
sible for the clinical manifestations of the condition promise to provide a whole new array
of pharmacological options (1,5). Other future potential (and in some cases theoretical)
therapies that are not yet near clinical application include genetic manipulation; tissue
engineering; characterization and manipulation of purinergic pathways, including
177
178 Part IIB / Overactive Bladder
Table 1
Potential Pharmacological Therapy for OAB
Anticholinergic agents
Musculotropic relaxants
Calcium antagonists
Potassium channel openers
Calcium channel modulators
Prostaglandin inhibitors
G-Adrenergic agonists
F-Adrenergic antagonists
Tricyclic antidepressants
Dimethyl sulfoxide (DMSO)
Phosphodiesterase inhibitors
Modulators of:
Serotonin
Nitric oxide
Calcitonin gene-related peptide
Vasoactive intestinal polypeptide
Neuropeptide Y
Endothelins
Bradykinins
GABA
Enkephalins
Nociceptin
Polysynaptic inhibitors
Tachykinin receptor antagonists
Purinergic antagonists
Source: Adapted from ref. 1.
modulation of the P2X receptor; phosphodiesterase inhibitors; tachykinin receptor

antagonists (neurokinin antagonists); and alteration of central dopaminergic, GABA-ergic,
and enkephalinergic pathways (6). However, because of their limited clinical utility at
present, these therapies are not considered further here.
For many years, widely available and well-studied agents for OAB in the United
States included oxybutynin, tolterodine, propantheline, dicyclomine, and hysocyamine.
Several new oral antimuscarinic agents have become available. This chapter attempts to
highlight some of the existing, clinically available therapies for the pharmacological
treatment of OAB.
UROSELECTIVITY
Most of the neurohumoral stimulus for physiological bladder contraction, both
volitional and involuntary, is from acetylcholine (ACh)-induced stimulation of auto-
nomic, postganglionic parasympathetic muscarinic cholinergic receptor sites on bladder
smooth muscle. The majority of current pharmacotherapy for OAB is therefore directed
toward the muscarinic receptor. Because autonomic innervation, receptors, and receptor
content are ubiquitous throughout the human body’s organ systems, there are no
agents in clinical use that are purely selective for action on the lower urinary tract, that
is, uroselective. Thus, the majority of side effects attributed to drugs facilitating bladder
Chapter 12 / Pharmacological Therapy for Overactive Bladder 179
storage or emptying are the collateral effects on organ systems that share some of the
same neurophysiological or neuropharmacological characteristics as the lower urinary
tract. The problems are (1) how to affect bladder function without interfering with the
function of other organ systems (uroselectivity) and (2) how to eliminate overactivity
without disturbing normal micturition (7).
In general, drug therapy for all lower urinary tract dysfunction is hindered by a lack
of uroselectivity, which may explain problems with efficacy and tolerability in OAB
pharmacotherapy (1,8). Many of the drugs described are highly effective agents;
however, dose-dependent systemic adverse effects can often limit the physician’s
ability to exploit a given drug’s therapeutic effects. Escalating dosages may lead to
increasing unwanted effects on other organ systems, which may result in not reaching
a therapeutic dose. Nevertheless, improvements in uroselectivity can be approached
in a number of ways: (1) receptor selectivity; (2) organ selectivity; and (3) alterations in
drug delivery, metabolism, and distribution. Receptor selectivity may be of little use
unless the receptor is not expressed in other organs or unless a receptor subtype exists
that is specific for the organ under treatment or its neurological connections.
Organ specificity indeed may be the “magic bullet” of drug therapy. The ideal organ-
selective drug for the lower urinary tract would exert desirable effects only on the bladder
and/or urethra thus eliminating side effects. Theoretically, the concept of organ speci-
ficity is attractive, but practically and clinically it is very difficult to achieve. Alternate
drug delivery systems may be helpful by increasing the target concentration of an
agent (e.g., intravesical therapy) or by changing the metabolism of a drug to lower the
concentration of a metabolite particularly productive of side effects. Certain drugs or
their metabolites may be prevented from gaining access to a potentially troublesome
site of activity (through the blood-brain barrier, e.g.) either by virtue of their innate
characteristics or by alteration.
Given our current state of imperfection in this area, it is important to distinguish
potential laboratory effects from real clinical effects, both beneficial and adverse.
Commercial or marketing claims of superiority of one agent based on organ or receptor
selectivity or alternative mechanisms of drug delivery should be subject to strong scrutiny
and be supported by both laboratory and clinical data. In the absence of such data, these
claims have little scientific merit and are more theoretical than real.
SPECIFIC AGENTS
Relatively Pure Antimuscarinic Agents
Antimuscarinic agents such as atropine inhibit normal and involuntary contractions
(IVCs) of the bladder (9–11). Generally, volume to the first IVC increases, the amplitude
of the IVC decreases, and the total bladder capacity increases (12). Anticholinergic
agents do not significantly alter bladder compliance in normal individuals or in those
with detrusor overactivity in whom the initial slope of the filling curve on cystometry is
normal prior to the IVC (12). The effect of pure antimuscarinics in patients who exhibit
only decreased compliance has not been well studied.
Although it is widely accepted that there is no sacral parasympathetic outflow to the
bladder during normal filling, antimuscarinic drugs increase and cholinomimetic and
anticholinesterase inhibitors decrease bladder capacity (13). It is during this phase of the
micturition cycle (filling and storage) that antimuscarinic agents are thought to exert
their favorable effects.
Andersson and Yoshida have proposed that one potential mechanism by which these
drugs act during bladder filling to reduce detrusor overactivity is via an effect on afferent
activity (14). Antimuscarinic drugs seem to affect the sensation of urgency during filling,
suggesting ongoing ACh-mediated stimulation of detrusor tone. Furthermore, a basal
release of ACh has been demonstrated from nonneuronal, perhaps urothelial, as well
as neuronal sources in the human bladder, which may be related to stretching of the
bladder wall as it fills (15). If this is the case, agents that inhibit ACh release or activity
during bladder filling could contribute to bladder relaxation or maintenance of low
bladder tone during this phase of the micturition cycle with a consequent decrease in
symptomatology unrelated to the occurrence of an IVC.
The designations M1 through M5 are used to describe the pharmacological and
molecular subtypes of muscarinic ACh receptors (16). Human urinary bladder smooth
muscle contains a mixed population of M2 and M3 subtypes, with a predominance of M2
receptors (80% of the total muscarinic receptor population) (17). Although the minor
population of M3 receptors is believed primarily responsible for mediating bladder
contraction (18), experimental evidence suggests that M2 receptors are also involved in
bladder contractility in some species and in certain types of lower urinary tract dysfunc-
tion (19–23). As mentioned, available antimuscarinic agents are limited by a lack of
selectivity that is responsible for the classic anticholinergic side effects. Although
M3-selective agents have the potential to eliminate some of these side effects, the M3
receptors in lower urinary tract tissues appear identical to those elsewhere in the body
(24). However, if some as-yet-undefined heterogeneity among M3 receptors in various
tissues is uncovered, then it may be reasonable to postulate a “uroselective” agent acting
only on the muscarinic receptors in the lower urinary tract.
The potential side effects of all antimuscarinic agents include inhibition of salivary
secretions (xerostomia or dry mouth); blockade of the sphincter muscles of the iris
and the ciliary muscle of the lens to cholinergic stimulation (blurry vision); tachycardia;
drowsiness; cognitive dysfunction; inhibition of gut motility (constipation); and inhibition
of sweat gland activity. Agents that possess ganglionic-blocking activity may also cause
orthostatic hypotension and erectile dysfunction at the high doses generally required for
manifestation of nicotinic activity. In general, antimuscarinic agents are contraindicated
in patients with narrow-angle glaucoma and should be used with caution in patients with
significant bladder outlet obstruction.
ATROPINE SULFATE (DL-HYOSCYAMINE)

Atropine sulfate (DL-hyoscyamine) is rarely used to treat OAB because of its adverse
systemic effects (19). The pharmacologically active portion of the racemic mixture of
atropine is L-hyoscyamine. This agent and hyoscyamine sulfate are reported to produce
anticholinergic actions and side effects similar to other belladonna alkaloids.
Hyoscyamine sulfate is also available in a sublingual formulation. The formulation
offers a theoretical advantage regarding absorption and metabolism, but controlled studies
of its effects on bladder hyperactivity are lacking (19).
PROPANTHELINE BROMIDE
Propantheline bromide is a nonselective antimuscarinic agent that, as a quaternary
ammonium compound, has low and varying biological availability. It is metabolized
quickly to inactive metabolites. The usual adult dose is 15–30 mg every 4–6 h, but titration
is often necessary, and higher doses sometimes are required. Little evaluable data on the
drug’s effectiveness in treating OAB is available. The Agency for Health Care Policy and
Research (AHCPR) Urinary Incontinence Guideline Panel reviewed five randomized
controlled trials (RCTs) of propantheline (25). Of the total number of patients enrolled,
82% were female. Reports of cure ranged from 0 to 5% (all figures refer to percentage
effect on drug minus percentage effect on placebo), reductions in urge incontinence ranged
from 0 to 53%, side effects ranged from 0 to 50%, and dropouts ranged from 0 to 9%.
TOLTERODINE TARTRATE
Developed specifically for treatment of OAB, tolterodine tartrate is not muscarinic
receptor subtype specific but demonstrates some selectivity for the bladder over salivary
gland in certain experimental models (26–28). Clinically, it seems to have a favorable
side-effect profile not only on dry mouth but also on bowel and central nervous system
(CNS) effects (17). The immediate-release (IR) formulation of tolterodine is available
in 1- and 2-mg tablets and is dosed twice daily. The drug is primarily metabolized by
the liver, with the primary hepatic metabolite possessing near-equivalent antimuscarinic
potency.
A number of clinical trials have evaluated the efficacy and tolerability of tolterodine.
Stahl and colleagues first studied the effect of a single 6.4-mg dose on bladder and
salivary function (29). At 5 h after administration, the effects on the bladder were
maintained, but no significant effects on salivation were detected. Stimulated salivation
was inhibited only near the time of peak serum levels.
Appell reported on a pooled analysis of 1120 patients in whom tolterodine (1 or 2 mg
twice daily) was compared with IR oxybutynin (5 mg three times daily) or placebo (30).
Compared with placebo, both active drugs significantly decreased the number of incon-
tinent episodes and micturitions occurring in 24 h and increased the volume voided per
micturition. Mean episodes of urge urinary incontinence (UUI) decreased from 40 to
60%, and frequency of urination decreased by approx 20% compared to baseline. The
2-mg dose of tolterodine (twice daily) and the 5-mg (three times daily) dose of oxybutynin
were equally efficacious, but tolerance was significantly better with tolterodine when
adverse events such as dry mouth (frequency and intensity), dose reductions, and patient
withdrawals were considered.
Chancellor and Freedman conducted a large double-blind study comparing tolterodine
(2 mg twice daily) with placebo (31). Tolterodine reduced urge incontinence episodes
and produced significant reductions in micturition frequency and pad use compared
with placebo. Of tolterodine-treated patients, 2% reported severe dry mouth, and 10%
reported moderate dry mouth, compared with 0 and 2%, respectively, of placebo
patients. Mild dry mouth was reported by 18% of drug-treated patients and by 6% of
placebo-treated patients. Constipation was reported by 7% of tolterodine recipients and
4% of placebo recipients. The profile and frequency of other adverse events in the two
treatment groups were similar. CNS adverse events were not significantly different
between the tolterodine and placebo groups.
Kreder et al. studied the effects of tolterodine IR in patients with pure UUI vs those
with urge-predominant mixed urinary incontinence (UI) (32). At the end of the 16-wk
trial, there was no statistical difference between the two groups with respect to reductions
in total UI episodes, patient-reported cure rate, or reduction in pad use (67 vs 75%, 39
vs 44%, and 21 vs 27%, mixed UI vs pure UUI, respectively; all difference not significant
[NS], p < 0.05). The reported incidence of side effects in this trial was similar to that
previously reported in other studies.
Tolterodine is available in an extended-release (ER), once-daily formulation. The

pharmacokinetic profile of the ER formulation (tolterodine ER) and dosing can be seen
in Tables 2 and 3, respectively. Von Kerrebroeck and colleagues compared this agent to
the twice-daily formulation and placebo as part of the largest trial ever performed in
patients with OAB (33). In this pivotal study, the median number of UI episodes in
patients receiving the once-daily formulation, the twice-daily formulation, and placebo
were reduced by 71, 60, and 33%, respectively. Both preparations were statistically
superior to placebo, and the once-daily preparation was statistically more effective
than the twice-daily preparation using this outcome indicator. Statistically significant
improvements in all other micturition diary variables were recorded for both formulations
over placebo. The incidence of dry mouth was 23% for once-daily tolterodine, 30% for
twice-daily tolterodine, and 8% for placebo. Khullar et al. compared tolterodine
ER with placebo in an 8-wk, double-blind, randomized, controlled trial involving
854 women with urge-predominant mixed UI. Tolterodine ER significantly reduced
weekly UUI episodes (12.3) and daily micturition frequency (2.1) and increased
the median volume voided/micturition (+34 mL) compared with placebo (8.0, 1.3,
and +19 mL, respectively; p < 0.0001) (34).
Furthermore, the overall efficacy of tolterodine ER does not seem to be markedly
different between those who have severe UI at baseline compared to those who have
less-severe UI. In a post hoc analysis from the Von Kerrebroeck study (33), Landis et al.
(35) compared those with severe UI (<20 episodes of UI per week) to those with less-
severe UI (<21 episodes of UI per week) and found that the improvement in UI episodes
was no different between the two groups (71 vs 68%, severe vs nonsevere; NS, p < 0.05).
Using an evidence-based approach, the pharmacology subcommittee from the
Proceedings of the Third International Consultation on Incontinence (ICI) recommended
tolterodine for the treatment of UUI (36).
TROSPIUM CHLORIDE
Trospium chloride is an antimuscarinic agent with atropine-like effects. It possesses
no selectivity for muscarinic receptor subtypes M1–M5. In contrast to other agents, it
contains a highly charged quarternary ammonium group that may limit penetration across
the blood-brain barrier (37). This may explain why few, if any, central anticholinergic
effects have been reported with administration of the drug (38,39). The pharmacokinetic
profile and dosing for trospium can be seen in Tables 2 and 3, respectively.
The exact metabolic pathway for trospium is not well defined, but approx 5–10% of
an oral dose undergoes absorption. Of this absorbed oral dose, 60% of the drug is
excreted in the urine as the active unaltered, unmetabolized compound. The presence of
unaltered, unmetabolized drug in the urine following oral dosing has been hypothesized
to be responsible for some of the favorable effects on the bladder relative to those seen
on the salivary gland (40).
In support of this, it is known that muscarinic receptor density in the urothelium is
significantly greater than that seen in the detrusor muscle, and that the urothelium may
modulate the activity of the underlying smooth muscle of the detrusor (41). It is interesting
to speculate whether these urothelial muscarinic receptors may have a role in bladder
overactivity and, if so, whether there exists any role for direct muscarinic blockade of
the urothelium in treating symptoms of the OAB. On the negative side of this argument,
however, is the fact that there is no evidence for augmented efficacy of this agent over
others that do not achieve a significant urinary concentration.
Table 2
Selected Pharmacokinetics of Commonly Used Antimuscarinic OAB Agents in the United States
Bioavailability Protein Excreted unchanged Active Effect of food on
Agent (%) tmax (h) t1/2 (h) bound (%) in urine (%) metabolites Metabolism pharmacokinetics
Tolterodine 10–74 2–6 8.4 >96 <1% (<14% Yes Liver: CYP2D6 No
extended including active and CYP3A4
releasea metabolite)
Oxybutynin 156–187% 11.8–12.7 12.4–13.2 n/a <0.1% Yes Liver: CYP3A4 No
extended greater than
releasea IR form (IR
form ~ 6)
Solifenacina 90 3–8 45–68 96 <15% Minimal Liver: CYP3A4 No
Darifenacina 15–19 5.2–7.6 12–19.95 98 <3% No Liver: CYP2D6 No
183
and CYP3A4
Trospiuma 4–16.1 5.3 18.3 50–85 60 No Not well defined Yes
but eliminated
at least in part
by active tubular
(renal) secretion
Oxybutynin n/a 10–48 7–8b n/a <0.1% Yes CYP3A4 No
patcha
tmax = time to maximum serum concentration.
t1/2 = terminal elimination half-life.
n/a, not available.
aFrom prescribing information/product label.
bFollowing removal of the patch.
Table 3
Recommended Dosing of Commonly Utilized Antimuscarinic Agents in the United States
Available doses Dose range Regimen
Tolterodine extended release 2- and 4-mg tablet 2–4 mg Daily
Oxybutynin extended release 5-, 10-, and 15-mg tablet 5–30 mg Daily
Darifenacin 7.5- and 15-mg tablet 7.5–15 mg Daily
Solifenacin 5- and 10-mg tablet 5–10 mg Daily
Trospium 20-mg tablet 20 mg Twice daily
Oxybutynin patch 3.9-mg/d patch 3.9-mg/d patch Every 3 d
Trospium is a well-studied compound; however, many of the earlier trospium studies

utilized urodynamic parameters (as opposed to voiding diaries) as end points, making
comparison to other antimuscarinic agents difficult. Cardozo et al. reported the results
of a randomized, double-blind, placebo-controlled study of 20 mg trospium twice daily
in 208 patients with idiopathic detrusor instability (42). Volume to first contraction and
bladder capacity were significantly improved in the treated as compared to the placebo
groups (p < 0.05), and there was more than a threefold difference in the number of
patients reporting significant improvement in their symptoms in favor of trospium. Side
effects and safety parameters were similar between groups, and no CNS effects were
reported in patients receiving trospium. Similar results have been reported by other
authors in patients without (43) and with neurogenic bladder dysfunction (44).
Results from two large, multicenter, double-blind, placebo-controlled studies have
been published, involving a total of 1181 patients with OAB (45,46). In both studies,
patients were randomly assigned to 20 mg trospium chloride twice daily or placebo for
12 wk. Symptoms were recorded in a voiding diary, and patients assessed the severity
of their urgency symptoms using the validated Indevus Urgency Severity Scale. In
both studies, trospium was associated with significantly greater reductions in urinary
frequency, number of urge incontinence episodes, and Indevus Urgency Severity Scale
scores and significantly greater increases in average volume voided per void compared
with placebo (p < 0.001). Treatment effects were apparent early on, with improvement
in all assessment parameters by week 1 (p < 0.005).
Trospium has been compared to other antimuscarinic agents, such as oxybutynin and
tolterodine. In one study, trospium was as effective as oxybutynin in patients with
hyperreflexia caused by spinal cord injury but had fewer adverse effects (37). Halaska
and colleagues reported on the long-term (52 wk) results of 358 patients with urge
syndrome treated with either 20 mg trospium twice daily or 5 mg oxybutnin twice daily
(47). There were statistically significant improvements for both drugs in diary parameters
such as micturition frequency, UI episodes, and urge episodes as well as urodynamic
outcome measures, including cystometric capacity. The risk of dry mouth during the
study was greater with oxybutynin, suggesting a favorable tolerability profile for trospium.
Reported in abstract form only, trospium was compared with tolterodine IR 2 mg twice
daily in a placebo-controlled study (48). The efficacy and safety profiles of the two agents
were similar, and both reduced urinary frequency relative to placebo.
The ICI Subcommittee on Pharmacology concluded, based on well-done clinical trials,
that trospium is an effective and safe option for the treatment of UUI (36).
DARIFENACIN
Darifenacin is a once-daily, relatively selective M3 receptor antagonist. The potential
implications of the high degree of M3 selectivity of this agent are interesting. It is well
established that activation of the M3 receptor in the detrusor is responsible, at least in
part, for both normal volitional bladder emptying and the involuntary bladder contractions
responsible for symptoms related to OAB. Thus, although it is possible to speculate that
highly selective blockade of the M3 receptor would be beneficial in maximally reducing
symptoms of OAB while sparing blockade of the other muscarinic subtypes throughout
the body, it is unclear whether such an agent would also result in improved tolerability
given its likely systemic effects on M3 receptors elsewhere, including those in the salivary
glands, gut, and CNS.
In addition, it is possible to consider that this particular agent, because of its relative
lack of selectivity for other muscarinic receptor subtypes, may have fewer collateral
effects on end organs possessing a significant density of muscarinic receptors other than
the M3 subtype, such as the heart (M2) and brain (M1, M2, M4, and M5), thus providing
an additional margin of safety. The pharmacokinetic profile and dosing of darifenacin
can be seen in Tables 2 and 3, respectively. Organ selectivity for the bladder over the
salivary glands has been demonstrated in some animal models (49,50), but the clinical
importance of this finding has not been established (19).
Small, early studies proved efficacy, but in small doses that did not cause salivary
problems, darifenacin was no more effective than placebo (51,52). Haab et al. (53)
reported on a multicenter, placebo-controlled trial of darifenacin. Patients (561) were
randomly assigned to three different doses of active drug (3.75, 7.5, and 15 mg) and
treated for 12 wk. At the higher doses (7.5 and 15 mg), median reductions in UI
episodes per week were statistically significant compared with placebo (67.7, 72.8,
and 55.9% for the 7.5 and 15 mg doses and placebo, respectively) and comparable to
that reported in other trials of antimuscarinic compounds in patients with OAB.
Statistically significant improvements in urinary frequency, mean volume per void,
number of urgency episodes per day, and severity of urgency were also reported.
Dry mouth was reported by 18.8, 31.3, and 8.5% of patients in the 7.5-mg, 15-mg, and
placebo groups, respectively, but there were no patient withdrawals caused by this
adverse event. Constipation was noted in 14.4, 13.9, and 6.7% of patients in 7.5-mg, 15-mg,
and placebo groups, respectively, but only 0.9% of patients discontinued the active drug
because of this event. CNS and cardiac safety profiles were comparable to placebo.
Steers et al. compared darifenacin to placebo in a large, multicenter RCT involving
398 patients with OAB (54). Efficacy was evaluated at 2 and 12 wk for primary end
points (change in incontinence episodes from baseline) and secondary end points, which
included frequency and urgency episodes/day, bladder capacity, urgency severity, nocturia,
and number of significant leaks/week. Dose escalation from 7.5 to 15 mg was permitted
in the darifenacin arm, and 59% of patients opted for the higher dose. Overall, there was
a significant reduction in the median number of incontinent episodes in the darifenacin-
treated group compared to placebo (62.9 vs 48.1%, drug vs placebo, respectively;
p = 0.035). Darifenacin also achieved statistically significant improvements in the
secondary efficacy variables of significant leaks/week, frequency, bladder capacity,
urgency, and urgency severity.
Cardozo and Dixon evaluated a novel efficacy parameter in a multicenter, double-blind
RCT with a primary end point of change in warning time (55). Warning time was
defined as the time from the first sensation of urgency to voluntary micturition or
incontinence. Treatment resulted in significant improvements in warning time when
compared to placebo, with a median increase of 4.3 min in the darifenacin-treated
patients compared with those treated with placebo (p = 0.003). In theory, increasing
warning time would extrapolate to improvements in symptoms and a decrease in incon-
tinence episodes, but these were not extensively assessed as additional variables, and
a change in warning time has not been correlated with a change in symptoms. There
was a statistically significant reduction in the severity of urgency vs placebo in the clinic
setting (p = 0.035) but not at home.
As mentioned, cognitive impairment with antimuscarinic agents may be caused by
interaction with other cholinergic receptors, including the M1 receptors. It has been
postulated that darifenacin with its M3 selectivity might be associated with fewer
unwanted CNS effects. Lipton et al. assessed the cognitive effects of darifenacin on
unimpaired/minimally impaired elderly patients in a double-blind, three-period
crossover trial (56). Darifenacin formulations used in the study were the IR tablets
(5 mg three times daily) and the sustained-released tablets (3.75, 7.5, or 15 mg daily) in
addition to a placebo arm. Patients were randomly assigned to three of these five treat-
ments for 2 wk at a time with a 7-d washout between treatments. There was no statistical
difference compared to placebo for the mean change from baseline of word recognition
sensitivity, speed of choice reaction time, and memory scanning sensitivity. Likewise,
no effect was seen on simple reaction time, digit vigilance speed or accuracy, or word
recognition speed. This held true for memory scanning speed as well, except for the
3.75-mg dose, which showed a decrease in this cognitive parameter when compared to
placebo. Last, there was no effect on self-rated alertness or contentment, but interestingly,
the 15-mg dose showed a decrease in self-rated calmness, and the 3.75-mg dose demon-
strated improvement (p = 0.007 and p = 0.046, respectively).
The ICS at the Third Consultation on Incontinence endorsed darifenacin as efficacious
and safe based on strong, good-quality RCTs (36).
SOLIFENACIN
Solifenacin is a novel once-daily antimuscarinic agent. It is an isoquinolone carboxy-
late derivative that may demonstrate organ selectivity for the bladder vs salivary glands
in some animal models (57–59). The half-life of the drug is quite long at almost 60 h;
however, the clinical significance of this unusual pharmacokinetic property is unclear.
Other pharmacokinetic parameters are outlined in Table 2.
Cardozo et al. randomly assigned 911 patients to receive either 5 or 10 mg solifenacin
or placebo in a 12-wk multicenter trial (60). The primary outcome variable was change
in urinary frequency. Secondary efficacy variables assessed included urinary urgency,
nocturia, volume voided, total incontinence episodes, and UUI episodes. As compared
to placebo (1.59), micturitions per 24 h were statistically significantly decreased with
5 mg solifenacin (–2.37, p = 0.0018) and 10 mg solifenacin (2.81, p = 0.0001). The 5-mg
solifenacin dose showed improvement in reduction in the number of nocturia episodes
compared to placebo, but this did not reach statistical significance. All other treatment
effects reached statistical significance. Based on a 3-d voiding diary, 50.3 and 49.7% of
patients treated with 5 and 10 mg solifenacin, respectively, had no incontinence at the
conclusion of the study; however, the percentage of dry patients in the placebo arm was
not reported. Side effects were more prominent in the 10-mg group, but both strengths
were well tolerated when compared to placebo.
Solifenacin has been compared to tolterodine in several studies. Chapple and colleagues
randomly assigned 225 patients to four different doses of solifenacin (2.5, 5, 10, or 20 mg
daily), IR tolterodine (2 mg twice daily), or placebo (61). The primary efficacy variable
was urinary frequency (mean number of micturitions per 24 h). The 5-, 10-, and 20-mg
dosages of solifenacin showed statistically significant changes in reducing urinary
frequency compared to placebo (mean reductions 2.21, 2.47, and 2.75 daily voids
for the 5-, 10-, and 20-mg doses, respectively vs 1.03 for placebo); however, the groups
receiving the 2.5-mg dose of solifenacin and tolterodine did not (mean reductions 1.45
and 1.79 for 2.5 mg solifenacin and tolterodine, respectively). Notably, there were no
statistically significant differences seen between solifenacin and tolterodine compared
to placebo in two other secondary outcome variables (mean reduction in incontinent
episodes and urgency episodes). Dry mouth was reported by 2.6% in the placebo group
compared to 14, 14, and 38% for the 5-, 10-, and 20-mg doses of solifenacin, respectively,
and 24% for the tolterodine group.
In another study by Chapple et al., 5 and 10 mg solifenacin were compared to IR
tolterodine (2 mg twice daily) and placebo in 1033 patients (62). The 5- and 10-mg
doses of solifenacin demonstrated statistically significant decreases in UUI episodes,
total incontinence episodes, and urgency episodes compared to placebo, but tolterodine
did not. All three active treatments showed statistically significant improvements in
mean volume voided per void and micturition frequency. Dry mouth was reported by
18.6% in the tolterodine group compared to 4.9% in the placebo group and 14 and
21.3% of patients receiving the 5- and 10-mg doses of solifenacin, respectively.
As with darifenacin, the Third Consultation on Incontinence endorsed solifenacin as
effective and with an acceptable adverse event profile based on strong, good-quality
RCTs (36).
Anticholinergic Agents With Mixed Actions
In addition to their antimuscarinic properties, anticholinergic agents with mixed
actions induce multiple in vitro actions, including an independent “musculotropic” or
“antispasmodic” action directly on smooth muscle. This effect occurs at a site that is
metabolically distal to the cholinergic or other contractile-receptor mechanism and is
possibly related to calcium channel blockade. In vitro, its direct smooth muscle relaxant
effects are reportedly 500 times weaker than its antimuscarinic effects (10). These drugs
may also possess some local anesthetic properties that, like the direct musculotropic
relaxant effects, may only be relevant when given intravesically. When administered
orally, the clinical relevance of these actions is unclear (10,17). However, if any of these
agents exerted a clinically significant direct inhibitory effect independent of their
antimuscarinic action, there would be a therapeutic rationale for combination therapy
with a relatively pure anticholinergic agent.
OXYBUTYNIN CHLORIDE
Oxybutynin chloride is a potent muscarinic receptor antagonist with some degree of
selectivity for M3 and M1 receptors. In human tissues, it has a higher affinity for muscarinic
receptors in the parotid gland than it does for those in the bladder (17). Oxybutynin was
originally developed to treat gastrointestinal hypermotility disorders. Diokno and
Lapides first reported on its urological applications in 1972 (2).
This agent is a well-absorbed tertiary amine that undergoes an extensive first-pass
metabolism. The pharmacological properties of its active metabolite are similar to those
of the parent compound, but they occur at concentrations six times higher. The major
metabolite is also thought to cause the majority of this agent’s adverse effects (63,64).
Reducing the extent of first-pass metabolism by intravesical administration and trans-
dermal or rectal administration are potential avenues to improve tolerability (65,66).
Oxybutynin’s side effects are antimuscarinic and are dose related.
An additional theoretical consideration is its physiochemical composition, which
might permit relatively greater penetration into the CNS through the blood-brain barrier.
The agent is relatively small, uncharged, and lipophilic. This may account for some
of the reports of adverse CNS effects seen with this agent, especially in the geriatric
population (67,68).
Initial reports documented the agent’s success in depressing detrusor overactivity in
patients with neurogenic bladder dysfunction; subsequent reports documented its success
in inhibiting other types of bladder hyperactivity as well (9). The recommended oral
adult dose of the IR formulation is 5 mg three or four times daily, although lower doses
have been suggested. No antimuscarinic drug has yet been objectively demonstrated as
more efficacious at relieving OAB symptoms than IR oxybutynin, and it remains the
most inexpensive agent in its class. However, given the multiple alternative agents now
available, the inconvenient dosing regimen, as well as the relatively unfavorable
antimuscarinic side effect profile, the IR form of this agent has only limited usage. The
AHCPR Urinary Incontinence Guideline Panel reviewed six RCTs (25). Reports of cure
ranged from 28 to 44%, reductions in urge incontinence from 9 to 56%, side effects
from 2 to 66%, and dropouts from 3 to 45%. In a review of 15 RCTs of 476 patients
treated with oxybutynin, Thüroff et al. reported a mean decrease in incontinence of 52%
and a mean reduction in frequency of micturitions for 24 h of 33% (69). The overall
subjective improvement rate was 74% (range 61 to 100%). Side effects were reported
by a mean of 70% (range 17 to 93%) of patients.
The once-daily formulation of oxybutynin considerably improved the convenience
and tolerability of this agent compared to the IR tablet. The ER formulation of oxybutynin
(oxybutynin ER) uses an innovative osmotic drug delivery system to release the drug
at a controlled rate over 24 h. This formulation overcomes the marked peak-to-trough
fluctuations in plasma levels of both the drug and the metabolites that occur with IR
oxybutynin (70). The pharmacokinetic profile of the ER formulation is seen in Table 2.
A trend toward a lower incidence of dry mouth with oxybutynin ER was attributed to
reduced first-pass metabolism and to the maintenance of lower and less-fluctuating
plasma levels of drugs.
Clinical trials of oxybutynin ER have concentrated primarily on comparing this drug
with IR oxybutynin, although trials comparing it to both IR tolterodine (71) and ER
tolterodine (72) have been published. Anderson et al. reported on a multicenter, random-
ized, double-blind study on 105 patients with urge incontinence or mixed incontinence
with a clinically significant urge component. This was a dose titration study, and all
had been prior positive responders to IR oxybutynin (73). The number of weekly urge
incontinence episodes decreased from 27.4 to 4.8 after ER and from 23.4 to 3.1 after IR
oxybutynin, and total incontinence episodes decreased from a mean of 29.3 to 6 and
from 26.3 to 3.8, respectively. Dry mouth of any severity was reported by 68 and 87%
of the controlled and IR groups, respectively, and moderate or severe dry mouth
occurred in 25 and 46%, respectively. The relatively high rate of dry mouth reported in
this study is likely because of its forced dose titration design, in which the investigators
increased the dosage until a maximal dose of 30 mg was achieved or the patient reported
intolerable side effects. Curiously, a statistically greater percentage increase in voiding

frequency was seen in the patients taking ER doses (54%) than in the patients taking
the IR form (17%). The reason for the increase in urinary frequency seen in this study
is unclear and is at odds with nearly all other antimuscarinic studies in which urinary
frequency was measured as an outcome parameter.
Another study included 226 patients with urge incontinence (74). These were prior
responders to anticholinergic therapy who had seven or more urge incontinence
episodes per week. Reductions in UUI episodes from baseline to the end of treatment
were from 18.6 to 2.9 per week (83% mean decrease) and from 19.8 to 4.4 per week
(76% mean decrease) in the ER and IR oxybutynin groups (difference nonsignificant),
respectively. The incidence of dry mouth increased with dose in both groups, but there
was no statistically significant difference in dry mouth rates between the groups: 47.7
and 59.1% for the ER and IR groups, respectively. However, a significantly lower
proportion of patients taking the ER form had moderate-to-severe dry mouth or any dry
mouth compared with those taking IR oxybutynin.
Appell and colleagues compared oxybutynin ER with tolterodine IR (71). Of 378
patients enrolled, 332 completed the 12-wk study. Compared to baseline, weekly urge
incontinence episodes were reduced (25.6 to 6.1 vs 24.1 to 7.8, oxybutynin ER and
tolterodine IR groups, respectively) as was urinary frequency (91.8 to 67.1 vs 91.6 to
71.5 episodes per week, respectively). There was a statistically significant difference
between the two drugs, favoring oxybutynin in both of these outcome parameters.
Diokno et al. directly compared the ER formulations of oxybutynin and tolterodine
in patients with severe UUI and found no difference in efficacy with respect to reducing
incontinent episodes (72). At the conclusion of the 12-wk study, there was no difference
between the two agents with respect to the reduction of UUI episodes from baseline (87
vs 81% reduction, oxybutynin vs tolterodine, respectively; p < 0.05); however, more
patients gained complete continence on oxybutynin (23 vs 17%, oxybutynin vs toltero-
dine, respectively). In comparison with oxybutynin ER, dry mouth was less frequently
reported with tolterodine ER (22%) than with oxybutynin ER (30%; p = 0.02).
The ICI committee recommended oral oxybutynin for the treatment of UUI based on
good-quality studies (36).
TRANSDERMAL OXYBUTYNIN CHLORIDE

A transdermal delivery system for oxybutynin was introduced. The patch is applied
for 3 d and then replaced. The potential advantages of this delivery method include
patient dosing convenience and the achievement of steady serum drug levels with
reduced portal delivery and thus a reduction in the hepatic metabolite.
Davila and colleagues reported the results of a randomized, double-blind, double-dummy,
dose escalation study comparing a transdermal delivery system to oral IR oxybutynin
for urodynamically confirmed UUI (77). All patients had previously been diagnosed
with motor urge incontinence and had demonstrated symptomatic improvement with
anticholinergic therapy. Compared to baseline, daily incontinence episodes decreased
significantly in both groups (66 vs 72% in the patch vs oral groups, respectively).
There was no significant difference in reduction in incontinence episodes between the
two groups (p = 0.39). Dry mouth of any type was noted in 38 and 94% of patients
in the patch and oral groups, respectively. Of patients in the active transdermal patch
group, 39% had some degree of erythema at the patch site compared to 22% in the
placebo group.
The transdermal patch was also evaluated by Dmochowski and colleagues in patients
with OAB and urge or mixed incontinence (78). Patients were randomly assigned to 12 wk
of double-blind daily treatment with a total of 1.3, 2.6, or 3.9 mg oxybutynin delivered
via a transdermal delivery system or a placebo patch administered twice weekly, followed
by a 12-wk open-label, dose titration period to assess efficacy and safety further.
Compared to placebo, the 3.9-mg patch significantly reduced the number of weekly
incontinent episodes (19.5 vs 14.5 episodes per week, patch vs placebo, respectively;
p = 0.0165); reduced daily urinary frequency (2.3 vs 1.7 micturitions per day, patch
vs placebo, respectively; p = 0.0457) and increased average voided volume (24 vs 6 cc
per void, patch vs placebo, respectively; p = 0.0063). Other than a significant increase in
volume voided with the 2.6-mg patch compared to placebo, there were no other differ-
ences between placebo and the 1.3- or 2.6-mg patch in any of the outcomes reported in
the double-blind portion of the study. In the open-label dose titration portion of the
study, a sustained reduction of almost three incontinence episodes per day was noted in
all groups. Overall, dry mouth was reported by 4.6, 6.8, and 9.6% of patients in the 1.3,
2.6-, and 3.9-mg patch groups, respectively, compared to 8.3% of patients receiving
placebo. This difference was not statistically significant. The most commonly reported
treatment-related adverse events were erythema at the patch site.
The transdermal delivery system (3.9-mg patch) was also compared to sustained-
release tolterodine (4 mg daily) in 361 patients with urge or mixed urinary incontinence
(79). Median reductions in urinary incontinence episodes and micturition frequency
were similar between the two agents. Dry mouth of any type was reported by 7.3, 4.1,
and 1.7% in the tolterodine, patch, and placebo groups, respectively. Patch site reactions
of any type (erythema, pruritis, etc.) were noted in 5.7, 26.4, and 6.9% in the tolterodine,
patch, and placebo groups, respectively.
Overall, the patch is well tolerated and may offer an alternative for some patients
with OAB. It does not appear to be more efficacious than either IR oxybutynin or
tolterodine. Some patients may experience local reactions at the patch site, however.
The patch site reactions are generally mild and self-limited. Some patients may use
topical corticosteroids to relieve local symptoms at the patch site.
DICYCLOMINE HYDROCHLORIDE
Dicyclomine hydrochloride is reported to possess a direct relaxant effect on smooth
muscle in addition to an antimuscarinic action. However, it is not widely used to treat
OAB. The ICI (Committee on Pharmacology) (36) rated this drug as effective based on
pharmacological and physiological evidence, but clinical evidence from good-quality,
randomized control trials was lacking. The ICI failed to recommend dicyclomine for
use (36).
FLAVOXATE HYDROCHLORIDE
Flavoxate hydrochloride was originally thought to be a weak anticholinergic agent and
to possess a direct inhibitory action. Some authors suggested that the agent demonstrates
no anticholinergic effects but does have moderate calcium antagonist activity, local
anesthetic properties, and the ability to inhibit phosphodiesterase (17). Overall, favorable
clinical effects have been reported in some series of patients with frequency, urgency,
and incontinence and in patients with urodynamically documented detrusor hyperreflexia
(80). However, Briggs and colleagues reported essentially no effect on neurogenic
detrusor overactivity in an elderly population (81). A similar conclusion was reached
by Chapple and associates in a double-blind, placebo-controlled, crossover study of

idiopathic detrusor overactivity (82). Reported side effects are few. The drug failed to
achieve a “recommended” assessment by the ICI, which noted that cogent evidence of
pharmacological or physiological efficacy (or both) was lacking for this agent as was
evidence for its efficacy from good-quality RCTs (36).
Tricyclic Antidepressants
Many clinicians believe that tricyclic antidepressants are useful agents for facilitating
urine storage because they decrease bladder contractility and increase outlet resistance
(83). These agents have been the subject of numerous pharmacological investigations to
determine the mechanisms of action responsible for their varied effects (84,85). Most
data are from attempts to explain the antidepressant properties of these agents and there-
fore are primarily from CNS tissue. The results, conclusions, and speculations inferred
from the data are extremely interesting, but it is unknown whether they have relevance
for the lower urinary tract.
All of these agents possess varying degrees of at least three major pharmacological
actions: (1) They have central and peripheral anticholinergic effects at some, but not all,
sites; (2) they block the active transport system in the presynaptic nerve ending, which
is responsible for the reuptake of the released amine neurotransmitters norepinephrine
and serotonin; and (3) they are sedatives, an action that occurs presumably on a central
basis but may be related to antihistaminic properties. Imipramine and doxepin are the
most commonly prescribed tricyclics for detrusor overactivity; data on their efficacy
and tolerability for this indication are reviewed next.
IMIPRAMINE
Although this agent has prominent systemic anticholinergic effects, it has only a weak
antimuscarinic effect on bladder smooth muscle (86). It does, however, exert a strong
direct inhibitory effect—which is neither anticholinergic nor adrenergic—on bladder
smooth muscle (87,88). The exact mechanism by which imipramine inhibits bladder
activity is unknown. It has been postulated that these effects may be caused by increased
serotonin activity (because of reuptake blockade) in the CNS. This may involve a direct
inhibition of normal excitatory pathways or a depression of afferent ascending neural
activity (89,90).
Clinically, imipramine has been effective in decreasing bladder contractility and
increasing outlet resistance (91,92). The AHCPR combined results for imipramine
and doxepin, citing only three RCTs and an unknown percentage of female patients
(25). Percentage cures were listed as 31%, percentage reduction in urge incontinence as
20–77%, and percentage side effects as 0–70%.
The usual daily adult dosage for voiding dysfunction is 25–75 mg. The effects of
imipramine on the lower urinary tract may be additive to those of the atropine-like
agents. Consequently, combining imipramine with an antimuscarinic or an antispas-
modic is sometimes especially useful for decreasing bladder contractility. However,
caution is advised because when imipramine is used in conjunction with an atropine-
like agent, the anticholinergic side effects of the drugs may also be additive. When used
in the larger doses employed for antidepressant effect, the most frequent side effects of
imipramine are anticholinergic. Although uncommon, serious other side effects can occur,
including CNS effects, postural hypotension, cardiac toxicity, weakness, and fatigue.
Botulinum Toxin
Botulinum toxin (BTX) is produced by the bacteria Clostridium botulinum and is one
of the most potent biological toxins known to man. Only recently has this agent been
adapted into a useful agent for the treatment of a variety of urological and nonurological
conditions. BTX has been used successfully for the treatment of striated sphincter
dyssynergia in patients with spinal cord injury (93) and has restored voiding by Valsalva
in some patients with detrusor acontractility (94). Intravesical injections have been
given for both neurogenic and nonneurogenic OAB (95).
There are four genetically distinct groups of the anaerobe that produce seven different
immunogenic toxins, labeled A to G. The mechanism of action, at least on the motor
side, is ultimately by the interruption of fusion of vesicles containing ACh to the plasma
membrane, preventing release of ACh at the neuromuscular junctions. The clinical
effects appear 24–72 h after injection, and reinnervation has continued for up to 12 mo,
at least in some striated muscles. Because patients with OAB also have reported a
marked reduction in urgency, there exists the possibility that, in addition to the motor
effects, an as-yet-undefined sensory effect may be present as well. Cholinergic block-
ade at the neuromuscular junction would not explain a sensory effect, and BTX-A is not
known to be toxic to afferent C fibers. BTX-A is known to improve certain chronic pain
conditions of neurological origin, and several authors have speculated that afferent
mechanisms are affected by some pathway currently unknown, possibly involving muscle
spindles, suburothelial myofibroblasts, or interstitial cells (95).
Detrusor striated sphincter dyssynergia, a neurologically mediated involuntary acti-
vation of the striated pelvic floor muscle coincident with a detrusor contraction seen in
some individuals with spinal cord lesions, has been relieved by transurethral or trans-
perineal injection after a single dose of 100 U, with the effects lasting for 3–9 mo. The
dose for OAB has varied between 100 and 300 U BTX-A injected in separate aliquots in
over 20–30 points throughout the bladder but sparing the trigone. The duration of effect
has been longer in these patients than in patients injected for DSSD, and this may
indicate a difference in response between smooth and striated muscle. Patients under-
going intradetrusor injection should be warned about urinary retention and the possibility
of requiring clean intermittent catheterization or even suprapubic drainage afterward.
The side effects in patients treated for urological problems have been rare. There is a
possibility of a rash or mild flulike illness, the latter occurring 1–2 wk after injection.
Reitz and Schurch reviewed 200 cases of neurogenic overactivity treated with BTX,
188 of whom were already on clean intermittent catheterization, with 12 on indwelling
catheter drainage (96). Dysfunction etiology was spinal cord injury in 167; there were
22 with myelomeningocele and 11 with multiple sclerosis. At 3 mo, the mean cystometric
bladder capacity increased from 272 to 420 mL, the mean maximal voiding pressure
from 61 to 30 cm H2O, and the mean bladder compliance increased from 32 to 72 mL/cm
H2O. Of the 180 incontinent patients, 132 reported complete continence after treatment;
48 reported improvement but some level of continuing incontinence. Anticholinergic
medication could be “considerably reduced” in 118 patients but discontinued entirely in
only 45. The duration of induced changes was 9 mo or more. There were no injection-
related complications or toxin-related side effects reported.
Schurch and colleagues treated 31 patients with neurogenic detrusor overactivity
with BTX injected directly into the detrusor muscle (97). Up to 30 injection sites were
used per patient. The authors noted a significant rise in maximum bladder capacity and
a significant decrease in mean maximum detrusor voiding pressure 6 wk following

injection. There were no adverse effects from therapy.
More recent studies have addressed the use of BTX in nonneurogenic detrusor over-
activity patients. Rapp et al., in a prospective open-label pilot study, injected 35 patients
transurethrally with a total of 300 U BTX-A at various sites in the bladder but avoiding
the area around the ureteral orifice (98). Patients were assessed by the Incontinence
Impact Questionnaire (IIQ-7) and the Urogenital Distress Inventory (UDI-6) pre- and
posttreatment. Urodynamic parameters or diary information were not end points. At 3 wk
posttreatment, there was a significant improvement in questionnaire scores. At 6 mo,
14 of the 24 patients who were evaluable maintained a statistically significant improvement
in scores. No major side affects were reported.
In another small prospective trial, Kessler et al. enrolled 22 patients; 11 had idiopathic
overactivity. In a similar fashion, 300 U BTX-A was injected among 30 sites (99). The
entire trigone in this study was spared. Patients were extensively evaluated pretreatment
and had clinical and urodynamic follow-up 7–10 d posttreatment and then were followed
clinically every 3 mo. There was a statistically significant improvement in frequency,
nocturia, number of pads in 24 h, maximum cystometric bladder capacity, bladder com-
pliance, maximum detrusor pressure, and pressure at maximum flow. When compared
to the patients with neurogenic overactivity, there were no statistical differences in
treatment effect or duration of effect.
Werner et al. reported on 26 women with detrusor overactivity with incontinence and
UUI who underwent transurethral injection of a total of 100 U BTX-A in 30 sites (100).
Again, the trigone was spared. Patients were evaluated at 4, 12, and 36 wk postinjec-
tion. There was a significant improvement in maximum cystometric bladder capacity
and compliance at 4 and 12 wk and volume at first desire to void and volume at strong
desire to void at 12 wk and significant reductions in frequency and nocturia at 4 and 12 wk.
There were no reports of retention or toxin-related side affects.
In summary, the intravesical use of BTX appears safe and effective, albeit invasive.
Larger controlled trials are warranted.
Decreasing Sensory Input

Decreasing afferent input would be an ideal treatment for sensory disorders and for
overactivity in a bladder with relatively normal elastic and viscoelastic properties in
which the sensory afferents constitute the first limb in an abnormal micturition reflex.
Maggi and coworkers have written extensively about this type of treatment, specifically
with reference to the properties of capsaicin (101–103).
Capsaicin
An irritant and algesiogenic compound obtained from hot red peppers, capsaicin has
highly selective effects on a subset of mammalian sensory neurons, including poly-
modal receptors and warm thermoreceptors (104). It activates polymodal nociceptive
neurons by opening a cation-selective ion channel, allowing an influx of calcium and
sodium ions that depolarize neuronal pain fibers (105,106). This ion channel is known
as the vanilloid-receptor subtype 1. Repeated administration of capsaicin desensitizes
and inactivates sensory neurons by several mechanisms. Systemic and topical capsaicin
produce a reversible antinociceptive and anti-inflammatory action after an initially
undesirable algesic effect. Local or topical application blocks C-fiber conduction and
inactivates neuropeptide release from peripheral nerve endings, accounting for local
antinociception and reduction of neurogenic inflammation.
DeRidder and Baert, in an excellent review article (107), summarized trials to date as
detailed by deSèze and colleagues (108). Of 49 patients with multiple sclerosis, 13 (27%)
reported excellent results, and 27 (55%) noted improvement. DeRidder and Baert also
cited double-blind trials that used placebo or a vehicle (30% ethanol in saline), showing
clearly that capsaicin produced the positive result.
RESINIFERATOXIN
Resiniferatoxin (RTX) is the principle active ingredient in the drug euphorbium, the
air-dried latex of the cactuslike plant Euphorbia resinifera, which is chemically related
to the phorbol esters (107,109). RTX is likewise a vanilloid and is, in fact, an ultrapotent
(1000X) analog of capsaicin, but with minimal initial excitatory effect. RTX may induce
desensitization in concentrations that are so low that no noxious effects are elicited
(109).
Neither capsaicin nor RTX is approved for clinical use in the United States. However,
the intravesical use of such agents has the potential to contribute significantly to the
treatment of bladder overactivity in patients with neurogenic and other types of lower
urinary tract dysfunction. Theoretically, activities affected by these agents should
include only those subserved by small unmyelinated afferent C fibers. A micturition reflex
stimulated via myelinated AI afferent fibers should not be affected by capsaicin-like
agents. Trials are ongoing with RTX in the United States.
Estrogens for Overactive Bladder

The role of estrogen therapy in the treatment of bladder overactivity and stress
incontinence has remained controversial. Unfortunately, most reported studies are
observational and not randomized, blinded, or controlled. The situation is further
complicated by the fact that a number of different types of estrogen have been used with
varying doses, routes of administration, and treatment duration—some with proges-
tational agents and some without. Some authorities even seem to advocate opposite
positions on this question in different articles. If estrogen has a role in treating lower
urinary tract symptoms in the postmenopausal female, then it is most likely through one
or more of the following mechanisms: (1) raising the sensory threshold of the bladder
or urethra; (2) increasing the F-adrenoceptor sensitivity in urethral smooth muscle;
(3) increasing urethral resistance by mechanism no. 2 or by another mechanism; or (4)
correcting underlying urogenital atrophy or other pelvic floor musculofascial pathology.
The Cochrane group reported on estrogen therapy for the treatment of urinary incon-
tinence (110), with 28 trials reviewed, which included 2926 women. In comparing
estrogen to placebo for the treatment of UI, the preponderance of evidence suggested
that estrogen was superior. Approximately 50% of subjects in the reviewed trials were
either cured or improved in the estrogen arms compared to only 25% of subjects in
the placebo arms. The effect appeared greater in patients with UUI as opposed to stress
UI, although it was stated in the analysis that it was unclear whether this was a real
difference or caused by artifact secondary to methodological problems. In this analysis,
it was suggested that combining estrogen therapy with a progestational agent may
negate the favorable effect of estrogens on UI. Finally, the optimal dosage, method of
administration, and duration of therapy remain poorly defined.
In contrast to the Cochrane review, Hendrix et al. reported on the urinary incontinence
outcomes of the Women’s Health Initiative (111). This was a multicenter, double-blind,
placebo-controlled trial that randomly assigned 27,347 postmenopausal women to
either conjugated equine estrogen or conjugated equine estrogen plus medroxypro-
gesterone acetate vs placebo. More than 23,000 women had outcome information avail-
able on urinary incontinence symptoms at baseline and after 1 yr. Subgroup analyses
were reported that divided the types of incontinence into stress, urge, and mixed in rela-
tion to multiple demographic and medical parameters. The analyses concluded that both
the estrogen alone and estrogen-plus-progestin groups had an increased relative risk of
worsening of the severity of existing UI symptoms (regardless of the type of inconti-
nence reported at baseline) and, furthermore, an increased risk of developing inconti-
nence in those who were continent at baseline. These authors recommended against the
use of estrogens or estrogens in combination with progestational agents for the treat-
ment of existing incontinence or as a preventive measure against the development of
incontinence in continent women.
CONCLUSION
Notwithstanding suggestions to the contrary, none of the existing pharmacotherapies
for OAB are either absolutely selective for the bladder or universally efficacious. Dose-
dependent side effects such as dry mouth and constipation limit the utility of the oral
antimuscarinic agents in particular. Furthermore, although statistically significant and
well-documented reductions in frequency, urgency, and urinary incontinence episodes
have been noted in published randomized, double-blind, placebo-controlled studies,
complete “cure” of OAB is not commonly seen clinically. A comprehensive systematic
review of currently available anticholinergic medications by the Cochrane group con-
cluded the following: “The use of anticholinergic drugs by people with OAB syndrome
results in statistically significant improvement in symptoms. However, the clinical
significance of these differences is uncertain…. Dry mouth is a common side effect of
therapy,” (112). Given this statement, it is hoped that ongoing and promising investiga-
tions into the etiology and therapy of OAB will lead to further improvements for the
pharmacological treatment of this highly prevalent condition.
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13 Intravesical Treatments for Overactive
Bladder
Craig B. Slotoroff, MD, Dolores Shupp-Byrne, PhD,

and Patrick J. Shenot, MD
CONTENTS
ANATOMY AND FUNCTION OF THE UROEPITHELIUM
EFFERENT INNERVATION OF THE URINARY BLADDER
INTRAVESICAL OXYBUTYNIN
AFFERENT INNERVATION OF THE URINARY BLADDER:
AI AND C FIBERS
VANILLOID PHARMACOLOGY
CLINICAL RESULTS OF INTRAVESICAL CAPSAICIN
CLINICAL RESULTS OF INTRAVESICAL RESINIFERATOXIN
TECHNIQUE OF INTRAVESICAL CAPSAICIN
AND RESINIFERATOXIN ADMINISTRATION
CONCLUSION
REFERENCES
Overactive bladder (OAB) is a recently defined symptom complex that includes urinary
urgency with or without urge incontinence, urinary frequency (voiding eight or more
times in a 24-h period), and nocturia (awakening two or more times at night to void)
(1–3). The overall prevalence of OAB in Western Europe and the United States is
16–17% (4,5). The symptoms of OAB can affect quality of life and are associated with
social, occupational, and psychological disruption.
Pharmacological treatment has become the cornerstone for treating OAB, with most
clinical therapies targeting the efferent branch of the micturition reflex. Oral antimus-
carinic drugs are currently the first-line pharmacological treatment for OAB, but these
medications are not always effective and are associated with side effects that can limit
their clinical use. As an alternative, intravesical (topical) therapies have been suggested
to achieve a profound inhibition of the overactive detrusor and to avoid high systemic
drug levels.
Currently available intravesical treatment options act either on the afferent arc of
the micturition reflex, such as vanilloids, or on the efferent cholinergic transmission to
the detrusor muscle, such as intravesical oxybutynin. Although intravesical oxybutynin
has been established as an effective therapy in patients with neurogenic bladder
dysfunction, it is not commonly utilized because of the need for frequent dosing via
urethral catheterization. Intravesical capsaicin has been shown to improve clinical

201
and urodynamic parameters in patients with various voiding dysfunction. This noxious
compound may, however, cause significant pain in some patients. Although the intra-
vesical instillation of resiniferatoxin (RTX) is a promising option, randomized placebo-
controlled studies to prove its safety and efficacy are still missing.
The exact mechanism of action for some of these agents is unknown, and the transport
of the drug across the urothelium is complex and not well understood. The penetration
of the agent to the target tissue depends on pressure gradients, time of exposure, pH of
the urine, molecular weight of the substance, degree of ionization of the molecule, and the
patient’s urinary output. All of these factors can potentially impact the efficacy of the
treatment. The purpose of this chapter is to review the various agents currently under-
utilized or under study for clinical use.
ANATOMY AND FUNCTION OF THE UROEPITHELIUM

The internal surface of the urinary bladder is lined with transitional epithelium. Three
distinct layers of the uroepithelium have been described (6). Large umbrella cells form
the superficial lining of the bladder urothelium. The permeability barrier of the urothelium
is maintained in this stratum by tight junctions that prevent the paracellular passage of
urinary solutes across this outer layer into the bloodstream. Umbrella cells are associated
with a group of crystalline protein plaques called uroplakins that also contribute to the
permeability barrier of the urothelium. Beneath the umbrella cell layer is the intermediate
layer of moderately sized cells and a basal layer of small cells (7).
In the bladder, suburothelial afferent fibers form a dense plexus that innervates the
both the detrusor itself and the basal layer of the urothelium (8). These afferent fibers
are critical for sending sensory input to the central nervous system. The uroepithelium
was once thought to serve only as a passive barrier to the contents of the bladder, but in
addition to its barrier function, there is a growing body of evidence that confirms
reciprocal communication between the neuronal system and the uroepithelium. This
implies that the uroepithelium likely plays a significant role in regulating bladder
activity via a number of neuronlike properties that modulate bladder sensory function
and may represent a potential novel therapeutic target for pharmacological intervention
for bladder dysfunction.
EFFERENT INNERVATION OF THE URINARY BLADDER

Acetylcholine, which interacts with muscarinic receptors on the detrusor muscle, is
the predominant peripheral neurotransmitter responsible for bladder contraction. Five
muscarinic receptor subtypes have been identified in the human bladder, with the M2
and M3 subtypes likely playing the greatest role in bladder contraction (9). Because
detrusor contractility is mediated by cholinergic muscarinic receptors, antimuscarinic
agents are the mainstay of therapy for OAB (10).
INTRAVESICAL OXYBUTYNIN
Oxybutynin, a nonselective antimuscarinic agent, has been extensively utilized
for over 30 yr in the management of lower urinary tract symptoms resulting from
detrusor overactivity (11). The efficacy of oxybutynin in the management of detrusor
overactivity has been confirmed in double-blind, placebo-controlled trials (12,13). Most
side effects have been related to the anticholinergic effects of oxybutynin, with dry
Chapter 13 / Intravesical Treatments for Overactive Bladder 203
mouth the most common complaint, often resulting in drug discontinuation or dosage
reduction (14–16).
Brendler et al. performed the first pilot study on the use of intravesical oxybutynin in
1989 (17). They reported the rationale to attempt intravesical treatment was that the
development of side effects could be minimized if systemic blood levels of oxybutynin
chloride could be reduced at the same time that high bladder tissue levels were achieved.
Oxybutynin was crushed and dissolved into 20 –30 mL water; then, the medication
was instilled twice daily with the solution retained for 30 min. In the 10 patients with
hyperreflexic bladders who were able to complete the study, the mean bladder capacity
increased from 224 to 360 mL, all 10 became continent, and the mean maximum filling
pressure decreased from 33 to 24 cm H2O. No side effects were observed. These findings
were corroborated by others, who demonstrated that intravesical oxybutynin has clinical
efficacy with minimal systemic side effects (18,19).
Despite the apparent efficacy of the intravesical administration of oxybutynin, this
mode of administration has not found widespread use. The need to catheterize multiple
times daily to instill this medication has limited its utility to patients on a regular schedule
of intermittent catheterization. In this population it does appear to be a safe, effective
and well-tolerated therapy.
AFFERENT INNERVATION OF THE URINARY BLADDER:

AI AND C FIBERS
Normal storage of urine is dependent on spinal reflex mechanisms that activate
somatic and sympathetic pathways to the bladder outlet and detrusor muscle as well as
tonic inhibitory pathways that suppress parasympathetic excitatory activity, leading to
detrusor relaxation and bladder filling. Micturition requires efferent nerve input to the
bladder from the spinal cord as well as afferent input from the bladder to the central
nervous system. Sensory information, including the sensations of bladder fullness and
pain, is conveyed to the spinal cord via afferent fibers in the pelvic and hypogastric
nerves. The most important afferents controlling the micturition process are small
myelinated AI fibers, which transmit signals mainly from mechanoreceptors that detect
wall tension and bladder fullness, and unmyelinated C fibers, which detect noxious
signals and initiate painful sensations (20–23). At other sites in the body, such as the
skin and mucous membranes, C-fiber afferents transmit nocioceptive information into
the central nervous system and modulate various reflex responses to noxious stimuli
such as hot temperatures.
Following suprasacral spinal cord injury, there is significant reorganization of micturi-
tion reflexes, which leads to the emergence of primitive spinal bladder reflexes triggered
by C-afferent neurons. Afferent C-fiber activation may also occur in infectious or irritative
conditions in the bladder and serve to facilitate or trigger voiding. This may be viewed
as a defense mechanism to eliminate bladder irritants or bacteria. Bladder wall C-fibers
may be responsible for afferent signals that trigger nonneurogenic detrusor overactivity.
As specific C-fiber neurotoxins, capsaicin and RTX, its ultrapotent analog, may be used
to study and treat lower urinary tract dysfunction (24).
VANILLOID PHARMACOLOGY
Current pharmacological treatment of the OAB relies on partially blocking the efferent
parasympathetic innervation to the detrusor with anticholinergic drugs. Often, these
Fig. 1. Chemical structures of capsaicin and resiniferatoxin.
drugs have troublesome side effects and are used in doses insufficient to provide signif-
icant clinical benefit. The afferent pathways of the voiding reflex may be targeted by
intravesical instillation of drugs with relative selectivity for sensory nerves. Capsaicin
and RTX are potent neurotoxins that desensitize these C-fiber afferent neurons that may
be responsible for signals that trigger detrusor overactivity.
Hot peppers have been eaten and used by humans since prehistorical times (25).
Hogyes, in 1878, reported that the pungent and irritant action of capsicol, an extract of
Capsicum, is mediated by sensory nerves (26). Capsaicin and its ultrapotent analog,
RTX, collectively belong to a class of neurotoxic agents referred to as vanilloids. RTX
is isolated from some species of Euphorbia, a cactuslike plant. These compounds are
characterized by a terminal homovanilloid moiety that interacts with a specific membrane
receptor (Fig. 1). The action of vanilloid compounds on sensory neurons is mediated via
interaction of the homovanilloid moiety with the vanilloid receptor TRPV1 (transient
receptor potential V1 or VR1 receptor), a nonspecific heat-gated cation channel that
mediates the influx of calcium and sodium resulting in depolarization of nociceptive
afferents to initiate a nerve impulse passing through the dorsal root ganglion into the
central nervous system (27,28). Vanilloid receptors are expressed not only by small
unmyelinated C fibers, but also by uroepithelial cells themselves.
As intracellular calcium levels rise, voltage-sensitive calcium channels are first
activated, leading initially to local transmitter release, and then inhibited, serving to
block the same response. Noxious temperatures are also sensed via this mechanism,
explaining the characteristic sensation of heat experienced when eating chili peppers
(29). Therefore, capsaicin mimics the action of physiological/endogenous stimuli that
activates the “nociceptive pathway.” At the molecular level, nociception is carried out
by ion channels or receptors.
Both capsaicin and RTX cause initial excitation of sensory neurons, with a sub-
sequent lasting refractory state termed desensitization. Jancso discovered that animals
treated with capsaicin, after a period of initial intense excitation of sensory neurons,
Table 1
Pungency of Capsaicin, Resiniferatoxin, and Various Peppers
Heat level comparison
Pepper Scoville value
Bell, sweet Italian 0–1
Perpperoncini 100–500
Jalapeño 1000
Cayenne 30,000–50,000
Thai 50,000–100,000
Jamaican hot 100,000–200,000
Habanero 100,000–300,000
Pure capsaicin 16,00,000
Resiniferatoxin 16,000,000,000
become unresponsive to noxious chemical stimuli and fail to develop inflammation

(30,31). Many studies have since confirmed this finding and established capsaicin as a
useful agent for the study of sensory neuron function (32).
Vanilloid Potency
The Scoville heat unit scale is commonly used commercially to compare the potency
of pepper strengths. Wilbur Scoville in 1912 calibrated the potency of peppers by
extracting capsicum in alcohol and diluting it until pungency was first detected after
placing a drop on his tongue (33). This technique has since been standardized using
high-pressure liquid chromatography. In fact, if all known peppers were measured using
this technique, then their scale of pungency would range from 1 Scoville unit for the bell
pepper up to 300,000 units for the habanero pepper. Pure capsaicin has a Scoville heat
unit score of 16 million, and RTX registers at 16 billion Scoville heat units, which is
1000 times the potency of capsaicin (Table 1).
Sensitization (Acute Excitatory Effects)

On first contact with capsaicin, afferent neurons are invariably stimulated, and there
seems to be no apparent difference whether the drug is applied to the peripheral or central
endings or to the cell bodies of sensory neurons. Administration of vanilloids to periph-
eral nerve endings results in depolarization and discharge of action potentials, which in
turn evokes a characteristic burning sensation via stimulation of C-fiber polymodal
nociceptors. Acute activation of the sensory neurons via the vanilloid receptor TRPV1
results initially in depolarization and transmitter (peptide) release with eventual neuronal
degeneration (34,35) (Fig. 2).
Desensitization (Secondary Neurotoxic Effects)

Following vanilloid-induced stimulation of primary afferent neurons, excitation subsides,
and the neurons become unresponsive to further applications of drug. Capsaicin desensiti-
zation is characterized by long-lasting, reversible suppression of sensory neuron activity
(36). The rate and duration of desensitization are related to the dose and time of expo-
sure to capsaicin and the time interval between consecutive dosing (37).
Fig. 2. The mechanism of vanilloid-induced neuronal excitation and desensitization.
Although C-fiber neurons have well-described afferent functions, they likely have
important efferent functions as well, including the local release in the periphery of sub-
stance P, neurokinin A, calcitonin gene-related peptides, and other neuropeptides that
directly and indirectly produce tissue inflammation (38–40). Desensitization of capsaicin-
sensitive nerve fibers is associated with eventual depletion of transmitter neuropeptides
(41–43).
CLINICAL RESULTS OF INTRAVESICAL CAPSAICIN

Hypersensitivity Disorders
Because capsaicin and RTX selectively activate sensory C fibers that convey information
about noxious stimuli to the central nervous system, the use of intravesical capsaicin
or RTX for interstitial cystitis and other types of sensory or inflammatory bladder
conditions is logical.
Maggi et al. reported the clinical urological application of intravesical capsaicin (44).
Intravesical instillation of capsaicin (0.1–10 RM) in six patients with bladder hypersensitivity
produced a concentration-related reduction of the first desire to void, bladder capacity, and
pressure threshold for micturition. All reported disappearance or marked attenuation of
their symptoms for a few days after capsaicin application. In three other patients,
intravesical instillation of the vehicle (0.1% ethanol in saline) alone did not produce
significant cystometric changes or modify the symptomatology, suggesting that capsaicin-
sensitive nerves exist in the human bladder. A second series of intravesical capsaicin, a
randomized placebo-controlled trial, in patients with bladder hypersensitivity confirmed
the beneficial effect of intravesical instillation of capsaicin on voiding parameters but did
not confirm improvement in pain score after capsaicin treatment compared to placebo (45).
Although intravesical capsaicin has been proposed as a treatment option for interstitial
cystitis, its utility has not been widely explored. One small pilot study of intravesical
capsaicin in five patients with interstitial cystitis using National Institute of Diabetes
and Digestive and Kidney Diseases criteria demonstrated subjective improvement in
both symptom and pain score in four of five patients (46).
Neurogenic Detrusor Overactivity

Fowler and associates reported the first clinical experience with capsaicin in neuro-
logically impaired patients with intractable incontinence caused by multiple sclerosis
and spinal cord injury (47,48). They reported that, after a single intravesical instillation
of capsaicin (1–2 mM) for 30 min, 10 of 14 patients exhibited an improved bladder
capacity for up to 9 mo without toxicity. Similar findings were noted in small studies in
other patients with neurogenic detrusor overactivity (49,50).
De Ridder et al. described the long-term outcome of intravesical capsaicin instillation
in 79 patients with spinal cord disease and treatment-resistant urinary incontinence (51).
Repeated intravesical instillation of intravesical 1–2 mM capsaicin in 30% ethanol
capsaicin was effective and persisted for up to 3–5 yr. In patients with phasic detrusor
hyperreflexia, complete continence was achieved in 44%, satisfactory improvement
occurred in 36%, and treatment failure occurred in 20%. Clinical benefit from a single
instillation lasted 3–6 mo and was repeated in some patients with similar improvement.
There was no clinical or urodynamic improvement in patients treated with the ethanol
vehicle alone and no reported long-term complications.
There have been only a few reported randomized placebo-controlled studies of
capsaicin in patients with neurogenic detrusor overactivity. The results of these trials have
been mixed. Wiart et al. reported that a single intravesical instillation of 1 mM capsaicin
resulted in clinical improvement with significant regression of urine leakage episodes
and urgency compared with those receiving vehicle (30% ethanol) alone (52). These
findings were supported by a later study in a similar population (53). A third placebo-
controlled crossover study of 12 patients by Petersen et al. showed no benefit to intravesical
capsaicin treatment therapy in patients with neurogenic detrusor overactivity (54).
Resiniferatoxin
RTX is an ultrapotent capsaicin analog present in the latex of the cactuslike plant
Euphorbia resinifera (55). It mimics most biological characteristics of capsaicin, with
approx 1000-fold higher potency and minimal initial acute excitatory effects (28). There
are significant differences in biologic response between RTX and capsaicin. RTX and
capsaicin show striking differences in relative potencies to excite and desensitize
primary sensory neurons. In most cases, when RTX and capsaicin differ in potency of
a particular biological end point, the response is such that RTX preferentially causes
desensitization, and capsaicin administration leads to profound excitation.
Intravesical RTX in concentrations as low as 100 nM induced full desensitization,
whereas capsaicin required 1 mM solutions to induce the same effect (56–58). In addi-
tion, 100 nM RTX solutions were much less irritating to bladder afferents than 1 mM
capsaicin solution. RTX-induced desensitization may occur at concentrations so low that
no noxious effect is elicited. Because of its potency and unique property of preferential
desensitization, there has been much interest in the application of RTX therapy for
patients with interstitial cystitis and detrusor overactivity.
CLINICAL RESULTS OF INTRAVESICAL RESINIFERATOXIN

Interstitial Cystitis
The positive findings of a number of small pilot studies evaluating the efficacy of
capsaicin in interstitial cystitis logically has led to interest in the utilization of RTX in
the treatment of this poorly understood condition. Most of these studies were poorly
controlled, but one small placebo-controlled study did suggest that RTX was effective
in the treatment of urinary frequency, urgency, and pelvic pain (59). A relatively large,
randomized, double-blind, placebo-controlled trial of a single dose of 0.01– 0.10 RM
RTX found that it was not effective in improving overall symptoms, pain, urgency,
frequency, nocturia, or voided volume during 12-wk follow-up (60).
Neurogenic Detrusor Overactivity
The first clinical use of RTX in patients with neurogenic detrusor overactivity was
reported by Cruz et al. in 1997 (56). They treated seven patients with intravesical instil-
lation of 50–100 nM RTX dissolved in 100 mL solution of 10% alcohol. Itching or mild
discomfort were the only symptoms evoked in four patients during the first minutes of
the treatment. Temporary exacerbation of bladder symptoms, as seen during the first
1–2 wk after capsaicin administration, did not occur. In five of the seven patients, urinary
frequency decreased by 33–58%, and this effect was detected as soon as the first day
after treatment. Three patients were incontinent and became dry most days. Improvement
was sustained up to 3 mo, the longest follow-up available. Four patients had urodynamic
improvement with a rise in maximum cystometric capacity, increasing from 50 to 900%
of pretreatment cystometric capacity.
Lazzeri et al. reported using intravesical RTX (10 nM) in eight normal patients and
seven patients with OAB (57). RTX did not decrease the volume required to elicit the first
desire to void and did not produce warm or burning sensations at the suprapubic or urethral
level during infusion in normal subjects. Mean capacity increased significantly in patients
with overactivity immediately after instillation but was not significantly increased after
4 wk. As a group, there was no significant improvement in bladder capacity, but two
patients with detrusor hyperreflexia did improve urodynamically in conjunction with
clinical improvement in frequency, nocturia, and incontinence episodes.
Although the results of several small studies suggest that intravesical RTX may have
a role in the treatment of refractory neurogenic detrusor overactivity, its efficacy has not
been conclusively confirmed in any randomized controlled trials (61– 64). RTX has
been demonstrated to adsorb to polyethylene, polyvinylchloride, and latex (but not silicone
or glass) catheters and containers. These materials were used in some of these studies,
possibly leading to lower-than-expected drug delivery, thereby confounding the results
obtained (Afferon Corp., Wayne, PA, unpublished data).
A double-blind, randomized, controlled study comparing the efficacy and tolerability
of RTX to capsaicin demonstrated significant clinical improvement in approximately
two-thirds of patients with neurogenic detrusor overactivity for 90 d after treatment with
either agent (65). Patients in the capsaicin arm were treated with capsaicin dissolved in
a novel glucidic solvent; the RTX used in this study was diluted in 10% ethanol. There
were no significant differences in the incidence, nature, or duration of side effects in
capsaicin- vs RTX-treated patients, suggesting the importance of considering the role of
vehicle solvent when interpreting the efficacy and tolerance of vanilloid instillation.
RTX has also been compared with intravesical botulinum type A toxin injections into
the detrusor muscle in patients with spinal cord injury and refractory detrusor overactivity
(66). With both treatments, there was a significant reduction in mean catheterization and
episodes of incontinence and a significant increase in mean first involuntary detrusor
contraction and in mean maximum bladder capacity at 6, 12, and 24 mo after therapy.
Both RTX and botulinum type A toxin resulted in beneficial clinical and urodynamic
results, with reduction of detrusor overactivity and restoration of urinary continence in
most patients. Botulinum type A toxin injection, however, provided better clinical and
urodynamic benefits than intravesical RTX.
Nonneurogenic Detrusor Overactivity
Enthusiasm for intravesical RTX as a treatment for neurogenic detrusor overactivity
has lead to its investigation as a potential therapy for nonneurogenic detrusor overactivity.
RTX instillation may delay or suppress involuntary detrusor contractions and increase
mean maximal cystometric capacity for at least 90 d (67). Relatively modest improve-
ments in clinical symptoms have been noted in several studies of patients with non-
neurogenic detrusor overactivity (68–70). To date, there has been no well-controlled
randomized trial.
TECHNIQUE OF INTRAVESICAL CAPSAICIN

AND RESINIFERATOXIN ADMINISTRATION
Neither capsaicin nor RTX is currently approved for routine clinical intravesical use.
Insertion of a small silicone urethral catheter with balloon occlusion of the bladder neck
is recommended. Care must be taken to avoid contact with polyethylene, polyvinylchlo-
ride, or latex, which may result in a diminished effective administered dose. Intravesical
lidocaine is commonly instilled prior to drug administration. Although a 1–2% lidocaine
solution is most commonly utilized, there is evidence that 4% lidocaine may improve
tolerability (61).
Capsaicin has generally been used utilized as l–2 mM solution dissolved in 30%
ethanol in saline. RTX is administered as a 0.05– 0.10 RM solution 10% ethanol. Both
agents are typically left in the bladder for approx 30 min.
CONCLUSION
Intravesical instillation of pharmacological agents appears to be a promising therapy
for the treatment of neurogenic and nonneurogenic detrusor overactivity. Although
direct instillation of oxybutynin appears to be effective, this mode of administration has

not been widely adopted because of the need for frequent instillation of this agent.
A single instillation of the vanilloids capsaicin or RTX, however, may result in long-
lasting desensitization of sensory nerves on the afferent limb of the voiding reflex without
systemic side effects. Numerous studies have demonstrated improvement in lower urinary
tract symptoms with minimal long-term complications. Despite over a decade of experience
with these neurotoxic agents, however, the true efficacy of these compound has not been
clearly defined. RTX, which appears to have efficacy similar to capsaicin but with fewer
side effects, holds greater promise as a safe, effective treatment for detrusor overactivity.
Prospective randomized, placebo-controlled studies are necessary to truly define the role
of intravesical vanilloid therapy in the management of patients with OAB.
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14 Urological Applications
of Botulinum Toxin
Courtenay K. Moore, MD
and Howard B. Goldman, MD
CONTENTS
INTRODUCTION
APPLICATIONS IN UROLOGY
INJECTION TECHNIQUES
ADVERSE EVENTS AND CONTRAINDICATIONS
CONCLUSION
REFERENCES
INTRODUCTION
Botulinum toxin is a neurotoxin produced by the Gram-positive, rod-shaped anaerobic
bacterium Clostridium botulinum (1). First discovered in 1897 by Professor Pierre
Emile van Ermengem of Ellezelles, Belgium botulinum toxin is the most poisonous
naturally occurring toxin known to man (2). Seven immunologically distinct antigenic
subtypes of botulinum toxin have been isolated: A, B, C1, D, E, F, and G (1). Only types
A and B are available for use clinically. Botulinum type A toxin (BTX-A), known as
Botox® in the United States and Dysport® in the United Kingdom, is more potent and has
a longer duration of action than type B (1,2). Type B is commercially available in the
United States as MyoBloc® and in Europe as NeuroBloc® (2).
Botulinum toxin exerts its effects by binding to the peripheral cholinergic terminals
and inhibiting the release of acetylcholine at the neuromuscular junction. As a result,
flaccid paralysis ensues. There are four steps involved in this process: binding, trans-
location, cleavage, and inhibition of neurotransmitter release (2). Botulinum toxin is
made within the bacterial cytosol and released as a 150-kDa polypeptide chain (2).
Proteolytic cleavage results in a heavy (100 kDa) and light (50 kDa) chain, which are
linked by heat labile disulfide bonds (1). Neither chain can exert neurotoxicity inde-
pendently (1). The heavy chain is responsible for binding to the nerve terminal at the
neuromuscular junction. The light chain, which is internalized by endocytosis, actively
cleaves a specific site on the protein complex responsible for docking and release of
vesicles containing neurotransmitters into the neuromuscular junction (1,3). By cleav-
ing protein receptors within the nerve terminals, botulinum toxin prevents the normal
vesicular transport and release of acetylcholine from the motor nerve terminals into
the neuromuscular junction (2).

213
Based on histological evidence, recovery of chemodenervation occurs after 3–6 mo.

This results from the turnover of the presynaptic molecules and nerves sprouting from
the nerve terminal forming a new functional synapse (1). Affected nerve terminals do
not degenerate, and axonal sprouting and formation of new synaptic contacts can
recover function. The time necessary to recover function after botulinum toxin paralysis
depends on the subtype of botulinum toxin as well as the type of nerve terminal (2).
Chemodenervation lasts between 3 and 6 mo when injected into the neuromuscular
junction of skeletal muscle and considerably longer, up to 1 yr, when injected into the
autonomic neurons of smooth muscle (2,3).
APPLICATIONS IN UROLOGY
Botulinum toxin was first approved by the Food and Drug Administration in 1989 for
use in patients with strabismus and blepharospasm (1). Since then, its use has been
extended to cervical dystonia, cosmesis, hypersecretory disorders, and overactive
muscle disorders. Although not Food and Drug Administration approved, botulinum
toxin has been used in urology to treat neurogenic and nonneurogenic detrusor over-
activity (DO), detrusor-sphincter dyssynergia (DSD), motor and sensory urge, and more
recently chronic pain syndromes.
Detrusor Overactivity in Adults

The use of botulinum toxin in neurogenic DO was first pioneered by Schurch in
2000 (2). BTX-A (200 or 300 U) was injected into the trigone of 21 spinal cord injury
(SCI) patients with DO and urge incontinence managed with clean intermittent
catheterization (4). At 6 wk, 17/19 patients were completely continent. Urodynamic
evaluation revealed significant increases in mean reflex volume, maximum cystometric
capacity, and postvoid residual urine and a decrease in detrusor voiding pressure. Of
the 11 patients available for follow-up at 16 and 36 wk, improvements in bladder func-
tion and urodynamic parameters persisted. Similarly, significant increases were noted
in cystometric bladder capacity, reflex volume, and bladder compliance and a decrease
in mean voiding pressures in a retrospective multicenter European study of 200 patients
with neurogenic DO (5).
Schurch compared two different doses of BTX-A in a double-blind, multicenter,
randomized, placebo-controlled study of 59 patients with neurogenic DO (6). Over 24 wk,
there was rapid and sustained reduction in the number of incontinence episodes, increase
in maximum cystometric capacity, and decease in mean detrusor pressure.
In a study of 66 patients with neurogenic DO, Grosse et al. examined the effect of
repeat detrusor injections of BTX-A. After each BTX-A injection, cystometric capacity
and reflex volume increased significantly, and the number of reflex contractions
decreased significantly from baseline (7). Repeat injections were as effective as the first
injection, indicating no evidence of drug resistance.
Given the benefits of botulinum toxin in patients with neurogenic DO, its use has
been expanded to patients with idiopathic refractory DO. Dykstra et al. conducted a
pilot study looking at the dose-escalation study of Botox-B in 15 women with idio-
pathic DO. All but one patient reported decreased urgency and frequency and no
incontinence (8). Although the degree of response was similar among all doses, the
duration of response was dose dependent, with the greatest duration seen at 10,000
and 15,000 U.
Chapter 14 / Urological Applications of Botulinum Toxin 215
Rapp et al. also looked at the effect of BTX-A in the management of 35 patients with
urgency, frequency, and urge incontinence (9). At 3 wk, the mean Incontinence Impact
Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) decreased significantly.
Overall, 60% of patients experienced improvement in voiding symptoms.
Rajkumar et al. had similar improvements using 300 U BTX-A in 15 women with
refractory idiopathic DO (10). In 14 of the patients, symptoms of urgency and fre-
quency improved immediately after treatment. Urodynamics revealed an increased
volume at first desire in 13 patients, an increase in maximum cystometric capacity in
10 patients, and elimination of DO in 6 patients. The improvement in symptoms
lasted up to 24 wk.
Although studies support the use of BTX-A in both neurogenic and idiopathic DO,
few studies have sought to answer the question in which population (neurogenic or idio-
pathic DO) is BTX-A most effective? Popat et al. in an open-label prospective study
compared the 4-d voiding diaries and urodynamics of 44 patients with neurogenic DO
to 31 patients with idiopathic DO (11). At 16 wk, both groups had an increase in max-
imum cystometric capacity, a decrease in maximum detrusor pressure, a decrease in the
number of voids per 24 h, and a decrease in the number of incontinent episodes. Patients
with neurogenic DO were more likely to require self-catheterization (69%) than those
patients with idiopathic DO (19.3%) (11). This difference may be partly because of the
differences in treatment dose; patients with neurogenic DO received 300 U BTX-A;
patients with idiopathic DO received 200 U.
Detrusor Overactivity in Children
Unlike the adult urology literature, there are only four published articles on the use
of BTX-A in children with neurogenic DO (12). In the first published study, 20 chil-
dren (median age 11.4 yr) with neurogenic DO were injected with 12 U/kg BTX-A
up to a maximum of 300 U at 30–50 sites (13). Urodynamic follow-up 2– 4 wk after
injections revealed significant increases in mean reflex volume and maximal bladder
capacity as well as a decrease in maximal detrusor pressure (13). At 6 mo, the change
in maximal bladder capacity persisted; however, the decrease in maximum detrusor
pressure did not.
Riccabona et al. looked at the effects of trigone-sparing BTX-A injections (10 U/kg
up to a maximum of 360 U) in 15 patients with myelomeningocele (mean age 5.8 yr)
(14). After the first injection, statistically significant changes were noted in mean reflex
volume, maximum detrusor pressure, maximum bladder capacity, detrusor compliance,
and urinary continence. Yet, unlike Schulte-Baukloh’s study, the mean durability of the
BTX-A injections was 10.5 mo (13).
Like adults, children show no evidence of drug tolerance after repeat BTX-A
injections. In a study by Schulte-Baukloh et al. of 10 children with neurogenic DO who
had undergone at least three BTX-A injections, there were no statistically significant
differences in urodynamic parameters between injections. The urodynamics outcomes
after the first BTX-A injections were similar to urodynamics outcomes after the third
and fifth injections (15).
To date there is only one published study on the use of BTX-A in children with
idiopathic DO (12). Eleven children (mean age 10 yr) with idiopathic DO refractory to
medical therapy were injected with either 125 or 250 U BTX-A (16). The patients
experienced an increase in functional bladder capacity and a decrease in idiopathic DO
and urgency symptoms.
Detrusor Sphincter Dyssynergia

The most widespread application of Botox for urethral conditions is for external
sphincter dyssynergia (3). Dykstra, in 1988, was the first to use botulinum toxin for
DSD (4). In a study of 11 patients with SCIs and DSD, Dykstra et al. injected BTX-A
into the external urethral sphincter (17). Of the 11 patients, 10 showed signs of sphincter
denervation on electromyography. Urethral pressure profiles and postvoid residual
volumes were decreased.
The largest series assessing the effect of BTX-A on patients with SCI and DSD was
conducted by Schurch et al. in 1996 (18). Three different protocols using two different
formulations of BTX-A toxin were injected into 24 patients; 87% (21/24) of patients
had improvements in urodynamic parameters regardless of the protocol or formulation
used. Complete disappearance of DSD was noted in 8/21 patients; mean maximum
urethral pressure during DSD decreased by 48%, mean duration of DSD decreased by
47%, and mean urethral sphincter pressure decreased by 20%.
More recently, de Seze et al. in a randomized, double-blind, lidocaine-controlled study
of 13 SCI patients with DSD, found botulinum toxin to significantly reduce postvoid resi-
duals and maximal urethral pressures at 1, 7, and 30 d when compared to lidocaine (19).
Urinary Retention/Voiding Dysfunction

Several studies have looked at the role of BTX-A injections into the external urethral
sphincter in patients with voiding dysfunction and urinary retention. Phelan et al., in a
prospective study of 21 patients with voiding dysfunction, injected 80–100 U BTX-A
into the external urethral sphincter. After the BTX-A injection, all but one patient were
able to void spontaneously, and all but two discontinued catheterization (20).
Kuo looked at the clinical effects and urodynamic parameters of 50 U BTX-A in 103
patients with various types of lower urinary tract dysfunction. Overall, 84.5% of patients
had a decrease in maximum voiding pressure, maximal urethral closure pressure, and
postvoid residual (21). Indwelling Foley catheters and clean intermittent catheterization
were discontinued in 87% of patients.
Pelvic Pain/Chronic Prostatic Pain/Interstitial Cystitis

Although several studies have begun to explore the use of BTX-A in the treatment of
pelvic pain, the mechanism of action by which BTX produces an antinociceptive effect
is unknown. Animal studies have shown that, in addition to blocking acetylcholine
release from motor neurons, BTX also inhibits the release of neurotransmitters involved
in sensory pathways (3). BTX has been shown to inhibit the release of substance P and
glutamate, neuropeptides involved in sensory and nocioceptive pathways (3). In another
cyclophosphamide-induced cystitis animal model, BTX-A inhibited the afferent neural
response via inhibition of mechanoreceptor-mediated release of adenosine triphosphate,
suggesting that intravesical instillation of BTX-A may alleviate the clinical symptoms
of urgency, frequency, and pain (22).
In an acetic acid-induced rat bladder pain model, calcitonin gene-related peptide, a
capsaicin-sensitive neuropeptide that helps regulate micturition and mediates painful
bladder sensation, was reduced in animals that received intravesical Botox. This finding
suggests that BTX inhibits calcitonin gene-related peptide release, thereby suppressing
bladder pain (23).
Clinically, the literature on BTX in the treatment of pelvic pain syndromes is limited.
Zermann et al. performed transurethral perisphincteric injection of BTX-A into 11 men
with chronic prostatic pain (24). Of the 11 patients, 9 reported subjective pain relief, with
an average decrease in pain on a visual analogue scale from 7.2 to 1.6. Postinjection
urodynamics showed a decrease in functional urethral length, urethral closure pressure,
and postvoid residual and an increase in the peak and average flow rates.
Jarvis et al. conducted a pilot study evaluating the effect of BTX-A injection into the
levator ani of 12 women with chronic pelvic pain and pelvic floor hypertonicity (25).
Under conscious sedation, women were injected with 40 U BTX-A into the puborectalis
and pubococcygeus bilaterally. Pelvic floor manometry showed a 37% reduction in
resting pressure at week 4 and a 25% reduction at week 12. Significant improvements
were noted in quality of life, dyspareunia, nonmenstrual pelvic pain, and dyschesia but
were not statistically significant.
Two studies looked at the antinociceptive effect of BTX on patients with interstitial
cystitis (IC). The first study conducted at the Cleveland Clinic Foundation and retro-
spectively evaluated the effect of two different treatment protocols on 10 patients meeting
the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC. The
first five patients received submucosal injections; the second five received intravesical
instillations. Neither group showed statistically significant changes in subjective or objec-
tive outcome measures (3).
The second study, conducted by Smith et al., injected the detrusor of 13 female
patients with refractory IC (26). Overall, 69% of patients noted subjective improvement.
Statistically significant improvements were noted in the Interstitial Cystitis Symptom
Index and Interstitial Cystitis Problem Index as well as daytime frequency, nocturia, and
pain. On urodynamics, statistically significant improvements were noted in first desire
to void and maximum cystometric capacity.
INJECTION TECHNIQUES
Bladder
This procedure is routinely performed in the outpatient setting. With the patient in the
lithotomy position, 100 cc 2% lidocaine solution are instilled in the bladder and allowed
15–20 min to take effect (3). In females, a 23-French rigid cystoscope with a collagen
injection needle is inserted per urethra. In males, the flexible cystoscope is used.
Depending on the institution, the bladder is injected with 100 –300 U Botox. Each vial
of Botox contains 100 U. Each vial is diluted into 3 mL normal saline, yielding a con-
centration of 33.3 U/1 mL. Approximately 30 submucosal injections are made into the
detrusor muscle, avoiding extravasation into the bladder serosa. Some have anecdotally
reported better results when diluting each 100 U Botox into 10 mL saline, yielding a
concentration of 10 U/1.0 mL. Theoretically, this may allow for greater dispersal of the
Botox within the detrusor muscle.
Injection sites vary, depending on whether the trigone-sparing technique is used. If
the trigone-sparing technique is used, then the 30 injections are distributed between the
bladder base and lateral walls, sparing the trigone (Fig. 1). If the trigone is injected, then
six injections (or 20% of the total volume) are injected into the trigone. Proponents of
trigonal injection argue that, by placing Botox in the trigone, an area of greater nerve
density, patients will have a better clinical response. However, opponents argue that
Fig. 1. Cystoscopic injection of BTX-A into the detrusor muscle. (Courtesy of the Cleveland Clinic
Foundation, Cleveland, OH.)
trigonal injection could result in distal ureteral paralysis and subsequent ureteral reflux.
This theoretical concern has not been observed clinically.
Urethral
The urethra can be injected in one of two ways: cystoscopically or periurethrally. The
first involves localization of the external sphincter using the rigid cystoscope and
collagen needle, and 100–200 U are injected into the sphincter under direct vision
equally at 3, 6, 9, and 12 o’clock (26). In women, an alternate technique, the periurethral
technique, can be performed easily. Using a spinal needle, 100–200 U Botox are injected
into the external sphincter muscle at the 2 and 10 o’clock positions (Fig. 2). Additional
guidance with auditory or needle electromyography may provide further confirmation
of the appropriate injection site.
ADVERSE EVENTS AND CONTRAINDICATIONS

Side effects of BTX are rare when used for urological applications. Not only are
the injections localized with little systemic absorption, but also the doses are well below
(a thousandth) the presumed fatal dose in a 70-kg male (2). However, in 2002 Wyndaele
and Van Dromme reported two cases of generalized muscle weakness in paraplegic and
tetraplegic patients (1,2). Interestingly, both patients had return of bladder spasticity
within 2 mo, prompting the authors to speculate that there was perivesical diffusion
through these thin-walled bladders (2). In addition, patients should be warned about
the possibility of urinary retention after BTX secondary to detrusor hypocontractility.
Repeat injection of BTX-A can cause immune responses in less than 5% of patients.
Patients undergoing repeat injections are at risk of forming neutralizing antibodies that
interfere with the efficacy of Botox therapy (3). Therefore, the use of other BTX
Fig. 2. Peri-urethral injection of BTX-A into the external splincter muscle at 2 and 10 o’clock
(X).(Courtesy of the Cleveland Clinic Foundation, Cleveland, OH.)
serotypes that do not cause immune reactions, like BTX-C, are under investigation
(2). In patients receiving Botox injections for cervical dystonia, spacing injection
cycles by a minimum of 12 wk has drastically reduced the formation of neutralizing
antibodies (3).
Contraindications to Botox injections include patients with a preexisting neuromuscular
disease such as myasthenia gravis, Eaton-Lambert syndrome, and amyotrophic lateral
sclerosis (Lou Gherig disease) (2,3). Botox should also be avoided in patients who are
breast-feeding, pregnant, or using agents that potentate neuromuscular weakness, such
as aminoglycosides (2,3). Patients should be informed that some formulations of BTX
include stabilizers such as albumin derived from human blood, which may be of religious
or cultural significance (3).
CONCLUSION
Botulinum toxin therapy is emerging as an alternative therapeutic option in adults
with debilitating chronic urological conditions such as DSD, neurogenic and nonneuro-
genic DO, and pelvic pain syndromes. The use of botulinum toxin is rapidly expanding
to include the pediatric population as well as patients with visceral pain syndromes.
Given its low side-effect profile and duration of action (9–12 mo), botulinum toxin
offers an attractive alternative to conservative medical therapy and invasive surgery.
REFERENCES
1. Leippold T, Reitz A, Schurch B. Botulinum toxin as a new therapy option for voiding disorders:
current state of the art. Eur Urol 2003;44:165.
2. Sahai A, Khan M, Fowler CJ, et al. Botulinum toxin for the treatment of lower urinary tract symptoms:
a review. Neurourol Urodyn, 2005;24:2.
3. Frenkl TL, Rackley RR. Injectable neuromodulatory agents: botulinum toxin therapy. Urol Clin North
Am 2005;32:89.
4. Schurch B, Stohrer M, Kramer G, et al. Botulinum-A toxin for treating detrusor hyperreflexia in spinal
cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol 2000;164:692.
5. Reitz A, Stohrer M, Kramer G, et al. European experience of 200 cases treated with botulinum-A toxin
injections into the detrusor muscle for urinary incontinence to neurogenic detrusor overactivity. Eur
Urol 2004;45:510.
6. Schurch B, de Seze M, Denys P, et al. Botox Detrusor Hyperreflexia Study Team. Botulinum toxin
type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment,
randomized, placebo controlled 6-month study. J Urol 2005;174:196–200.
7. Grosse J, Kramer G, Stohrer M. Success of repeat detrusor injections of botulinum A toxin in patients
with severe neurogenic detrusor overactivity and incontinence. Eur Urol 2005;47:653.
8. Dykstra D, Enriquez A, Valley M. Treatment of overactive bladder with botulinum toxin type B: a pilot
study. Int Urogynecol J Pelvic Floor Dysfunct 2003;14:424.
9. Rapp DE, Lucioni A, Katz EE, et al. Use of botulinum-A toxin for the treatment of refractory overactive
bladder symptoms: an initial experience. Urology 2004;63:1071.
10. Rajkumar GN, Small DR, Mustafa AW, et al. A prospective study to evaluate the safety, tolerability,
efficacy and durability of response of intravesical injection of botulinum toxin type A into detrusor
muscle in patients with refractory idiopathic detrusor overactivity. BJU Int 2005;96:848.
11. Popat R, Apostolidis A, Kalsi V, et al. A comparison between the response of patients with idiopathic
detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botu-
linum-A toxin. J Urol 2005;174:984.
12. Schurch B, Corcos J. Botulinum toxin injections for paediatric incontinence. Curr Opin Urol 2005;15:264.
13. Schulte-Baukloh H, Michael T, Sturzebecher B, et al. Botulinum-a toxin detrusor injection as a novel
approach in the treatment of bladder spasticity in children with neurogenic bladder. Eur Urol 2003;44:139.
14. Riccabona M, Koen M, Schindler M, et al. Botulinum-A toxin injection into the detrusor: a safe alter-
native in the treatment of children with myelomeningocele with detrusor hyperreflexia. J Urol 2004;
171:845.
15. Schulte-Baukloh H, Knispel HH, Stolze T, et al. Repeated botulinum-A toxin injections in treatment
of children with neurogenic detrusor overactivity. Urology 2005;66:865.
16. Schulte-Baukloh H, Michael T, Sturzebecher B, Knispel HH. Botulinum-a toxin detrusor injection as a
novel approach in the treatment of bladder spasticity in children with neurogenic bladder. Eur Urol
2003;44:139–143.
17. Dykstra DD, Sidi AA, Scott AB, et al. Effects of botulinum A toxin on detrusor-sphincter dyssynergia
in spinal cord injury patients. J Urol 1988;139:919.
18. Schurch B, Hauri D, Rodic B, et al. Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia:
a prospective study in 24 spinal cord injury patients. J Urol 1996;155:1023.
19. de Seze M, Petit H, Gallien P, et al. Botulinum a toxin and detrusor sphincter dyssynergia: a double-
blind lidocaine-controlled study in 13 patients with spinal cord disease. Eur Urol 2002;42:56.
20. Phelan MW, Franks M, Somogyi GT, et al. Botulinum toxin urethral sphincter injection to restore
bladder emptying in men and women with voiding dysfunction. J Urol 2001;165:1107.
21. Kuo HC. Botulinum A toxin urethral injection for the treatment of lower urinary tract dysfunction.
J Urol 2003;170:1908.
22. Smith CP, Vemulakonda VM, Kiss S, et al. Enhanced ATP release from rat bladder urothelium during
chronic bladder inflammation: effect of botulinum toxin A. Neurochem Int 2005;47:291.
23. Chuang YC, Yoshimura N, Huang CC, et al. Intravesical botulinum toxin a administration produces
analgesia against acetic acid induced bladder pain responses in rats. J Urol 2004;172:1529.
24. Zermann D, Ishigooka M, Schubert J, et al. Perisphincteric injection of botulinum toxin type A.
A treatment option for patients with chronic prostatic pain? Eur Urol 2000;38:393.
25. Jarvis SK, Abbott JA, Lenart MB, et al. Pilot study of botulinum toxin type A in the treatment of
chronic pelvic pain associated with spasm of the levator ani muscles. Aust N Z J Obstet Gynaecol
2004;44:46.
26. Smith CP, Radziszewski P, Borkowski A, et al. Botulinum toxin a has antinociceptive effects in treating
interstitial cystitis. Urology 2004;64:871.
15 Nonsacral Neuromodulation
Richard C. Bennett, MD, Andrew Bernstein, MD,

and Kenneth M. Peters, MD
CONTENTS
INTRODUCTION
TIBIAL NERVE STIMULATION
ANOGENITAL ELECTRICAL STIMULATION
PUDENDAL NERVE STIMULATION
CONCLUSION
REFERENCES
INTRODUCTION
Neuromodulation is becoming a mainstay as a treatment modality for idiopathic
voiding dysfunction. Neuromodulation and neurostimulation have been applied to the
sacral nerves and their more distal branches at the level of the anus, vagina, and penis.
Sacral nerve stimulation has been approved by the Food and Drug Administration
(FDA) since 1997 for the treatment of urinary urge incontinence, urgency, frequency,
and refractory retention. Neuromodulation utilizing more distal branches of the sacral
nerve roots may have added outcome-related benefits and can be less invasive.
TIBIAL NERVE STIMULATION

Percutaneous posterior tibial nerve stimulation has emerged as a form of neuromodu-
lation that is both inexpensive and minimally invasive. The posterior tibial nerve is a
mixed nerve containing L5–S3 fibers, and it originates from the same spinal segments as
the parasympathetic innervation of the bladder. Stimulation of the nerve inhibits bladder
activity by depolarizing somatic sacral and lumbar afferent fibers. Afferent stimulation
provides central inhibition of the preganglionic bladder motor neurons through a direct
route in the sacral cord (1).
Tibial nerve stimulation was first described in 1983. McGuire and colleagues
showed efficacy in the treatment of a variety of voiding dysfunctions related to detrusor
overactivity by electrical stimulation of the tibial nerve. His group reported on 16
patients with involuntary bladder contractions of varying etiology who were treated
with common peroneal or posterior tibial nerve patch electrode stimulation. Initially,
12 patients were dry, 3 were improved, and 1 was “possibly improved” (2). Okada
and coworkers in 1998 reported a positive experience with transcutaneous stimulation
of the thigh muscle in 19 patients with detrusor overactivity; the maximal cystometric
capacity was increased by 57% in 11 of 19 patients (3). Vereecker and associates,
221
however, were unable in 1984 to suppress hyperactivity by this method in patients with
suprasacral spinal cord injury or disease (4).
Posterior tibial nerve stimulation is typically performed with patients in the supine
position with the knees abducted and the soles of the feet together. A 34-gage needle is
inserted 3 cm into the skin at a level three fingerbreadths cephalad to the medial malleolus.
An electrode is placed on the arch of the ipsilateral foot (Fig. 1). The amplitude of the
stimulation is increased until the large toe curls or the toes fan. Each session lasts for
approx 30 min.
Vandoninck et al. in 2004 reported on their outcomes in 39 patients with chronic
voiding dysfunction who were treated with tibial nerve stimulation. All patients had
detrusor underactivity with elevated postvoid residual urine or complete urinary
retention; each patient performed self-catheterization. Each patient underwent 12
weekly tibial nerve stimulations at the medial malleolus for 30 min each. In measuring
objective success, the primary outcome was measured as total voided volume along
with total catheterized volume. In 41% of the patients, 24-h catheterized volume was
reduced by 50%. An additional 26% noted 25–50% reduction in their residuals.
Subjectively, 59% of the patients chose to continue treatment. Urodynamic testing
was also performed. Although patients’ cystometric capacity remained the same,
detrusor pressure at maximum flow increased from 25 to 33 cm H2O, a statistically
significant difference. In addition, both the bladder contractility index (BCI = Pdet ×
Qmax + 5 × Qmax) as well as the bladder voiding efficiency [BVE = 100 × (Voided
volume/Total bladder capacity)] showed statistically significant increases. Detrusor
instability did exist in five patients at baseline. After stimulation, detrusor instability
appeared in three patients, disappeared in two, and appeared de novo in seven patients.
No significant side effects were reported (5).
Van Balken et al. reported on their treatment of patients with bladder overactivity as
well as idiopathic urinary retention. In 37 patients with overactive bladder, 22 reported
subjective improvement and requested continuation of therapy. However, all 37 showed
significant improvement in day and night voiding frequency. In 30 urge incontinent
patients, all 30 showed reduction in their incontinent episodes, pad use, and severity of
leakage. Finally, for 12 patients with idiopathic urinary retention, a decrease in number
and volume of catheterizations was reported, but this did not reach statistical significance.
They concluded that percutaneous tibial nerve stimulation is a promising, cost-effective,
and easily applicable treatment for lower urinary tract dysfunction (6).
Ruiz reported on 51 patients treated over 3 yr for similar symptom complexes; 25
patients described the frequency-urgency syndrome, 22 described urge incontinence,
and 3 carried a diagnosis of interstitial cystitis (IC). Patients underwent 10, 30-min
sessions in which the tibial nerve was stimulated using a similar technique as in prior
articles. Mean follow-up was 21 mo. Across the entire patient population, they reported
statistically significant improvement in all seven categories measured: daytime frequency,
daytime voided volume, daytime leakage episodes, nighttime frequency, nighttime leakage
episodes, nighttime voided volume, and hypogastric/suprapubic pain (7).
Posterior tibial nerve stimulation was also evaluated in the acute setting by Amarenco
et al. in 2003. They studied 44 patients with irritative lower urinary tract symptoms,
including uninhibited detrusor contractions as seen on filling cystometrogram (CMG).
The etiology was demonstrable in 37 patients, including multiple sclerosis, spinal cord
injury, brain injury, and Parkinson’s disease; the remaining 7 patients had idiopathic detru-
sor overactivity. Cystometry was performed at a rate of 50 cc/min using an 8-French
Chapter 15 / Nonsacral Neuromodulation 223
Fig. 1. Stimulation of the posterior tibial nerve.
catheter. Patients were filled until they experienced uninhibited bladder contractions,
leakage was observed, or they achieved a volume of 400 cc. A CMG was performed
again after posterior tibial nerve stimulation was initiated. A positive test consisted of
an increase in the bladder volume at which a contraction occurred of 100 cc or greater
or if that involuntary contraction occurred at a bladder volume that was 50% greater
than baseline. Of 44 cases, 22 (50%) tested positive. Further urodynamic data were
collected. Mean bladder volume at which the first involuntary contraction occurred was
162 cc at baseline and increased to 232 cc after stimulation. Maximum cystometric
capacity was 221 cc at baseline, which increased to 277 cc after stimulation (1).
Finally, posterior tibial nerve stimulation has been applied to the IC population, a
subset of patients with voiding dysfunction. Zhao et al. applied posterior tibial nerve
stimulation to 14 patients diagnosed with IC. Patients were treated during a total of 10,
30-min sessions. One patient withdrew from the study, leaving 13 patients who com-
pleted the course of therapy. The results did not meet clinical significance in pain,
voided volume, and quality-of-life scores (8).
Clearly, neuromodulation is a feasible, efficient, and effective treatment modality for
a variety of lower urinary tract dysfunctions. Posterior tibial nerve stimulation has
emerged as a subdivision of this growing field. The lure of the tibial nerve is that it is
easily accessible without requiring an operating room or an anesthetic. As with all novel
techniques, the data were initially anecdotal and are now becoming more standardized.
Studies with modest numbers have shown efficacy. Larger studies need to be performed,
particularly in a randomized, blinded fashion to truly examine the long-term efficacy of
this exciting technique.
ANOGENITAL ELECTRICAL STIMULATION

Literature began to appear in the 1970s regarding the treatment of overactive bladder
with electrical stimulation. The technique can now be considered an established
treatment option (9). An overall review of the literature since that time shows a dichotomy
of response rates and cure rates.
The method of anogenital stimulation is via vaginal/anal plugs equipped with electrodes
or circular penile electrodes. Two strategies exist for anogenital electrical stimulation:
long term and short term. Long-term outpatient stimulation is mainly used to treat stress
incontinence. This form of treatment requires months of home stimulation for several
hours per day. Short-term treatment consists of maximal stimulation for a limited number
of 10- to 15-min sessions. Maximal stimulation utilizes the highest intensity the patient
will tolerate, usually 1.5–2 times the perception threshold (10). This form of treatment
can be either home based or in the physician’s office. Optimal results have been reported
using a frequency of 20 Hz in the physician-supervised setting (11). The minimum
number of treatments is not well established. Primus and Kramer found that some
patients did not improve until 5 treatments had been given and recommended giving at
least 10 treatments (12).
Patient selection has shown to have a great impact on the success rate of anogenital
stimulation. The subjective cure or improvement rate is reportedly as high as 85%.
Primus and Kramer obtained a success rate of 64% at 2 yr in patients with idiopathic
detrusor instability. However, all patients with multiple sclerosis who responded initially
relapsed within 2 mo (12). Poor results have been reported in elderly cognitively impaired
patients and patients with spinal cord injuries (11). Failure of pharmacotherapy does not
appear to portend a poor response to anogenital stimulation (12,13).
Few long-term studies are available regarding the efficacy of anogenital stimulation.
In a 2-yr follow-up of the 45 patients studied by Primus and Kramer, 64% still reported
satisfaction. Several patients need retreatment to remain satisfactory, and the remainder
relapsed (12). The 85% initial success rate reported by Eriksen et al. in 48 patients with
idiopathic detrusor instability dropped to 77% at 1 yr (13). Ten years later, 27 of these
patients were available for review; 78% had symptoms of urge incontinence. However,
30% leaked less than once a week, and 60% reported satisfaction with maximal electrical
stimulation and would recommend it to a friend (14).
PUDENDAL NERVE STIMULATION

Contemporary sacral nerve root stimulation consists of implantation of a tined
electrode in the S3 sacral foramen with subsequent connection to an implantable pulse
generator (IPG) (InterStim®, Medtronic Inc., Minneapolis, MN). Sacral root neuromodu-
lation inhibits the micturition reflex through stimulation of spinal tract neurons and
afferent pathways (9). One limitation of the selection of S3 is that only one of the three
afferent pathways inducing the inhibitory reflex is stimulated.
Selection of the pudendal nerve as a site of stimulation provides afferent stimulation
of S2, S3, and S4. Afferent pudendal nerve stimulation has been demonstrated to inhibit
the micturition reflex, abolish uninhibited detrusor contractions, and increase bladder
capacity in animals and humans (15–22). Vodusek et al. (18) showed that detrusor
contractions at low volumes of bladder filling were reduced or abolished by stimulating
the dorsal penile or clitoral nerves transcutaneously in patients with spinal cord lesions.
By stimulating the pudendal nerve close to the ischial spine using bipolar electrodes,
Vodusek et al. later reported electrical stimulation increased the micturition threshold
and inhibited detrusor activity.
Fig. 2. Pudendal nerve anatomy.
Anatomy of the Pudendal Nerve

The pudendal nerve originates from the S2, S3, and S4 sacral nerve roots. The main
trunk of the pudendal nerve takes an extrapelvic course superficial to the coccygeus
muscle. The main trunk passes over the ischial spine and enters Alcock’s (pudendal)
canal. In the upper half of the pudendal canal, the pudendal nerve gives rise to the
inferior rectal nerve. The inferior rectal nerve exits the pudendal canal medially and
extends motor and sensory branches. Motor branches innervate the levator ani; the
cutaneous branches innervate the perianal skin and the scrotum or labia. The inferior
rectal nerve terminates in multiple branches to the external anal sphincter. At the end of
the pudendal canal, the pudendal nerve gives rise to two branches, the perineal nerve
and the deep dorsal nerve of the clitoris/penis. The deep dorsal nerve continues as a
terminal branch to the penis or clitoris. The perineal nerve divides into the scrotal/labial
branch and two muscular branches to the bulbocavernosus and the striated urethral
sphincter (23,24). The optimum point of pudendal nerve stimulation is at the level of the
ischial spine, proximal to the branch points (Fig. 2).
Devices Available for Pudendal Nerve Stimulation

Currently, the pudendal nerve can be stimulated on a chronic basis using either a
tined quadripolar lead (Medtronic) or an implantable microstimulator (bion®, Advanced
Fig. 3. Tined quadrapolar lead.
Bionics, Valencia, CA). Neither of these applications is FDA approved for pudendal
stimulation. The development of a tined lead for sacral nerve stimulation allows for
implantation of the lead without suture fixation (Fig. 3). This feature makes it possible
to deploy the lead at other sites, such as the pudendal nerve. The advantage is that the
lead can be placed at the pudendal nerve via a posterior approach, externalized, and
tested as an outpatient to assess clinical response. If the patient demonstrates significant
improvement in voiding symptoms, then a permanent IPG can be placed in a subcuta-
neous pocket in the upper buttock.
The bion microstimulator is a miniature, self-contained, rechargeable implantable
neurostimulator that is designed as a platform technology and is intended to treat a wide
variety of disorders through direct electrical stimulation. This device is approved in
Europe for commercial use in pudendal nerve stimulation and is in clinical trials in the
United States for urinary urge incontinence, urgency/frequency, and chronic headache.
The fully integrated microstimulator contains a rechargeable battery, a radio transmitter
and antenna for bidirectional telemetry, a programmable microchip, and a stimulating
electrode. The implant measures 28 mm in length and 3.2 mm in diameter and has a
mass of only 0.7 g (Fig. 4).
Patient Selection
Chronic pudendal neuromodulation is not yet approved by the FDA for the treatment
of voiding dysfunction. With appropriate informed consent, patients suffering from
Fig. 4. The bion microstimulator.
refractory voiding dysfunction, including urinary urgency, frequency, urge incontinence,

and nonobstructive urinary retention, could be candidates for pudendal neurostimulation.
In addition, patients who trialed sacral nerve stimulation but did not respond may
benefit from pudendal nerve stimulation. Other disease states that may be considered
include IC and neurogenic bladder, including partial spinal cord injury, multiple sclerosis,
Parkinson’s disease, and other neurological disorders.
A voiding diary should be completed that evaluates time of voids, voided volumes,
incontinent episodes, urge scores, pain scores, bowel function, and catheterized volumes
if in retention. This baseline information allows accurate postoperative evaluation of
patient progress. Because at the present these procedures can only be done “on protocol,”
appropriate Human Investigation Committee approval is required with signature of an
informed consent form.
Procedure
USING INTERSTIM TINED QUADRIPOLAR LEAD
Preoperative Preparation and Patient Positioning. Administer broad-spectrum
intravenous antibiotics such as ampicillin and gentamycin. Place the patient in the prone
position with appropriate padding and support. Provide light sedation such as Versed®.
Perform a thorough betadine prep of the lower back, buttock, and anus. Place either
needle or patch electrodes at the external anal sphincter and connect to an electromyo-
graphic (EMG) device (Fig. 5). Use fluoroscopy to image the pelvis in the lateral
position to identify the ischial tuberosity and ischial spine (Fig. 6).
Fig. 5. EMG electrode at external anal sphincter.
Fig. 6. Lateral radiograph of sacral and pudendal quadrapolar leads.
Identification of the Pudendal Nerve. Palpate the ischial tuberosity posteriorly;

anesthetize the skin 1 cm medial to the tuberosity with 1% lidocaine. Advance a 5.0-
in. foramen needle through the skin toward the ischial spine. Stimulate the proximal
end of the foramen needle with the standard clip-on stimulating cord (Fig. 7). Begin
Fig. 7. Stimulation of foramen needle near ischial spine.
stimulation at 1 Hz and slowly increase from 1 to 10 mA while examining the anal

sphincter and monitoring the EMG tracing. Typical motor response is contraction of
the external anal sphincter. This should be confirmed as pudendal stimulation by seeing
a classic compound muscle action potential consistent with pudendal stimulation (Fig. 8).
Assess the patient’s sensory response. A typical response is comfortable pulsating
noted in the vagina, scrotum, perineum, or rectum. The nerve of the obturator internus
sits close to Alcock’s canal; be certain there is no leg rotation noted during the acute
testing. If leg movement is seen, then reposition the needle until only the pudendal
stimulation is identified.
Placement of Quadripolar Tined Lead. Once the pudendal nerve is identified,
advance the directional guide wire and remove the foramen needle. Make a small skin
nick alongside the wire. Next, advance the lead introducer over the directional guide
wire toward the ischial spine using fluoroscopy. The proximal metal trochar of the lead
introducer can be stimulated with the standard stimulation cord. Reconfirm pudendal
stimulation and advance the quadripolar lead through the lead introducer and test each
electrode in the standard fashion (Fig. 9). The ideal placement would be identification
of pudendal stimulation on all four electrodes. Deploy the tines by removing the lead
introducer.
Externalizing the Percutaneous Extension Lead. The current quadripolar lead is too
short to reach the upper buttock, where a future IPG will be placed. Thus, the lead is
tunneled to a 1-cm midbuttock incision and connected to the temporary percutaneous
extension lead. This lead is tunneled out the contralateral side and externalized. A redundant
lead is placed in a subcutaneous pocket underneath the skin, and the incision is closed.
Stage I Test. Patients are discharged with the standard Medtronic stimulation box,
and stimulation is set to a comfortable sensation for the patient. Voiding diaries are kept
Fig. 8. Compound muscle action potential, consistent with pudendal stimulation.
Fig. 9. Quadrapolar lead advanced through lead introducer.
for 7–14 d, and if 50% or greater improvement is noted, then the lead is connected to
an IPG. If no improvement is noted, then the lead is explanted.
Implantation of IPG or Removal of Lead. If the subject does not respond to the
stimulation, the midbuttock incision is opened, and the tined lead is removed by gentle
traction. If an IPG is to be placed, then a standard site is chosen on the upper buttock,
and a subcutaneous pocket is created. A 25-cm extension lead is attached to the IPG
and tunneled to the midbuttock incision. The tined lead is freed from this incision;
the percutaneous extension lead is removed. Then, the distal end of the 25-cm IPG
extension is connected to the proximal end of the tined lead in the standard fashion. The
lead and its connector are placed in the midbuttock subcutaneous pocket.
Outcomes of Pudendal Stimulation Using a Tined Quadripolar Lead. A direct
comparison of the efficacy of pudendal and sacral nerve stimulation has been completed.
This was a randomized, single-blinded, single-center trial in which each subject had
both a sacral and a pudendal lead placed as part of an approved protocol. Subjects were
randomly assigned to begin stimulation on either the sacral or pudendal electrode. In a
blinded fashion, each lead was tested for 7 d. Voiding diaries and questionnaires were
completed. Subjects rated their percentage improvement on each lead and based on
response chose the one to be implanted to a permanent generator. Analysis of the data
demonstrated the time to place the sacral lead was 25.85 vs 23.71 min for the pudendal
lead (p = 0.57). Of 30 subjects, 24 (80%) responded and had an IPG implanted, with
19/24 (79.2%) choosing pudendal and 5/24 (20.8%) choosing sacral. The order in which
the lead was stimulated had no impact on the final lead implanted. Pudendal nerve
stimulation had significantly higher improvement in symptoms than sacral nerve
stimulation, 51 vs 37%, respectively (p = 0.02). On a seven-point scale from markedly
worse to markedly better, pudendal nerve stimulation was superior to sacral nerve
stimulation for pelvic pain (p = 0.024), urgency (p = 0.005), frequency (p = 0.007), and
bowel function (p = 0.049). This preliminary study demonstrated that pudendal nerve
stimulation is feasible, safe, and effective using a tined quadripolar lead (25).
PUDENDAL NERVE STIMULATION USING THE BION
The bion is placed at Alcock’s canal in a minimally invasive fashion through a small
incision in the perineum. Its stimulation parameters can be adjusted using a physician
programmer, and the patient has a personal remote, allowing for adjustment of the level
of stimulation. The battery is recharged by sitting on a charging pad daily for 20–60
min, and the battery life is 15–20 yr.
Percutaneous Screening Test. Prior to implantation of a permanent bion, a percu-
taneous test is performed in the office. The patient is placed in the lithotomy position
at a 45° angle; the vagina and perineum are prepped and draped in the normal sterile
fashion. Surface EMG electrodes are placed at the anal sphincter. A computerized CMG
is performed at a fill rate of 25 cc/min while measuring the volume at first sensation,
first urge, maximum cystometric capacity, and volume at first unstable contraction.
Next, the ischial tuberosity is palpated and marked with a marking pen. The ischial spine
is palpated through the vagina or rectum (site of Alcock’s canal). The skin is anesthe-
tized approx 1.5 cm medial to the ischial tuberosity. With a finger in the vagina or rectum,
palpating the ischial spine, a stimulating needle is advanced through the perineum
toward the ischial spine while applying electrical stimulation (Fig. 10).
Compound muscle action potentials are measured. Muscle contractions are assessed
by direct vision and palpation. A good response is contraction of the bulbocavernosus
muscle and external anal sphincter. Poor response includes contraction of the obturator
internus, leg adductors, or lower extremity muscles. Sensory response is determined, and
a pulsating or tingling in the vaginal, vulvar, or anal regions is optimum. Poor responses
include leg or foot twitching or pain. Once needle placement is confirmed, the pudendal
nerve is stimulated for 15 min at a pulse frequency of 20 Hz, pulse width of 200 Rs, 50%
duty cycle, and pulse amplitude up to 10.0 mA. The bladder is emptied with a catheter,
and the urodynamic catheter is replaced. The CMG is repeated while stimulation
Fig. 10. Percutaneous screening test.
continues. A 50% increase in the volume of first sensation, first urge, cystometric capacity,
or volume at unstable bladder contraction constitutes a positive test supporting implan-
tation of the permanent bion® device.
Implantation of the Bion. For implantation of the bion, preoperative broad-spectrum
antibiotics are administered. The patient is brought to the operating room, lightly sedated,
and placed in the lithotomy position. The perineal area is prepped and draped in the
normal sterile fashion. Surface EMG electrodes are placed on the outside of the anal
sphincter and connected to an electrodiagnostic monitor. The medial aspect of the
ischial tuberosity is marked; the skin is infiltrated with 1% lidocaine approx 1.5 cm
medial to the tuberosity, and a 2- to 3-mm incision is made. The bion implant tools
include a blunt dissector/stimulator, introducer, bion holder, and placement device
(Fig. 11). With a finger palpating the ischial spine through the vagina or rectum, the blunt
dissector and introducer are inserted together toward the target (Fig. 12). Fluoroscopy
in the lateral position can help direct the bion toward the ischial spine. Clinical and
electrophysiological responses facilitate placement as described.
Once the pudendal nerve is confirmed, the blunt dissector is removed, leaving the
introducer in place. The bion in its holder is advanced through the introducer, and the
placement tool is advanced through the bion holder and locked in place by rotating
Fig. 11. Implantation tools.
Fig. 12. Implantation of bion microstimulator.
clockwise until it “clicks” into place. The bion is turned on and activated with a
frequency of 20 Hz, pulse width of 200 Rs, continuous duty cycle, and 5- to 10-mA
amplitude. Sensory, motor, and electrodiagnostic responses are assessed. Once the
location is optimized, the bion is delivered by retracting the bion holder. Retraction is
performed by turning the thumbscrew clockwise until it can be turned no further. This
deposits the bion at the site of stimulation. The bion is deactivated, the introducer is
removed, and a Steri-Strip™ is placed over the skin incision site.
Postoperative Follow-Up. At 1 wk following implantation, the patient returns to the
office for programming of the bion and education regarding the system components.
The clinician’s programmer communicates with the bion and allows the stimulator to be
activated and adjusted. Possible adjustments include frequency, pulse width, burst
mode, and stimulation limits. The programmer monitors battery life and time the device
was activated and gives a history of recharging events. The patients have their own
home kit consisting of a remote control, base station/charger, and chair pad used to
charge the bion. The bion should last 15–20 yr and can be recharged even if the battery
is allowed to deplete completely. The benefits of the bion are its small size and mini-
mally invasive approach to implantation. The results of the clinical trials will determine
its future in treating voiding dysfunction.
CONCLUSION
The use of neuromodulation has led to a major advance in our ability to treat patients
suffering from voiding dysfunction who have been refractory to standard therapies. In the
past, these patients either continued to suffer from their disease or underwent irreversible
surgeries such as bladder augmentation or urinary diversion to control their symptoms.
Neuromodulation continues to be developed, and the pudendal nerve appears to be
a safe and effective area to stimulate. Studies are ongoing to assess the feasibility of
placing a tined quadripolar lead or the bion microstimulator at the pudendal nerve. More
patients and longer-term follow-up are needed before this approach is considered
standard of care.
REFERENCES
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tibial nerve stimulation in overactive bladder. J Urol 2003;169:2210–2215.
2. McGuire EJ, Shi-Chun Z, Horwinski ER. Treatment for motor and sensory detrusor instability by
electrical stimulation. J Urol 1983;129:78–84.
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the treatment of detrusor overactivity. Br J Urol 1998;81:560–564.
4. Vereecker RL, Das RJ, Grisar P. Electrical sphincter stimulation in the treatment of detrusor hyper-
reflexia of paraplegia. Neurourol Urodyn 1984;3:145–149.
5. Vandoninck V, van Balken MR, Finazzi Agro E, et al. Posterior tibial nerve stimulation in the treat-
ment of voiding dysfunction. Neurourol Urodyn 2004;23:246–251.
6. Van Balken M, Vandoninck V, Gisolf KW, et al. Posterior tibial nerve stimulation as neuromodulative
treatment of lower urinary tract dysfunction. J Urol 2001;166:914–918.
7. Ruiz BC. Peripheral afferent nerve stimulation for treatment of lower urinary tract irritative symptoms.
Eur Urol 2004;45:65–69.
8. Zhao J, Nordling J. Posterior tibial nerve stimulation in patients with intractable interstitial cystitis.
BJU Int 1994;94:101–104.
9. Weil EH, Ruiz-Cerda JL, Erdmans PH, Janknegt RA, Bemelmans BL, van Kerrebroeck PE. Sacral
root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized
clinical trial. Eur Urol 2000;37:161–171.
10. Geirsson G, Fall M. Maximal functional electrical stimulation in routine practice. Neurourol Urodyn
1997;16:559–565.
11. Ohlsson BL. Effect of some different pulse parameters on the perception of intravaginal and intra-anal
electrical stimulation. Med Biol Eng Comput 1988;26:503–508.
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urgency and/or urge incontinence. Neurourol Urodynam 1996;15:187–194.
13. Eriksen BC, Bergmann S, Eik-Nes SH. Maximal electrode stimulation of the pelvic floor in female
idiopathic detrusor instability and urge incontinence. Neurourol Urodynam 1989;8:219–230.
14. Bratt H, Salvesen KA, Eriksen BC, Kulseng-Heanssen S. Long-term effects ten years after maximal
electrostimulation of the pelvic floor in women with unstable detrusor and urge incontinence. Acta
Obstet Gynecol Scand 1998;77(suppl 168):22–24.
15. Fall M, Erlandson BE, Carlsson CA, Lindstrom S. The effect of intravaginal electrical stimulation on
the feline urethra and urinary bladder. Neuronal mechanisms. Scand J Urol Nephrol 1978;344(suppl
pt 2):19–30.
16. Lindstrom S, Fall M, Carlsson CA, Erlandson BE. The neurophysiologic basis of bladder inhibition in
response to intravaginal electrical stimulation. J Urol 1983;129:405–410.
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of the pudendal nerve. J Urol 1986;135:198.
18. Vodusek D, Light J, Libby J. Detrusor inhibition induced by stimulation of pudendal nerve afferents.
19. Erickson B, Bergmann S, Eik-Nes S. Maximal electrostimulation of the pelvic floor in female idio-
pathic detrusor instability and urge incontinence. Neurourol Urodyn 1989;8:219–230.
20. Lindstrom S, Sudsuang R. Functionally specific bladder reflexes from pelvic and pudendal nerve
branches: an experimental study in the cat. Neurourol Urodyn 1989;8:392–393.
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16 Sacral Neuromodulation
for the Treatment of Overactive Bladder
Anurag K. Das, MD, FACS

CONTENTS
INTRODUCTION
CASE 1
CASE 2
HISTORY
MECHANISM OF ACTION
INDICATIONS
TEST PROCEDURE
IMPLANTABLE PULSE GENERATOR IMPLANTATION PROCEDURE
RESULTS
COMPLICATIONS
CASE STUDIES
DISCUSSION
REFERENCES
INTRODUCTION
Urinary frequency/urgency and urinary urge incontinence, collectively referred to as
overactive bladder, represent common problems in the urologist’s practice. Although
pharmaceutical management and pelvic floor rehabilitation combined with behavioral
modification helps many patients with overactive bladder symptoms, a substantial
minority of patients are refractory to these interventions. In such refractory cases, sacral
neuromodulation, a minimally invasive and reversible treatment, provides an attractive
alternative prior to consideration of more invasive and irreversible treatment modalities.
This chapter reviews the current state of sacral neuromodulation for the treatment of
refractory voiding dysfunction, with emphasis on the techniques, efficacy, risks, and
benefits of this procedure.
Overactive bladder (OAB) is a common syndrome defined by the International
Continence Society as “urgency with or without urge incontinence, usually with frequency
and nocturia in the absence of other pathological or metabolic conditions to explain
these symptoms” (1). Most cases of OAB are idiopathic, and many respond to behavioral
modification or antimuscarinic medications. However, it is not uncommon for patients
not to respond to these interventions and be classified as having refractory OAB
symptoms. Two such refractory cases are illustrated next.

237
CASE 1
A 42-yr-old white female presents with complaints of urinary urge incontinence. She
leaks in large amounts, generally on her way to the bathroom, but also with changes in
position, such as getting out of a chair or bed. She has been tried on various combi-
nations of anticholinergic and tricyclic medications without significant improvement at
tolerable doses, and the medications further worsened her constipation, which is already
a problem for her. She has been taught guarding maneuvers, behavioral modification,
and pelvic floor rehabilitation without satisfactory improvement in her symptoms. Past
medical history is otherwise unremarkable, and past surgical history is remarkable for
appendectomy and hysterectomy (for large fibroids). There is no history of back problems
or neurological disease. Physical examination is unremarkable and urogenital examination
reveals a normal meatus, minimal cystourethrocele, and normal neurological examination,
including perianal sensation and rectal sphincter tone.
Voiding diary reveals a functional bladder capacity of 300 mL, average voided volume
of approx 160 mL, and two or three large-volume leakage episodes daily. Urodynamic
studies in the standing position at a fill rate of 60 mL/min with room temperature sterile
contrast material reveal phasic detrusor overactivity starting at volumes of 120 –140 mL
with large-volume leakage. Bladder is normally oriented, and the patient is able to void
to completion with low voiding pressures.
CASE 2
A 32-yr-old white female presents with complaints of urinary frequency and urgency.
She was a bedwetter as a child until the age of 8, suffered from numerous “urinary tract
infections,” and had undergone a urethral dilation. She also complains of irritable bowel
syndrome with alternating diarrhea and constipation but denies migraine headaches,
fibromyalgia, or other pain or discomfort. She believes she has always voided more
frequently than her friends and siblings, but over the last 2 yr, the situation has worsened
to the point at which it is interfering with her work and life. She voids at least every
hour, and if she is “stressed,” then she may void as often as every 15 min. She has been
treated for multiple urinary tract infections, but there are no positive bacterial cultures.
She has been tried on anticholinergic medications without any improvement and on
tricyclics with mild improvement. Formal biofeedback and pelvic floor rehabilitation
have been partly efficacious, and a 6-mo trial of Elmiron was not helpful. Past medical
and surgical histories are otherwise unremarkable.
On examination, she is anxious, but otherwise the examination is unremarkable. On
genitourinary examination, there is increased pelvic floor tone, and neurological exami-
nation is normal. Voiding diary reveals 20 voids in 24 h with a functional bladder capacity
of 250 mL (first morning void); the average voided volume is 90 mL. Urodynamic studies
reveal first sensation at a volume of 25 mL and urge at 75 mL. Patient is unable to void
with catheters in place. Bladder capacity under anesthesia is 900 mL, and no significant
glomerulations or submucosal hemorrhages are noted.
Both these patients represent significant challenges to therapy. Although frequency/
urgency syndromes and urge incontinence are common and many patients can be ade-
quately managed with combinations of behavioral therapy, pelvic floor rehabilitation,
and pharmaceutical therapy, a significant minority of patients do not respond adequately
to these measures and desire further treatment. Options are generally limited and require
major surgical procedures such as augmentation cystoplasty, which can often result
Chapter 16 / Sacral Neuromodulation for OAB 239
in incomplete emptying and need for intermittent catheterization, an alternative not

acceptable for many such patients. Sacral neuromodulation (SNS), a minimally invasive
treatment alternative, has been used in the treatment of refractory OAB with reason-
able success rates in appropriately selected patients. This chapter reviews the history,
indications, mechanism of action, techniques, and outcomes of SNS.
HISTORY
The use of electrical stimulation for treatment of various disorders has a long and
colored history. Electrical stimulation was used for such disease processes as excess libido
and, of course, depression. Caldwell and coworkers (2,3) used electrical stimulation of
the pelvic floor using implanted electrodes in an attempt to treat stress urinary inconti-
nence and attempted to treat neurogenic incontinence with an implantable stimulator.
With advances in cardiac pacing and the improved understanding and miniaturization
of electronic instruments, interest in neuromodulation of bladder function was revived
in the 1970s and 1980s. The Department of Urology at the University of California,
San Francisco, led by Drs. Richard Schmidt and Emil Tanagho, was instrumental in
performing some of the early work and laying the foundation for the use of SNS for
the treatment of refractory voiding dysfunction. Drs. Craggs and Fowler in London and
Drs. DeGroat and Chancellor at the University of Pittsburgh have performed further
work on the mechanism of action of SNS.
The initial large-scale trials were performed in the mid-1990s when Medtronic
Incorporated bought the technology from a struggling startup company and completed
the Food and Drug Association trials, leading to the approval of SNS for the treatment
of urge incontinence in 1997 and for frequency/urgency in 1999. Initially, SNS was
performed as a two-stage procedure, and the quadripolar lead electrode was placed
through an open sacral incision; the implantable pulse generator (IPG) was placed in the
abdomen. The procedure was relatively involved and took approx 2 h to perform.
The first major change was placement of the IPG in the upper buttock region. This
helped decrease both the time needed to perform the procedure and the rate of infection.
The next major change was the development of the tined lead, allowing percutaneous
lead placement under fluoroscopy. This change made the procedure less invasive and
further decreased the time needed to perform it.
Initially, there was significant resistance from the established urologic community,
especially in the United States, in accepting a treatment option that did not involve tradi-
tional treatments of the bladder or urethra, but SNS has become much more accepted as
a reasonable alternative for the treatment of refractory voiding dysfunction (4).
MECHANISM OF ACTION
The mechanism of action of SNS is not completely understood. Chancellor and
coworkers (5,6) have suggested SNS improves somatic afferent inhibition of sensory
processing in the spinal cord. Because the S2–S4 nerve roots provide the primary
autonomic (parasympathetic through the pelvic nerve) and somatic (pudendal nerve)
innervation to the bladder, urethra, and pelvic floor, SNS somehow helps in the treat-
ment of OAB by “inhibiting” these nerve roots. Further data to support the view that
afferent pathways play a role in SNS-related symptom improvement came from Fowler
and colleagues (7,8), who suggested that neuromodulation affects afferent pathways,
probably through mediating changes in spino-bulbo-spinal pathways to the pontine
micturition center. Because visceral afferents require higher stimulation amplitudes (9),
it is more likely that somatic afferents play a more important role in the mechanism
involved, thus the term somatic afferent inhibition.
Thon and Jonas (10) have noted that the beneficial effect of SNS can occur without
efferent activation of muscle fibers. Others, including Schmidt, have felt strongly that
efferent-mediated strengthening of the pelvic floor and external sphincter results in
improved voiding dysfunction through augmentation of the guarding reflex (personal
communication). It is likely that both efferent and afferent mechanisms play a role,
with patients primarily with frequency and urgency helped more through afferent
sensory mechanisms, and those with primarily urge incontinence improving as a
result of increased efferent activity. Unfortunately, animal models have been difficult
to develop, especially for sensory frequency, but previous work in rats and pigs suggests
a role for both afferent and efferent mechanisms (11–13).
INDICATIONS
SNS is indicated for the treatment of refractory urge incontinence and refractory
urinary frequency/urgency syndromes, or refractory OAB, depending on one’s preference.
Generally, patients who have failed or could not tolerate more conservative therapies, such
as behavioral modification, pelvic floor rehabilitation (including pelvic floor biofeedback/
muscular vaginal electrical stimulation), and anticholinergic/antimuscarinic medications,
are given a trial of SNS. Some physicians exhaust all possible options, including high-
dose combinations of antimuscarinics and tricyclic antidepressants, before considering
neuromodulation as an option, the step prior to significantly more invasive options such
as augmentation enterocystoplasty; others will move to SNS earlier.
In the United States, the current approval is for the treatment of refractory urinary
frequency/urgency syndromes and urinary urge incontinence of nonneurogenic etiology.
It is important to remember that patients with neurological disease were excluded in the
pivotal trials, and although there is some evidence that patients with certain neurological
diseases may respond well to SNS, this population has not been studied in any well-
designed, systematic, prospective clinical trials. Furthermore, it is not possible in the
scope of this text to discuss an acceptable definition of interstitial cystitis, but the pre-
vailing data would suggest that patients with significant frequency and urgency but
without significant pain respond exceedingly well to SNS. Some investigators have
achieved good results in patients with a significant component of pelvic pain (14–16);
others, myself included, have noted that patients with significant chronic pelvic pain,
especially pelvic pain without frequency and urgency, do not respond well in the long
term, although they may have an initial good result lasting 3– 6 mo.
All patients considered for SNS should have a complete history and physical exami-
nation, including a genital, rectal, and neurological examination. These patients should
perform accurate voiding diaries and undergo urodynamic studies to confirm the diagnosis
and ascertain whether they are suitable candidates. These patients should have failed or
could not tolerate more conservative therapies such as behavioral modification or appro-
priate medications. One suitable algorithm is shown in Fig. 1.
TEST PROCEDURE
The test procedure can be performed in two distinct locations and provides a short-term
trial of SNS. It lets the patient and physician decide whether the benefits of permanent
Fig. 1. Algorithm for refractory overactive bladder.
IPG implantation is worth weighing the benefits, risks, and costs of the therapy. The
patient performs a 2- to 3-d voiding diary prior to the test procedure. The test proce-
dure can be performed in the office, ambulatory surgery unit, or operating room setting
under straight local anesthesia under fluoroscopy guidance. The early pioneers of the
procedure performed it without fluoroscopy, but most practitioners perform it with
fluoroscopic guidance.
The patient is placed in the prone position with one or two pillows under the lower
abdomen to improve the sacral approach. The sacrum is prepped with antiseptic solution,
and the sacral notches and coccygeal drop-off are identified by palpation or fluoroscopy.
S3 is usually located 1.5–2 cm lateral to the midline at the level of the sacral notches or
about 9 cm above the coccygeal drop-off. Local anesthesia is achieved from S2–S4 over
the underlying skin and subcutaneous tissues, making certain not to enter the foramen.
Utilizing the previously mentioned landmarks and fluoroscopic guidance, primarily
with lateral imaging, insulated foramen needles are placed percutaneously in the S3 and S4
foramen (Fig. 2), and the sensory and motor responses are identified. Sensory responses
generally include a tingling, pulling, or vibratory sensation in the vagina and rectum in
women and in the scrotum, phallus, and rectum in men. Motor responses include levator
tightening (bellows response) and plantar flexion of the big toe. Sometimes, at S3 plantar
flexion of the entire foot is noted. In such cases, S4 may be the more appropriate foramen
as most patients are significantly bothered by such a foot response.
Once the appropriate responses have been obtained, an insulated wire is placed
through the 18-gage needle into the foramen, and the needle is removed. Two or more
such wires can be left in, and the patient can try out left and right sides or S3 and S4
and decide on the best response because these temporary wires are inexpensive and
easy to place. The wires are taped in place and attached to an external neurostimulator,
which the patient is taught how to adjust for optimal results. The patient maintains
Fig. 2. Bilateral needle placement in S3 foramen. The approach is at an approx 60° angle.
stimulation at a comfortable level (it should not be painful) and completes a voiding
diary to provide objective data while undergoing neuromodulation.
Based on the patient’s subjective experience and the objective data obtained
through the voiding diary, a final decision can be made to proceed or not proceed with
permanent implantation. Usually, the patient needs to exhibit significant subjective
improvement, and the voiding diary should show at least 50% improvement in void-
ing parameters to warrant proceeding. In equivocal cases, or if the insulated wires
move, a trial can be carried out with a quadripolar tined electrode before making a
final decision.
Alternatively, the test stimulation can be carried out with a permanent quadripolar
tined lead. The initial procedure is similar to the test stimulation described but cannot
be performed in the office setting. Broad-spectrum antibiotics are given, and adequate
monitored anesthesia care anesthesia is obtained. Once the needles have been placed
in the appropriate foramen and the sensory and motor responses obtained, a decision is
made to use the best responses. The needle’s stylet is removed, a guide wire is inserted,
and the tract is dilated over the guide wire under fluoroscopic guidance once the needle
has been removed. The sheath from the dilating apparatus is then left in; the tined lead
(so called as it has tines that hold it in place) is inserted, and its position is optimized
by again checking the neural responses. The sheath is then removed, and the tines hold
the lead in place. The tined lead is now tunneled to the location of the eventual IPG,
where it is connected to an externalizing wire, and then another tunnel is created to

externalize the connection and to prevent infection.
One advantage of this procedure is that the same responses should be obtained once
the external neurostimulator is replaced by the permanent IPG because the lead-nerve
interface does not change. The tined lead also does rarely migrates, and thus a 1- to
2-wk trial can be easily done; such long trials are less common with the insulated wire
leads, which migrate at an approx 10–15% rate. Disadvantages include the cost (~$2000
for one lead only, not including related operating room costs); the inability to place
more than one lead (without further increasing costs); and the need to remove the lead
with local anesthesia, usually in the operating room setting, if there is not sufficient
improvement for the patient. Nonetheless, the majority of physicians performing SNS
in the United States perform it with the tined lead.
IMPLANTABLE PULSE GENERATOR IMPLANTATION PROCEDURE

Patients who have undergone successful test stimulation with the tined lead are
brought back to the operating room. The site of the connection in the upper buttock
area, 4 cm below the posterior iliac crest, is opened after broad-spectrum intravenous
antibiotic coverage is provided. An appropriate size pocket is created at a depth of
1.5–2 cm. The previous connection is taken down, and a new connection is made from
the lead to a 10-cm connecting lead, which is then connected to the IPG (Fig. 3). After
copious amounts of antibiotic irrigation, the incision is closed in two layers. If the
patient underwent traditional insulated wire test stimulation, then the wire leads are
generally removed in the office.
After an interval of 2 wk or more, the patient is brought back to the operating room
and a tined quadripolar lead electrode is placed as described. An incision is made over
the upper buttock area, 4 cm below the posterior iliac crest, and an appropriate pocket
is created. The connections are then made from the lead to the 10-cm connecting lead
to the IPG. Incision is closed with no tension on the skin, and the patient is kept on oral
antibiotics for 1 wk. The procedure is performed on an outpatient basis. Figure 4 depicts
a plain film lateral view of lead at S3 and implantable pulse generator in place.
The IPG is programmed, and the patient is taught to set the unit at a comfortable setting
at which the stimulation can be felt but is not painful. The patient is able to control the
amplitude and to turn the unit on and off; the IPG is completely programmable using an
external programmer. Thus, the various parameters can be adjusted on a routine basis as
necessary to provide optimal stimulation and results. Some investigators have performed
bilateral stimulation, and although this is theoretically appealing, currently there are not
enough data to differentiate if this approach may provide better results (17).
RESULTS
The results of the prospective, randomized, multicenter study (MDT-103 study
sponsored by Medtronic), which led to the Food and Drug Administration approvals for
urge incontinence and frequency/urgency, represent the best-available objective data.
Schmidt (18) reported the urge incontinence data in 1999. Based on voiding diary
data, patients with refractory urge incontinence underwent test stimulation. Those with
a successful test stimulation were randomly assigned to an immediate stimulation and
a delayed group. The immediate group included 34 patients who underwent implanta-
tion and were followed for 6 mo. The delay group comprised 42 patients who received
Fig. 3. Implantable pulse generator being placed in upper buttock subcutaneous pocket.
Fig. 4. Later plain film showing quadripolar lead and IPG in place. Note that generally two or three
electrode leads are anterior to the sacrum.
standard medical therapy for 6 mo and then were offered implantation. At 6 mo, the
number of daily incontinence episodes, severity of episodes, and number of absorbent
pads or diapers replaced daily because of incontinence were significantly reduced in the
immediate stimulation group compared to the delay group (all p < 0.0001). Of the 34
stimulation group patients, 16 (47%) were completely dry, and an additional 10 (29%)
demonstrated a greater than 50% reduction in incontinence episodes 6 mo after implanta-

tion. Efficacy was sustained for 18 mo. Complications included IPG site pain in 15.9% of
the patients, implant site pain in 19.1%, and lead migration in 7.0%. Surgical revision was
required in 32.5% of patients. There were no reports of permanent injury or nerve damage.
As reported by Hassouna et al. (19) in 2000, their frequency/urgency group consisted
of 51 patients from 12 centers who underwent baseline assessment, including a detailed
voiding diary, urodynamic evaluation, and office-based test stimulation under local
anesthesia of the sacral nerves at S3 or S4. Patients demonstrating a satisfactory response
to trial stimulation were randomly divided into a stimulation group (25 patients) and a
control group (26 patients). An IPG was implanted immediately in the stimulation group
and after 6 mo in the control group. Patients were followed at 1, 3, and 6 mo and at
6-mo intervals for up to 2 yr after implantation of the IPG. The primary study variables
included the number of voids daily, volume voided per void, and degree of urgency prior
to voiding. Compared to the control group, 6-mo results demonstrated statistically
significant improvements (p < 0.0001) in the stimulation group with respect to the
number voids daily (16.9 ± 9.7 to 9.3 ± 5.1); volume voided per void (118 ± 74 to 226 ±
124 mL); and degree of urgency based on a 0–3 scale (2.2 ± 0.6 to 1.6 ± 0.9). Patients
in the control group showed no significant changes in voiding parameters at 6 mo.
Significant improvements were also noted in the short-form-36 quality-of-life parameters
in favor of the stimulation group.
Many short-term uncontrolled studies have also shown significant improvement in
OAB symptoms (20–22). Shaker and Hassouna (22) reported on 18 patients with
refractory urge incontinence who had an average follow-up of 18.8 mo (range 3–83).
SNS in these patients showed a marked reduction in leakage episodes, from 6.49 to
1.98 times per 24 h. Eight patients (44%) became completely dry, and 4 had average
leakage episodes of 1 or less daily.
Dijkema (21) reported that 19 of 23 patients with an implanted neuroprosthesis for
neuromodulation had a more than 50% improvement in their main symptoms after a
median follow-up of 12 mo. In urge-incontinent patients, the number of leakage
episodes decreased from 7.4 to 1.5/d, and the functional capacity increased from 135
to 227 mL.
Grunewald and Jonas (20) reported on 55 patients with a mean postoperative follow-up
of 44.3 mo. Lasting symptomatic improvement of more than 50% was achieved in 16 of
21 patients with motor urge incontinence (76.2%).
Quality-of-life improvements have also been noted. Das et al. (23) reported on a
cohort of patients from the MDT-103 study in which the Beck Depression Index and
the Medical Outcomes Study Short-Form 36 were used to assess depression and
health-related quality of life (HRQOL) at baseline and at two follow-up visits. The
subjects had detectable levels of depression and reduced quality of life at baseline.
Those implanted with the neurostimulator reported significant improvements in both
HRQOL scores and depression at 3 and 6 mo; those assigned to the delayed implant
group showed a slight worsening of HRQOL and depression from baseline to 3 mo that
continued through the 6-mo visit.
Several authors have also reported good results in patients with interstitial cystitis.
Comiter, Peters, Whitmore and coworkers (14,16,24) have all shown short-term effective-
ness in this population. There is certainly an issue of semantics as some of these patients
primarily had frequency and urgency with a relatively small component of chronic
pelvic pain, and those patients should be expected to do reasonably well.
Comiter (14) reported on 17 patients undergoing IPG placement. At an average

follow-up of 14 mo, mean daytime voids improved from 17.1 to 8.7 (p < 0.01). Mean
voided volume increased from 111 to 264 mL (p < 0.01). These results are similar to
most other studies in patients with frequency/urgency. However, he also reported that
average pain score decreased from 5.8 to 1.6 points on a scale of 0 to 10 (p < 0.01), and
the Interstitial Cystitis Symptom and Problem Index (a validated questionnaire for inter-
stitial cystitis-related symptoms) scores decreased from 16.5 to 6.8 and 14.5 to 5.4,
respectively (p < 0.01). The effectiveness of SNS for significant, chronic pelvic pain
remains unclear, although one study demonstrated decreased narcotic requirements in
this population (15).
On the other hand, few long-term data are available. Elhilali et al. (25) reported
long-term (13-yr) data on 52 patients who were followed closely. Of the 52 patients,
11 were not available for evaluation. Of the 41 remaining patients, 22 had urgency/
frequency syndrome, 6 had urgency incontinence, 9 had urinary retention, and 4 had
interstitial cystitis with intractable pelvic pain. Five required explantation and were
offered reimplantation but declined. Of the 22 patients in the urgency/frequency group,
10 (45%) had persistent improvement. In the urge incontinence group, 3 of the 6 patients
required explantation, and only 1 (17%) reported lasting improvement in the frequency
of incontinence episodes.
Similarly, I presented (26) data looking at long-term quality-of-life changes based
on SF-36 scores, which showed significant improvement lasting through 3 yr, but by 5 yr
there were no statistically significant differences in quality-of-life scores compared
to baseline. Interestingly, based on the same study cohort, there continued to be statistically
significant improvements in frequency/urgency and urge incontinence based on voiding
diary data presented by Van Kerrebroeck (26).
If unilateral stimulation is helpful, then can bilateral stimulation provide better
results? Scheepens et al. (27), in a prospective, randomized, crossover trial, investigated
33 patients who were randomly assigned to start with bilateral or unilateral stimulation.
Between the stimulation episodes, a 2-d washout interval was scheduled. Results were
based primarily on voiding diaries. No statistically significant improvement was
credited to bilateral stimulation compared to unilateral stimulation. Hohenfellner et al.
(28) also investigated this topic, but the procedure their group performed included a
sacral laminectomy with placement of cuff electrodes and thus was far more morbid
than current procedures. Thus, their data are difficult to compare with data of most other
investigators.
COMPLICATIONS
Over the years, percutaneous test stimulations have been exceedingly safe as only a
20-gage needle and thin wires that passed through this needle were used. The main
problem with the procedure, as discussed, was lead migration, occurring in about 15%
of cases. With the advent of the coiled wire, the lead migration rate dropped, although
this has never been quantified in a randomized trial. In the multicenter MDT-103 trial,
about 33% of patients undergoing permanent implantation of lead (open) and IPG
required revision surgery. The probability of such a revision decreased from 29% in the
first 6 mo to 12% in the second 6 mo. Most common reasons for revisions included pain
at the lead or IPG site, lead migration, or infection. Similar complication and revision
rates have been found in other trials (25,29). There were no reported permanent nerve
injuries in this series. With placement of the IPG in the upper buttock region as opposed
to the abdomen, some decrease in IPG site pain has been recorded as the IPG no longer
wedges between the anterior superior iliac spine and the rib cage.
Today, most physicians, at least in the United States, have moved to the two-stage
implant utilizing the tined quadripolar lead electrode. Spinelli et al. and Vasvada and Hijaz
reported the rate of lead migration with this electrode as relatively low (30,31). However,
migration of the tined lead does occur and may be more common in thinner patients
(32). Pain at the site of the electrode with this approach is less common. However, the
infection rate in the Vasavada and Hijaz series was 10% or slightly higher than for the
multicenter series (6%). Their overall revision rate was about 20%, moderately lower
than for the multicenter series. With continued technical improvements, further lowering
of the revision rates can be expected.
CASE STUDIES
Returning to the cases presented at the beginning of this chapter, the first case study
patient underwent a trial of SNS utilizing percutaneous wires placed at both S3 nerve
roots. The trial was performed for 7 d, 3 on the left and 4 on the right. There was signi-
ficant subjective improvement, and objective voiding diaries showed a decrease in
incontinence episodes to only two small-volume episodes in 3 d on the left side. The
right side also showed significant improvement, but the patient subjectively felt the left
side was better. The patient underwent open implantation of quadripolar lead electrode
and IPG under general anesthesia and has been followed for over 5 yr with minimal
incontinence requiring use of a liner primarily for safety.
The second case study patient underwent placement of a tined quadripolar lead
electrode under monitored anesthesia care and local anesthesia. Both S3 roots were
tested, and the electrode was placed on the left side. The patient did have moderate
discomfort at the site of electrode placement, but voiding function improved subject-
ively and objectively. The average volume voided increased to almost 200 mL, and
number of voids decreased to 10 –11/24 h. Urgency also improved, and the patient
was able to sleep through the night on two of the seven nights. She underwent IPG
placement under the same anesthetic regimen and has been stable for over 2 yr,
requiring no medications. She does have complaints of some discomfort at the site of
the IPG, but this does not require pain medications and has not bothered her enough
to warrant change of the IPG site.
These cases represent the best possible results obtained with the use of SNS, and
certainly there are many other patients who do not respond to the test stimulation or
after responding to the test stimulation only respond to the implanted device for a short
time period. Nonetheless, in this difficult population with limited therapeutic choices,
SNS represents the most appropriate therapeutic option once behavioral treatments and
pharmacotherapy have failed.
DISCUSSION
SNS has become a useful and necessary technique for the treatment of refractory
OAB. From 1997, when fewer than a dozen physicians in the United States were
using this technique, there have been tremendous changes. Today, most residents are
exposed to SNS in their training programs, and there are few urogynecologists or
urologists specializing in female urology and incontinence who are not well versed
in SNS practice. Attention is now turned to even smaller devices with rechargeable
batteries to make the procedure increasingly minimally invasive. Furthermore, electrode
placement to directly stimulate the pudendal nerve (33,34) by a variety of techniques
is under study.
Although minimally invasive, some of these techniques currently do have some
significant limitations, although with some technical advances these limitations can be
remedied. However, it is unclear whether pudendal stimulation may successfully treat
some of the patients refractory to SNS treatment. It is also unclear if long-term puden-
dal stimulation may be better tolerated by patients when compared to SNS. It is hoped
that well-designed, randomized, prospective clinical trials will help answer some of
these questions.
In the meantime, patients presenting with OAB symptoms not responding to pharmaco-
therapy and behavioral therapy are best managed with SNS. Whether the more traditional
percutaneous test stimulation is initially carried out or whether the tined quadripolar
lead is initially placed remains the preference and judgment of the surgeon in discussions
with the patient. With the continued evolution of the procedure, it has become less inva-
sive, and the complication and revision rates are gradually decreasing. Future advances
will likely lead to increasingly minimally invasive procedures with a smaller IPG and
the likely use of pudendal nerve stimulation in selected patients.
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3. Caldwell KP, Flack FC, Broad AF. Urinary incontinence following spinal injury treated by electronic
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urge incontinence. BJU Int 2003;91:355–359.
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Am 2005;32:11–18.
6. Yoshimura N, Seki S, Chancellor MB, de Groat WC, Ueda T. Targeting afferent hyperexcitability for
therapy of the painful bladder syndrome. Urology 2002;59(5 suppl 1):61–67.
7. Fowler CJ, Swinn MJ, Goodwin RJ, Oliver S, Craggs M. Studies of the latency of pelvic floor
contraction during peripheral nerve evaluation show that the muscle response is reflexly mediated.
J Urol 2000;163:881–883.
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9. van Balken MR, Vergunst H, Bemelmans BL. The use of electrical devices for the treatment of bladder
dysfunction: a review of methods. J Urol 2004;172:846–851.
10. Thon WF, Baskin LS, Jonas U, et al. Neuromodulation of voiding dysfunction and pelvic pain. World
J Urol 1991;9:138–141.
11. Mersdorf A, Tanagho EA, Jakse G. Electrical neurostimulation in the male Wistar rat: proximal stimu-
lation of the nervi pelvicus sive pudendus. Investig Urol (Berl) 1994;5:152–156.
12. Mersdorf A, Schmidt RA, Tanagho EA. Urodynamic evaluation and electrical and pharmacologic
neurostimulation. The rat model. Urol Res 1993;21:199 –209.
13. Schultz-Lampel D, Jiang C, Lindstrom S, Thuroff JW. Experimental results on mechanisms of action
of electrical neuromodulation in chronic urinary retention. World J Urol 1998;16:301–304.
14. Comiter CV. Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis:
a prospective study. J Urol 2003;169:1369 –1373.
15. Peters KM, Konstandt D. Sacral neuromodulation decreases narcotic requirements in refractory inter-
stitial cystitis. BJU Int 2004;93:777–779.
16. Peters KM, Carey JM, Konstandt DB. Sacral neuromodulation for the treatment of refractory interstitial
cystitis: outcomes based on technique. Int Urogynecol J Pelvic Floor Dysfunct 2003;14:223–228;
discussion 228.
17. Hohenfellner M, Schultz-Lampel D, Dahms S, Matzel K, Thuroff JW. Bilateral chronic sacral neuro-
modulation for treatment of lower urinary tract dysfunction. J Urol 1998;160(3 pt 1):821–824.
18. Schmidt RA, Jonas U, Oleson KA, et al. Sacral nerve stimulation for treatment of refractory urinary
urge incontinence. Sacral Nerve Stimulation Study Group. J Urol 1999;162:352–357.
19. Hassouna MM, Siegel SW, Nyeholt AA, et al. Sacral neuromodulation in the treatment of urgency-
frequency symptoms: a multicenter study on efficacy and safety. J Urol 2000;163:1849–1854.
20. Gruenewald V, Jonas U. Neurostimulation for lower urinary tract voiding problems. Curr Urol Rep
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21. Dijkema HE, Weil EH, Mijs PT, Janknegt RA. Neuromodulation of sacral nerves for incontinence and
voiding dysfunctions. Clinical results and complications. Eur Urol 1993;24:72–76.
22. Shaker HS, Hassouna M. Sacral nerve root neuromodulation: an effective treatment for refractory urge
23. Das AK, Carlson AM, Hull M. Improvement in depression and health-related quality of life after
sacral nerve stimulation therapy for treatment of voiding dysfunction. Urology 2004;64:62–68.
24. Whitmore KE, Payne CK, Diokno AC, Lukban JC. Sacral neuromodulation in patients with intersti-
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discussion 308–309.
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experience of one center. Urology 2005;65:1114–1117.
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refractory voiding dysfunction. AUA Annual Meeting May 9, 2004, San Francisco, CA.
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17 Augmentation Cystoplasty
Michael A. Aleman, MD, Joseph B. Abdelmalak, MD,

and Raymond R. Rackley, MD
CONTENTS
INTRODUCTION
INDICATIONS AND CONTRAINDICATIONS
ALTERNATIVES TO AUGMENTATION
SURGICAL TECHNIQUE OF BLADDER AUGMENTATION
RESULTS AND COMPLICATIONS
CONCLUSION
REFERENCES
INTRODUCTION
Many disease processes can result in an “end-stage” bladder that has a small capacity,
poor compliance, and high storage pressures. When surgical intervention is contemplated,
the ultimate goals are the preservation of renal function and the restoration or preservation
of continence. In carefully selected patients, augmentation cystoplasty can be used to
achieve those goals.
INDICATIONS AND CONTRAINDICATIONS

Augmentation cystoplasty is typically indicated for many conditions that result in
a small, contracted, poorly compliant bladder. These can include tuberculosis, schisto-
somiasis, radiation cystitis, chemotherapy-induced cystitis, or multiple previous bladder
operations. Perhaps most commonly in the United States, augmentation cystoplasty is
performed in patients with neuropathic bladder dysfunction or refractory detrusor
instability. Augmentation has been used in interstitial cystitis, with poorer results noted
in patients with larger bladder capacities under anesthesia and those requiring self-
catheterization postoperatively (1).
Augmentation cystoplasty may also be used as a method of urinary undiversion in
patients with neuropathic bladders or lower urinary tract anomalies who have previously
had urinary diversion (2). In renal transplant candidates, augmentation may safely be
performed prior to transplantation or after transplantation, with good results seen in
both adult and pediatric populations (3,4). Simultaneous transplantation and bladder
augmentation may be associated with a higher risk of infectious complications (5).
As the risk of urinary retention requiring intermittent self-catheterization ranged
from 14 to 100% in several series, a patient’s inability or unwillingness to perform
intermittent self-catheterization is a contraindication. Insufficient healthy bowel, as in
251
short-gut syndrome, Crohn’s disease, or radiation enteritis, is another contraindication.

Impairment in renal function can be a relative contraindication; however, the risk of
renal functional decline from the augmentation must be weighed carefully against the
risk of decline caused by the patient’s high-pressure, poorly compliant bladder. As there
are no prospective randomized studies examining this question, the use of augmentation
in patients with impaired renal function should be done only after a careful evaluation
and risk assessment.
ALTERNATIVES TO AUGMENTATION
Before the consideration of augmentation cystoplasty, all less-invasive options for
the treatment of the low-compliance, low-capacity, overactive bladder should be tried.
These include pelvic floor rehabilitation, behavioral modifications (timed and prompted
voiding), and antimuscarinic agents.
The role of augmentation cystoplasty in cases of refractory detrusor overactivity
changed with the introduction of two less-invasive treatment modalities. Sacral neuro-
modulation and botulinum toxin injection therapy have demonstrated efficacy in cases
of detrusor overactivity refractory to medical therapy and are discussed elsewhere in
this book. It should be noted, though, that studies examining predictors of failure of
these modalities have begun to appear in the literature; success rates of botulinum
toxin (6) are lower in patients with small, poorly compliant bladders, and sacral neuro-
modulation appears to have higher failure rates in neurogenic voiding dysfunction
(7)—both populations in which augmentation is often considered. Still, the less-
invasive nature of these procedures, combined with their reversibility and favorable
side-effect profiles, suggest that they should be attempted in many cases prior to
considering augmentation cystoplasty.
SURGICAL TECHNIQUE OF BLADDER AUGMENTATION

Patients receive a bowel prep the day before surgery. Regardless of the section of
bowel selected, several principles apply to all cases of augmentation cystoplasty. The
bowel segment should be detubularized to prevent rhythmic peristaltic contractions,
which can lead to incontinence or high storage pressure, and to provide the maximum
increase in bladder volume for a given length of bowel. Absorbable sutures should be
used wherever there is contact with the intraluminal surface of the bladder or augment.
The bowel segment needs to have an adequate mesentery to reach the opened bladder
without tension. The opening in the bladder can be transverse, longitudinal, or cruciate,
but in all cases it should be opened as wide as possible. This helps to prevent the anasto-
mosis of the bowel and bladder from contracting, such that the augment effectively
becomes a poorly draining diverticulum. Finally, it is routinely recommended that a
suprapubic catheter be placed through the native bladder wall and a drain left in the
space of Retzius near, but not on, the anastomotic line to allow adequate bladder
drainage and drainage of any extravasated urine, respectively.
There is no distinct advantage of any bowel segment over another, with perhaps the
exception of the jejunum, which leads to greater metabolic derangements than other
segments when used in urinary diversions (8). When ileum is utilized, a segment 25 cm long
(or longer, depending on the desired capacity) is typically harvested at least 25 cm
proximal to the ileocecal valve (to prevent bile acid malabsorption) (9). The cecum,
with its large lumen, has been used without detubularization (10), but detubularization
Chapter 17 / Augmentation Cystoplasty 253
is currently preferred to prevent colonic contractions (11). The ileocecal segment can be
detubularized to create an augment; historically, this segment has been avoided because
of concerns of diarrhea and malabsorption (12).
More recently, as the ileocecal segment has been successfully used as a continent
catheterizable diversion, the use of this segment as a catheterizable augment segment
has become an option (13). The lack of severe metabolic derangements or diarrhea in
this series of 23 patients, along with larger reports of ileocecal diversion causing meta-
bolic derangements and diarrhea in 5.5 and 2.7% of patients, respectively (14), suggest
that the use of this segment is a viable option, especially if the patient desires a continent
catheterizable augment and has an inability to use the native urethra.
The sigmoid colon is ideally located for use as an augment, and is often large in
patients with neurological voiding dysfunction. It may be associated with a lower rate
of bowel obstruction than ileum (15).
Finally, stomach may be harvested as an augment patch, using the antrum with the
left gastroepiploic artery as its blood supply or the body with a blood supply from either
the right or left gastroepiploic artery. Although the stomach’s lack of significant electrolyte
absorption makes it appealing in cases with impaired renal function and a resultant
acidosis, the acid-secreting nature of the stomach can cause the hematuria-dysuria
syndrome, hypochloremic hyponatremic alkalosis, and hypergastrinemia (16). The gastric
complications of partial gastrectomy (dumping syndrome, early satiety), combined with
the bladder complications, have relegated the use of stomach in augmentation to a last
resort role.
A low-midline incision is typically used for augmentation cystoplasty; a Pfannensteil
incision may also be used, but this can limit the surgical options if ileum or sigmoid
colon intraoperatively appears suboptimal. If the cecum and right colon are utilized,
then this usually requires extension of the midline incision several centimeters above the
umbilicus. Laparoscopic augmentation has been reported as either a completely laparo-
scopic technique (17) or with the bowel harvesting, reanastomosis, and detubularization
performed extracorporeally via a 2-cm extension of the umbilical stoma (18).
The port sites for laparoscopic augmentation are shown in Fig. 1. In all cases of
augmentation cystoplasty, whether open or laparoscopic, the basic steps are identical.
Access is gained to the peritoneal cavity. The space of Retzius is entered, and the loose
areolar tissue around the bladder is bluntly dissected to expose the anterior bladder neck
and perivesical spaces. The bladder is filled with sterile irrigant, and a wide cystotomy
is created (horizontally, vertically, or in a cruciate fashion). It may be preferable to delay
the cystotomy until the bowel has been harvested and detubularized as the cut bladder
edges will often retract significantly. The appropriate bowel segment is harvested on its
mesentery; bowel continuity is reestablished, and the bowel segment is detubularized
(Fig. 2). The bowel segment is then sewn to the opened bladder in a watertight fashion
with absorbable sutures (Fig. 3). Prior to placing the last few sutures, a cystostomy
catheter is placed through the native bladder and out through a suprapubic stab incision.
The bladder is then irrigated through the urethral or suprapubic catheter to ensure a
watertight anastomosis. A closed drain is left in the pelvis, near but not directly over the
bowel–bladder anastomosis.
When a continent catheterizable stoma is desired, we typically harvest the ileocecal
segment and detubularize the cecum. The detubularized cecum is then sutured half-
closed, with the dependent portion left open for anastomosis to the bladder. The terminal
ileum is tapered by firing a stapler lengthwise alongside a 14- or 16-French catheter
Fig. 1. Typical port positions for laparoscopic augmentation cystoplasty.
(Fig. 4). The ileocecal valve is then intussuscepted using permanent sutures passed
through the serosal surface of the ileum and cecum. The cecum is then sutured to the
widely opened bladder, and a catheterizable stoma is matured at the umbilicus (Fig. 5).
Postoperatively, the patient is instructed to irrigate the suprapubic tube and urethral
catheter several times a day to prevent mucus plugging; this irrigation is typically later
reduced to an as-needed basis; in patients with sensory impairment, it may be wise to
continue a standard irrigation protocol, especially for stone prevention (19). The closed
drain is typically removed when outputs have been consistently low (less than 100 cc
per day) and the patient is ambulatory or regularly out of bed. The bladder is left to
continuous drainage via the suprapubic tube, the urethral catheter, or both for 3–4 wk.
After the urethral catheter is removed, the patient can begin voiding trials by clamping
the suprapubic tube. If a continent catheterizable stoma was created, then a catheter is
left in place in the stoma for 4–6 wk, at which time the patient begins intermittent
catheterization. The suprapubic tube is typically removed at 4–6 wk postoperatively.
Fig. 2. The ileal segment is detubularized by opening its antimeseteric edge, forming a U, and suturing
the adjacent sides of the U together.
Fig. 3. A watertight bowel-bladder anastomosis is created with a running suture.

Fig. 4. The cecum is detubularized, and the terminal ileum is tapered by firing a GIA stapler along-
side a 14- to 16-French catheter.
Follow-up of patients should include a functional lower urinary tract study (video-
urodynamics, or at least voiding diary, flow rate, and postvoid residual) within the first
6–12 mo to determine capacity and voiding efficiency; blood chemistries including
electrolytes, serum urea nitrogen, and creatinine should also be followed periodically
along with upper tract sonography. As there have been several reports of bladder cancer
(typically adenocarcinoma) developing in augmented bladders with a lag time of less
than 20 yr (20), annual cystoscopic surveillance should begin within 10 years after
augmentation.
RESULTS AND COMPLICATIONS

The “success” of augmentation cystoplasty is difficult to define simply as most studies
deal with distinct patient populations with different expectations, ranging from children
with myelomeningocele to adults with refractory overactive bladder. Also, concomitant
procedures are often performed to address deficiency of the urinary sphincter (sling
procedures or artificial urinary sphincter). Finally, the definition of success varies
among studies, with renal function, continence, voluntary voiding, and quality of life as
measured outcomes indicative of success or failure. With success defined as continent
with stable renal function, most studies report success rates between 63 and 100% (21).
Patients continent preoperatively have higher continence rates, and those with an
open bladder outlet on videourodynamic evaluation preoperatively have lower rates
(22). There is some debate regarding whether an artificial urinary sphincter should be
implanted at the time of augment; although this has been shown not to increase infec-
tion rates (23), given that some incontinent patients will gain sufficient control with
augmentation alone, it is questionable whether they should be subjected to an additional
procedure that may be unnecessary. The decision to perform anti-incontinence
procedures at the time of augmentation needs to be individualized, perhaps selecting
Fig. 5. The continent catheterizable stoma can be matured at the umbilicus (shown) or in the right
lower quadrant.
only the patients with a high likelihood of postoperative incontinence for concomitant
procedures.
Early complications of augmentation include those common to all major abdominal
operations involving bowel resection and anastomosis: hemorrhage in 0.6–6.7%, infec-
tion in 1.5–9%, small bowel obstruction in 1.5–8.7%, deep vein thrombosis/pulmonary
embolism in 1.1–7.1%, myocardial infarction in 0–1.7%, and death in 0–3.2% (21).
Fistulas can occur in up to 29.7% of cases and typically involve the anastomotic line
between the bladder and bowel segment. This can typically be managed successfully
with adequate drainage; only 1–2% require an additional operative procedure to treat
the fistula (24).
Late complications include bowel dysfunction, metabolic derangements, bladder
calculi, bladder perforation, and increased carcinoma risk. Bowel dysfunction includes
diarrhea, which may occur in up to 16% of cases (25), and B12/bile salt malabsorption
if the terminal ileum is utilized. Acid reabsorption from the urine in ileal and colonic
augments results in increased serum chloride and decreased bicarbonate; typically,
frank acidosis does not occur if renal function is normal, although occasionally alkali
therapy with bicarbonate supplements is necessary. This is avoided when gastric segments
are used, but their unique complications are discussed above.
Calculi formation occurs in up to 50% of patients depending on the length of follow-up,
with struvite stones the most common type. A strict protocol of biweekly saline/gentamicin
irrigation appeared to reduce the incidence of stone formation from 43 to 7% in one series
(19). Although asymptomatic bacteruria is common after enterocystoplasty, it is usually
left untreated unless the patient is symptomatic or the organism is a urea-splitting bacteria,
which may lead to struvite stone formation.
Bladder perforation has been reported in 3–9% of patients with augments, often in
patients using clean intermittent catheterization with poor technique or compliance
(26). However, “spontaneous” perforations in patients voiding voluntarily have also
been reported (24), so this diagnosis should always be suspected in any augment patient
with signs of peritonitis.
Bladder carcinoma risk, particularly adenocarcinoma, appears to be increased several-
fold over the general population. The lag time appears to be under 20 yr, and therefore
surveillance cystoscopy should begin at postoperative yr 10 (20).
Complications, both minor and severe, are common after augmentation cystoplasty;
this is evidenced in a study with long-term follow-up (mean 8 yr), which reported a need
for a subsequent procedure in 46% of patients (27). Even with this high reoperative rate,
most patients in this series reported satisfaction with their augmentation cystoplasty.
CONCLUSION
Augmentation cystoplasty is a time-tested procedure that has been shown in several
retrospective studies to effectively increase bladder storage capacity, maintain stable
renal function, improve quality of life, and promote continence in patients with small,
poorly compliant bladders. Its role may be diminishing with the advent of botulinum
toxin therapy and neuromodulation, but in the severely afflicted patient, it will likely
remain an option for the foreseeable future. Complications and the need for subsequent
procedures are common, and the decision to proceed with augmentation cystoplasty
requires a long-term commitment from the clinician and a lifelong follow-up regimen
for the patient.
REFERENCES
1. Webster GD, Maggio MI. The management of chronic interstitial cystitis by substitution cystoplasty.
J Urol 1989;141:287–291.
2. Gonzalez R, Sidi AA, Zhang G. Urinary undiversion: indications, technique and results in 50 cases. J Urol
1986;136:13–16.
3. Fontaine E, Gagnadoux MF, Niaudet P, Broyer M, Beurton D. Renal transplantation in children with
augmentation cystoplasty: long-term results. J Urol 1998;159:2110–2113.
4. Power RE, O’Malley KJ, Khan MS, Murphy DM, Hickey DP. Renal transplantation in patients with
an augmentation cystoplasty. BJU Int 2000;86:28–31.
5. Thomalla JV, Mitchell ME, Leapman SB, Filo RS. Renal transplantation into the reconstructed bladder.
J Urol 1989;141:265–268.
6. Altaweel W, Jednack R, Bilodeau C, Corcos J. Repeated intradetrusor botulinum toxin type A in children
with neurogenic bladder due to myelomeningocele. J Urol 2006;175:1102–1105.
7. Hohenfellner M, Humke J, Hampel C, et al. Chronic sacral neuromodulation for treatment of neuro-
genic bladder dysfunction: long-term results with unilateral implants. Urology 2001;58:887–892.
8. Klein EA, Montie JE, Montague DK, Kay R, Straffon RA. Jejunal conduit urinary diversion. J Urol
1986;135:244–246.
9. Hofmann AF, Poley JR. Role of bile acid malabsorption in pathogenesis of diarrhea and steatorrhea in
patients with ileal resection. I. Response to cholestyramine or replacement of dietary long chain
triglyceride by medium chain triglyceride. Gastroenterology 1972;62:918–934.
10. Whitmore WF 3rd, Gittes RF. Reconstruction of the urinary tract by cecal and ileocecal cystoplasty:
review of a 15-yr experience. J Urol 1983;129:494–498.
11. Sidi AA, Reinberg Y, Gonzalez R. Influence of intestinal segment and configuration on the outcome
of augmentation enterocystoplasty. J Urol 1986;136:1201–1204.
12. Fromm D. Ileal resection, or disease, and the blind loop syndrome: current concepts of pathophysiology.
Surgery 1973;73:639–648.
13. Sutton MA, Hinson JL, Nickell KG, Boone TB. Continent ileocecal augmentation cystoplasty. Spinal
Cord 1998;36:246–251.
14. Webster C, Bukkapatnam R, Seigne JD, et al. Continent colonic urinary reservoir (Florida pouch):
long-term surgical complications (greater than 11 yr). J Urol 2003;169:174–176.
15. Shekarriz B, Upadhyay J, Demirbilek S, Barthold JS, Gonzalez R. Surgical complications of bladder
augmentation: comparison between various enterocystoplasties in 133 patients. Urology
2000;55:123–128.
16. Plawker MW, Rabinowitz SS, Etwaru DJ, Glassberg KI. Hypergastrinemia, dysuria-hematuria and
metabolic alkalosis: complications associated with gastrocystoplasty. J Urol 1995;154:546–549.
17. Elliott SP, Meng MV, Anwar HP, Stoller ML. Complete laparoscopic ileal cystoplasty. Urology
2002;59:939–943.
18. Gill IS, Rackley RR, Meraney AM, Marcello PW, Sung GT. Laparoscopic enterocystoplasty. Urology
2000;55:178–181.
19. Hensle TW, Bingham J, Lam J, Shabsigh A. Preventing reservoir calculi after augmentation cystoplasty
and continent urinary diversion: the influence of an irrigation protocol. BJU Int 2004;93:585–587.
20. Soergel TM, Cain MP, Misseri R, Gardner TA, Koch MO, Rink RC. Transitional cell carcinoma of the
bladder following augmentation cystoplasty for the neuropathic bladder. J Urol 2004;172:1649–1651.
21. Greenwell TJ, Venn SN, Mundy AR. Augmentation cystoplasty. BJU Int 2001;88:511–525.
22. Medel R, Ruarte AC, Herrera M, Castera R, Podesta ML. Urinary continence outcome after augmen-
tation ileocystoplasty as a single surgical procedure in patients with myelodysplasia. J Urol 2002;168:
1849–1852.
23. Catto JW, Natarajan V, Tophill PR. Simultaneous augmentation cystoplasty is associated with earlier
rather than increased artificial urinary sphincter infection. J Urol 2005;173:1237–1241.
24. Flood HD, Malhotra SJ, O’Connell HE, Ritchey MJ, Bloom DA, McGuire EJ. Long-term results and
complications using augmentation cystoplasty in reconstructive urology. Neurourol Urodyn 1995;
14:297–309.
25. Wood GA, Heathcote PS, Nicol DL. Bowel motility after enterocystoplasty. Br J Urol
1998;81:565–568.
26. Elder JS, Snyder HM, Hulbert WC, Duckett JW. Perforation of the augmented bladder in patients
undergoing clean intermittent catheterization. J Urol 1988;140:1159–1162.
27. Quek ML, Ginsberg DA. Long-term urodynamics follow-up of bladder augmentation for neurogenic
bladder. J Urol 2003;169:195–198.
18 Mixed Incontinence
Defining Symptoms, Management, and Outcomes
Roger Dmochowski, MD, FACS

and Harriette M. Scarpero, MD
CONTENTS
INTRODUCTION
DEFINITIONS AND APPROACH
EXPECTATIONS FOR RESULTS
CONCLUSION: WHAT WE DO
REFERENCES
INTRODUCTION
Mixed urinary incontinence (MUI) has been presumed to account for at least one-third
of all cases of incontinence in women, yet estimates of this symptom complex have
ranged as high as 60%. The wide range of incidence rates associated with MUI arise
in part because of vastly differing definitions and measures of the components (urge
and stress urinary symptoms) that contribute to the composite presentation of MUI.
General suppositions regarding MUI have been generally that the mixed scenario
responds less favorably to intervention, regardless of type. Behavioral, pharmaco-
logical, and surgical strategies have all been proposed for the management of MUI;
however, no clear approach yet exists for management of the unique woman present-
ing with symptoms of MUI. Evidence exists to support the primary and durable role of
surgical intervention for the stress component, but study design issues (such as repro-
ducible outcome parameters) make generalization of any reported results to the broad
population problematic.
DEFINITIONS AND APPROACH

MUI is loosely defined as the occurrence of stress (activity/exertion related)
incontinence concomitantly associated with bothersome urinary irritative symptoms
(urinary frequency, urgency, and urge incontinence). Moreover, approx 30–50% of women
with MUI will misperceive stress incontinence as an urgency event. Nonurge, nonstress
incontinence (insensate, unconscious, or spontaneous incontinence) represents another,
less clearly ascribable symptom that is posited to arise from detrusor overactivity occur-
ring in the absence of sensory urgency (motor detrusor overactivity uncoupled from any
bladder sensation). Further complicating the MUI presentation is the superimposition of
urinary frequency as a behavioral response to the bothersome urinary symptoms.
261
Perhaps the most difficult symptom to categorize is the gravitational loss of urine
occurring on nocturnal arising (or awakening) with a full bladder because this may be a
varying mix of the two main symptomatic components. We still find this the most prob-
lematic scenario in which to obtain reasonable success. Therefore, the symptoms of MUI
must clearly be assessed prior to intervention so possible treatment-related outcomes
can be reported lucidly.
Evaluation of the woman with MUI must use tools that are reproducible, clearly assess
and stratify component symptoms, and adequately assess patient approbation of thera-
peutic impact. We suggest a rather simplistic approach. Components of the screening
assessment include history and physical (including a provocative stress test), assessment
of symptom-specific quality of life (using instruments such as the overactive bladder
questionnaire), and one item evaluation of symptom impact (such as the Patient Perception
of Bladder Condition).
Certainly, more exhaustive evaluation, including pad testing and urodynamics, can be
insinuated into the paradigm at this stage; however, if initial intervention is nonsurgical
(behavioral or pharmacological), then the screening assessment is sufficient. Any patient
who does not achieve acceptable symptomatic response or who is considering surgical
intervention should then be considered for more invasive evaluation to objectify symptoms
better. Incumbent in this assessment is an early appraisal of patient expectations and a
realistic discussion of outcomes as symptomatic modulation with therapy will run the
gamut from cure of symptoms to abject failure, with exacerbation of one or all components
of the MUI presentation.
EXPECTATIONS FOR RESULTS

The outcomes of a variety of interventions have been reported for MUI. Comparability
of these outcomes is difficult because of inherent differences in entry populations, study
design, and outcome reporting.
Behavioral and Pharmacological Outcomes

Pharmacological intervention for MUI is usually coupled with conservative measures
such as behavioral therapy in clinical practice and in drug trials (the impact of diary
record keeping and repetitive symptom assessment cannot be minimized in a symptom
complex with so strong a behavioral overlay). A variety of conservative measures has
been utilized for urgency and urge incontinence in those patients with mixed symptoms;
these measures include behavioral therapies, biofeedback, and treatment with anti-
cholinergic agents. Approximately two-thirds of patients derive benefit for their urgency
with anticholinergic agents.
Post hoc review of large-scale clinical trials concluded that anticholinergic agents
were beneficial for reducing incontinence episodes, urinary frequency, and urinary
urgency in patients with mixed symptomatology, and that these reductions were retained
throughout the trial period. Although these data are specific to one agent, we presume,
based on our clinical experience, that the degree of benefit of combined therapy can be
generalized to the entire MUI population (1,2).
Topical estrogen has been extensively evaluated as an isolated intervention for
MUI (although usually for the component symptoms of urge or stress). Therapeutic
results are of minimal magnitude (except for the possible response of subjective
urgency).
Chapter 18 / Mixed Incontinence 263
Surgical Outcomes
Surgical intervention for stress-predominant MUI, regardless of whether motor
bladder overactivity is identified preoperatively, is more likely to be successful (in terms
of symptom improvement or resolution) than in the case of MUI with predominant
preoperative urge. A caveat to this generalization is the circumstance of high-pressure
(over 25 cm H2O) detrusor overactivity at low bladder volumes, which militates against
surgical success. Although reported symptom improvement or cure rates vary with
surgical management in the stress-predominant group, this group had measurably greater
improvement than their urge-predominant peers (2.5 times greater).
Modern surgical series consistently demonstrate improvement in surgical outcomes
for stress-predominant MUI regardless of sling type. In studies that have segregated
urgency as either motor or sensory, a salubrious effect of intervention has been noted for
both symptoms, although to different degrees. In general, cure (58.5%) and improve-
ment (17.1%) in urgency/urge incontinence are more commonly seen in patients with
evidence of motor overactivity on urodynamics compared to only 39.3% (cure) and
39.1% (improvement) in those women with no identifiable motor overactivity (sensory
instability). Using an arbitrary value of 15 cm H2O, women with motor overactivity
below this magnitude had a better chance of symptomatic resolution than those with
phasic detrusor pressures greater than this value (3).
Midurethral slings have also demonstrated efficacy in women with mixed symptoma-
tology. Although the magnitude of benefit is less than in those women with “pure” stress
urinary incontinence (SUI; 95.5%), women with MUI (78.1%) do demonstrate benefit
from midurethral procedures. The authors of this study suggested that poor urethral func-
tion contributes to persistent urgency symptoms. However, modulation of low-pressure
outlet may benefit at least some individuals with MUI; therefore, primary surgery may
be useful in well-selected patients (4,5).
Others have also found benefit for MUI in women undergoing midurethral slings.
Resolution rates of 85% in MUI patients have been reported; however, urodynamics
were not used to characterize the study populations. Other authors have concluded that
these response rates justify the use of midurethral slings in these populations.
Therefore, data exist to support the benefit of minimally invasive midurethral
slings for patients with MUI. In general, resolution of urgency in patients undergoing
surgical procedures for SUI occurs in 50–70%; however, these rates are dependent
on initial quantification and definition of the symptomatic components of the MUI
complex.
CONCLUSION: WHAT WE DO
Our philosophy is that the most bothersome symptom should be approached first
possibly to lessen the impact of the secondary symptom. The use of the proposed para-
digm for assessment is a reasonable starting point. The addition of a short-term (3-d)
voiding diary allows additional objectification of the presenting symptoms and is a
facile tool for defining baseline severity and for monitoring outcomes. No reproducible
instrument yet exists to clearly assess MUI component contributions and severity; there-
fore, a combination of tools is best to accomplish this task. Urodynamic studies may have
predictive benefit for some patients with mixed symptoms to elucidate the gravity of
urethral dysfunction and certain aspects of detrusor dysfunction (such as high-pressure
detrusor overactivity) that may have an impact on outcome.
Using this paradigm, initial intervention can be promulgated to address the most
bothersome symptom. After initial response is established, tailored therapy for secondary
symptoms can then be undertaken. For example, stress-predominant MUI could undergo
intervention for SUI with secondary interventions for urge urinary incontinence predi-
cated on results of the primary intervention. MUI with a strong urge component could
undergo therapy to modulate the urgency symptoms, including anticholinergics or sec-
ondary treatments in pharmacological failures (neuromodulation or botulinum toxin),
followed by SUI interventions for persistent outlet symptoms.
Individualized therapy based on symptomatic segregation, with therapy promulgated
based on the most bothersome symptom, with secondary interventions reserved for
either persistence of the primary symptom or bother arising from the less-prominent
initial symptom. In those individuals with relatively equal bother or who are unable
to segregate their symptoms, more intensive evaluation (such as urodynamics) may
provide guidance to initiate therapy. Alternatively, conservative or minimally invasive
intervention may be initiated to establish response, followed by more intensive interven-
tion for nonresponse. Ideally, patients should be informed regarding which symptoms
may persist or become problematic postintervention.
REFERENCES
1. Khullar V, Hill S, Laval KU, Schiotz HA, Jonas U, Versi E. Treatment of urge-predominant mixed
urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial. Urology
2004;64:269–274; discussion 274–275.
2. Kreder KJ Jr, Brubaker L, Mainprize T. Tolterodine is equally effective in patients with mixed incon-
tinence and those with urge incontinence alone. BJU Int 2003;92:418–421.
3. Segal JL, Vassallo B, Kleeman S, Silva WA, Karram MM. Prevalence of persistent and de novo over-
active bladder symptoms after the tension free vaginal tape. Obstet Gynecol 2005;104:1263–1269.
4. Abdel-Hady ES, Constantine G. Outcome of the use of tension-free vaginal tape in women with mixed
urinary incontinence, previous failed surgery, or low Valsalva pressure. J Obstet Gynaecol Res
2005:31:38–42.
5. Lin LY, Yeh NH, Lin CY, et al. Comparisons of urodynamic characteristics between female patients
with overactive bladder plus stress urinary incontinence. Urology 2004;64:945–949.
19 Evaluation and Management
of Anterior Vaginal Wall Prolapse
Sandip P. Vasavada, MD
and Matthew D. Barber, MD, MHS
CONTENTS
INTRODUCTION
EVALUATION
SURGICAL TECHNIQUES
OUTCOMES
COMPLICATIONS
REFERENCES
INTRODUCTION
Prolapse of the anterior vaginal wall is the most common presentation of pelvic organ
prolapse. Studies suggested that, of the various segments of the vagina that may be
involved in prolapse (anterior, posterior, or apical), the anterior vaginal wall is the
segment most likely to demonstrate recurrent prolapse after reconstructive surgery. In
addition, normal anterior vaginal support plays an important role in supporting the
urethra, and loss of this support can contribute to the development of stress urinary
incontinence. It is therefore important that the pelvic reconstructive surgeon understand
the normal support mechanisms of the anterior vaginal wall and the full spectrum of
techniques for correction of anterior vaginal prolapse and cystoceles.
Underlying the vaginal epithelium is the vaginal muscularis, a well-developed layer
primarily made up of smooth muscle along with collagen and elastin (7). Some have
labeled this layer of the anterior vaginal wall the pubocervical fascia or vesicopelvic
fascia. In actuality, the use of the term fascia is a misnomer as it does not accurately
reflect the histology of the vagina.
There are four defects one may see in advanced anterior vaginal prolapse, including
(1) defects or attenuation of the vaginal muscularis in the midline (central defect),
(2) loss of lateral attachments from the anterior vagina to the pelvic sidewall (lateral
or paravaginal defect), (3) loss of bladder neck support, and (4) separation of the
cardinal-uterosacral ligament complex from the vaginal apex (superior defect). These
four defects accompany most large cystoceles and must be corrected to achieve good
support, elevation of the bladder base, and a solid, durable repair.

267
268 Part IIC / Prolapse
EVALUATION
History
Patients with anterior vaginal prolapse often complain of symptoms directly related
to the prolapse as well as symptoms of bladder dysfunction. Patients with prolapse at
or beyond the level of the hymen often complain of pelvic pressure and bulging. Stress
urinary incontinence commonly occurs in association with anterior vaginal prolapse,
and approximately one-third of women with stage II or greater prolapse will complain
of symptoms of urinary urgency, frequency, or urge incontinence. Symptoms of voiding
dysfunction such as a feeling of incomplete emptying, intermittent or reduced urine
flow, or the need to splint to complete urination are common in women with prolapse
beyond the hymen. Sexual difficulty is also a common complaint of women with
advanced prolapse. In addition to this functional assessment, a detailed history of pre-
vious prolapse or antiincontinence surgery should also be elicited.
Physical Examination
A pelvic examination should be performed with the patient in the lithotomy position.
A detailed assessment of the support of all segments of the vagina should be made using
the International Continence Society’s Pelvic Organ Prolapse Quantification (POP-Q)
system. In addition, an assessment for central, lateral, and superior anterior vaginal support
defects should be performed. If physical findings do not correspond to symptoms or if
the maximum extent of the prolapse cannot be confirmed, then the woman should be
examined in the standing position.
A curved ring forceps is placed in the lateral vaginal sulci and directed toward the
ischial spines along the course of the arcus tendineus fasciae pelvis (ATFP) to reproduce
the lateral support of the vagina. A Sims speculum is placed posteriorly to expose the
anterior vaginal wall and reduce any posterior prolapse. The patient is asked to strain
maximally, and if complete reduction of the anterior prolapse occurs with the ring forceps
in this position, she is thought to have paravaginal defects. If, when she strains, the anterior
vagina continues to bulge between the arms of the ring forceps without any evidence of
reduction, then this suggests a midline loss of support. If supporting the lateral vagina
results in partial reduction of the prolapse, then she is thought to have lost both midline
and lateral support. Unilateral elevation of each vaginal sulcus allows differentiation
of bilateral and unilateral paravaginal defects.
Diagnostic Tests
URODYNAMICS
Symptoms of urinary incontinence and voiding dysfunction are common in women
with advanced vaginal prolapse. In addition, because significant anterior vaginal prolapse
often results in urethral kinking that may mask underlying stress incontinence, it is our
practice to obtain preoperative urodynamics with vaginal packing or pessary placement
to evaluate the lower urinary tract in these patients.
CYSTOSCOPY
To detect concurrent bladder pathology, preoperative office cystoscopy is useful
in the evaluation of the prolapse patient with lower urinary tract symptoms such as
urinary urgency, hematuria, and obstructed voiding. In addition, we have found it useful
Chapter 19 / Anterior Vaginal Wall Prolapse 269
to use a “light test” to differentiate a cystocele more accurately from other types of
vaginal prolapse. This is performed during cystoscopy with the tip of the cystoscope
aimed downward to confirm the cystocele from an enterocele. Although this test is simple,
it can yield important information as well.
SURGICAL TECHNIQUES
Surgical correction of anterior vaginal prolapse can be accomplished through a vaginal,
abdominal, or laparoscopic approach. The appropriate route of surgery is determined
by several factors, including the preoperative evaluation of anterior vaginal support
defects, the presence of other vaginal support defects, history of previous reconstruc-
tive or antiincontinence surgery, the patient’s surgical risk, and surgeon skill and
preference. It is quite important to realize that, in our experience, it is rare that a
patient with advanced anterior vaginal prolapse has an isolated anterior support
defect; almost universally, an apical support defect exists when the prolapse is beyond
the hymen.
For this reason, it is essential to include a vaginal vault suspension procedure as part
of the surgical correction of anterior vaginal prolapse in these women. In addition,
because of the contribution of anterior vaginal support to the urinary continence mecha-
nism, preferential support of the bladder neck using a pubovaginal sling, retropubic
urethropexy, bladder neck plication, or some similar technique should be performed
routinely as part of any anterior vaginal reconstruction.
Anterior Colporrhaphy
Anterior vaginal prolapse resulting from a central defect is best corrected through
a transvaginal approach. The anterior colporrhaphy was popularized by Howard Kelly
in 1912 (9), and although no longer an acceptable treatment for stress urinary inconti-
nence, it remains a commonly used technique for transvaginal correction of anterior
vaginal prolapse. Although many variations of this technique have been described in the
last century, the basic approach is similar to that originally described by Kelly.
There has been growing interest in the use of synthetic mesh or biologic grafts in the
surgical repair of cystoceles to reduce the risk of prolapse recurrence. The role of mesh
or tissue grafts in the surgical correction of prolapse is currently unknown as few
randomized trials investigating these techniques exist. However, the limited evidence
that is available remains promising. We describe our technique for both the traditional
anterior colporrhaphy and the mesh or graft patch repair.
TRADITIONAL APPROACH
Traditionally, the patient is placed in dorsal lithotomy position in candy cane or Allen
stirrups. A Foley catheter is placed for dependent drainage. A weighted speculum is
placed in the vagina, and a midline vaginal incision is made with a scalpel. Sterile saline
or local anesthetic can be injected into the anterior vaginal wall prior to incision if
desired. If performed along with a vaginal hysterectomy, then it is useful to complete
the hysterectomy before beginning the anterior vaginal dissection. Sharp dissection
is carried laterally to remove the vaginal epithelium from the vaginal muscularis up to
the lateral sulcus. The retropubic space is entered sharply with the curved Mayo scissors
to allow palpation of the pubic bone if simultaneous pubovaginal sling is required. Alter-
natively, it can be preserved if a tension-free or other midurethral sling is to be performed.
Also, one may curtail the incision immediately below the bladder neck to allow a tension-
free midurethral sling to be placed through a separate incision.
After completing the dissection, the vaginal muscularis is plicated in the midline
using several interrupted stitches of delayed absorbable or permanent suture, thereby
repairing the central defect and elevating the bladder base and anterior vagina. If a sling
is not performed, then the bladder neck can be preferentially supported by plicating
the periurethral tissue underneath the bladder neck (Kelly plication). After completing
the anterior colporrhaphy, repair of lateral or apical support defects is then performed.
The excess vaginal epithelium is then trimmed, and the incision is closed using a 2-0
polyglycolic acid suture. A vaginal pack is then placed for postoperative hemostasis.
Cystoscopy should then be performed to ensure bladder and ureteral integrity (see
Tables 1 and 2).
Mesh or Graft Patch Repair

A central defect repair using mesh or tissue graft patch begins similar to the traditional
repair. After completion of the vaginal dissection, the cardinal ligaments are isolated
and plicated with 2-0 polyglycolic acid sutures to correct their separation and laxity.
The sutures are placed into the levator fascia on each side, thereby preventing the slid-
ing defect herniation of the bladder base. In addition, the cardinal ligaments form the
base of the cystocele repair and anchor the posterior portion of the patch (Fig. 1).
The vaginal muscularis is plicated after the central defect cystocele may be reduced
with use of an absorbable mesh. The fascia is reapproximated with horizontal mattress
sutures of delayed absorbable or permanent suture. The tissue is brought to the midline,
over the mesh, to facilitate reapproximation without tension; this maneuver also helps
reduce the incidence of ureteric injury. Prior to this, intravenous indigo carmine dye is
administered to ensure patency of the ureters. A separate set of polyglycolic acid sutures
is placed into the levator fascia distally at the level of the bladder neck to support the
distal portion of the patch.
A segment of allograft, xenograft, or synthetic mesh is then fashioned such that the
width spans from the obturator fascia to the contralateral side. The sutures are placed in
the corners of the patch 5 mm from the edge. The length of the patch segment depends
on the size of the cystocele and the distance between the pubic bone and the cardinal
ligaments. A 5- to 7-cm segment will usually fit this distance appropriately. The lower
set of sutures (through the cardinal ligaments) is placed through the patch segment in a
similar fashion (Fig. 2). The excess vaginal epithelium is then trimmed, and the incision
is closed using a 2-0 polyglycolic acid suture incorporating the underlying mesh to
prevent any dead pace for fluid accumulation. A vaginal pack is then placed for post-
operative hemostasis (see Tables 3 and 4).
Paravaginal Defect Repair

The goal of the paravaginal defect repair is to correct anterior vaginal wall prolapse
that results from loss of lateral support by reattaching the lateral vaginal sulcus to its
normal lateral attachment site. The lateral vagina attaches to the levator ani muscle on
each side along a line from the anterior pubic rami to the ischial spine, known as the
white line or ATFP. The ATFP is formed from a condensation of the obturator internus
and levator ani fascia and is composed primarily of organized fibrous collagen, making
the lateral connective tissue attachment of the vagina denser than the superior/apical
Table 1
Outcome of Anterior Colporrhaphy Alone for Treatment of Anterior Vaginal Prolapse
No. of Mean Recurrence
Author (year) patients Study design follow-up (%)
Macer (1978) (11) 76 Retrospective cohort 5–20 yr 20
Walter et al. (1982) (27) 86 Prospective cohort 1–2.5 yr 0
Stanton et al. (1982) (26) 73 Prospective cohort 2 yr 15
Porges and Smilen (1994) (17) 486 Retrospective cohort 2.6 yr 3
Smilen et al. (1998) (25) 245 Retrospective cohort 6 mo 9.4
Weber et al. (2001) (28) 74a RCT 23.3 mo 54–70
RCT, randomized controlled trial.
aA total of 114 subjects were enrolled in this trial; 74 subjects underwent either a traditional anterior
colporrhaphy (n = 39) or an “ultralateral” anterior colporrhaphy (n = 33) without graft augmentation.
Table 2
Anterior Colporrhaphy and Needle Suspension for Treatment of Anterior Vaginal Prolapse
Mean
No. of follow-up Recurrence
Author (year) patients Study design (yr) (%)
Raz et al. (1989) (18) 120 Retrospective cohort 0.5–5 2.5
Miyazaki and Miyazaki (1994) (15) 27 Retrospective cohort 3.5–4 59
Bump et al. (1996) (3) 32 RCT 0.5 50
Dmochowski et al. (1997) (5) 47 Retrospective cohort 1.25–6.75 17–40
Migliari and Usai (1999) (13) 15 Retrospective cohort 1.5–3.25 7
connective tissue support of the cardinal and uterosacral complex. The paravaginal
defect repair can be performed retropubically or vaginally.
RETROPUBIC APPROACH
The retropubic approach for the repair of paravaginal defects can be performed via
laparotomy or laparoscopy. In our opinion, the surgical technique for these two
approaches, other than the means of access to the retropubic space, should be identical.
The patient is placed in modified lithotomy position using low leg holders such as
Allen stirrups and is draped to allow both abdominal and vaginal access. The bladder
is drained with a Foley catheter. The abdomen may be entered through either a trans-
verse or a vertical abdominal incision or laparoscopy. The retropubic space is entered,
and the bladder is retracted medially to expose the lateral aspect of the retropubic
space. The pubic bone, obturator muscle, obturator fossa, and neurovascular bundle are
identified. Blunt dissection is used to identify the lateral vagina, urethra, and ischial
spine. The normal site of lateral vaginal attachment on the pelvic sidewall from the
interior aspect of the superior pubic ramus to the ischial spine is then identified. If the
lateral vagina is avulsed from this attachment site, then a paravaginal defect is present.
As physical examination is less than perfect in identifying paravaginal detachment,
Fig. 1. Application sutures of zero polyglycolic and through pubocervical fascia to bring back to
toward the midline.
Fig. 2. Patch augmentation of anterior vaginal wall prolapse repair.

Table 3
Anterior Colporrhaphy and Simultaneous Sling/Anti-Incontinence Procedure
for Treatment of Anterior Vaginal Prolapse
No. of Mean Recurrence
Author (year) patients Study design follow-up (yr) (%)
Cross et al. (1997) (4) 42 Retrospective cohort 1–3.25 8–17
Safir et al. (1999) (21) 130 Retrospective cohort 0.5–3.5 4–5
a bilateral assessment of paravaginal support should be made in all patients in whom

paravaginal defects are suspected.
The surgeon’s nondominant hand is the placed into the vagina and used to elevate
the lateral superior vaginal sulcus to its site of normal attachment along the course
of the ATFP. Typically, four to six simple interrupted stitches of nonabsorbable
suture (0 or 2-0) are used to reattach the lateral vagina to the ATFP. The first suture
is placed through full thickness (excluding the vaginal epithelium) of the lateral vagi-
nal apex and then through the ATFP and the aponeurosis of the levator ani muscle just
distal to the ischial spine. This suture is tied and cut. Additional sutures are placed
at 1-cm intervals through the lateral vaginal wall and into the levator ani aponeurosis
along the entire course of the ATFP. In patients with a cystocele and genuine stress
incontinence, many surgeons combine an abdominal paravaginal repair with a Burch
colposuspension.
At the end of the procedure, cystoscopy should be performed to document ureteral
patency and the absence of intravesical sutures. Closed-suction drainage of the retropubic
space is rarely indicated. Postoperatively, the bladder is drained with either a trans-
urethral or suprapubic catheter until normal voiding occurs (see Table 5).
Vaginal Approach
Paravaginal defect repair using the transvaginal approach can be more challenging
than the retropubic approach but offers the advantage of avoiding an abdominal incision
and facilitating a concurrent central defect repair for those women with loss of midline
as well as lateral anterior vaginal support. The technique begins similar to that of the
central defect repair. A midline vertical incision is made through the vaginal epithelium
from the midurethra to the vaginal apex. The vaginal epithelium is then sharply dissected
off the underlying vaginal muscularis, and the dissection is continued laterally to the
pelvic sidewall from immediately behind the pubic rami to the level of the ischial spine.
Visualization of the adipose tissue of the retropubic space from this transvaginal
approach confirms the presence of a paravaginal defect as normal lateral attachment of
the anterior vaginal wall would preclude this. If visualization is limited, then gentle
palpation of the lateral attachment site can be used. The ability of the examining finger
to enter the retropubic space indicates a paravaginal defect. Every precaution should
be taken to avoid iatrogenic creation of paravaginal defects with dissection, palpation,
or retractors.
Once a paravaginal defect is identified, the normal site of lateral attachment of the
vagina should be clearly visualized. This can be facilitated by placing a gauze sponge
through the paravaginal defect into the retropubic space and using a narrow Deaver
retractor to retract the sponge, underlying adipose tissue, and lateral bladder anteriorly.
Table 4
Anterior Colporrhaphy With Patch Augmentation of Repair
for Treatment of Anterior Vaginal Prolapse
No. of Mean
Author (year) Patch material patients Study design follow-up Recurrence
Groutz et al. Cadaver fascia 21 Retrospective 20 mo 0%
(2001) (8) cohort
Kobashi et al. Cadaver fascia 50 Prospective 6 mo 0%
(2000) (10) cohort maximum
Migliari et al. Polypropelene 12 Retrospective 20.5 mo 25% grade I
(2000) (14) mesh cohort cystocele
Weber et al. Polyglactin 910 35 RCT 23.3 mo 58%
(2001) (28) mesh
A Briesky-Navratil retractor can then be used to retract the remainder of the bladder
medially, thereby clearly exposing the levator ani muscle and the course of the ATFP
from the ischial spine to the inferior aspect of the pubic ramus.
Four to six interrupted nonabsorbable sutures (0 or 2-0) are placed through the ATFP
and the aponeurosis of the levator ani muscle from the level of the ischial spine to the
pubic symphysis at 1-cm intervals and their needles left on. Once all of the stitches are
placed through the ATFP, the sponge in the retropubic space is removed. Each stitch is
then placed through the lateral edge of the detached vaginal muscularis (pubocervical
or vesicopelvic fascia) at their corresponding level and then tied.
Once paravaginal support has been assessed and, if necessary, restored on both sides,
a midline plication of pubocervical fascia (anterior colporrhaphy), a bladder neck plica-
tion, or sling can be performed as necessary. The vaginal epithelium is then trimmed
and closed. If a vaginal hysterectomy is needed, then this should be performed prior to
the paravaginal defect repair. If a vaginal vault suspension or culdeplasty is necessary,
then these sutures should be placed prior to the paravaginal defect repair but not tied
until the paravaginal defect repair has been completed. As with the retropubic approach,
cystoscopy should be performed at the end of the procedure to confirm ureteral patency
and the absence of intravesical sutures. Transurethral or suprapubic bladder drainage
should continue until normal voiding occurs (see Table 6).
OUTCOMES
Anterior Colporrhaphy
Outcomes of the traditional anterior colporrhaphy are largely limited to retrospective
reviews and case series. Reporting of outcomes has been extremely subjective, and prior
to the advent of the POP-Q system, pre- and postoperative staging has been variable
between surgeons. Nonetheless, the reported recurrence rates after anterior vaginal wall
prolapse repair have been high (range 0 to 59%).
A randomized trial performed by at the Cleveland Clinic compared traditional
anterior colporrhaphy, an ultralateral anterior colporrhaphy technique, and a traditional
anterior colporrhaphy with polyglactin 910 mesh for treatment of symptomatic anterior
vaginal prolapse. After a median follow-up of 23.3 mo, the recurrence rate (defined as
Table 5
Outcomes of Abdominal Paravaginal Repair for Treatment of Anterior Vaginal Prolapse
No. of Mean
Authors (year) patients Study design follow-up Cure (%)
Richardson et al. (1976) (19) 60 Retrospective cohort 20 mo 97
Richardson et al. (1981) (20) 233 Retrospective cohort NR 95
Shull and Baden (1989) (23) 149 Retrospective cohort 48 mo 95
Bruce et al. (1999) (2) 52 Retrospective cohort 17 mo 92
Scotti et al. (1998) (22) 40 Prospective cohort 39 mo 97
NR, not reported.
Table 6
Outcomes of Vaginal Paravaginal Repair for Treatment of Anterior Vaginal Prolapse
No. of Mean
Author (year) patients Study design follow-up Cure (%)
White (1909) (29) 19 Retrospective cohort NR 100
Shull et al. (1994) (24) 62 Retrospective cohort 1.6 yr 76
Farrell and Ling (1997) (7) 27 Retrospective cohort 8 mo 80
Nguyen and Bhatia (1999) (16) 10 Retrospective cohort 1 yr 100
Elkins et al. (2000) (6) 25 Retrospective cohort NR 76
Mallipeddi et al. (2001) (12) 35 Retrospective cohort 20 mo 97
Young et al. (2001) (30) 100 Retrospective cohort 11 mo 78
NR, not reported.
prolapse that extends 1cm proximal to the hymen or greater) was 30–46%, and there
was no difference in efficacy between the three groups (28).
Insofar as patch augmentation of standard anterior colporrhaphy is concerned, there
exist few peer-reviewed manuscripts on the subject. This is largely because follow-up is
short, and often postoperative evaluations have not rigorously adhered to pre- and post-
operative POP-Q measurements to ascertain differences in the repairs. Nonetheless, the
few reports in the literature are encouraging and suggest that routine use of patch aug-
mentation with a variety of materials may decrease the alarmingly high rate of recurrent
anterior vaginal wall prolapse and do so with minimal morbidity.
Paravaginal Repair
The paravaginal defect repair has been widely used for correction of anterior vaginal
prolapse thought to result from lateral vaginal detachment. Like anterior colporrhaphy,
current evaluation of the success rate of this procedure for treatment of anterior vaginal
prolapse is limited to case series and retrospective reviews. Reports of retropubic para-
vaginal repair demonstrate anatomic success rates ranging from 92 to 97% for the
abdominal approach.
There are few long-term data on the efficacy of laparoscopic paravaginal repair for
the treatment of anterior vaginal prolapse. Reports of vaginal paravaginal repair demon-
strate success rates of 76–100% (see Table 6) after variable lengths of follow-up. Failure
or recurrence of anterior vaginal prolapse after paravaginal defect may occur laterally,
centrally, or both. Studies that have differentiated lateral from central recurrence have
revealed that central recurrence (22–25%) is more common than lateral recurrence
(2–8%). To date, there are no studies comparing paravaginal defect repair with or without
midline anterior repair to traditional anterior colporrhaphy alone.
COMPLICATIONS
Intraoperative complications after repair of anterior vaginal prolapse are, for the most
part, infrequent. Febrile morbidity occurs in 6–20% of patients and is most often self-
limited. Lower urinary tract injury occurs in 0–4%, similar to other pelvic reconstructive
procedures. Excessive blood loss may occur, requiring blood transfusion. This is infrequent
with anterior colporrhaphy and retropubic paravaginal repair.
Although paravaginal repair through the vaginal approach offers some potential
advantages over the retropubic approach, including shorter recovery time, the ability
simultaneously to correct midline anterior defects, and the avoidance of an abdominal
incision, it may have a higher rate of intraoperative hemorrhage and blood transfusion,
as high as 9–12% in some series. This is in contrast to a transfusion rate of 0–4% in
series of abdominal paravaginal defect repair. The limited exposure and technical
challenge of the vaginal approach likely explains this difference.
Postoperative complications from the repair of advanced anterior vaginal prolapse
are not unlike those of other vaginal reconstructive procedures. These may include
prolonged urinary retention, de novo urinary urge or stress incontinence, recurrent pro-
lapse, or vaginal shortening. Urinary retention is usually a transient phenomenon and
often resolves on its own. Rarely, one may require a prolonged course of suprapubic
catheter drainage or intermittent catheterization until satisfactory spontaneous voiding
occurs. De novo urinary incontinence (urge or stress) may occur in a small portion of
patients, possibly those with higher-grade prolapse and long-term obstruction. Urge
incontinence may subside with time but often requires behavioral therapeutic modifica-
tions as well as anticholinergic therapy to assist in controlling symptoms. New-onset
stress incontinence may result from inadequate bladder neck and urethral support or be
caused by intrinsic sphincteric dysfunction. Accordingly, some advocate routine placement
of a sling or some form of bladder neck support to minimize this potential.
In our experience, patients with stage III–IV cystoceles often require concomitant
surgical procedures to correct other, often-severe defects in pelvic floor support in the
form of enterocele, rectocele, or uterine prolapse. Simply repairing the cystocele without
addressing these other potential defects in pelvic support may lead to recurrent vaginal
bulges and require secondary procedures. As the anterior vaginal wall is transferred
superiorly, this may allow a weakened cul de sac and posterior vaginal wall to prolapse
in the form of an enterocele or rectocele. Vaginal shortening can be avoided by mini-
mizing the amount of anterior vaginal wall tissue that is excised; thus, this should be
a rare complication.
Ureteric obstruction may occur postoperatively despite demonstration of patency on
cystoscopic examination as kinking of the ureters results from the support sutures. If
this occurs, then one must address the obstruction by placement of either a stent or
percutaneous nephrostomy tube and passage of a guide wire down the narrowed chan-
nel. After a period of observation, if no patency ensues, then one may proceed with
ureteric reimplantation. Our preference is to not disturb the repair site and therefore
avoid transvaginal exploration.
REFERENCES
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assessment of paravaginal defects in women with anterior vaginal wall prolapse. Am J Obstet Gynecol
1999;181:87–90.
2. Bruce GR, El-Galley RES, Galloway NTM. Paravaginal defect repair in the treatment of female stress
urinary incontinence and cystocele. Urology 1999;54:647–651.
3. Bump RC, Hurt WG, Theofrastous JP, et al. Randomized prospective comparison of needle colpo-
suspension versus endopelvic fascia plication for potential stress incontinence prophylaxis in woman
undergoing vaginal reconstruction for stage III or IV pelvic organ prolapse. Am J Obstet Gynecol
1996;175:326–333.
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large cystoceles and stress incontinence. J Urol 1997;158:431–434.
5. Dmochowski RR, Zimmern PE, Ganabathi K, et al. Role of the four-corner bladder neck suspension
to correct stress incontinence with mild to moderate cystocele. Urology 1997;49:35–40.
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repair: a useful adjunctive procedure in pelvic relaxation surgery. J Pelvic Surg 2000;1:11–15.
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approach. Am J Obstet Gynecol 1978;13:203–207.
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20 Treatment of Vaginal Wall Prolapse
David A. Ginsberg, MD, FACS

CONTENTS
INTRODUCTION
ANATOMY
SYMPTOMS
DIAGNOSIS
INDICATIONS FOR SURGERY
SURGICAL REPAIR OF RECTOCELE
CONCLUSION
REFERENCES
INTRODUCTION
A rectocele occurs secondary to a defect in the supporting fascia of the rectum, which
results in herniation of the anterior rectal and posterior vaginal wall into the lumen of
the vagina. The true incidence of rectocele is clearly not well identified, as exemplified
by prior literature, which places the prevalence at a range from 18 to 80% of the general
population (1,2). Wells et al. reported a 12% incidence of rectoceles on physical exami-
nation when evaluating patients complaining of urinary incontinence (3). However, Raz
et al. noted the need for rectocele repair in 65% of patients who underwent repair of a
grade IV cystocele (4).
The natural history of rectocele (and all types of pelvic organ prolapse) is also poorly
studied and poorly understood. Handa et al. evaluated a total of 412 women with annual
pelvic examinations over a 2- to 8-yr period. They noted a baseline rectocele rate of 5.7
cases (12.9%) over 100 women-years. The progression rate for stage I rectocele was
noted to be 13.5 per 100 women-years; the regression rate for stage I rectocele was
noted to be 22 per 100 women-years (5). This high spontaneous regression rate suggests
that mild rectoceles should be managed conservatively secondary to allowing for natural
resolution of the defect.
Anatomic alterations to the pelvic floor secondary to childbirth are usually the primary
predisposing factor leading to rectocele formation. Other risk factors include aging, loss
of estrogen, obesity, smoking, strenuous work/physical activity, and chronic abdominal
straining, which is often seen in patients with chronic respiratory diseases/cough,
constipation, and other defecatory disorders and bladder outlet obstruction. Changes
to the vaginal axis seen after colposuspension can also result in loss of supporting
structures to the posterior vaginal wall and subsequent rectocele formation.
281
Fig. 1. Illustration of supporting fascial layers of rectum. The pararectal fascia attaches laterally to
the pelvic sidewall and sweeps medially to surround the rectum. The prerectal fascia is positioned
anterior to the rectum, from the cul-de-sac to the central tendon, and forms the anterior border of the
rectovaginal space. (Reprinted from ref. 53 with permission from Elsevier.)
ANATOMY
To understand the concepts underlying repair of pelvic floor relaxation, the anatomy
of the normal pelvic floor support system should be briefly reviewed. The fascial
support of the rectum consists of the prerectal fascia and the pararectal fascia. The
prerectal fascia runs anterior to the rectum, from the pouch of Douglas to the central
tendon, and has also been referred to as endopelvic fascia, vaginal fascia, rectovaginal
septum, Denonvillier’s fascia, and the fibromuscular wall of the vagina (6–10). No
matter what this entity is called, it is this layer of tissue that prevents protrusion of the
rectum into the vagina. A virtual space exists between the posterior vaginal wall and
the prerectal fascia, which offers a convenient plane of dissection during rectocele repair.
The pararectal fascia originates from the lateral pelvic sidewall and sweeps medially to
the rectum, splitting into anterior and posterior sheets and forming a fibrous envelope
around the rectum (Fig. 1).
The normal vaginal axis seen in the well-supported pelvic floor conveniently protects
against rectocele formation and further pelvic prolapse. Two distinct areas of the vagina
are seen if a normal vaginal axis is maintained. The proximal vagina lies at a 110–120°
angle to the horizontal. The distal vagina, with the slinglike support provided by the
levators, forms an angle of 45° from the vertical, which results in a midvaginal angle
of 110–130°. In women with significant pelvic floor prolapse, levator plate laxity, and
Chapter 20 / Treatment of Vaginal Wall Prolapse 283
levator hiatus, widening results in a disappearance of the normal curvature of the vagina
and a near-vertical vaginal axis, which facilitates rectocele formation.
Childbirth results in several events that weaken the pelvic floor support system: (1)
Passage of the child’s head through the birth canal stretches the prerectal and pararectal
fascia and detaches the prerectal fascia from the perineal body (11); (2) the levator
musculature and its fascia are weakened, which allows the levator hiatus to widen and
causes sagging of the levator plate (12); (3) the normal compensatory narrowing of the
vaginal opening is rendered ineffective secondary to widening of the anogenital hiatus
and damage to the UG diaphragm.
There are several sites where “breaks” of the rectovaginal septum have been commonly
noted, leading to rectocele formation (Fig. 2) (13,14). The most common site is a transverse
separation above the perineal body attachment, leading to a low rectocele. Other common
sites include a midline vertical defect and an apical transverse break, which can be
secondary to a poorly repaired (or poorly healed) episiotomy. A lateral separation on one
side has also been described but is much less commonly seen.
SYMPTOMS
Many rectoceles are asymptomatic when diagnosed and are purely an incidental
finding at time of examination. If symptoms are present, then a wide variety of complaints
has been noted with relaxation of the posterior floor, both specific and nonspecific to
the prolapse. The most commonly noted complaint is constipation, identified in up to
75–100% of patients with rectoceles (1). Other rectal symptoms can include a sense of
incomplete defecation; stool pocketing; the need to manually compress the vagina,
rectum, or perineum to allow for stool passage; rectal bleeding; and fecal or flatal
incontinence (15–18).
The causal relationship of rectal symptoms to the anatomic findings is not always
clear, and often the correlation between the two is poor (19). The fact that many patients
continue to complain of constipation after rectocele repair exemplifies the poor correlation
between anatomic findings and symptoms (20). In addition, other colorectal disorders
can cause symptoms that are similarly seen with posterior floor relaxation. Other symptoms
related to the prolapse itself may include complaints of a vaginal bulge, dyspareunia,
perineal or lower abdominal pressure, and low back pain, which worsens during the day
and improves with lying down.
DIAGNOSIS
History
History should focus on issues related to bowel and sexual function. Constipation is
a common complaint in older adults, and it should not be assumed that all patients with
constipation and posterior floor relaxation have this secondary to rectocele. Constipation
is often of multifactorial origin, and if significant bowel dysfunction is noted, then referral
to a gastroenterologist or colorectal surgeon should be considered prior to undertaking
any type of pelvic reconstructive procedure.
Examination/Grading
Assessment for a posterior wall defect should be part of any routine pelvic examination
made for the evaluation for urinary incontinence or pelvic organ prolapse. The patient
Fig. 2. Illustration of defect-directed rectocele repair. The upper inset demonstrates the layers
involved in repair (cross section), and the lower inset demonstrates the potential location of tears in
the rectovaginal fascia.
is first examined in the lithotomy position. Evaluation of the posterior compartment

is best accomplished using half of a vaginal speculum to displace the anterior vaginal
wall anteriorly. Bulging of the posterior vaginal wall with Valsalva maneuver or cough
suggests the presence of a rectocele. A rectovaginal examination allows for evaluation
of the rectovaginal septum. Isolated breaks of the septum may be identified by placing
a finger in the rectum and lifting up the posterior vaginal wall at the location of maximal
laxity. A high rectocele may be difficult to distinguish from an enterocele. Rectovaginal

exam may help with this differentiation, as may exam in the upright position. Defects
of the perineal body should also be noted during pelvic examination. A perineal body
defect is associated with a widened introitus with straining and a decreased distance
from the posterior vaginal margin to the anterior anal margin.
Grading of rectocele can be done with either the Baden-Walker grading system or the
Pelvic Organ Prolapse Quantification (POP-Q) system. The POP-Q system focuses on
the descent of the vaginal wall and has been found to be highly reproducible (21). However,
it is complex and avoids terms such as cystocele, rectocele, and the like, which allows
for description of what is involved in the prolapse. Measurement of the perineal body
and genital hiatus are standard components of the POP-Q system.
The final component of examination of the posterior compartment includes evaluation
of the anal sphincter. This includes assessment of resting tone, identification of the
patient’s ability to actively contract the sphincter (and teaching of this maneuver if
needed), and reflex sphincteric activity. Poor sphincter tone and activity can contribute
to fecal and flatal incontinence and can have an impact on the success of repair. Thus,
identification of this prior to surgery is important, and the potential implication of these
findings can be discussed prior to surgical intervention. In addition, if poor sphincter
tone and activity are thought to be secondary to neurological defects, then this should
also be evaluated prior to any surgical intervention.
Investigations
The sensitivity and positive predictive value of physical examination alone to correctly
identify all posterior floor defects was found to be less than 40% (22). In addition, the
differentiation between a high rectocele and an enterocele can often be a challenge. This
has led to the use of various radiographic techniques to aid in the diagnosis of posterior
floor defects.
Defecating proctography involves filling the rectum with barium and fluoroscopically
evaluating the patient at rest, on contraction of the pelvic floor, with Valsalva, and
during defecation. However, proctography does not appear to have significantly greater
sensitivity compared to physical examination to identify rectocele. In addition, Shorvon
et al. showed that 60% of asymptomatic volunteers have rectoceles of moderate size
or larger as identified by proctography (23). The identification of postdefecation trapping
of barium was initially thought to be of clinical significance with proctography and
would suggest that the patient would benefit from repair. However, subsequent studies
have shown little correlation among clinical symptoms, barium trapping, and presence
of a rectocele (24–27). The applicability of this test to identify patients with sympto-
matic rectoceles requiring surgical repair and its ability to predict outcome do appear
to be limited (28).
A more useful test is dynamic magnetic resonance imaging, which allows for evaluation
of the entire pelvis in addition to the posterior floor. Images are obtained at rest and with
straining. This test can provide for evaluation of pelvic organ prolapse of each compart-
ment and can be especially helpful when examination alone is unable to identify the
exact location of a defect. In addition, other pelvic pathology, such as rectal intussus-
ception or urethral diverticulum, could be identified preoperatively, which would have a
significant impact on operative decision making.
Ultrasound has been unsuccessfully used in the past to assess prolapse size and
location (29). Endoanal ultrasound is best used to evaluate for sphincter integrity. If a
Fig. 3. Dynamic MRI of the pelvic floor. Midline sagittal image obtained during evacuation of rectal
contrast demonstrates marked posterior bulging of the pelvic floor (arrow).
sphincter defect is present, then this may lead to collaboration with a colorectal surgeon
for repair. Last, colonic transit studies can be helpful in the evaluation of patients with
chronic constipation and posterior floor relaxation; if a significantly slow transit time
throughout the colon is identified, then that patient may not be helped with rectocele
repair, and a potentially unnecessary surgery can be avoided.
INDICATIONS FOR SURGERY
The majority of rectocele repairs are done coincident with repair of associated pelvic
floor relaxation and organ prolapse. Patients with symptomatic posterior vaginal wall
defects should undergo surgical correction. Common symptoms of a rectocele include
sensation of a vaginal bulge, constipation, dyspareunia, the need to splint to defecate,
and a sense of incomplete defecation. The repair of asymptomatic defects coincident
with other vaginal surgery is not as well accepted. Arguments against repair of an
asymptomatic rectocele include postoperative coital dysfunction and rectal injury.
Jeffcoate described a 30% rate of discontinued coitus or dyspareunia after anterior and
posterior repair (30). However, reviews evaluating outcomes using present-day techniques
of rectocele repair described a 0–9% incidence of coital dysfunction (31–33), and rectal
injury has not been a concern.
Arguments favoring repair of asymptomatic pelvic floor relaxation during concomitant
vaginal surgery include the risk of larger and symptomatic pelvic prolapse (i.e., rectocele,
enterocele, uterine prolapse) if repair is not accomplished and the possibility that
results of simultaneous antiincontinence surgery are improved if repair is done.
Antiincontinence procedures orient the vagina in a vertical axis; however, pelvic floor
repair helps restore the normal, near-horizontal axis of the vagina. Restoration of this
axis should minimize the risk of postoperative prolapse, result in a more effective
transmission of intra-abdominal pressure to the pelvis, and should improve the results
of antiincontinence surgery by helping provide a strong backboard against which the
bladder neck and urethra (which are secondarily supported by the pelvic floor) can be
compressed. These arguments, combined with the ability to accomplish this surgery
without introducing significant perioperative morbidity, lend to the recommendation
that asymptomatic moderate or severe pelvic floor weakness be corrected at the time
of concurrent vaginal procedures.
SURGICAL REPAIR OF RECTOCELE

The essential goals of rectocele repair include (1) plication of the prerectal and
pararectal fascia; (2) narrowing of the levator hiatus by reapproximating the prerectal
levator fibers; and (3) repair of the perineal body. Several techniques have been
described for repair of posterior floor relaxation; these are reviewed. Preoperative
preparation for repair includes a clear liquid diet beginning 2 d prior to surgery and
bowel preparation with the use of oral laxatives. Broad-spectrum intravenous antibiotics
to cover anaerobes, Gram-negative bacilli, and group D enterococci are administered
preoperatively. In addition, several months of hormone replacement therapy can be
instituted prior to repair in patients with evidence of atrophic vaginitis to allow for
healthier vaginal tissue at the time of repair.
Traditional Posterior Colporrhaphy

The patient is positioned in the dorsal lithotomy position, and labial retraction sutures
can be placed to aid in exposure. Allis clamps are placed in the midline of the posterior
vaginal wall from the vaginal apex to 1–2 cm above the hymen. If a perineal repair is
to be done, then Allis clamps are also placed midline between the hymen and anus (to
mark the inferior extent of the repair) and bilaterally on the labia minora to allow for
estimation of the caliber of the repaired vaginal introitus. The final hiatus should easily
admit three fingerbreadths to avoid excessive postoperative narrowing. The four inferior
Allis clamps serve as markers for a diamond-shaped incision, and the overlying mucosa
is removed (Fig. 4). A midline incision is then made from vaginal apex to the top of this
diamond, and the overlying vaginal wall is laterally freed off of the attenuated fascia and
rectum with a combination of sharp and blunt dissection.
Repair is performed using 0 or 00 absorbable sutures. Initially, the lateral rectovaginal
fascia is plicated together, followed by a levator ani layer, which is plicated in the midline.
Some surgeons elect to place a finger in the rectum during this point of the repair.
Displacement of the rectum downward helps to identify the appropriate layers of tissue
and can protect the rectum during suture placement. Perineal repair involves placement
of deep plication sutures into the puborectalis portion of the levator ani muscle. Excess
Fig. 4. Illustration of posterior colporrhaphy. The upper inset demonstrates the layers involved in
repair (cross section).
vaginal wall is excised, and the vaginal wall is closed. Patients are sent home on stool
softeners for 1 mo and instructed to refrain from sexual activity for 6 wk.
With a mean follow-up of 42.5 mo, Kahn and Stanton retrospectively reviewed their
results with posterior colporrhaphy and found an anatomical cure rate of 76% (34). The
primary concern with this procedure is postoperative vaginal scarring, narrowing, and
dyspareunia. Repair of the defect with a levatoroplasty provides good anatomic support
in terms of recurrence of prolapse. However, this is fundamentally a nonanatomic repair,
which can lead to a suboptimal clinical outcome. Dyspareunia has been reported in
20–50% of patients (20,31,34,35), and residual issues with bowel emptying have been
reported in 49–62% of patients undergoing posterior colporrhaphy (16,20,34). In addition,
the study by Kahn and Stanton noted de novo bowel symptoms in a good number of
patients, including complaints such as incomplete emptying (22%), constipation (23%),
and fecal incontinence (8%).
Plication of Prerectal and Pararectal Fascia and Levator Reconstruction

The patient is placed in the dorsal lithotomy position, and a rectal packing is placed
to aid in identification of the rectum intraoperatively. Anti-incontinence surgery, cystocele
repair, enterocele repair, and vaginal hysterectomy, if indicated, are accomplished first.
Labial retraction sutures and a ring retractor with hooks, applied to the perineum, aid in
lateral exposure of the vaginal vault. The anterior vaginal wall is retracted upward with
a Haney or right-angle retractor to improve visualization and help prevent excessive
narrowing of the vagina.
The repair begins with the placement of two Allis clamps at the posterior margin of
the introitus at the 5 and 7 o’clock positions. Utilizing a V-shaped incision, a triangular
segment of perineal skin is excised between the Allis clamps, exposing the attenuated
perineal body. Allis clamps are then placed in the midline of the posterior vaginal wall,
grasping and elevating the rectocele at its midpoint. An inverted V-shaped incision is
then made from the site of the previous incision, with the apex of the incision up to the
proximal aspect of the rectocele. This is a superficial incision through the vaginal wall
only; a deeper dissection at this point risks injury to the rectum.
Metzenbaum scissors are then used to sharply develop a plane from the lateral margins
of the incision, dissecting between the herniated rectal wall and the vaginal wall. Staying
as close as possible to the vaginal wall to avoid injury to the rectum, dissection is per-
formed between the herniated rectal wall and the vaginal wall, exposing the attenuated
prerectal fascia. The triangular island of posterior vaginal wall created by the inverted
V-shaped incision is sharply excised off the prerectal levator fascia and fibers. The pre-
rectal fascia is exposed by sliding the Metzenbaum scissors under the posterior vaginal
wall from the apex of the previous incision to the cuff of the vagina. The posterior
vaginal wall is then incised along the midline, and an appropriately sized rectangular
strip of excess posterior vaginal wall is excised (greater severity of prolapse necessitates
a wider resection of posterior vaginal wall), exposing the attenuated pararectal and
prerectal fascia proximally.
At this point, attention is turned toward repair of the rectocele. The anterior vaginal
wall is retracted upward, and the distal rectum is retracted downward with a Haney
or right-angle retractor. This protects the rectum, reduces the rectocele, helps avoid
excessive vaginal narrowing during the repair, and facilitates reapproximation of the para-
rectal and prerectal fascia. Reconstruction begins at the apex of the rectocele and is
carried out to the level of the levator hiatus with a running, locking, 2-0 polyglycolic
acid suture. Each needle passage incorporates the edge of the vaginal wall and generous
bites of the prerectal fascia and the pararectal fascia bilaterally (Fig. 5). The initial bite
of this portion of the repair attempts to reapproximate the sacrouterine/cardinal ligament
complex to decrease the risk of subsequent enterocele formation. The repair of the floor
is finished with reapproximation of the levator hiatus using a figure-of-eight 2-0 poly-
glycolic acid suture, closing the distal posterior vaginal wall to the level of the perineum.
Reapproximation of the prerectal levator fascia at this level restores the normal caliber
of the introitus.
The repair is completed perineally using vertical mattress sutures of 2-0 polyglycolic
acid to approximate the bulbocavernosus, transverse perineal, and external anal sphincter
muscles. This brings together the muscles of the Urogenital (UG) diaphragm, recon-
structing and providing support to the central tendon. The perineal skin is closed with
a running 4-0 polyglycolic acid suture and an antibiotic-impregnated vaginal packing is
placed. Patients are sent home on stool softeners for 1 mo and instructed to refrain from
sexual activity for 6 wk.
The results of this technique have been reviewed in a total of 380 patients with an
average follow-up of 22 mo. The majority of patients (69%) had an asymptomatic recto-
cele that presented with concomitant other pelvic pathology (i.e., stress incontinence,
cystocele, etc.). Rectocele recurrence rate grade II or higher was noted in 4% of
patients, resulting in anatomic success in 96% of patients. The most common present-
ing complaint related to the rectocele was constipation. which was noted in 26% of
patients preoperatively and was improved in 67% of these patients after repair (36).
Fig. 5. Illustration of plication of prerectal and pararectal fascia. Absorbable suture is placed in a
running fashion, incorporating pararectal fascia, prerectal fascia, and vaginal wall.
Defect-Specific Rectocele Repair

Defect-specific rectocele repair was originally described in 1993 by Richardson (37).
With this technique, the repair of the posterior vaginal floor is not universally plicated,
but rather repair is directed at specific fascial defects.
Initially, a diamond-shaped incision is made from the perineum to the apex of the
vagina. The width of this incision is based on the approximation of the introitus to a
postoperative diameter of three fingerbreadths. The perineal skin is excised, and the
posterior vaginal wall is mobilized off the anterior rectal wall from the apex to the
tendinous arch of the levators laterally and to the perineal body inferiorly. It is important
to leave all of the fascial layers on the rectum during this dissection and not remove or
disturb these supporting tissues when mobilizing the posterior vaginal wall.
At this point, the repair is performed using 2-0 absorbable sutures. The surgeon’s
nondominant index finger is placed in the rectum. Elevation of the anterior rectal wall
facilitates identification of fascial defects. The most commonly noted defect is a low
transverse break between the rectovaginal septum and the perineal edge with repair
reapproximating the tear transversely (Fig. 6). Another commonly noted defect is a
Fig. 6. Illustration of defect-specific rectocele repair. Absorbable, interrupted sutures are used to
repair a low transverse defect.
longitudinal midline defect, which is repaired with interrupted sutures in the midline
(Fig. 7). As illustrated in Figs. 6 and 7, the direction of the suture line conforms to the
shape and direction of the defect. Any other residual breaks that are palpable should be
repaired as well. Excess vaginal wall is then excised and closed with a 3-0 absorbable
suture; if needed, a perineal repair is performed.
Theoretically, this repair is attractive as only the defect is repaired, thus minimizing
excessive dissection and plication of tissue layers unnecessarily. With follow-ups ranging
from 12 to 36 mo, anatomic cure was noted from 77 to 92% of patients in four studies
that reviewed patients undergoing this repair (38– 41).
Porter et al. evaluated perioperative dyspareunia using the Watts Sexual Function
Questionnaire. They found dyspareunia improved in 73%, worsened in 19%, and noted
as a de novo complaint in 2.4% of patients (38). Cundiff et al. reported an 84% improve-
ment in constipation (39), although that degree of improvement was not reflected in
other studies (38,40). The fact that by 1 yr postoperatively 64% of patients in the study
by Kenton et al. (40) had returned to their preoperative practice of splinting reflects the
multifactorial nature of defecatory dysfunction in these patients and suggests that these
Fig. 7. Illustration of defect-specific rectocele repair. Absorbable, interrupted sutures are used to
repair a midline longitudinal defect.
bowel issues are often reflective of much more than just the anatomic defect noted
with a rectocele. Finally, a retrospective comparison of site-specific repair vs standard
posterior colporrhaphy (without levator placation) by Abramov et al. found the defect-
specific repair to be associated with higher recurrence rates. There were no significant
differences between the two repairs regarding postoperative bowel symptoms (42).
Rectocele Repair With Mesh

The use of graft material to augment rectocele repair has been described with both
defect-directed repairs and traditional colporrhaphy. Grafts have also been used with
laparoscopic techniques, which are described in the next section. The increased use of
various grafts to help provide further posterior support has coincided with the increased
popularity of both synthetic and allograft materials in the repair of anterior laxity and
for the treatment of stress urinary incontinence.
Kohli and Miklos reviewed their experience using a rectangular segment of cadaveric
dermis to augment a defect-directed repair in 43 women. After the repair, the dermal
graft was secured proximally to the rectovaginal fascia, laterally to the arcus tendinus,
and distally to the perineal body. They found a 93% cure rate in 30 women available
for examination with a mean follow-up of 12.0 mo (43). de Tayrac et al. reviewed their
results using polypropylene mesh attached to a combined bilateral sacrospinous fixation
proximally and to the perineal body distally. No other posterior repair was done; all of
the support posteriorly was based on the mesh. With a median follow-up of 22.7 mo in
26 patients, they reported 92.3% anatomic cure rate and improvement in symptoms and
quality of life for all but 1 patient. They also noted a 12% rate of vaginal erosion and
a 7.7% rate of dyspareunia (44).
Mesh erosion can be a serious problem, with vaginal erosion leading to vaginal
discharge, bleeding, and dyspareunia. Erosion of mesh into the rectum is an uncommon
but potentially serious complication of this class of repair that can lead to rectovaginal
fistula, the need for fecal diversion with colostomy construction, and significant morbidity
(45). With this potential morbidity, it is important to evaluate whether graft material allows
for a greater improvement in anatomic and symptomatic cure while not increasing
perioperative morbidity and complications.
Sand et al. did evaluate 143 patients prospectively, with 70 women undergoing tradi-
tional colporrhaphy and 73 women undergoing traditional colporrhaphy and placement
of a polyglactin mesh in conjunction with other prolapse repair. There was no difference
in recurrence rates with or without mesh; quality-of-life issues such as bowel and sexual
function were not assessed in this study (46).
Clearly more studies are needed in the future to ascertain whether there is an optimal
graft to use in rectocele repair and, if so, whether the material is able to decrease
recurrence rates, improve quality of life, and minimize morbidity. It is also important to
remember that grafts can shrink over time when measuring graft size at the time of repair.
If the graft shrinks too much, the result can be loss of posterior wall flexibility and
rectal compression, which can lead to fecal urgency, obstruction, and dyspareunia.
Finally, several authors have described the use of mesh transabdominally, often done
in conjunction for total pelvic prolapse with concomitant abdominal sacrocolpopexy.
Baessler and Schuessler described using posterior extensions of Gore-Tex in 31 women
undergoing concomitant abdominal sacrocolpopexy. With a mean follow-up of 26 mo,
they noted a 57% rectocele recurrence rate and have abandoned the procedure (47).
Sullivan et al. evaluated their experience in 205 patients with a mean follow-up of 60
mo. This group, using Marlex mesh secured between the sacrum and the perineal body,
noted an anatomic cure rate of 100%. Erosion of Marlex into rectum or vagina was
noted in 5% of patients, and overall satisfaction for the correction of the patient’s pri-
mary symptoms were 68, 73, and 74% with early (0.5–3 yr), middle (>3–6 yr), and late
(> 6 yr) follow-up, respectively (48).
Laparoscopic Repair
The use of laparoscopy to correct posterior floor laxity has been described in a few
reports. Repair has been described in conjunction with laparoscopic sacrocolpopexy
and has also been done using graft materials (49). Without the use of an adjuvant graft
material, the repair should be done laparoscopically as it would be done open. The
rectovaginal space is opened to the perineal body. The perineal body is sutured to the
rectovaginal septum, and any defects that are noted in the rectovaginal septum itself
are repaired. If the rectovaginal fascia is detached from the iliococcygeus fascia, then
it should be reattached, and the medical aspect of the levator muscles can be plicated,
taking care to avoid a posterior vaginal ridge (50).
Lyons and Winer first described laparoscopic rectocele repair. They incorporated
a polyglactin mesh from the uterosacral ligament complex to the perineal body and
cited an 80% success rate at 1 yr (51). Gadonneix et al. reviewed their experience
using meshes placed anteriorly and posteriorly in 47 women undergoing laparoscopic
sacrocolpopexy. They noted a 12% recurrence rate, which only occurred in women also
undergoing simultaneous laparoscopic Burch (49).
CONCLUSION
Rectocele is a common defect seen in patients with pelvic prolapse. A variety of
symptoms can be associated with rectocele. Many of the complaints associated with
laxity of the posterior vagina floor are related to sexual dysfunction, bowel dysfunction,
or other nonspecific symptoms. The goal of repair is to restore the normal vaginal axis,
repair the widened vaginal hiatus, maintain vaginal length, and maintain (or improve)
bowel and sexual function. Several techniques have been described to surgically address
these goals; however, it is important to note that comparative studies between different
techniques do not exist. The optimal procedure is likely the technique that each individual
surgeon is most comfortable performing.
Anatomic cure does not necessarily equal a good functional outcome. This is often
seen with bowel dysfunction associated with a rectocele preoperatively. This is often of
multifactorial etiology and may not be improved with repair. In addition, postoperative
dyspareunia remains an issue. Therefore, the management of patient expectations in terms
of functional outcomes is important. Finally, a prospective, randomized trial to compare
both anatomic cure and quality-of-life outcomes between the various techniques is needed
in the future.
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21 Diagnosis and Management
of Apical Prolapse
Daniel S. Elliott, MD
CONTENTS
INTRODUCTION
PREOPERATIVE EVALUATION
MANAGEMENT OF APICAL PROLAPSE
CONCLUSION
REFERENCES
INTRODUCTION
It is estimated that one in nine women in the United States will undergo a hysterectomy
during their lifetime, and up to 10% of these women will need surgical repair for treat-
ment of a symptomatic vaginal vault prolapse (1). The search for the repair that offers
the best combination of the most effective, safest, and most durable for the treatment of
apical prolapse is an ongoing process, as evidenced by the multiple surgical approaches
available to treat this problem. Clearly, no one surgical approach is ideal for every
patient. However, as the known risk factors for prolapse, such as age, obesity, and hyste-
rectomy, continue to increase in the United States, so does the need for continuing the
search for better means to repair vaginal vault prolapse (2– 4).
Prior to discussion of the treatment options for this condition, it is imperative for the
treating surgeon to have a good understanding of the preoperative evaluation, including
an awareness of the symptoms and how to diagnose posthysterectomy prolapse.
PREOPERATIVE EVALUATION
It is important to be cognizant that defects of vaginal support may occur with and
without any concurrent symptoms. Therefore, it is imperative for the evaluating physician
not only to ask the pertinent questions during the history taking but also to perform an
accurate physical exam. Symptoms may be falsely attributed to a prolapse that may
actually be caused by other underlying and unrelated medical conditions, which if missed
may compromise the success of the prolapse surgery or may lead to false expectations
by the patient. Therefore, proper counseling of the patient can help reduce postoperative
patient dissatisfaction.

297
Table 1
Predisposing Factors to Posthysterectomy Prolapse
Race
History vaginal delivery
Increased age and menopause
Obesity
Smoking
Lung disease/chronic cough
Chronic constipation
Heavy lifting
Adapted from ref. 41.
Past Medical History

There are several factors that predispose a given patient to prolapse (and subsequent
postoperative recurrence) and need to be sought during the preoperative evaluation. A
preponderance of significant risk factors should be weighed into the equation in deter-
mining the best treatment option for a patient. Factors known to either increase or directly
cause not only posthysterectomy prolapse but all pelvic organ prolapses in general are
noted on Table 1. Any factors that predispose the patient to repetitive lifting or coughing
or factors that can affect proper healing should be especially focused on because this
may affect the type of repair chosen.
Apical Prolapse Symptoms

Symptoms possibly associated with apical prolapse are outlined in Table 2. There are
no true absolutely specific symptoms of a prolapse that will guide the physician to the
diagnosis. This is an especially important issue when counseling patients with a history
of pelvic pain, pelvic pressure, dyspareunia, and urinary frequency/urgency. The surgeon
must discuss these symptoms with the patient preoperatively so that the patient has real-
istic expectations and goals of surgery. If a patient with pelvic pain preoperatively
falsely expects her symptoms will be either partially or completely resolved following
repair of her apical prolapse and they are not, then the surgeon can expect a long and
drawn out postoperative time period with the patient.
A good voiding history needs to be obtained from all patients with prolapse. Mayne
and Assassa reported that up to 45% of women will have a complaint of concurrent
voiding dysfunction, and up to 26% of these women will have clinically significant
symptoms that will require therapeutic intervention (5). The presence of frank or occult
stress incontinence needs to be sought during the history taking and during the physical
exam. If overactive bladder symptoms are present, then consideration should be given
to managing this problem before treatment of the prolapse because many women will
falsely attribute the urge symptoms to the presence of the prolapse. It is true that urge
symptoms may be secondary to the prolapse; however, as stated, urge symptoms may
be unrelated and therefore consideration of attempted management should at least be
given before surgical intervention.
Patient lifestyle issues should be discussed, focusing on aspects such as a patient’s
need for repetitive lifting or exercise expectations. An individual with a sedentary vs
an active lifestyle will need to be counseled differently on the treatment options and
Chapter 21 / Diagnosis and Management of Apical Prolapse 299
Table 2
Pelvic Prolapse Symptoms
Pelvic pressure
Pelvic pain
Dyspareunia
Voiding complaints
Hesitancy
Poor emptying
Splinting
Frequency/urgency
Fecal complaints
Constipation
Splinting
Fecal urgency/incontinence
the potential risk of prolapse recurrence. Also, a patient’s sexual activity level and
expectations should be discussed in an open matter because various prolapse repairs
can affect sexual activity and intercourse.
Physical Exam
The physical exam remains the cornerstone of diagnosis. Several factors will need to
be considered while performing the exam:
1. The exam needs to be done with the patient straining to fully assess the degree of prolapse.
2. All components of the vaginal vault must be independently evaluated.
3. If an anterior component prolapse is present, then this should be reduced, and the patient
should Valsalva to evaluate the presence or absence of concurrent urinary incontinence.
Certain patients are unable to Valsalva with sufficient force to allow adequate exami-
nation. In these patients, it may be helpful for the exam to take place with the patient
sitting more upright or standing. An apical prolapse and a large anterior or posterior
compartment prolapse may be difficult to distinguish on physical exam. Anatomically,
the enterocele extends down from the apex, and a half speculum placed either anteriorly
or posteriorly aids in determining the exact location of the prolapse. Also, a concurrent
rectal exam while the patient strains aids in accurate diagnosis. While the patient strains,
the rectovaginal septum can be palpated to determine if an enterocele bulge exists.
Failure to assess all vaginal compartments and the presence or absence of urinary
incontinence accurately will lead to an insufficient treatment plan for the patient and
subsequent failure of whichever procedure is chosen. However, once the correct diag-
nosis is made, then choosing a treatment plan and correct counseling of the patient
becomes much easier.
MANAGEMENT OF APICAL PROLAPSE

Observation
Patients, especially ones with a mild prolapse or only minimal symptomatology need
to be counseled on the potential benefit of observation. This is especially important
when considering the high (up to 30%) reoperation rate (6).
Nonsurgical
Pessaries are the mainstay of nonsurgical management of apical prolapse. Several
investigators have shown that although pessaries may be an effective treatment option
for women who decline surgery, over 20% of those women eventually discontinued their
use (7). Complications from long-term pessary use include vaginal mucosa irritation and
ulceration, which can lead to fistula formation and bowel herniation (8–10).
Surgical
The choice of surgical approach depends on multiple factors. Factors to be considered
include the precise support deficit, the etiology of the defect (i.e., chronic lifting, posthys-
terectomy, chronic cough, status after previous attempted repair, and route of previous
repair), and to no small extent, the experience of the surgeon.
The surgical approach can be divided into three main categories: vaginal, abdominal,
and laparoscopic.
TRANSVAGINAL REPAIR
Transvaginal repairs have the goal of either restoring a more normal vaginal anatomy
or being obliterative. Obliterative procedures such as colpectomy or colpocleisis have
cure rates ranging from 85 to 100% (11,12). Ideal patients for such obliterative procedures
include patients who no longer desire sexual intercourse. Complications are rare with
these procedures; however, the most common complication is de novo development of
stress urinary incontinence in 1–9% (13,14).
Table 3 outlines the multiple types of transvaginal apical repairs (6,15–23). The type
of surgical repair chosen should be dictated by surgeon’s preference and past experience.
No single transvaginal procedure has clearly been vastly superior in either anatomical or
symptomatic cure (6). However, the surgeon’s skill level with a given approach should
always be considered an important factor when choosing an operative approach, espe-
cially when considering the high failure rate and subsequent reoperation rate when the
procedure is performed perfectly and in experienced hands. There is no reason to further
increase the odds of failure by attempting a procedure with which one feels uncomfortable
without assistance from another, more experienced surgeon.
A detailed description of each transvaginal repair is beyond the scope of this text.
However, briefly, a sacrospinous ligament fixation procedure involves the fixation of the
apex of the vagina to the sacrospinous ligament and suspends the upper vagina over the
levator plate. Because of the anatomic proximity of the pudendal nerve and vessels, sciatic
nerve, ureter, and rectum, the surgeon needs to be careful not to incorporate the adjacent
structures into the suspension (16). However, if the anatomic relationships are carefully
noted during the case, the sacrospinous ligament suspension can be performed safely.
Uterosacral ligament suspension or Mayo culdoplasty involves placing one or more
McCall sutures into the uterosacral ligaments. This will accomplish two things. First, it
will approximate the uterosacral ligaments, thereby obliterating the enterocele by closing
the cul-de-sac. Second, it will elevate and support the vaginal vault (19–22). As with
any transvaginal procedure, adjacent anatomic structures can be inadvertently injured.
Specifically with the uterosacral suspension, the ureters, bowel, and bladder can be either
directly injured or indirectly “kinked,” as in the case with the ureters. However, careful
intraoperative observation should detect these injuries, and they can be corrected with
minimal sequelae.
Table 3
Case Series Cure Rates for Transvaginal and Transabdominal Procedures for Apical Prolapse
Repair Ref. No. of patients Follow-up (mo) Anatomic cure Symptomatic cure
Sacrospinous 15 122 24 79 92
fixation
16 26 30 87 100
17 36 19 67 94
18 81 1.5 81 Not reported
Uterosacral 19 28 33 94 81
suspension
20 168 Jun-36 87 Not reported
21 46 16 94 90
Iliococcygeus 17 36 21 53 91
suspension
24 110 36 96 Not reported
Adapted from ref. 6.
In experienced hands, transvaginal repair “success rates” range between 67 and

100%, and symptomatic cure rates range from 92 to 100% (6). In comparison, trans-
abdominal sacrocolpopexy has been shown in multiple studies to have one of the highest
long-term success rates for durable repair of severe vault prolapse (93–100%) (25–33).
Unfortunately, data available that compare transvaginal vs transabdominal apical repairs
are sparse. Two prospective randomized studies have been completed comparing the
results of transvaginal vs transabdominal repairs (34,35).
Benson et al. performed a randomized study comparing bilateral sacrospinous fixation
vs abdominal sacrocolpopexy with a mean follow-up of 2.5 yr. In the 80 women who
completed the study, the sacrocolpopexy group was twice as likely to have a successful
outcome and 50% less likely to require reoperation (16 vs 33%) (34). The results led the
authors to terminate the study early.
However, in contrast, in a study completed by Maher et al., 95 women were randomly
assigned to two treatment arms (sacrocolpopexy vs sacrospinous fixation). This study
determined, at a mean follow-up of 24 mo, that there was no difference in subjective
success rate (94% sacrocolpopexy vs 91% sacrospinous fixation), and there were no
differences in the objective cure rate (76 vs 69%, respectively) (35). Maher et al. concluded
that because there were no differences in cure rates and the complication rate, operating
time, and time to recovery were higher in the sacrocolpopexy group, that for most patients
the transvaginal repair would be sufficient. Both studies, however, did agree that the
sacrocolpopexy had better anatomical results.
TRANSABDOMINAL
As mentioned, the transabdominal sacrocolpopexy has been shown in multiple studies
to have one of the highest long-term success rates for durable repair of severe vault
prolapse (93–100%) (25–33). In addition to a high success rate and durable results,
other advantages of the sacrocolpopexy approach with the use of synthetic material to
repair vault prolapse can be summarized as follows:
1. Support of the vaginal vault to the anterior surface of the sacrum preserves (or restores)
the normal axis of the vagina.
2. Maximal vaginal depth can be preserved, which is especially important in patients who
desire continued sexual activity and in patients with an already foreshortened vagina
from previous surgery.
3. Use of synthetic suspensory material can provide a source of strength in patients for
whom the native tissue with prolapse is weak.
Potential candidates for the open procedure tend to be younger, more active, and more
likely to be leading an active lifestyle. Other important indications are concurrent medical
conditions such as chronic cough, chronic obstructive pulmonary disease, and asthma.
These conditions place chronic and repeated increased intraabdominal pressure on the
repair. Unfortunately, because of the morbidity of the open transabdominal procedure,
many patients are unable to tolerate the surgery. Therefore, many of these patients are
treated via a transvaginal approach.
Goals of every surgical repair of vaginal vault prolapse include restoration of
proper anatomy, maintenance of sexual function, and durability. The main advantage
to the vaginal approach has historically been decreased morbidity, including shorter
hospitalization and convalescence (20,36). Unfortunately, long-term success rates with
transvaginal repairs are consistently lower compared to an abdominal approach, such as
sacrocolpopexy (34).
In an effort to balance the benefit of the open sacrocolpopexy (durable repair) with the
advantage of a vaginal repair (reduced morbidity), many attempts have been made to
treat the vault prolapse via laparoscopic sacrocolpopexy (37,38). Unfortunately, technical
difficulties in actually accomplishing the procedure and the potentially significant increase
in operative time have greatly limited its widespread use. To address these specific
limitation of laparoscopic repairs, advances in robotic surgery may be an answer.
Telerobotics provide technical features such as three-dimensional vision, increased
robotic instrument maneuverability, and physiologic tremor filtering. These factors pro-
vide an ergonomic environment for the surgeon that simplifies performance of complex
laparoscopic tasks. The technique of robotic-assisted laparoscopic sacrocolpopexy can
use any type of synthetic graft material utilized in the open procedure. The ultimate goal
of the robotic-assisted laparoscopic sacrocolpopexy should be threefold: (1) provide the
most durable repair for vaginal vault prolapse; (2) minimize the morbidity associated
with transabdominal procedures; and (3) provide a procedure that can be accomplished
within a reasonable operative time (39).
ROBOTIC-ASSISTED LAPAROSCOPIC SURGICAL TECHNIQUE

The daVinci® robot (Sunnyvale, CA) is an integrated computer-based system consisting
of two interactive robotic arms, a camera arm, and a remote control with three-dimensional
vision capability. The daVinci robot uses instruments with 6° of freedom that provide
the same flexibility as the human wrist. The working robotic arms are attached to
reusable 8-mm trocars; the camera is placed through a standard 12-mm laparoscopic
port. For optimal robot function and to minimize risk of collisions, the angle created
by the camera port and each working robotic port should be obtuse and the distance
between the ports at least one handbreadth.
With robotic surgery, the motions of the surgeon at the remote control unit are replicated
by the robotic arms placed within the patient. Tactile feedback is not available with
Fig. 1. Port site for laparoscopic sacrocolpopexy.
daVinci; therefore, increased reliance on visual input is required. During robotic surgery,
an assistant surgeon is scrubbed at the operating table. The assistant performs a variety
of important robot-related tasks, including alignment and exchange of instruments on
the robotic arms. Furthermore, the assistant performs operative maneuvers with conven-
tional instruments, including tissue countertraction, hemostasis, hemoclip application,
suction, and assistance during suturing. Most important, the scrubbed assistant is available
in the event that an emergent conversion would be required.
For the procedure, the patient is placed in the dorsal lithotomy position on the operating
table. After general anesthesia is established, a nasogastric tube is placed, and both arms
are tucked beside the torso. The patient is prepped from the nipples to proximal thigh,
including the vagina.
After abdominal insufflation using a Varus needle, a periumbilical Visiport is placed
under direct vision to avoid visceral or vascular injury. Two standard laparoscopic ports
are next introduced under direct vision: one 10-mm port right subcostal lateral to the
rectus and one 5-mm port one handbreadth inferior laterally (Fig. 1). These ports are used
for retraction during the procedure. Next, two 8-mm robotic ports are placed lateral to the
rectus two fingerbreadths superior to the iliac crest.
At this point, using standard laparoscopy, a retracting suture is placed through the
sigmoid tenia eventually to help in exposing the sacral promontory. The next step is
dissection of the bladder from the anterior vaginal wall using forceps and scissors
with cautery. A customized handheld vaginal retractor manufactured at the Mayo Clinic
(Fig. 2) is used to facilitate the dissection, which should be a relatively bloodless plane.
Posteriorly, the peritoneal reflection is then incised to mobilize the vagina. Both of these
dissections should be carried out as distal (toward the introitus) as possible to maximize
the support given by the Y graft. After adequate vaginal mobilization, the sacral dissec-
tion, with careful attention to avoid sacral venous complexes, is accomplished. Once the
shiny periosteum is exposed, the polypropylene Y graft (IntePro™, American Medical
Systems, Minnetonka, MN) (Fig. 3) is brought into the field through the 10-mm port.
Fig. 2. Handheld vaginal retractor.
Fig. 3. Polypropylene Y graft (IntePro).

The robot is now docked with the base positioned at the foot of the bed. The main
reason to utilize the robot at this point is to facilitate and greatly reduce the operative
time needed for suturing of the graft to the vagina and the sacrum. The Y-shaped graft
is inserted via a port. The graft is then robotically sutured using 1.0 Gore-Tex. The 30°
lens and vaginal retractor maximize exposure for placement of the sutures. The posterior
sutures are passed first because they are more difficult, followed by suturing the ante-
rior portion of the Y graft to reduce the difficulty of the process. The tail end of the graft
is then sutured to the sacral promontory using three or four interrupted sutures, with
careful attention to avoid any undue tension on the vagina. A standard Halban’s culdo-
plasty with plication of the uterosacral ligaments further aids the prevention of recurrent
vaginal prolapse. The posterior peritoneum is then closed to completely retroperitonealize
the graft (40).
CONCLUSION
The cornerstone of management of apical prolapse must be an accurate preoperative
evaluation and diagnosis. Good arguments can be made with transvaginal, transabdom-
inal, or laparoscopic management of apical prolapse; however, if incorrect or insufficient
evaluation of the concurrent problems of a patient is performed, then the patient will most
likely be less than satisfied with the end result.
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17. Maher CF, Murray CJ, Carey MP, Dwyer PL, Ugoni AM. Iliococcygeus or sacrospinous fixation for
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19. Amundsen CL, Flynn BJ, Webster GD. Anatomical correction of vaginal vault prolapse by uterosacral
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22 Evaluation and Management
of Vesicovaginal Fistulas
Matthew P. Rutman, MD, Donna Y. Deng, MD,

and Larissa V. Rodríguez, MD
CONTENTS
INTRODUCTION
ETIOLOGY
PREVENTION
DIAGNOSIS
CONSERVATIVE MANAGEMENT
OPERATIVE MANAGEMENT
COMPLEX FISTULAS
TISSUE INTERPOSITION
POSTOPERATIVE MANAGEMENT (TRANSVAGINAL REPAIR)
OUTCOMES
CONCLUSION
REFERENCES
INTRODUCTION
A vesicovaginal fistula (VVF) is an abnormal communication between the bladder
and vagina, resulting in continuous leakage of urine through the vagina. It is one of the
most significant and devastating conditions in female urology and urogynecology. VVFs
have been recognized and described since ancient times, but successful repair was not
reported until James Marion Sims’ first paper in 1852 (1). His transvaginal repair included
the use of silver wire sutures. Many principles he originally described are still applicable.
Subsequent advances included the first “layered” repair by Mackenrodt (2) and the
interposed labial fat graft of Martius (3) in the late 1920s.
The most common cause of VVF in developing countries remains obstetric trauma.
Prolonged and obstructed labor leads the fetal head to cause pressure necrosis of the
anterior vaginal wall and the underlying bladder neck and urethra, resulting in a large area
of tissue damage. This is in stark contrast to developed countries, where the large majority
of fistulas are the result of complications of gynecological and other pelvic surgery.
Regardless of the cause, surgical repair remains the gold standard and primary treatment
of VVF. This chapter focuses on VVF secondary to causes other than obstetric trauma.

309
310 Part IID / Reconstruction
ETIOLOGY
In the United States and other industrialized nations, VVFs occur as a result of surgical
trauma, with the most common cause laparoscopic, abdominal, or vaginal hysterectomy.
Inadvertent suture placement into the bladder during vaginal cuff closure results in tissue
necrosis and subsequent fistula formation. Excessive blunt dissection of the bladder
can result in ischemia or an unrecognized tear in the posterior bladder wall, with resultant
fistula formation. Around 75% of VVFs are reported to occur after hysterectomy for benign
disease (4). The overall incidence of VVF after hysterectomy is approx 0.5–1% (5).
VVFs have also been documented after sling procedures, cystocele repair, colposuspension
procedures, and urethral or bladder diverticulectomy. Overall, approx 90% of VVFs in
North America are caused by obstetric and gynecologic procedures. Six percent are caused
by radiation, and the remaining 4% are caused by one of the following: advanced local
malignancy (vaginal, cervical, and endometrial); inflammatory bowel disease; foreign
bodies; and infectious processes of the urinary tract (4).
PREVENTION
Recognizing that the majority of VVFs result as a complication of hysterectomy, it
is paramount that the surgeon takes critical steps to prevent their occurrence. Risk
factors for fistula development include history of cesarean section, endometriosis,
cervical conization, and radiation treatment (6). The bladder is most often injured during
the dissection of the posterior bladder wall from the anterior surface of the uterus at the
level of the vaginal cuff during an abdominal hysterectomy. Placement of an indwelling
Foley catheter and meticulous sharp dissection can diminish inadvertent bladder injury.
Iatrogenic injuries can be nearly impossible to avoid with difficult reoperations and
the resulting dense adhesions that obliterate surgical planes. This is an accepted risk,
but every attempt should be made to diagnose and repair the injury intraoperatively.
Instilling the Foley catheter with methylene blue to check for leakage is a simple but
effective way to ensure bladder integrity. If a bladder injury occurs, then it should be
repaired with a two-layer closure, and a drain should be placed. An interposition flap
should be used in selected cases if there is any doubt about the repair. Discovery and
repair of a bladder injury intraoperatively will mandate keeping the bladder drained
with a catheter for longer than the usual 1–2 d posthysterectomy.
DIAGNOSIS
Symptoms and Signs
Typically, patients will present with continuous urinary drainage (day and night)
from the vagina shortly after gynecologic/pelvic surgery. Any patient who presents
with urinary incontinence early after pelvic surgery should evaluated for a VVF. The
fistula may manifest itself immediately postoperatively but often becomes clinically
apparent days to weeks later. Of patients with a VVF, 10% have an associated
ureterovaginal fistula (7). VVFs tend to present earlier than ureterovaginal fistulas. In
the early postoperative period, patients may present with fevers, ileus, abdominal pain,
hematuria, or lower urinary tract symptoms.
VVFs after prior radiation therapy may present anywhere from 6 mo to 20 yr after
treatment (8). Fluid draining from the vagina can be urine, lymph, peritoneal fluid,
fallopian tube fluid, or vaginal secretions. Other diagnoses to consider in the differential
Chapter 22 / Evaluation and Management of Vesicovaginal Fistulas 311
include urethrovaginal fistula, ureterovaginal fistula, ectopic ureter, peritoneal fluid

drainage, and vaginal cuff infection.
Diagnosis
To confirm that the fluid leaking from the vagina is urine, it can be sent for creatinine
level. Elevated levels of creatinine, relative to serum, will confirm a fistula between the
urinary tract and the vagina. Physical examination remains the most critical element in
the evaluation of a woman with a suspected fistula. The depth, diameter, mobility, and
mucosa of the vagina must be evaluated. In addition, concomitant prolapse, urethral
hypermobility, and incontinence should be assessed. Vaginal examination with two half
speculums can assist in isolating the point of leakage. After hysterectomy, VVF are most
commonly found at the level of the vaginal cuff. Pooling of urine at the vaginal apex
and in the fornices can often be visualized. The neighboring vaginal mucosa may appear
erythematous and edematous, making it difficult to identify the opening. Placing a Foley
catheter into the bladder can assist if the balloon is seen.
If all of these measures fail to identify a fistula, then dye tests are performed for
confirmation. Methylene blue can be instilled through the Foley catheter and the vagina
inspected for leakage of blue fluid. Having the patient ambulate with a vaginal pack in
place will often stain the packing. If this does not confirm the diagnosis, then the patient
should be given oral phenazopyridine, which stains the urine orange. The vagina is then
packed, and orange staining confirms a fistula. A positive phenazopyridine test with
a negative methylene blue instillation strongly suggests a ureterovaginal fistula.
Patients with a urinary fistula should undergo cystoscopy and an upper tract evalu-
ation. Cystoscopy typically identifies the size and location of the fistula and its relationship
to the ureteral orifices. It is important to ascertain adequate bladder capacity and rule
out foreign body as the source of the fistula. Careful surveillance for multiple fistulas
is imperative. For patients with a radiation- or malignancy-associated fistula, biopsy
of the site is mandatory prior to repair. Upper tract evaluation can be done with intra-
venous pyelography, retrograde pyelography, or computed tomography. Although the
ipsilateral kidney can appear normal with prompt drainage, ureteral involvement can be
demonstrated by hydronephrosis or extravasation on intravenous pyelography. Retrograde
pyelography remains the most sensitive test to evaluate for ureteral involvement in the
presence or absence of a VVF. Voiding cystourethrogram helps to identify the presence
and location of a fistula and should be performed in all patients. Coexisting vesicoureteral
reflux, urethral diverticulum, stress incontinence, or cystocele can be identified, which
may alter the surgical plan. Furthermore, voiding cystourethrogram can help elucidate
fistulas involving the rectum or uterus. Finally, vaginoscopy can assist in identifying the
vaginal communication.
CONSERVATIVE MANAGEMENT
Small VVFs may close spontaneously with continuous Foley catheter drainage in up
to 10% of cases. By the time patients have sought consultation with a specialist, this has
usually been attempted. Three weeks of drainage is a reasonable option if the fistula is
discovered early in the postoperative period. Antibiotic therapy and estrogen replacement
may assist with spontaneous closure. Surgical repair must be considered if this measure
fails. Mature fistula tracts are unlikely to resolve with this technique.
Another conservative treatment option includes fulgurating the lining of the fistula
tract. However, this should not be attempted with large fistulous tracts. In fistulas less
than 3 mm, Stovsky et al. reported closure in 11 of 17 patients with fulguration and 2 wk
of catheter drainage (9). Reports have shown success with fibrin therapy to treat small
VVFs (10). Most conservative measures ultimately fail in the attempt to cure VVFs.
Formal surgical repair remains the gold standard. For larger, complex, and radiation-
induced fistulas, there is little role for conservative treatment.
OPERATIVE MANAGEMENT
Preoperative Considerations
Prior to formal repair of a VVF, multiple factors must be considered to optimize the
chances of a successful first repair. Historically, most authors advocated waiting 3–6 mo
prior to surgical repair to allow the fistula to mature completely (11,12). This allowed a
maximal healing period during the posthysterectomy inflammatory stage. Women with
VVFs experience enormous social, physical, and psychological stress, hindering their
quality of life. Many contemporary authors have reported excellent results with early
repair, avoiding the great patient distress throughout the waiting period (13,14).
Early transvaginal repair is typically performed 2–3 wk after the time of injury. This
early repair is most commonly performed in women who develop fistulas after abdominal
hysterectomy. Because of the distressing nature of VVF, we advocate early repair in
the large majority of patients. Patients with pelvic abscesses or vaginal cuff infections
are not early repair candidates and must be treated with long-term antibiotics prior
to any attempt. In addition, patients with prior failed repairs and radiation-associated
fistulas are not candidates for early intervention and should wait several months prior to
formal repair.
The most appropriate approach to surgical repair of VVF is the one most familiar to
the individual surgeon. Utilizing an abdominal, vaginal, or laparoscopic approach will
depend on the surgeon’s training, experience, and comfort level. Regardless of the
approach, the highest success rates are associated with the first operation. Classically,
the location of the fistula dictated the surgical approach. Supratrigonal fistulas were
repaired transabdominally, and infratrigonal and bladder neck fistulas were repaired
vaginally. Good surgical technique with tissue interposition allows even complex high
VVFs to be repaired with a transvaginal approach.
The main advantage of the abdominal approach is the ability to perform simultaneous
procedures for coexisting intraabdominal pathology. These include ureteral reimplantation,
augmentation cystoplasty, and repair of bowel fistulas. The vaginal approach avoids the
morbidity of an abdominal incision with possible bladder bivalving. It is associated with
a shorter hospital stay and quicker patient convalescence. We prefer the transvaginal
approach for the overwhelming majority of VVFs. This approach is the major focus of
the chapter.
Many principles are integral in fistula repair regardless of the approach. Excellent
exposure with watertight, tension-free closure utilizing multiple, nonoverlapping suture
lines provides an approx 90% chance of cure on the first attempt. Continuous catheter
drainage postoperatively is mandatory. If any question exists concerning integrity of the
repair, then interpositional grafts augment the chance for cure.
Outpatient preoperative antibiotics clear any associated infection and provide a sterile
environment for repair. Routine urine culture should document absence of infection
prior to surgery. Estrogen-containing vaginal cream is used in the postmenopausal or

posthysterectomy patient to improve the quality of the vaginal tissues. Broad-spectrum
intravenous antibiotics are provided in the preoperative area.
Traditional repair of VVFs included excision of the tract to provide clean and vascular
edges, which was thought to increase chances for cure. Raz and associates demonstrated
excellent results and no adverse outcomes without excising the fistulous tract (15,16).
Excision of the fistula not only enlarges the tract but also potentially causes iatrogenic
bleeding, requiring hemostatic measures that may inhibit healing. Excising a fistulous
tract located near the ureteral orifices may result in injury to the trigone and ureters and
require concomitant ureteral reimplantation.
The surgeon must be familiar with several techniques for interposition of tissue. It is
difficult to predict accurately which fistulas will require the additional layer of coverage
to avoid a tenuous repair. These grafts are often necessary in large, complex, postradiation,
and failed primary repairs.
Preoperative evaluation should identify those patients who have concomitant stress
urinary incontinence. The incidence of stress urinary incontinence after VVF repair
ranges from 7 to 27% (17–20). Simultaneous sling procedure or bladder neck suspension
can be performed to avoid the need for a second procedure. Concomitant repair for
stress incontinence has been shown to have no increase in fistula recurrence rate (21).
Simultaneous repair obviates the need for a second incontinence procedure and the
patient distress of persistent incontinence despite a successful VVF repair.
It is extremely important to consider the sexual function of the patient and ensure
preservation of vaginal depth in the sexually active patient. Local estrogen replacement
should be used in patients with vaginal atrophy. Patients who are sexually active may
require rotational flaps in cases with vaginal stenosis or large fistulas.
Transvaginal Operative Technique

We routinely repair VVFs through a vaginal approach and describe the basic technique.
This avoids the morbidity of a laparotomy and is performed on an outpatient basis.
STEP 1: PATIENT PREPARATION
The patient is placed in the low lithotomy position and prepped in standard sterile
fashion with an iodine-based wash. The labia are sutured apart and a ring retractor
is placed for optimal exposure. Cystoscopy with ureteral catheterization is done when
the fistula is located in close to the ureteral orifices. A headlight provides excellent visua-
lization for the primary surgeon. A urethral Foley catheter is placed, and the bladder is
filled with normal saline. A curved Lowsley retractor assists in placement of a 16-French
suprapubic catheter through a small suprapubic puncture. A relaxing incision (postero-
lateral episiotomy) may be necessary for vaginal vault exposure in cases with a narrow
or stenotic vagina. An Allis clamp is used to elevate the anterior vaginal wall, and a poste-
rior weighted speculum is positioned.
STEP 2: ISOLATION OF FISTULA
The fistulous tract is identified and catheterized with an 8- or 10-French Foley
catheter aiding in retraction throughout flap dissection (Fig. 1). Metal sounds may assist
in dilating the tract prior to catheter placement. Intravesical methylene blue may help
visualize the tract. An inverted J incision is made, with careful attention paid to circum-
scribe the fistulous tract (Fig. 2). The long end of the J should extend to the apex of the
Fig. 1. Catheterization of fistulous tract.
Fig. 2. Inverted J incision around the fistulous tract.

Fig. 3. Development of vaginal flaps.
vagina, facilitating later advancement and rotation of a posterior flap. Fistulas located
high in the vaginal cuff may require an inverted incision, with the base of the flap facing
the urethral meatus.
STEP 3: CREATION OF FLAPS
Anterior- and posterior-based vaginal flaps are dissected on each side of the fistulous
tract, beginning with healthy tissue away from the opening of the fistula (Fig. 3). This
allows a natural plane of dissection and helps prevent enlargement of the fistulous tract
or inadvertent bladder perforation. The ring of vaginal tissue circumscribing the fistulous
tract is left intact. The flaps are developed at least 2–4 cm away from the fistulous tract
to expose the underlying perivesical fascia. The flaps are now retracted with the hooks of
the ring retractor.
STEP 4: CLOSURE OF FISTULA
The standard VVF repair is done in three layers. The first layer closes the epithelialized
edges of the fistula tract and a few millimeters of the surrounding tissue (including bladder
wall) with interrupted 3-0 absorbable sutures (Vicryl) in a transverse fashion (Fig. 4). The
Fig. 4. First layer of repair: transverse closure of fistulous tract without excision.
fistula catheter is removed, and the sutures are tied, closing the fistulous tract. The second
layer of repair incorporates the perivesical fascia and deep muscular bladder wall using the
same suture material (Fig. 5). The sutures are placed at least 1 cm from the prior suture line
and secured tension-free, imbricating the first layer. The suture should be placed in a line
perpendicular to the first suture layer to minimize overlapping suture lines.
The bladder is filled with indigo carmine diluted in saline, and the integrity of the repair
is tested. In a standard VVF repair (without tissue interposition), the procedure is now
completed. The previously raised posterior flap is rotated beyond the fistula closure site
by at least 3 cm (Fig. 6). Excess vaginal flap tissue is excised. The vaginal wall is closed
using a running, locking absorbable 2-0 suture (Vicryl) covering the tract with healthy
vaginal tissue and providing a third layer of closure with no overlapping suture lines. An
antibiotic-impregnated vaginal pack is placed, and the urethral and suprapubic catheters
are left to dependent drainage.
The majority of uncomplicated VVFs require a three-layer, tension-free repair.
Complicating factors that mandate additional protection include prior radiation, failed
prior surgery, and poor tissue quality. These conditions require tissue interposition and are
described.
Transabdominal Technique
In our hands, the abdominal approach is utilized only in select patients requiring
concomitant abdominal procedures such as augmentation cystoplasty or ureteral reim-
plantation. Preoperative bowel preparation is mandatory when bowel augmentation is
Fig. 5. Second layer of repair: imbricate first layer with perivesical fascia.
anticipated. The patient is placed supine with the legs slightly abducted for intraoperative
vaginal access. The vagina and lower abdomen are prepped in standard fashion, and a
suprapubic tube is placed with a Lowsley retractor. A urethral catheter is placed into the
bladder for maximal drainage. A Pfannenstiel or lower midline incision is made, and the
space of Retzius is developed. An extraperitoneal approach can be used, although an
intraperitoneal approach assists in optimizing exposure and allowing an omental flap to
be positioned.
Identification of the fistula may be aided by intravesical instillation of methylene blue.
The dome of the bladder is elevated, and dissection is performed between the base of the
bladder and vagina toward the fistulous tract. The bladder is dissected free from the vagina
with margins of at least 3 cm, and the fistulous tract is identified. The bladder is opened
only in the area of the fistula without excising the fistula or bivalving the bladder. The
bladder and vaginal defects are each repaired in two layers using interrupted, absorbable
suture. Interposition with omentum, perivesical fat, or peritoneum provides an addi-
tional layer of coverage. Unless a transvesical approach is taken, there is no need for
pelvic drainage. The abdominal wound is then closed, and the suprapubic and urethral
catheters are left to dependent drainage.
Other Techniques
Other authors advocate the O’Conor technique, a transvesical approach with bivalving
of the bladder (11). An anterior cystotomy is made in the sagittal plane and extended
posteriorly to the fistula. The bladder is mobilized completely from the vagina, and
Fig. 6. Third layer of repair: vaginal flap advancement.
the fistula is excised. The openings in the bladder and vagina are closed separately in
two layers with interrupted 2-0 absorbable suture. An omental flap is placed between the
vagina and bladder, and the wound is closed. Reported success rates range from 87 to
100% (22–24).
The Latzko operation, described in 1942, uses a partial colpocleisis to treat VVFs
(25). The operation consists of denuding of the surrounding vaginal wall and preserva-
tion of the fistulous tract. A separate layered closure is then performed, including the
bladder, VVF, and vagina. A theorized drawback to this procedure is vaginal shortening.
However, success rates of 93 and 95% have been reported in two series of 43 and 20
patients, respectively, with no significant patient-reported sexual dysfunction or vaginal
shortening (26,27). The technique is still commonly performed by gynecologists today
because of its technical ease and minimal morbidity.
Transurethral suture cystorrhaphy with fistula tract preservation has been described
as a minimally invasive alternative for smaller fistula (5–8 mm) located away from the
ureteral orifices. The technique requires fulguration of the tract and surrounding bladder
mucosa. This is followed by combined transurethral/abdominal endoscopic suture place-
ment. A minimum 2- to 3-wk period of bladder drainage is necessary. Eight of 11 patients
(73%) treated with this technique were cured (28).
VVF repair has been described laparoscopically with the explosion of minimally
invasive surgery (29). The approach was first described in 1994 and has undergone
various modifications, including use of an endostapler, omental interposition, as well

as layered closure (30). Robotic-assisted laparoscopic repair has also been successfully
performed (31).
COMPLEX FISTULAS
Complex VVFs include those associated with prior radiation or malignancy, recur-
rent fistulas, large (greater than 2 cm) fistulas, fistulas involving the trigone and bladder
neck, and those associated with poor tissue quality (ischemia or hormone deficiency) or
difficult closure. These cases mandate additional steps to the standard transvaginal VVF
repair. Multiple techniques of tissue interposition exist; all provide an additional layer
of closure and enhance the quality of the fistula repair.
Radiation Fistulas
Radiation-induced VVFs require special consideration. The fistulous tract typically
forms in the trigone region because it is in a relatively fixed position, and radiation
effects are more likely to occur. Radiation fistulas have been reported in 1–5% of
patients treated for cervical or uterine carcinoma. The fistulas often present in a delayed
fashion and can present 15–20 yr later (32). Fistulas occurring after radiation should
always be biopsied to rule out recurrence of the primary malignancy.
Radiation-induced fistulas occur secondary to obliterative endarteritis in the irradi-
ated field (32). The microvascular injury compromises healing and affects the tissues
surrounding the fistula, complicating an already-difficult repair. Videourodynamics and
cystoscopy allow assessment of compliance and bladder capacity. If there is adequate
compliance and capacity, then transvaginal repair is performed with certain modifications.
Tissue interposition with a Martius graft or omental flap is critical, as is prolonged post-
operative catheter drainage. If the bladder has small capacity and poor compliance, then
augmentation cystoplasty is required, and an abdominal approach is taken. Careful
inspection of the bowel is necessary to ensure usage of a nonirradiated segment. Tissue
interposition and prolonged catheter drainage are necessary steps, regardless of the
approach, when repairing radiation-induced VVFs.
TISSUE INTERPOSITION
Martius Graft
The Martius graft (fibrofatty labial flap) was first described in 1928 (3). This technique
is commonly used in reconstructive surgery and has great utility in VVF, rectovaginal
fistula, urethrovaginal fistula, and urethral reconstruction. It has high reported success
rates in complex fistula repair and is a convenient source of interposition in transvaginal
vesicovaginal repair (33). We use a Martius flap when the fistula is located high in the
urethra and bladder neck region.
The Martius graft is a long band of adipose tissue from the labia majora. It has excellent
vascularity and strength (contains end fibers of round ligament). The blood supply is
threefold: (1) Branches of the external pudendal artery supply the graft superiorly and
anteriorly; (2) obturator branches enter the graft at its lateral border; (3) inferior labial
artery and vein supply the graft inferiorly. The graft may be mobilized superiorly or
inferiorly depending on the desired location of transfer.
The first two layers of the fistula are closed as described. The vaginal flaps are left intact,
and the labial retraction suture is removed. A vertical incision is then made over the labia
Fig. 7. Mobilization of Martius flap based on inferior pedicle.
majora, and the subcutaneous tissues are dissected laterally to the lateral border of the dis-
section, the labiocrural fold. The flap is dissected posteriorly to Colles fascia and medially
to the labia minora/bulbocavernosus muscle. The main vascular supply is at the base, and
the entire thickness of the fat pad is encircled by a Penrose drain. The superior and anterior
segment of the graft is clamped, transected, and suture ligated. The remaining dissection
is completed, and the flap is now freed, except at its base (Fig. 7A). A tunnel is then created
between the vaginal wall and the perivaginal tissues. The graft is then passed from the labial
area to the vaginal area (through the tunnel) with the aid of a hemostat (Fig. 7B). The Martius
graft is placed over the fistula site and secured tension free with interrupted absorbable suture.
The posterior vaginal wall flap is advanced and closed as described, providing a fourth layer
of closure. A light pressure dressing may be applied, and ice packs are routine. Most series
report success rates greater than 90% in fistula repairs with Martius flap (20,34–36). Eilber
et al. reported a 97% cure rate with transvaginal repair using Martius graft interposition in 34
patients with complex fistulas (37).
Peritoneal Flap
We utilize a peritoneal flap in the repair of high fistulas located at the vaginal vault,
which are seen most commonly after hysterectomy. Extending a Martius graft to this
location may result in inadvertent vaginal shortening. A peritoneal flap is an easily
available, well-vascularized tissue and can be harvested without a second incision.
Fig. 8. Transfer of Martius flap to cover fistula repair.
The fistula repair begins as described in the first three steps of the transvaginal
technique. The fistula is now circumscribed, and vaginal flaps are prepared. A catheter
in the fistula can help in dissection of the flap. Sharp dissection is used to expose the
peritoneum and preperitoneal fat. The fistulous tract is then closed in two layers as
described. The preperitoneal fat and peritoneum are now advanced to cover the fistula
repair and secured to the perivesical fascia with tension-free interrupted sutures (Fig. 8).
The posterior vaginal flap is then advanced and closed. Raz et al. reported a 91%
success rate in their initial experience using a peritoneal flap in 11 patients with VVF
(38). Eilber et al. reported a 96% cure rate using a peritoneal flap in 83 patients who
underwent complex fistula repair (37). It has high success rates, minimal morbidity, and
equal outcomes to a Martius graft without a second incision.
Omental Interposition
Omental interposition is the preferred source of tissue interposition in the abdominal
approach for fistula repair, although it can be accessed transvaginally in women who have
had previous procedures. Understanding the blood supply to the omentum is critical.
Vascular supply to the omentum is derived from the right gastroepiploic artery (branch off
the gastroduodenal artery) and the left gastroepiploic artery (branch off the splenic artery).
The right and left omental arteries take origin from their respective gastroepiploic
branches and unite at the inferior aspect of the stomach in a U-shaped fashion. Variably,
there is a middle omental artery that bisects the U into two sections. Omental flaps are
typically based on the right gastroepiploic artery as it is the dominant supply in the
majority of cases.
The omentum can be redundant in certain cases and reaches into the pelvis with min-
imal or no mobilization. Prior surgery or radiation may affect the mobility and amount
of omentum available. If the omentum only requires minimal mobilization, then an
L-shaped incision below the transverse colon (based on the right omental artery) may
be all that is necessary. Additional length can be obtained by dissecting the omentum
off its attachments to the transverse colon. In cases requiring major mobilization, the
left short gastric arteries are taken down, the transverse colon attachments are dissected
off, and an incision is made down the center of the omentum. Regardless of the harvest
technique, the result is an omental graft that can be placed between the bladder and
vagina for an additional layer of protection.
Full-Thickness Labial Flap

In complex cases with loss of vaginal wall, insufficient vaginal epithelium may
prevent primary vaginal closure. A full-thickness labial flap can be rotated to substitute
for the missing vaginal wall. This provides a well-vascularized fibrofatty layer and
full-thickness skin coverage. The fistula is closed as described, and the vascularized flap
is rotated to provide full-thickness skin coverage.
After closure of the fistula, a U-shaped incision is made over the labia, including the
lateral labial skin and underlying tissue (Fig. 9). The base of the flap is at the level of
the posterior fourchette. The flap is dissected from the fascia overlying the pubic bone
and then rotated to cover the repair. Interrupted absorbable sutures are used to secure
the edges in place (39). Small series have reported excellent results. Carr and Webster
reported excellent outcomes in four patients (40). Margolis et al. reported initial 100%
success in four patients, with one delayed recurrence (33). Postoperative complications
include sensory deficit at the harvest site, poor cosmetic result, wound infection, and
flap sloughing.
Gluteal Skin Flap

Gluteal skin flaps are used mainly in patients with postradiation fistulas or severe
vaginal wall atrophy with no other available and viable skin source. The first two layers
of the fistula are closed and the vaginal flaps raised as described for uncomplicated VVF
repair. A longitudinal incision is made in the vaginal wall toward the midportion of the
labia majora. This is then extended in a semicircular fashion in the gluteal skin. The skin
is undermined, and the flap is rotated and advanced into the vaginal canal to cover the
fistula repair. The flap is secured with interrupted, absorbable sutures, and the vaginal
flaps are secured to the skin flap edges (41). Complications include wound infection,
sloughing of the flap, and injury to the anal sphincter (42). Careful surgical technique
is mandatory to avoid the last complication.
Myocutaneous Gracilis Flap

The gracilis muscle-based myocutaneous flap has been frequently described in
association with repair of the postradiation VVF in patients with vaginal atrophy or
absence. The gracilis muscle is a long, slender muscle that extends from the inferior
Fig. 9. Peritoneal flap advancement.
pubic symphysis to the medial condyle of the femur. It is an accessory muscle used
for thigh adduction and knee flexion and can be sacrificed without loss of function. It
sits between the adductor longus laterally and the adductor magnus medially. Its
blood supply is derived from a branch of the deep femoral artery: the medial femoral
circumflex artery.
The flap is harvested with a tennis racquet incision on the medial aspect of the thigh
over the gracilis muscle. It begins 10 cm below the pubic tubercle and extends 20 cm
toward the knee (Fig. 10). The skin island should not include the distal third of the
muscle. The skin and underlying muscle are mobilized, with care taken to preserve
the vascular supply. The gracilis is transected at its distal insertion. A tunnel is then
created underneath the medial aspect of the thigh and labia, and the flap is transferred
to the vaginal area for additional coverage of the fistula tract and reconstruction of the
vaginal canal. This can result in considerable cosmetic scarring, but there is no func-
tional defect. No large series exists documenting the gracilis flap, but several authors
reported good outcomes in small series (42–44).
Bleeding and ureteral injury represent the two major potential intraoperative com-
plications. Hemostasis is critical during the vaginal flap dissection. Electrocautery
Fig. 10. Gracilis myocutaneous flap.
should be avoided and bleeding controlled with fine absorbable sutures. Anything less
than perfect hemostasis can cause hematoma formation and possible disruption of the
fistula repair.
Ureteral catheterization is recommended for fistulas close to the trigone because of
the higher risk of iatrogenic ureteral injury. Fistulas located elsewhere do not require
this maneuver. If there is any concern about ureteral injury, then perform cystoscopy
after intravenous indigo carmine is administered to ensure integrity. Ureteral cathete-
rization can be performed if any doubt exists.
POSTOPERATIVE MANAGEMENT (TRANSVAGINAL REPAIR)

Postoperatively, the vagina is packed with an antibiotic-impregnated gauze that is left for
several hours. Surgery for transvaginal repair is performed on an outpatient basis. The
suprapubic and Foley catheters (joined to a Y connector) are left to dependent drainage for
a minimum of 2–3 wk. Anticholinergics are given to minimize bladder spasm and augment
patient comfort. An oral quinolone or cephalosporin is continued for 1 wk. Patients are
instructed to resume normal activity except for strenuous exercise. In addition, sexual inter-
course is prohibited for 12 wk. The urethral catheter is removed 2–3 wk after surgery, and
a suprapubic cystogram is performed. If the cystogram demonstrates no extravasation, then
the suprapubic catheter is removed.
OUTCOMES
Many factors must be considered when assessing patient outcomes. Cure rate, mor-
bidity, and patient satisfaction are critical factors in determining patient success and the
ideal approach. There have been no prospective, randomized studies comparing vaginal
and abdominal approaches in VVF repair. Future efforts should address these critical factors
missing in the reported literature. Many series have shown success rates of 90–100%
with both approaches (15,45–47). The best approach remains the one with which the
surgeon has the most technical expertise and experience.
Early postoperative complications include vaginal bleeding, bladder spasms, and
vaginal infection. These must be treated immediately and aggressively to avoid fistula
recurrence. Secondary vaginal bleeding is treated with repacking and bed rest. Anti-
cholinergics should minimize bladder spasms. B and O suppositories can be used if
required. Ileus after abdominal approaches is not uncommon. Perioperative antibiotics
continued in the postoperative period are important in preventing vaginal infections.
The most important delayed complication is fistula recurrence. Others include vaginal
shortening and stenosis and unrecognized ureteral injury. Tension-free, multilayer closure
with tissue interposition as needed results in a greater than 95% success rate. Fistula
recurrence does not mandate an abdominal approach. A second vaginal repair may be
performed with a Martius graft or peritoneal flap. A 3-mo waiting period after prior
repair allows for resolution of postoperative inflammation. Care must be taken to mini-
mize excess resection of the vaginal wall and avoid significant shortening and stenosis.
In these cases, secondary vaginoplasty is required. Unrecognized ureteral injury typically
presents as an obstruction, not a leak. An antegrade approach with percutaneous nephro-
stomy is preferred. A retrograde procedure via a transurethral approach can disrupt the
repair and should not be performed.
CONCLUSION
VVF represents one of the devastating morbidities in the female after gynecologic
and pelvic surgery. Transvaginal surgical repair is an outpatient procedure associated
with high success rates, minimal morbidity, and quick convalescence times. It remains
our preferred method of repair in all but the select few cases requiring concomitant
abdominal surgery.
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23 Female Urethral Diverticula
Erin Gibbons, MD and Wendy W. Leng, MD

CONTENTS
INTRODUCTION
ETIOLOGY
CLASSIFICATION
INCIDENCE
PRESENTATION AND EVALUATION
TREATMENT
PATHOLOGY
CONCLUSION
CASE 1
CASE 2
CASE 3
REFERENCES
INTRODUCTION
The first clinical description of a female urethral diverticulum is credited to Dr. John
Hey in 1805. In his essay “Of Collections of Pus in the Vagina,” Dr. Hey described the
diagnosis and treatment of this entity, which included a transvaginal incision, and packing
of the diverticular sac with lint (1). Over the next 150 yr, the medical literature offers
scant references pertaining to the topic of female urethral diverticula. However, in 1956,
with the advent of a new diagnostic tool in the form of positive pressure urethrography
(PPU), the detection and diagnosis of female urethral diverticula demonstrated a pre-
dictable dramatic increase (2).
ETIOLOGY
Since the first reports of a female urethral diverticulum, clinicians have debated
whether the condition represented a congenital vs acquired process. In 1890, Routh
proposed a pathogenesis mechanism of obstruction and infection within the periurethral
glands (3). However, during much of the 20th century, several authors argued that the
primary etiology was congenital. Johnson described several possibilities for congenital
diverticula, including Gartner’s ducts, fusion of primal folds, primordial cell rests, vaginal
wall inclusion cysts, and dilation of the paraurethral glands (4).
It was not until Huffman detailed the fine network of periurethral glands communi-
cating with the urethral lumen that an infectious process for the development of urethral

327
diverticula was deemed plausible. By combining transverse sections of the urethra with
paraffin wax modeling; Huffman was able to demonstrate that the majority of peri-
urethral ducts empty into the middle and distal third of the urethra, with the highest
concentration located dorsolaterally. In addition, he demonstrated that inflammation
was common within these ducts (5). It is now widely accepted that obstruction of the
periurethral glands leads to swelling, pain, infection, and often a palpable urethral mass.
CLASSIFICATION
Several classification systems over since the mid-20th century have been proposed
to better describe the characteristics, location, and treatment of female urethral diver-
ticula. It is important to review the diverticular anatomy to understand these different
classifications better.
Urethral diverticula are commonly cystic and communicate with the urethral lumen
by an ostium. Typically, the mean diameter of a detected urethral diverticulum sac is
1.5–2.0 cm; the ostium size ranges from 1 to 5 mm (6 – 8). As Huffman had delineated
with his meticulous anatomic characterization of the periurethral glandular system, the
highest concentration of periurethral ducts converge at the middle third of the urethra,
more specifically, at the posterolateral aspect. Therefore, it is not surprising that the ostial
opening of most urethral diverticula are detected within the middle third of the urethra
on the posterolateral aspect. The cystic component of the diverticula can take the form
of varying shapes: a single sphere, multiloculated, saddle shaped, or near circumferential.
In a series of 61 patients, Leach et al. reported that 55 (90%) of urethral diverticula were
single spheres (8).
Lang and Davis described the earliest classification system in 1959 (9). This system
was based on morphology as evident with the newly described diagnostic technique of
PPU. They classified the diverticulum as simple, multiple, or complex. However, no indi-
cation of urethral location is included in their categorization. Subsequently, Ginsburg and
Genadry proposed a modified classification system based on the location of the diverticula
within the proximal, mid-, or distal urethra (10).
A more complex contemporary classification proposed by Leach et al. incorporates
several characteristics of the diverticula (8). The acronym LNSC3 is used to describe
the following six parameters: location (L) to the distal, mid-, or proximal urethra;
number (N) of diverticula as single or multiple; size (S) in centimeters; configuration
(C1) as single, loculated, or saddle shaped; communication (C2) of the ostium to the
distal, mid-, or proximal urethra; and urinary continence (C3). This system, although too
complex for widespread clinical use, does allow for improved comparison of various
research study populations.
Another classification system that may prove more helpful to the operative planning
is based on the integrity of the periurethral fascia. Leng and McGuire divided their
series of 18 patients into true diverticula vs pseudodiverticula. A true diverticulum is
described as having an intact periurethral fascia with a narrow neck ostium. This is the
classically described diverticulum that occurs as a result of obstruction and inflammation.
The pseudodiverticulum, in contrast, represents a mucosal extrusion through a defect in
the periurethral fascia. Typically, this clinical entity is more characteristic of a patient
with a history of prior urethral, vaginal, or bladder surgeries (i.e., bladder neck suspension,
anterior colporrhaphy, or prior urethral diverticulectomy) in which the periurethral fascial
layer had been violated (11).
Chapter 23 / Female Urethral Diverticula 329
INCIDENCE
The diagnosis of female urethral diverticula in the general population is rare. With
improvement in diagnostic methods, the incidence has remained between 0.6 and 5%,
with the majority of women presenting in the third to fifth decades of life (12,13).
Nevertheless, the true prevalence and incidence of the condition remains unknown. In
one of the few clinical series of its kind, Andersen in 1967 tried to gage the incidence
of female urethral diverticula within his patient population. He performed PPU on a
cohort of 300 consecutive women patients without voiding symptoms and discovered
that 3% of these women had asymptomatic urethral diverticula (13). On the other
hand, of the collective experience from contemporary case series describing women
with long-term voiding symptoms, urethral diverticula have been identified in up to
40% (14).
No specific risk factors have been identified that predispose some women to the
development of urethral diverticula. Previously, multiparity and traumatic childbirth
were thought to increase the risk of diverticula development. However, in one case
series, 31% of the patients were nulliparous (12). With respect to pseudodiverticula,
Leng and McGuire found that the defect was clearly related to prior diverticulectomy or
urethral/anterior vaginal surgery (11). Although not a risk factor, stress urinary inconti-
nence is commonly diagnosed in combination with urethral diverticula. Several clinical
series have reported that between 28 and 60% of patients diagnosed with urethral diver-
ticula also have evidence of concomitant stress urinary incontinence (6,11,14).
PRESENTATION AND EVALUATION

Much of the difficulty in the diagnosis of female urethral diverticulum stems from the
variable clinical presentations. As the case vignettes in this chapter highlight, patients
can present with a wide range of fairly common and nonspecific lower urinary tract
symptoms. Although the classic textbook description refers to the three Ds (symptoms
of dribbling, dyspareunia, and dysuria), more commonly patients present with vague
complaints of irritative voiding symptoms. In several studies, the most common voiding
symptoms were urinary incontinence (33–60%) and urinary frequency (22–50%). Com-
plaints of recurrent urinary tract infections (33–61%) can occur secondary to urinary
stasis in the diverticulum, leading to bacterial cystitis. However, the typical patient with
this condition has persistent lower urinary tract symptoms in the absence of documented
bladder infection. Pressure from the diverticulum can lead to dyspareunia (5–70%) and
ill-defined pelvic pain (5–60%) (14–18).
Not surprisingly, given the difficult nature of diagnosis, we can only speculate
regarding the natural history of female urethral diverticula. The available literature
would suggest that the duration of symptoms prior to the diagnosis of a urethral diver-
ticulum varies from a few months to several years. Patients have often been treated by
several physicians for a range of urologic conditions before definitive diagnosis. In a
review of 46 women diagnosed with urethral diverticulum, Romanzi et al. reported that
83% of patients were referred for evaluation of persistent lower urinary tract symptoms.
Prior diagnoses included vulvodynia (42%), chronic pelvic pain syndrome (27%), and
interstitial cystitis (19%) (15). Thus, more often than we care to admit, such patients are
more likely given the diagnoses of despair. This can then set them up for a lifetime of
chronic symptom management and poorly defined diagnostic and treatment algorithms
rather than a discrete, treatable condition.
A detailed clinical history is paramount in the evaluation for urethral diverticula. As

detailed, a history of persistent lower urinary tract symptoms despite adequate treatment
for more common urologic conditions should increase suspicion of a potentially undia-
gnosed urethral diverticulum. In addition, a previous history of surgical procedures for
incontinence or urethral reconstruction may indicate a pseudodiverticulum. The physical
exam should include a careful inspection and palpation of the urethra to locate a tender
mass along its course. In a review by Romanzi et al., 52% of patients had a distinctly
palpable mass on exam, and 25% had fluid expressed from the diverticulum into the
urethra (15). Although a palpable urethral mass is concerning for a urethral divertculum,
the differential diagnosis must necessarily include ectopic ureterocele, urethrocele,
Gartner’s duct cysts, and urethral carcinoma.
Along with a careful history and physical exam, several diagnostic studies can be
used to aid in the diagnosis and characterization of urethral diverticula. There has been
much debate surrounding the most accurate and cost-effective diagnostic modality.
Although easy to perform, urethroscopy is no longer preferred for diagnosing urethral
diverticula. Urethral folds can make identification of the pinpoint tracts difficult, and
anterior vaginal wall pressure will not always milk fluid into the urethral lumen. So, in
general, the diagnostic yield of urethroscopy is too low to justify the potential exacer-
bation of symptoms associated with urethral manipulation by this technique.
Traditionally, the use of voiding cystourethrography (VCUG) has served as the main-
stay for diagnosing urethral diverticula. To begin, a scout film should show the inferior
pubic rami to ensure that the urethra will be visible. Next, the bladder is filled with 20%
iodinated contrast until the patient feels full. In the upright position, the patient is asked
to void while fluoroscopy is used to obtain posterolateral, anterior-posterior, and
oblique views of the pelvis. Although VCUG is a commonly utilized diagnostic tool in
urology, the reported sensitivity of VCUG for detection of urethral diverticula varies
widely, from 44 to 95% (17,19).
In 1956, Davis and Cian described the use of a specialized double-balloon catheter
for performing PPU (2). The triple-lumen, double-balloon catheter is placed into the
bladder, and the first balloon is inflated to 30 mL and seated at the trigone to create a
bladder neck seal. The second balloon can either be fixed or sliding, is inflated to 20 mL,
and forms another seal at the urethral meatus. Thus, this customized diagnostic catheter
allows for isolation of the urethra between the balloons. Using fluoroscopy, contrast is
injected through the catheter, flowing out the midurethral port of the catheter to allow
urethral distension and, theoretically, filling of any diverticulum cavity. Interestingly,
with the advent of double-balloon PPU, Davis and Telinde reported that the subsequent
year yielded a dramatically increased diagnosis rate of 50 cases of female urethral diver-
ticula at Johns Hopkins Medical Center. This was clearly a vast increase in annual
detection rate considering the fact that in the preceding 50-yr interval at Johns Hopkins
Hospital only nine cases of female urethral diverticula had been identified (20).
Traditionally, PPU has been considered difficult to perform compared to VCUG
because of leakage around the double balloons, and patient discomfort warranted sedation.
However, the instillation of viscous lidocaine in patients with discomfort on prior pelvic
exams has been reported to aid in performing PPU, obviating the need for routine
patient sedation (17). Several studies have compared PPU with VCUG. In a contem-
porary series by Jacoby et al., the sensitivity of PPU and VCUG were reported to be 100
and 44%, respectively. The diverticula, which had been undetected with VCUG, were
determined to have a relatively small diameter, less than 15 mm (17). Several other
studies have confirmed the increased sensitivity of PPU over VCUG, especially with
respect to smaller diverticula (21,22).
Other radiological modalities have been tested for the diagnosis of urethral diverti-
cula. Lee and Keller first described the use of sonography for the identification of urethral
diverticula in 1977 (23). Since the 1970s, advancements in sonography with development
of higher frequency probes for transvaginal, transperineal, and endourethral approaches
have led to better sonographic visualization. Urethral diverticula appear as hypoechoic
cavities when compared to surrounding periurethral tissue. Calculi or debris within the
diverticula can be identified because of acoustic shadowing. In a prospective study, Siegel
et al., using just such a range of diagnostic tools, evaluated 19 patients with urethral
symptoms. VCUG was compared with transvaginal, transperineal, or urethral sonography.
Although both VCUG and sonography diagnosed 86% of the urethral diverticula, sono-
graphy was better able to identify the neck of the diverticula and characterize the extent
of the lesion (24). Intraoperative urethral ultrasound has also been used to better identify
the size and orientation of lesions even when preoperative VCUG, PPU, and transvaginal
ultrasounds were negative (25). Yet, despite these cited theoretical advantages, sonography
has not displaced contrast urethrography as the diagnostic test of choice. Sonography
remains highly operative dependent, offers a small field of view, and cannot reliably dif-
ferentiate types of periurethral lesions.
The use of magnetic resonance imaging (MRI) for the evaluation of the female
urethra has also increased. Ongoing advancements in MRI technology with external,
endorectal, and endovaginal coils have enhanced the sensitivity of MRI in detecting
pathology of the female urethra. In a retrospective review of 129 woman with lower
urinary tract symptoms, Lorenzo et al. found that endorectal coil MRI was useful in
diagnosing and characterizing patients with periurethral fibrosis, urethral diverticula,
and periurethral inflammation (26). Regarding female urethral diverticula, both T1- and
T2-weighted images are obtained. On T1-weighted images, urethral diverticula have a low
signal intensity; however, on contrast-enhanced T1-weighted images, the diverticulum
has an increased signal intensity after voiding. Diverticula appear as high-intensity signals
on T2-weighted images (27).
Several studies have compared the diagnostic capabilities of MRI, PPU, and VCUG
in the detection and characterization of urethral diverticula. Neitlich et al. reviewed the
results of 13 patients with clinically suspected urethral diverticula. All patients under-
went both PPU and MRI evaluation for urethral diverticulum. After the initial evaluation
with PPU, all were reevaluated with an external coil MRI. Of the four patients with MRI-
detected and surgically confirmed urethral diverticula, three had been missed with
urethrogram imaging (28).
With respect to MRI vs VCUG, Blander et al. retrospectively reviewed a series of 27
women radiographically diagnosed with urethral diverticula. All patients had been
evaluated with VCUG and endoluminal MRI. In all cases, endoluminal MRI identified
the diverticulum, compared with 23 of 27 cases detected with VCUG. In addition, at time
of surgical exploration, the VCUG findings underestimated the size and complexity of the
diverticula in 52% of the cases (29).
Similarly, MRI also demonstrates the added capability of defining noncommunicating
periurethral cysts, which may cause the same clinical symptomatology. Daneshgari et al.
described three clinical cases in which urethral MRI revealed noncommunicating
intraurethral wall diverticula. All three patients had long-standing histories of lower
urinary tract symptoms, unremarkable urethrography imaging, and prolonged treatments
for presumed interstitial cystitis. In each of these cases, diverticulectomy was successful,
and each patient became symptom free postoperatively (30).
With advancements in computed tomographic (CT) imaging and software applications,
multidetector CT (MDCT) scanners allow rapid scanning and improved resolution.
Reports in the radiologic literature suggest that MDCT scanning in conjunction with
instilled cystogram contrast allows far superior urethral imaging than traditional VCUG.
The examples of the three-dimensional reformatted images of the urethra taken with this
protocol offer superior detailed imaging. Two cases have been reported for which MDCT
delineated the ostium of the urethral diverticulum. In both of these cases, preceding
conventional VCUG, transvaginal ultrasound, and MRI failed to identify the ostium.
Furthermore, intraoperative identification of the ostium correlated with the MDCT
findings in both cases (31).
MDCT scanning has also been used for so-called virtual CT urethroscopy. The
authors cited a particular example for which conventional VCUG proved unremarkable
in a woman with a suspected urethral diverticulum. Comparative MDCT scanning, on the
other hand, revealed an impressive horseshoe-shaped diverticulum as well as the location
of its ostium (32). Although such state-of-the-art CT imaging of the lower urinary tract is
impressive to behold, the future role for this imaging modality is evolving. There are per-
tinent limitations to consider: (1) The scan is still relatively time consuming; (2) it requires
that the patient be able to void in the prone position; and (3) the necessary radiation
exposure must be taken into consideration given that most patients are of reproductive age.
TREATMENT
As discussed, several different classification systems have evolved in efforts to
better categorize urethral diverticula. Although the classification systems use different
criteria, each is intended to integrate findings from the history and physical exam and
imaging modalities to assist in treatment planning. Although surgical excision of the
diverticulum is the most common treatment option, there are instances when conservative
management is preferred or worthwhile. In particular, a patient with minimal symptoms
might choose to try conservative therapy. This essentially entails suppression-dose anti-
biotics, low-dose anticholinergic agents, and sitz baths. Certainly, there will be occasions
when the diverticulum is too small in caliber to allow surgical delineation and excision.
Then, diverticulotomy may offer relief, but with the patient’s understanding that recur-
rence is possible. In addition, some have described that dilation of the diverticular orifice,
manual decompression after voiding, and packing of the diverticulum can allow for some
relief of symptoms without invasive surgery (14).
Several surgical approaches have been developed throughout the years as the awareness
of the condition and anatomy of female urethral diverticula grew. Historically, techniques
have included incision and drainage with packing of the defect, endoscopic incision, and
open marsupialization.
Ellik first described incision and drainage in the 1950s, followed by packing of
the cavity with cellulose (Oxycel [BD, Franklin Lakes, NJ] or Gelfoam [Pharmacia,
Kalamazoo, MI]), thus leading to obliteration of the cavity by fibrosis (33). However,
adequate packing of large, multiloculated diverticula can be difficult, if not unfeasible.
Mizrahi and Bitterman described using polytetrafluoroethylene (polytef [Gore-Tex Inc,
Flagstaff, AZ]) as a packing agent with demonstration of a normal appearing urethra on
urethrography at one year (34).
Although endoscopy has long been used in the diagnosis of urethral diverticula, it can
also serve as an intraoperative tool for localizing the ostium of the diverticulum. Lapides
described an endoscopic diverticulotomy useful for immediate drainage of the cavity. A
transurethral incision of the diverticular ostium and roof with a curved knife electrode
allows for drainage of the diverticular contents into the urethra (35).
In 1970, Spence and Duckett described an open marsupialization technique in which
the posterior wall of the urethra is split open from the ostium to the meatus. The wall of
the diverticulum is then approximated to the vaginal mucosa with locking chromic
sutures. Clearly, this type of meatotomy was only recommended for diverticula in the
distal third of the urethra (36). Although in a long-term follow-up by Roehrborn there
were no recurrences in all 16 patients, 3 patients did report stress incontinence (37).
The current treatment of choice is complete excision of the urethral diverticulum.
Whenever feasible, this approach theoretically reduces the risk of diverticulum recur-
rence. In fact, historically, as far back as 1890, Routh recommended complete excision
and closure of the vaginal mucosa when inflammation and infection were not a concern
(3). Some references describe techniques to better identify the boundaries of the diver-
ticular cavity during operative dissection, such as transurethral packing of the cavity,
transvaginal placement of a Foley catheter into the diverticulum, and staining of the
diverticular walls with methylene blue (38–40).
Rovner and Wein described an innovative surgical technique for the excision of
complex, near-circumferential urethral diverticula. They describe urethral transection
to allow improved exposure and resection of the dorsal aspect of the diverticular sac.
At the conclusion, the urethra is reanastomosed in a primary end-to-end fashion.
Alternatively, when extensive dissection leads to a compromised segment of urethral
wall with significant surrounding dead space, the urethra can be wrapped with the
dorsal surface remnants of the diverticular wall to reinforce the urethral reconstruc-
tion (41). Although this does not allow for the ideal complete excision, the authors
contended that postoperatively these patients remain relatively asymptomatic. Their
article highlights the lack of literature available to guide management for these most
complex of female urethral diverticula.
Although a number of technical variations on the operative excision have been
described, all essentially adhere to the principles of careful mobilization of periurethral
tissue layers, preservation of the periurethral fascial layer, and complete excision of the
diverticular sac down to the level of the communicating ostium at the urethra. At the end
of the operation, careful attention to reapproximation of the periurethral layers will help
prevent development of pseudodiverticula.
In our practice, we begin with either a general or spinal anesthetic and then place the
patient in a modified dorsolithotomy position. Rigid cystoscopy is not always necessary
at the beginning of the procedure. However, if the diverticulum is not easily identified
or if it is decompressed, then a small stent coiled into the diverticulum may aid in the
dissection.
After placement of a 16-French urethral Foley catheter, a Lone Star perineal retractor
and weighted vaginal speculum are placed to aid operative exposure. We begin with an
inverted U incision centered over the bulge of the diverticulum and dissect the vaginal
mucosa off the periurethral fascia. Using a transverse incision, the periurethral fascia
is incised and sharply dissected from the diverticular sac. As the ostium of the sac is
encountered, it is transected at the level of the urethra. Closure of the urethral mucosa
is accomplished with a running 4-0 absorbable suture in a vertical direction. A Martius
flap may be placed adjacent to the urethral closure if tissue vascularity is poor or if
multiple repairs have previously been performed. Next, the muscularis is reapproxi-
mated with 3-0 absorbable sutures. The periurethral fascia is then closed so the suture
line is perpendicular to the urethral closure with a 3-0 absorbable suture.
If preoperative urodynamics indicate the coexistence of stress urinary incontinence,
then a pubovaginal sling can also be placed at the same setting. There are sufficient
reports in the contemporary literature to suggest that concomitant retropubic manipu-
lation to place a pubovaginal sling is not contraindicated in this setting. The vaginal
mucosa is then reapproximated using interrupted or a running 2-0 absorbable suture.
Meticulous hemostasis is required throughout the closure to avoid the development of
a hematoma.
The presence of a pseudodiverticulum may not be discernible until the time of surgery.
In such a scenario, urethroscopy under anesthesia reveals a wide-mouthed ostium to the
diverticulum sac, thus demonstrating that a sizable defect in the periurethral fascia
exists. When a urethral pseudodiverticulum is encountered, the edges of the periurethral
fascial defect are identified and carefully dissected away from the diverticular sac.
Excision of the sac and closure of the urethra are carried out as described. Closure of
the periurethral fascia is dependent on the quality of the fascia and the size of the defect.
If the defect is small, then the fascia can be closed primarily with 3-0 absorbable sutures
as described. However, with larger defects, autologous or allograft fascia may be used
to patch the periurethral fascia. When stress incontinence is demonstrated by preopera-
tive urodynamics, the placement of a concomitant pubovaginal sling serves a dual role:
to correct the underlying stress incontinence and to patch the fascial defect (11).
Potential postoperative complications include urethrovaginal fistula development and
recurrence of the diverticulum. The true incidence of diverticula recurrence remains
unknown. In one effort to assess such complications, Ganabathi et al.’s case series of 56
transvaginal diverticulectomy patients reported complications that included urethrovaginal
fistula in 1.7%, recurrent diverticula in 3.5%, and transient early urinary tract infections
in 10.7% (19).
PATHOLOGY
Surgical management of urethral diverticula may be complicated or altered by co-
existing pathology, such as calculi or tumors. Urinary stasis and infection facilitate the
formation of stones, which can be identified in up to 10% of cases. Wang and Wang
reported 7.7% of women undergoing diverticulectomy were found to have calculi
within the diverticular cavity (21).
Carcinoma arising from a urethral diverticulum was first reported by Hamilton and
Leach in 1951 (42). Unlike primary urethral carcinomas, which are most commonly
squamous cell in origin, those arising from a urethral diverticulum are more likely to be
either adenocarcinoma or transitional cell carcinoma. In a review of 59 cases of urethral
diverticular carcinoma, Clayton et al. reported adenocarcinoma in 56%, transitional cell
in 29%, and squamous cell in 15% (43). The most common presenting symptom was
urethral bleeding in 51% of patients.
There is no consensus regarding optimal treatment strategies as female urethral
carcinoma is such a rare entity. Experience with treatment regimens have spanned the
gamut of diverticulectomy alone, radiation alone or after diverticulectomy, anterior
exenteration, and chemotherapy with radiation (44,45). In a review of the collective

experience reported in the medical literature, Rajan et al. described the presentation,
treatment, and outcomes of 68 cases. Rajan et al. concluded that anterior exenteration
with total urethrectomy and wide vaginal wall excision appeared to be more successful
than diverticulectomy alone, radiation, or combination therapy (45).
CONCLUSION
Although still believed to be a rare clinical entity, urethral diverticulum should be
suspected in a woman presenting with long-standing irritative voiding symptoms. A
detailed history and physical exam, along with appropriated diagnostic studies, can
elucidate the diagnosis. With further advancements in imaging technology, the ability to
detect urethral diverticula and plan surgical treatment should continue to improve. Prior
to surgical management with diverticulectomy, evaluation for concomitant stress urinary
incontinence is imperative for successful outcomes. In addition, knowledge of compli-
cating factors and diverticular pathology aids in successful surgical management.
CASE 1
U. D., a 28-yr-old African-American woman in otherwise excellent health, described
the onset of several days of voiding symptoms, namely, dysuria, frequency, urgency,
hesitancy, and weak stream. By the time she presented to her local emergency room, she
complained of lower abdominal pain, urgency, and inability to void with significant
straining. CT scan of the abdomen and pelvis was notable for a markedly distended
bladder and a fluid-filled structure, measuring approx 3 × 4 cm, just below the base of the
bladder. A urethral Foley catheter was placed and evacuated a 1000-mL bladder volume.
The patient was then referred for subspecialty urology care at our clinic. With the
urethral Foley catheter still in place, a urethral MRI was performed a few weeks later.
This demonstrated the same predominantly fluid-filled structure just below bladder
neck (see Fig. 1), consistent with a large proximal urethral diverticulum. The thick-
walled diverticulum was circumferential and measured 3.7 × 3.6 cm. The diverticulum
ostium appeared to be located at the left posterolateral aspect. With this anatomic
delineation of the urethral diverticulum, we then proceeded with transvaginal urethral
diverticulectomy soon afterward. Postoperatively, a pull-out urethrogram demonstrated
no evidence of contrast extravasation, and the patient remains asymptomatic.
CASE 2
N. C. is a 60-yr-old Caucasian woman who presented for evaluation of repeated
flare-ups of lower urinary tract symptoms, namely, vaginal pressure, urgency, and
dysuria. The patient reported that she was diagnosed with urethral stenosis in the 1970s,
for which she had undergone periodic urethral dilations. At that time, evaluation had
included unremarkable intravenous pyelography and cystoscopy. Whereas in the past
urethral dilations appeared to quell her symptoms, more recent urethral dilations by her
local urologist had exacerbated the above-described dysuria, urgency, and nagging
sensation of vaginal pressure.
Between symptom flares, the patient described normal voiding patterns without
dysuria, incontinence, and postvoid dribbling. She was not sexually active. Her exam
demonstrated normal external genitalia. The anterior vaginal wall was well supported
Fig. 1. Sagittal magnetic resonance imaging shows this large circumferential proximal urethral diver-
ticulum, just below the bladder base, causing urethral obstruction symptoms.
without palpable urethral mass or cystic structure. No discharge was emitted from the
urethral meatus during exam.
Although the patient did have a history of sporadic documented urinary tract infections,
her urine culture from this evaluation was negative. Office cystoscopy was unremarkable
for bladder pathology, urethral stricture, or suggestion of urethral diverticulum. The
patient continued to experience waxing and waning lower urinary tract symptoms,
mostly nagging urethral pressure, with episodic urgency and frequency of urination. She
voiced her frustrations with the unpredictable nature of her symptoms.
At this point, a urethral MRI was ordered (see Fig. 2). The MRI demonstrated a
small, 2- to 3-mm focus of high signal intensity adjacent to the urethra on T2-weighted
images, which appeared consistent with a small urethral diverticulum.
Given the small size of this lesion, surgical excision was not deemed feasible.
Conservative management has helped to control the symptoms.
Fig. 2. Magnetic resonance image of patient described in Case 2. T2-weighted fast spin echo image
in coronal plane shows the small focus of high signal intensity adjacent to the midurethra, consistent
with a urethral diverticulum.
CASE 3
M. X. is a 21-yr-old Caucasian woman with a 2-yr history of lower urinary tract
symptoms. She distinctly recalled that her problem began 2 yr ago with the acute onset
of vaginal swelling, and a bulge developed. She described intermittent voiding symptoms
(urinary hesitancy, intermittency), as well as dysuria, postvoid dribble, and dyspareunia.
However, what she initially believed to be a bout of cystitis yielded repeatedly unremark-
able urinalyses and cultures. She was seen and treated by a number of specialists for
possible interstitial cystitis and possible endometriosis. Despite trials of overactive bladder
pharmacotherapy, cystoscopic hydrodistension, and a course of intravesical dimethyl
sulfoxide, the patient was no better.
She presented to our subspecialty clinic at the university for consultation. In addition to
the above-described lower urinary tract symptoms, the urine dipstick was unremarkable.
Fig. 3. (A) Transverse plane; (B) coronal planes. For the patient described in Case 3, two magnetic
resonance images reveal the small, 5 × 10 mm midurethral diverticulum just left of the midline axis.
Physical exam revealed a tender urethra with a small cystic mass deviating the meatus.
Therefore, a urethral MRI was ordered (see Fig. 3). This demonstrated a 5 × 10 mm
midurethral diverticulum just left of midline. Given the relatively small size of this
lesion, we opted to try conservative management for 4 wk. However, because her symp-
toms were not much improved, operative urethral diverticulotomy was performed. This
offered significant relief of her lower urinary tract symptoms. However, the patient does
understand that a symptomatic diverticulum may recur in the future.
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1. Hey W. Practical Observations in Surgery, Humphreys, Philadelphia, 1805, p. 303.
2. Davis HJ, Cian LG. Positive pressure urethrography: a new diagnostic method. J Urol 1956; 75:753–757.
3. Routh A. Urethral diverticula. Obstetrical Society of London. BMJ 1890;1:361–362.
4. Johnson CM. Diverticula and cysts of the female urethra. J Urol 1938;39:506–516.
5. Huffman JW. The detailed anatomy of the paraurethral ducts in the adult human female. Am J Obstet
Gynecol 1948;55:86 –101.
6. Hoffman MJ, Adams WF. Recognition and repair of urethral diverticula: a report of 60 cases. Am
J Obstet Gynecol 1965;92:106 –109.
7. Kim B, Hricak H, Tanagho EA. Diagnosis of urethral diverticula in women. Value of MR imaging.
AJR 1993;161:809–815.
8. Leach GE, Sirls LT, Ganabathi K, et al. LNSC3: a proposed classification system for female urethral
diverticula. Neurourol Urodyn 1993;12:523–531.
9. Lang EK, Davis HJ. Positive pressure urethrography: a roentogenographic diagnostic method for urethral
diverticula in the female. Radiology 1959;108:401–405.
10. Ginsburg D, Genadry R. Suburethral diverticulum: classification and therapeutic considerations.
11. Leng WW, McGuire EJ. Management of female urethral diverticula: a new classification. J Urol 1998;
160:1297–1300.
12. Davis BL, Robinson DG. Diverticula of the female urethra: assay of 120 cases. J Urol 1970;104:850–853.
13. Andersen FJF. The incidence of diverticula in the female urethra. J Urol 1967;98:96–98.
14. Fortunato P, Schettini M, Gallucci M. Diverticula of the female urethra. BJU 1997;80:628–632.
15. Romanzi LJ, Groutz A, Blaivas JG. Urethral diverticulum in women: diverse presentations resulting
in diagnostic delay and mismanagement. J Urol 2000;164:428–433.
16. Gerrard ER, Lloyd LK, Kubricht WS, Kolettis PN. Transvaginal ultrasound for the diagnosis of urethral
diverticulum. J Urol 2003;169:1395–1397.
17. Jacoby K, Rowbotham RK. Double balloon positive pressure urethrography is a more sensitive test than
voiding cystourethrography for diagnosing urethral diverticulum in women. J Urol 1999;162:2066–2069.
18. Rufford J, Cardozo L. Urethral diverticula: a diagnostic dilemma. BJU 2004;94:1044–1047.
19. Ganabathi K, Leach GE, Zimmern PE, Dmochowski R. Experience with the management of urethral
diverticulum in 63 women. J Urol 1994;152:1145–1452.
20. Davis HJ, Telinde RW. Urethral diverticula: an assay of 121 cases. J Urol 1958;80:34–39.
21. Wang AC, Wang CR. Radiologic diagnosis and surgical treatment of urethral diverticulum in women:
a reappraisal of voiding cystourethrography and positive pressure urethrography. J Reprod Med 2000;
45:377–382.
22. Golumb J, Leibovitch I, Mor Y, Morag B, Ramon J. Comparison of voiding cystourethrography and
double-balloon urethrography in the diagnosis of complex female diverticula. Eur Radiol 2003;
13:536–542.
23. Lee TC, Keller FS. Urethral diverticulum: diagnosis by ultrasound. AJR 1977;128:691–691.
24. Siegel CL, Middleton WD, Teefey SA, Wainstein MA, McDougall EM, Klutke CG. Songraphy of the
female urethra. AJR 1998;170:1269–1274.
25. Chancellor MB, Liu JB, Rivas DA, Karasick S, Bagley DH, Goldberg BB. Intraoperative endo-luminal
ultrasound evaluation of urethral diverticula. J Urol 1995;153:72–75.
26. Lorenzo AJ, Zimmern P, Lemack GE, Nurenberg P. Endorectal coil magnetic resonance imaging for
diagnosis of urethral and periurethral pathologic findings in women. Urology 2003;61;1129–1133.
27. Kim B, Hricak H, Tanagho EA. Diagnosis of urethral diverticula in women: value of MR imaging.
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28. Neitlich JD, Foster HE, Glickman MG, Smith RC. Detection of urethral diverticula in women: com-
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29. Blander DS, Rovner ES, Schnall MD, et al. Endoluminal magnetic resonance imaging in the evalua-
tion of urethral diverticula in women. Urology 2001;57:660 –665.
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communicating intraurethral wall diverticula in women. J Urol 1999;161:1259–1261.
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of female urethral diverticula: initial experience. AJR 2005;184:1594–1596.
32. Chou CP, Huang JS, Yu CC, Pan HB, Huang FD. Urethral diverticulum: diagnosis with virtual CT
urethroscopy. AJR 2005;184:1889–1890.
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34. Mizrahi S, Bitterman W. Transvaginal, periurethral injection of polytetrafluoroethylene (polytef) in the
treatment of urethral diverticula. Br J Urol 1988;62:280.
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in women. Surg Gynecol Obstet 1988;167:191–196.
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51:90 –97.
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44. Awakura Y, Nonomura M, Itoh N, Maeno A, Fukuyama T. Adenocarcinoma of the female urethral
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and review of management. J Urol 1993;150:1911–1914.
1 Recurrent Stress Urinary Incontinence
A 45-yr-old woman with pure stress urinary incontinence underwent a synthetic

midurethral sling. Postoperatively, she continued to have significant incontinence
requiring six heavy pads per day. A bulking agent was tried without any improvement.
Valsalva leak-point pressure is 38 cm H2O. She had minimal urethral mobility.
How would you proceed with management of this patient? Any thoughts on why she
may have failed the initial procedures?
COMMENTARY BY JERRY BLAIVAS, MD

This woman has significant incontinence, as evidenced by saturating six heavy pads
a day. She has a low leak-point pressure (38 cm H2O), indicative of severe sphincteric
incontinence and minimal urethral hypermobility.
First, to dispense with the necessities, treatment of incontinence is elective, and after
two failed procedures, the patient might elect to use pads or adopt behavioral techniques
specifically designed to improve the incontinence. They may suffice but will not cure
the condition.
In our judgment, treatment of persistent stress incontinence depends as much (or more)
on the experience and expertise of the surgeon as it does on the underlying pathophy-
siology of the incontinence. What we recommend is based on our personal experience,
not the literature. We do some things better than the literature reports; we do other things
worse, so we try to do what we do best.
For patients with little or no urethral hypermobility and low leak-point pressure, we
believe that slings work much better than all other procedures. So, we would do another
sling, and in our hands, it would be an autologous rectus fascial sling. We harvest the
sling through a 6- to 8-cm skin incision just below the pubic hairline. The resulting scar
is usually invisible (to all except those who shave their pubic hair).
The sling should be about 2 cm wide and long enough so that both ends are well into
the retropubic space (usually about 8 cm). We place the sling at the bladder neck with
no tension, and even in a patient like this, we expect to get two fingers between the rectus
fascia and the suture, tying the two ends of the sling together over the fascia; we do not
try to make the sling tighter than usual just because she has failed two procedures. We
test bladder neck mobility by pulling up on the sutures attached to either end of the
sling, and if there is restricted mobility, we do a partial (posterior and lateral) urethro-
lysis. We do not routinely look for or incise the synthetic sling unless it is in the way of
the surgery. Of course, cystoscopy and vaginal inspection should be routinely performed;
if there is urethral or vaginal erosion, as much as possible of the synthetic sling should
be removed.

343
344 Part III / Case Studies
Fig. 1.
Can another synthetic sling be done instead? I suppose so, but not by us.
SOURCES
Blaivas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract sympto-
matology. Neurourol Urodyn 2000;19:553–554.
Chaikin DC, Rosenthal J, Blaivas JG. Pubovaginal fascial sling for all types of stress urinary incontinence:
long-term analysis. J Urol 1998;160:1312–1316.
EDITOR’S COMMENTS BY HOWARD B. GOLDMAN, MD

There are a number of different ways that treatment for this patient can be
approached, but my personal approach would be similar to that of Dr. Blaivas. One has
to wonder what degree of mobility and intrinsic sphincteric deficiency this patient had
before the original midurethral synthetic sling was placed. There is evidence that the
success rates of midurethral synthetic slings decrease with less urethral mobility. On the
other hand, there have been some reports showing equivalent outcomes in patients with
hypermobility and those without. Whichever side of that debate one wants to take and
though it may have been reasonable to try a midurethral sling the first time, probably at
this point with significant intrinsic sphincter deficiency and minimal mobility a differ-
ent procedure would be advised. I believe that an autologous fascial sling remains the
gold standard and is what I would do as well in this case.
2 Recurrent Urinary Tract Infections
and Pelvic Organ Prolapse
A 65-yr-old woman presents with a history of chronic urinary tract infections (UTIs)
for the past 8 mo. As soon as appropriate antibiotics are stopped, she gets another UTI.
Antibiotic prophylaxis has not helped. She also notes recent onset of some urge incon-
tinence and straining to void. On exam, she has significant atrophic vaginitis and a cys-
tocele to the introitus with strain. There is a question of some apical prolapse as well.
Postvoid residual (PVR) is 180 cc.
How would you evaluate and manage this woman?
COMMENTARY BY JENNIFER TAKACS, MD

AND PHILIPPE ZIMMERN, MD
In the evaluation of this patient, additional information needs to be extrapolated from
her history regarding possible mechanisms for her chronic UTIs. Key history items
include presence of general risk factors for recurrent UTI, such as diabetes mellitus,
immunosuppression, or any apparent neurological conditions that could either affect
bladder function and contribute to her PVR or render her more susceptible to a UTI and
to its recurrence. Localized risk factors such as a history of prior gynecological or
incontinence procedure or both are also important, not only for developing a differen-
tial diagnosis, but also for planning surgical intervention.
Because it is common for patients to be vague regarding the nature and extent of a prior
pelvic or anti-incontinence procedure, it is best to retrieve the operative notes and review
them carefully for undisclosed bladder injuries, types of sutures used (absorbable vs non-
absorbable), and possible synthetic material (e.g., polypropylene sling, prior cystocele
repair with mesh interposition). In a prospective study to evaluate the presence and associ-
ation of risk factors in postmenopausal women referred to an infectious disease clinic for
evaluation of recurrent UTI and compared to age-matched controls, PVR, reduced urine
flow, history of urogynecological procedures, incontinence, and cystocele were associated
with recurrent UTIs (1). Finally, in this patient with a large residual, it is also important to
inquire about medications that could reduce detrusor contractility such as anticholinergic
drugs or antidepressants. Cessation of these medications could improve voiding.
Based on the reported physical examination, we assume that this patient has not
undergone prior incontinence or gynecological procedures. If she had such procedures,
then location of vaginal scars and degree of urethral mobility would be particularly
important to assess. In this patient with prolapse to the introitus with strain, the bulging
vaginal wall must be carefully inspected for mucosal ulcerations because such finding
may preclude the use of a synthetic mesh for repair. Ulcerations and atrophic vaginal

345
tissue changes can be improved by topical estrogen replacement therapy prior to surgical
repair (2).
Although uncommon, large multiloculated urethral diverticuli or urethral leiomyoma
can distort the anterior vaginal wall to the point of mimicking a cystocele. Therefore,
palpation for a mass, tenderness, or expression of purulent material is recommended.
The examination would be completed by Pelvic Organ Prolapse Quantification
measurements and possibly using a handheld mirror to allow the patient to visualize her
prolapse.
At the initial visit, we would obtain a urine culture and initiate low-dose antibiotic
prophylaxis during the coming weeks to prevent another UTI while the patient is under-
going further testing. If atrophic vaginitis was the sole etiology for her recurrent
UTIs, then topical estrogens might decrease the number of recurrences (3). However, in
this patient with straining to void, a cystocele with apical prolapse, and a large PVR, this
would not be sufficient, and further testing is warranted, including a complete urological
work-up and a more focused assessment of the prolapse as a possible etiology of this
patient’s recurrent UTIs.
Routine evaluation of recurrent UTIs includes upper tract imaging (i.e., renal ultrasound
or intravenous pyelogram) and lower tract evaluation with cystoscopy. Renal ultrasound
will exclude an unsuspected upper tract pathology (tumor, stone) or some element of
hydronephrosis. Uni- or bilateral hydronephrosis has been reported with a large (Baden
Walker grade 4 or stage IV) cystocele, but its clinical degree here seems insufficient to
explain such a finding, therefore continued evaluation to identify the etiology would
be recommended. Cystoscopy will evaluate the urethra for inflammatory polyps at the
bladder neck or areas of pus or urethritis; specific attention should be paid to identification
of a diverticular os or glandular secretions, which may be enhanced by palpation and
milking of the anterior vaginal wall. Then, the bladder wall will be inspected for presence
of bladder wall trabeculations, tumor, stone, foreign body, or areas of cystitis. Urine
cytology may be indicated if carcinoma in situ is suspected. Discovery of a bladder calculi
or tumor would require standard urological intervention.
Assuming no prior surgery, a normal neurological examination, no general risk factors,
and a completely negative urological work-up of the upper and lower urinary tracts,
further evaluation of the cystocele as a possible source for these recurrent UTIs would
be pursued and could include pelvic ultrasound, standing cystogram (voiding cysto-
urethrography [VCUG]), or a urodynamic study (UDS) with and without prolapse
reduction. Pelvic ultrasound is important to evaluate the size, appearance, and position of
the uterus and ovaries. This establishes whether there are abnormalities of these organs
that could influence the decision and approach to corrective surgery of this cystocele
and apical prolapse.
The VCUG may identify reflux, define the bladder contour and degree of trabecula-
tions, and discover a urethral diverticulum on the voiding or postvoid views. In addition,
the VCUG will provide objective documentation regarding the degree of bladder prolapse
in the standing position, comparing lateral views at rest and with straining and the same
for the urethral support. This patient with prolapse to the level of the introitus would
likely have a grade II cystocele on VCUG, with a bladder base descent at 2–5 cm below
the inferior ramus of the pubic symphysis (4) (Fig. 1). Around 6 mo postoperatively, a
repeat VCUG may be helpful to document correction of the cystocele, adequate urethral
support, and improved bladder emptying, especially in a woman with continuing UTIs for
whom the concern may be that the repair was not successful (5).
Case 2 / Recurrent Urinary Tract Infections and Pelvic Organ Prolapse 347
Fig. 1. Voiding cystourethrography demonstrating a grade 2 cystocele (grade 1: 0–2cm; grade

2: 2–5cm; grade 3: >5 cm5). (A) Lateral view with straining at capacity. (B) AP view of post-
voidal residual.
Because this patient has new onset of urge incontinence and straining to void, UDS
may assist in determining the etiology of her lower urinary tract symptoms and the
mechanism for her PVR. In this situation, the goals of UDS are to unmask stress incon-
tinence by cough or Valsalva maneuvers, detect detrusor overactivity during filling, and
then assess detrusor contractility during voiding. Cystocele reduction is recommended
to undo the mechanical kinking at the urethrovesical junction. To limit patient interfer-
ence during the test, we have used a vaginal pack gauze but pessary, sponge-stick, hand,
or speculum reductions have all been reported.
The importance of knowing the contractile state of the bladder is critical in managing
the urethral outlet, especially if stress urinary incontinence is unmasked by prolapse
reduction. In the presence of a hypo- or acontractile bladder or in a Valsalva voider,
increasing urethral resistance with a sling would place the patient at high risk for
permanent urinary retention postoperatively. Obstruction, as suggested by a high
detrusor pressure at peak flow with an associated low flow rate (6), should resolve once
the bladder and urethra are surgically returned to a more normal anatomic position.
Detrusor overactivity is often undetected during conventional UDS without triggering
maneuvers. However, its detection linked to urge incontinence should serve in preoper-
ative counseling as it may indicate some permanent bladder wall changes that may or
may not improve after bladder repair.
After review of some or all of these tests, and assuming that the cystocele is the pre-
sumed source of her UTIs by inducing chronic retention, that she has normal detrusor
parameters on UDS and no abnormal uterine or ovarian findings on pelvic ultrasound,
we would discuss with this patient a hysterectomy and bilateral salpingo-oophorectomy
by our gynecology team, followed by an anterior vaginal wall suspension (7) and vault
support repair. We recognize that there are a number of different techniques that could
be used to correct her anatomic defects, including transvaginal, laparoscopic, and
abdominal approaches alone or with a variety of tissue interposition; their advantages
and risks are beyond the scope of this case discussion.
Postoperatively, this patient’s PVR should be carefully monitored. Straining to void
could contribute to prolapse recurrence and should be avoided. In rare instances when
UTIs continue despite a successful repair of the cystocele, no urinary incontinence, no
or limited PVR, and a normalized voiding pattern, a complete reassessment may be
needed. Some patients who were bothered by the cystocele preoperatively may have
subsequently returned to sexual activity. If a relationship between UTI and intercourse
is noted, then coital prophylaxis should be considered. When urgency and urge inconti-
nence persist despite an adequate cystocele repair, anticholinergic medications can be
useful, but in this older woman PVR should be monitored at regular intervals to confirm
adequate bladder drainage.
REFERENCES
1. Raz R, Gennesin Y, Wasser J, et al. Recurrent urinary tract infections in postmenopausal women. Clin
Infect Dis 2000;30:152–156.
2. Klutke JJ, Bergman A. Hormonal influence of the urinary tract. Urol Clin North Am 1995;22:629.
3. Raz R, Stamm W. A controlled trial of intravaginal estriol in postmenopausal women with recurrent
urinary tract infections. N Engl J Med 1993;329:753–756.
4. Zimmern PE. The role of voiding cystourethrography in the evaluation of the female lower urinary
tract. Problems Urol 1991;5:23–41.
5. Showalter PR, Zimmern PE, Roehrborn CG, Lemack GE. Standing cystourethrogram: an outcome
measure after anti-incontinence procedures and cystocele repair in women. Urology 2001;58:33–37.
Case 2 / Recurrent Urinary Tract Infections and Pelvic Organ Prolapse 349
6. Defreitas G, Zimmern P. The role of urodynamics in women with stress urinary incontinence. EAU
Update Series 2003;1:135–144.
7. Wilson TS, Zimmern PE. Anterior vaginal wall suspension. In: Female Urology, Urogynecology,
and Voiding Dysfunction (Vasavada SP, Appell RA, Sand PK, Raz S, eds.), Dekker, New York: 2005,
p. 283.
EDITOR’S COMMENTS BY SANDIP P. VASAVADA, MD

Dr. Takacs and Dr. Zimmern have nicely discussed a variety of potential evaluations as
well as therapeutic options for a patient with prolapse in the setting of incomplete
emptying and recurrent UTIs. It is often difficult to evaluate a patient who has mild-
to-moderate prolapse, and is not emptying the bladder well. We should always remember
that a spot or a single postvoid residual measurement may not be completely indicative
of the entire situation for a patient’s voiding dysfunction. Therefore, the residual urine
should often be retested to ensure that this is truly the case, such as in this patient’s
situation for which she had a 180-cc residual. Certainly, this can be impacted by her
prolapse; however, one must also be certain to eliminate other causes, including detrusor
hypocontractility or certainly upper tract causes, as was nicely reviewed by the discussants.
It seems that when conservative measures fail, operative intervention may be required,
and the patient should be appropriately counseled that she may still have problems in
the future but she should empty better once the prolapse is corrected. It should help
reduce the likelihood of continued infections as well.
3 Mixed Incontinence
A 57-yr-old woman presents with significant mixed incontinence requiring six heavy
pads per day. She says both aspects of the incontinence (stress urinary incontinence
[SUI] and urge incontinence [UI]) are equally bothersome. She has failed pelvic floor
exercises and multiple anticholinergics. Physical exam reveals no prolapse, but she does
have some urethral hypermobility. No other testing has been done.
How would you proceed with your evaluation and treatment?
COMMENTARY BY WACHIRA KOCHAKARN, MD, FACS

This patient presents with mixed incontinence, and both of the symptoms (stress
and urge) are equally bothersome. Both pelvic floor exercises and anticholinergic
medications have failed to improve her symptom complex. To improve her quality of life
and keep her dry, further investigation and treatment will be needed. Surgical treatment,
in particular cystourethropexy, should be considered. The pubovaginal sling is my pre-
ference because many studies have shown acceptable results with long-term follow up
(1). Morgan and colleagues treated 247 patients with mixed incontinence and reported
an 88% continence rate, with more than 90% having a high degree of satisfaction after
4 yr of follow-up (2). Schrepferman et al. (3) also reported a success rate of 91.3% after
cystourethropexy for mixed incontinence as well as with motor urge with low-amplitude
detrusor overactivity.
The mechanisms of mixed incontinence are unclear, but we find that 35–65% of
patients with stress incontinence have subjective urgency or abnormal detrusor contractions
during conventional urodynamic testing (4). Petros and Ulmsten (5) found a sudden
decrease in urethral pressure following the onset of urge symptoms with a rising detrusor
pressure. They concluded that supporting the urethra with a sling could improve urge
symptoms in this group of patients. However, the tension-free vaginal tape (TVT) or
other minimally invasive procedure with a similar mechanism did not work well in the
patients with mixed incontinence. Farrell and Halifax reported a high failure rate of
81.2% after TVT procedure in the patients who had mixed incontinence (6).
Biologic pubovaginal slings can be harvested from autologous rectus fascia or fascia
lata. Cadaveric fascia is commercially available and can be used depending on the
patient’s preference and the surgeon’s expertise. However, in my hands, I almost
always use autologous rectus fascia as the sling material and have had minimal compli-
cations (7).
Before the procedure is performed, routine laboratory tests, including urine examination
to check for infection or hematuria, should be performed. Abdominopelvic ultrasono-
graphy is another test that should be included, and a postvoid residual urine volume can

351
Fig. 1.
be estimated. Significant residual urine (more than 100 mL) may result from other
pathology, such as neuropathic bladder dysfunction, that mimics symptoms similar to
those of mixed incontinence (8).
A multichannel urodynamic study should be done, and abdominal leak-point pressure
measurement should be recorded. Many studies have shown that leak-point pressure and
presence or absence of abnormal detrusor contractions are two important factors that
predict the outcome after treatment (3,4). The patients with low-amplitude detrusor
overactivity showed higher success rates than those with high-amplitude detrusor over-
activity (3,4). Regarding leak-point pressures, some surgeons have reported using
alternative techniques, such as bladder neck suspension or a TVT procedure, if urody-
namic testing shows high leak-point pressures (greater than 90 mL H2O) (9). However,
we do not have long-term results of TVT in this specific (mixed) group of patients and
thus must have a fully informed discussion with the patient, weighing pros and cons of
a TVT or similar procedure in such a setting.
Overall then, my preference for a patient with mixed incontinence who has
already failed conservative therapy for the urge component is to proceed with an
autologous rectus fascial sling to treat the SUI with the knowledge that a significant
number of these patients will also note a diminution in their urge problem after such
surgery.
Case 3 / Mixed Incontinence 353
REFERENCES
1. Chou E, Flisser A, Panagopoulos G, Blaivas J. Effective treatment for mixed urinary incontinence with
pubovaginal sling. J Urol 2003;170:494–497.
2. Morgan TO, Westney OL, McGuire EJ. Pubovaginal sling: 4-yr outcome analysis and quality of life
3. Schrepferman CG, Griebling TL, Nygaard IE, Kreder KJ. Resolution of urge symptoms following
sling cystourethropexy. J Urol 2000;164:1628–1631.
4. Heslington K, Hilton P. The incidence of detrusor instability by ambulatory monitoring and conven-
tional cystometry pre and post colposuspension. Neurourol Urodyn 1995;14:416–417.
5. Petros PE, Ulmsten U. Bladder instability in women: a premature activation of the micturition reflex.
6. Farrell SA, Halifax NS. Tension-free vaginal tape (TVT) procedure. J Obstet Gynecol Can
2003;25:692–694.
7. Kochakarn W, Leenanupunth C, Ratana-Olarn K, Roongreungsilp U, Siripornpinyo N. Pubovaginal
sling for the treatment of female stress urinary incontinence: experience of 100 cases at Ramathibodi
Hospital. J Med Assoc Thai 2001;84:1412–1415.
8. Milleman M, Langenstroer P, Guralnick ML. Post-void residual urine volume in women with overac-
tive bladder symptoms. J Urol 2004;172:1911–1914.
9. Osman T. Stress incontinence surgery for patients presenting with mixed incontinence and a normal
cystometrogram. BJU Int 2003;92:964–968.
COMMENTARY BY GARY E. LEACH, MD

This patient is not unusual in that about 60% of the women we have operated on for
SUI have some component of urgency (mixed incontinence) with a predominance of
stress symptoms. The difficult aspect of this situation is that she states that her symptoms
are evenly “split” between both urge incontinence and stress incontinence. In recent
studies (in press), we have found that the urge component resolves in about 70% of
women following a sling procedure, with 30% having continued urgency following the
sling. Also, when we have examined the “predictors” of failure following a sling proce-
dure, the only preoperative variable that clearly correlated with a less-than-satisfactory
postoperative outcome was the presence of preoperative urge incontinence.
Given these findings, I would clearly prefer to control this patient’s urge symptoms
as the initial step in management, followed by treatment of the stress incontinence (if
necessary) once the urgency is controlled. Before embarking on treatment, I would also
perform a detailed multichannel urodynamic study to clearly define the causes of her
incontinence (i.e., demonstrate SUI, evaluate the presence of detrusor instability [DI],
and evaluate the patient’s ability to empty her bladder). However, many patients have
complaints of urgency and urge incontinence with a totally stable bladder on urody-
namic evaluation (UDE). The stable bladder on the UDE does not mean the patient does
not have DI, it just means that the DI was not seen during the study. When the patient
has major complaints of urge or urge incontinence, the presence or absence of DI on the
urodynamic study does not influence our treatment recommendations.
Control of Urgency/Urge Incontinence

In addition to standard oral anticholinergic medications, there is a variety of additional
treatments that can help control the urgency and frequency symptoms. These treatments
include dietary modification (i.e., avoiding foods/drinks that tend to irritate the bladder,
limiting fluid intake); computer-assisted pelvic floor training/biofeedback; vaginal
estrogen cream in those women with atrophic vaginitis; and following a timed voiding
program. When these additional measures in combination with standard anticholinergic

therapy do not control the urgency symptoms, we frequently add a second medication
(10 or 25 mg imipramine three times a day) to the treatment program. When this program
is not effective, consideration is given to a trial of the Interstim bladder pacemaker device.
The Interstim device is placed initially as a test stimulation with the tined lead
placed under fluoroscopic control adjacent to the S3 nerve root as an outpatient proce-
dure under local anesthesia. The patient wears an external stimulation device attached
to the tined lead for 7–10 d to gage the response to neurostimulation with a
voiding/incontinence diary. When the patient returns in 1 wk, the response to the
Interstim is evaluated.
When the patient has significant improvement in her urgency symptoms with
neurostimulation (seen in approx 70%), the Interstim generator is implanted as a sec-
ond-stage outpatient procedure under local anesthesia. Should the patient have
complaints of significant residual SUI following the Interstim procedure, the UDE
would be repeated to document the presence of SUI and adequate bladder volume with
a stable bladder.
Should the patient not respond to the first-stage Interstim trial, the stimulation electrode
is removed, and a trial of Botox injection (200–300 U) into the bladder wall could be con-
sidered. In our experience, approx 50% of patients respond to the Botox, with a maximum
response time of 6 mo and with a small risk of short-term post-Botox retention.
Treatment of Stress Urinary Incontinence

After Control of Urgency Symptoms
Commonly, the degree of residual SUI following control of the urge symptoms is a
minimal problem and frequently well tolerated by the patient who is experiencing
significant improvement in quality of life. When the residual SUI with urethral hyper-
mobility is a significant problem for the woman, our surgical procedure of choice is a
sling procedure. We have had extensive experience with the CATS procedure (transvaginal
sling with bone anchors and nonfrozen cadaveric fascia lata). With maximum follow-up
of more than 6 yr, the SUI recurrence rate is 11%. More recently, we have utilized the
transobturator synthetic sling with early encouraging results.
Summary
When urge symptoms either predominate or are equivalent to the stress symptoms in
the woman with mixed incontinence, control of urgency symptoms before treatment of
SUI is prudent to avoid patient dissatisfaction with the surgical result because of con-
tinued or exacerbated postoperative urgency. When the SUI symptoms predominate, a
sling procedure is performed with a 70% chance that the urge symptoms will be
improved postoperatively. Should the patient be in the 30% group and need postsling
treatment for her urge symptoms, the previously described options are offered.

Typically, if one type of incontinence—either the stress or urge—predominates, it is
relatively simple to know how to proceed. We try to treat the one that is most bother-
some. However, the fact that this patient finds her stress and urge incontinence equally
troubling makes the decision a little more difficult. Although, as Dr. Kochakarn points
Case 3 / Mixed Incontinence 355
out, many patients who have a sling will have resolution of the urge symptoms after the
sling, as Dr. Leach eloquently states those who do not have resolution will frequently
feel that their sling procedure was not effective.
In my practice, I would attempt to treat the urge component in a similar fashion as
Dr. Leach. However, if the stress component seems particularly significant, I would con-
sider doing a sling prior to proceeding with Interstim, with the patient understanding
that there is a high likelihood that she will need an Interstim after the sling. In some
cases, if the urge component resolves after the sling, that is all that needs to be done. In
the other cases when they have continued urge symptoms, we proceed with the Interstim
within a few months of the sling.
Occasionally, if someone has significant stress incontinence it can make it hard to
interpret the results of the test stimulation with the Interstim as they are still having sig-
nificant leakage and wearing a significant number of pads because of the SUI and may
not fully realize the benefit of the Interstim. Therefore, by taking care of the stress
incontinence, one may be able to have a more accurate idea of whether the Interstim will
ultimately be beneficial for the urge incontinence.
4 Urinary Tract Infections and Pelvic Pain
A 34-yr-old woman presents with a history of having had her first urinary tract infec-
tion (UTI) 6 mo ago. Since that time, she has had multiple UTI recurrences, dysuria,
pelvic pain, and dyspareunia. Physical exam reveals an area of tenderness along the
distal anterior vaginal wall.
How would you evaluate and treat this patient?
COMMENTARY BY SUZETTE E. SUTHERLAND, MD

Step 1: Physical Exam and Labs
With this history, the suspicion for a symptomatic urethral diverticulum is high. The
differential diagnosis for a suburethral anterior vaginal wall mass can be seen in
Table 1. The first step, however, is to ensure the accuracy of the recurrent UTI diagno-
sis through a review of all typical and atypical urine cultures in the last 6 mo. Following
this, a thorough physical exam should be telling.
Along with tenderness, palpation of the anterior vaginal wall may also reveal a mass,
soft or hard, from which purulent material or urine can be expressed— through the
meatus— on di rect compression of the mass and underlying urethra. Full bimanual
pelvic exam with assessment of baseline tonicity of the pelvic floor musculature is an
important adjunct to possible understanding of the associated development of chronic
pelvic pain in this woman. Repeat pelvic insults (i.e., UTIs, painful intercourse
attempts, persistent inflamed mass) can result in chronic spasticity of the levator muscle
complex, resulting in referred chronic pelvic pain, irritative bladder and bowel symptom,
and vaginismus-related dyspareunia. If all such symptoms are not relieved following
surgical correction of urethral diverticulum, then pelvic floor rehabilitation with
biofeedback and manual manipulative techniques should be considered.
Step 2: Office Cystourethroscopy
Office flexible cystourethroscopy can help document the presence and location of a
urethral ostium, with most located posterolaterally. Concomitant compression of the
anterior vaginal wall mass may aid in ostium localization through direct visualization of
expressed fluid from the opening of the diverticulum. Viewed transvaginally, the mass
may also enlarge during urethral infusion of fluid, thereby confirming the diagnosis of
a communication between the urethra and the mass.
Step 3: Diagnostic Imaging
There are multiple imaging modalities available today to confirm the diagnosis of
urethral diverticulum (see Table 2). Although voiding cystourethrography (VCUG)

357
Table 1
Differential Diagnosis for a Suburethral Anterior Vaginal Wall Mass
Urethral diverticulum
Gartner’s duct cyst
Skene’s gland infection
Solid vaginal wall mass (leiomyoma, schwannoma)
Urethral neoplasm
Mucosal prolapse
Urethral caruncle
Ectopic ureter
Table 2
Diagnostic Studies for Urethral Diverticulum
Cystourethroscopy
Voiding cystourethrogram
Positive pressure urethrography
Transvaginal ultrasonography
Intravenous pyelogram
Pelvic MRI
has traditionally been the initial imaging technique of choice— in terms of sensitivity,
specificity, availability, patient comfort, and cost—
it does not always provide definitive
anatomical information. Retrograde positive pressure urethrography (PPU) with a dou-
ble-balloon catheter has been used for diagnosis since the 1950s and is more sensitive
than VCUG, but it can be uncomfortable for the patient (1,2). Transvaginal ultrasono-
graphy provides a quick, noninvasive means for diagnosis and can help distinguish
multiple diverticula from a single, large, loculated diverticulum. With significant tender-
ness of the anterior vaginal wall, a comfortable evaluation via ultrasound may not be
possible (3). If an ectopic ureter is suspected, then an intravenous pyelogram is certainly
indicated (4).
Owing to its degree of definitive anatomical detail, pelvic magnetic resonance
imaging (MRI) has become the new gold standard for documenting urethral diverticula
(5). A distinct advantage of pelvic MRI is an appreciation for the extent and complex-
ity of the diverticulum about the urethra. Not only does it aid in surgical planning, but
it provides more information to guide preoperative patient counseling concerning the
likelihood of possible postoperative complications (such as urinary incontinence with
large proximal diverticula). Although rare, preoperative visualization of concomitant
intradiverticular pathology (i.e., tumors, stones) is likewise useful (6). For anything
other than a simple, small distal urethral diverticulum that is readily appreciated on
physical exam and office cystourethroscopy, pelvic MRI is my imaging modality of
choice for definitive diagnosis and preoperative planning.
Step 4: Treatment
Total diverticulum excision offers the best long-term outcome in those patients who
are good surgical candidates. A variety of techniques have been described, but the ultimate
surgical goal is complete excision of the diverticular neck and ostium, followed by a
Case 4 / Urinary Tract Infections and Pelvic Pain 359
watertight urethral closure, complete excision or obliteration of the diverticular sac, and
a multilayer closure of the periurethral fascia and vaginal mucosa in as nonoverlapping
suture fashion as possible. Marsupialization provides another viable option for a distal
diverticulum with associated abscess, for which excision would be fraught with conside-
rable difficulty because of the extent of peridiverticular and periurethral inflammation.
REFERENCES
1. Davis JH, Cian LF. Positive pressure urethrography: a new diagnostic method. J Urol 1956;75:
753–757.
2. Wang AC, Wang CR. Radiologic diagnosis and surgical treatment of urethral diverticulum: a re-
appraisal of voiding cystourethrography and positive pressure urethrography. J Reprod Med 2000;45:
377–382.
3. Fontana D, Porpiglia F, Morra I, et al. Transvaginal ultrasonography in the assessment of organic
diseases of the female urethra. J Ultrasound Med 1999;18:237– 241.
4. Blacklock AR, Shaw RE, Geddes JR. Late presentation of ectopic ureter. Br J Urol 1982;54:106– 110.
5. Blander DS, Rovner ES, Schnall MD, et al. Endoluminal magnetic resonance imaging in the evalua-
tion of urethral diverticula in women. Urology 2001;57:660–665.
6. Applewhite JC, Hall MC, McCullough DL. Urethral carcinoma in women. In: Adult and Pediatric
Urology, 4th ed. (Gillenwater JY, Grayhack JT, Howards SS, Mitchell ME, eds.), Lippincott, Williams,
and Wilkins, Philadelphia, 2002, pp. 1800– 1804.

Dr. Sutherland correctly points out the salient diagnostic choices in a patient with a
likely urethral diverticulum. As such, MRI is rapidly emerging as the gold standard not
only to diagnose the diverticulum, but also to evaluate its extent. This second point is
important in that certain diverticula may be amenable to simple excision and closure,
whereas diverticula with more extensive proximal or superior extent (horseshoe or
saddlebag) may require more complex reconstructions with or without addition of
Martius flaps or even pubovaginal slings. Still, half the battle is getting to the proper
diagnosis prior to embarking on therapy.
5 Multiple Sclerosis and Voiding Dysfunction
A 42-yr-old woman with a 10-yr history of multiple sclerosis presents with worsen-
ing voiding complaints. For the past 3 yr, she has had increasing frequency, which was
treated successfully with anticholinergics. Recently, she has noticed worsening urgency
and has also begun to have hesitancy and straining to void. Physical exam is normal.
Postvoid residual (PVR) is 240 cc. Urodynamics demonstrates detrusor overactivity and
detrusor-sphincter dyssynergia (DSD). She voids with a detrusor pressure of 37.7 cm
H2O with a maximum flow of 5.4 cc/s.
How would you evaluate and treat this patient?
COMMENTARY BY E. JAMES WRIGHT, MD

Management of patients with multiple sclerosis and the wide spectrum of symptoms
and voiding dysfunction this disease can cause is a challenge. I think it is helpful to
stratify the type and site of dysfunction to organize treatment strategies and to follow
progress and therapy effects. Multiple sclerosis presents a “moving target” in terms of
voiding dysfunction, and one should remain vigilant and flexible in assessment and
treatment planning. Employing the simple 4 × 4 matrix with headings for bladder, outlet,
storage, and emptying is useful for directing diagnosis and intervention.
In addition to urinary tract assessment, attention in multiple sclerosis should be paid
to bowel function. Difficulties with fecal urgency, fecal incontinence, constipation, and
impaction can be a source of poor quality of life and exacerbation of lower urinary tract
symptoms. Improvement in bowel evacuation and relief of fecal incontinence can assist
the management of voiding complaints.
In this case of a 42-yr-old woman with recent progression of voiding complaints, the
finding of DSD documented on urodynamic testing warrants further evaluation and
therapy. This should include a renal ultrasound study and serum creatinine to ensure
safety of the upper tracts. A 72-h frequency and volume voiding diary may also be helpful.
The patient has difficulty with both urine storage and emptying, and both the bladder
and outlet are involved. The bladder is overactive with the appearance of adequate
contractility but fails to empty efficiently in light of a 240-cc residual volume.
Regarding the urethra and bladder outlet, storage function appears satisfactory.
Emptying is impaired because of DSD. In this context, therapy should be directed at
maximizing bladder storage and reduction of outlet resistance. The dilemma facing this
goal is therapies to improve urine storage often require a trade-off regarding emptying.
Voiding by Valsalva should be discouraged in this patient as it may lead to compro-
mise of renal function and further deterioration of bladder function. An empiric trial of
an F-blocker is reasonable in an effort to decrease outlet resistance and lower voiding
pressures. Although evidence is anecdotal, I have seen improvement in both symptoms

361
Fig. 1.
and urodynamic parameters with F-blockade. When helpful, hesitancy and emptying
efficiency may improve as well as PVR and additional concerns of cystitis and urgency
symptoms.
In progressing along a treatment algorithm, the patient should be told of the difficulty
in restoring completely normal function. When pushed to the side of urine storage, the
balance of voiding function is often most comfortable. A trial of self-catheterization
(SIC) may show that elimination of PVR and voiding against a resistant outlet yields
improvement in bothersome urgency, frequency, and hesitancy. This could be done on a
twice-daily (morning and evening) regimen with increased frequency as necessary to
assess effectiveness. A program of SIC can also be combined with a repeat trial of anti-
cholinergic medication without concern for worsening the emptying side of the equation.
When SIC is undesirable, unfeasible, or ineffective, the intensity of intervention can
be increased. Application of botulinum toxin injection into the external sphincter has
yielded improvement in voiding function for some patients with multiple sclerosis and
DSD. Neuromodulation may also have some benefit for this patient as a way to decrease
the sensory bother from urgency and frequency. Temporary placement of a sacral stim-
ulation lead can allow a therapeutic trial to assess possible benefit.
In conclusion, there is no “one size fits all” in the approach to patients with multiple
sclerosis and resultant voiding dysfunction. Therapy should be tailored to the needs and
abilities of the patient. Preservation of the upper tracts, satisfactory continence, an effec-
tive mechanism for bladder emptying, independence, and a satisfactory quality of life
Case 5 / Multiple Sclerosis and Voiding Dysfunction 363
Table 1
Event Summary
Annotation Time Pves Pabd Pdet EMG EMGR Flow Volume
First sensation 17.9 19 21 2 4 1 0 1
First desire 35.9 19 22 3 5 4 0 1
Strong desire 55.6 21 21 1 10 5 0 0
Image 2:15.9 35 26 9 12 1 0 0
Image 2:23.1 35 27 8 16 4 0 0
Image 2:44.3 51 35 16 16 9 0 0
Image 2:45.7 51 34 17 8 1 0 0
Urge 2:48.7 49 34 15 27 3 0 0
Image 3:33.9 61 30 31 6 1 0 2
Image 3:35.8 59 29 30 6 0 0 2
Uroflow start 4:28.4 64 31 32 49 20 1 5
Peak flow 4:31.1 66 28 38 8 5 5 19
Image 4:34.8 62 28 34 15 10 1 33
Uroflow stop 4:36.7 60 28 32 36 35 1 36
Image 4:37.2 59 28 32 30 17 1 37
Image 4:41.4 53 28 25 12 3 0 38
Image 7:19.5 44 28 16 7 2 0 39
Image 10:18.7 56 35 21 14 5 0 42
Uroflow Summary
Dev (Female)
Maximum flow: 5.4 mL/s ****
Average flow: 4.1 mL/s ****
Voiding time: 8.4 ****
Flow time: 7.5
Time to peak flow: 2.8 ****
Voided volume: 31 mL
Flow at 2 seconds: 4.9 mL/s
Acceleration: 1.5 mL/s/s
Pressure at peak flow: 37.7 cm H2O
Flow at peak pressure: 4.9 mL/s
Mean Pressure: 35.6 cm H2O
PVR: 92 mL
*, moved event.
are the goals of therapy. The principles of managing neurogenic voiding dysfunction
remain the same, but the “recipe” is often unique.

As Dr. Wright notes, patients with multiple sclerosis and bladder dysfunction can
represent a moving target as things can change. In this patient with overactive bladder
and DSD, evaluation and monitoring of the upper tract is important. If the patient has
good manual dexterity and is not opposed to intermittent catheterization, then trying to
put the bladder to rest and instituting intermittent catheterization may be the easiest
approach. If that is unsuccessful or the patient does not desire intermittent catheterization,
then Botox injection into the external sphincter may allow resumption of relatively normal
voiding. Interstim sacral neuromodulation can be useful in this sort of situation, but it
is important to discuss with the patient that she may have difficulties obtaining magnetic
resonance imaging in the future as the presence of an Interstim or similar device is
currently a contraindication to magnetic resonance imaging. In severe cases for which
nothing else works, different types of diversion (e.g., an ileal vesicostomy) have proven
useful for these types of patients.
6 De novo Overactive Bladder Symptoms
After a Sling
A 45-yr-old woman with pure stress urinary incontinence (SUI) undergoes a sling
procedure. Preoperatively, she had no irritative voiding symptoms and no voiding com-
plaints. After the sling is done, she notes some mild increase in her urinary frequency.
At her 6-wk follow-up visit, she complains of onset of urge incontinence requiring two
pads per day. She has no SUI. She notes her stream has slowed a bit since the surgery.
How would you evaluate and treat this patient? Is there really such a thing as de novo
overactive bladder (OAB)?
COMMENTARY BY VICTOR W. NITTI, MD, FACS

This woman is experiencing new-onset urge incontinence, which was preceded by
increased urinary frequency 6 wk after sling surgery for SUI. An additional new symp-
tom is a somewhat slowed urinary stream. De novo, or newly acquired, OAB symptoms
are reported in all types of incontinence surgery, including slings (pubovaginal and
midurethral). De novo OAB symptoms have been reported in 0–14% of sling procedures
(1), but the occurrence of the symptoms appear to be at the lower end for tension-free
vaginal tape (TVT) and other similar procedures. When one considers these symptoms
that did not appear to exist prior to surgery, there are four possible explanations:
1. The symptoms actually did exist before but were masked by the more predominant
stress symptoms. Now that the stress incontinence is cured, the OAB symptoms and
urge incontinence are obvious to the patient.
2. The OAB symptoms truly are de novo and occurred after the operation or even as a
result of the operation. Possible explanations for this include:
a. Surgery, or surgical manipulation, of the lower urinary tract has caused changes
(perhaps based on neurological innervation) that are responsible for the symptoms.
b. Surgery has caused a more obvious problem, such as bladder outlet obstruction,
known to be associated with OAB symptoms. Obstruction requiring intervention has
been reported in about 2–3% of cases of pubovaginal slings and midurethral synthetic
slings (2–4). Erosion of the sling into the bladder or urethra can also cause de novo
OAB symptoms.
3. The apparent urge incontinence is actually persistent SUI but may appear different in
some way to the patient, and thus history is not an accurate representation of the under-
lying cause of the symptoms.
4. The OAB symptoms are caused by an acute problem such as a urinary tract infection
(UTI).

365
In this particular case, voiding has changed slightly, so the suspicion of obstruction
is raised, although many clinically unobstructed patients will complain of a stream that
has slowed a bit. Nevertheless, the suspicion is raised.
As in all cases of incontinence, the evaluation of this patient starts with a good history
and physical exam. Every effort should be made to characterize the new storage and
voiding symptoms and temporal association with surgery. If questionnaires were given
preoperatively that assessed these, then now is a good time to repeat them. Physical
exam should assess for bladder distension, vaginal healing, and prolapse that may have
been missed or become apparent after surgery. A urine analysis should be done to rule
out infection.
Another standard postoperative test is a postvoid residual (PVR). If bladder emptying
is significantly impaired from preoperatively, then this will raise the suspicion of obstruc-
tion. In this case, even if the PVR is in an acceptable range (similar to preoperative), a
noninvasive uroflow can be considered because of the patient’s voiding complaints. With
these simple tests, history, and physical exam, we are armed to make our first decisions
regarding further evaluation or treatment.
Anything obvious, such as a UTI, should be treated and the patient reevaluated. If
there is a problem with healing of the vaginal incision, then this should raise the suspicion
of a problem, such as a vaginal extrusion (especially if synthetic material was used) or
even erosion into the urinary tract. Significant hematuria in the absence of an infection
or recurrent UTIs early in the postoperative period should also raise the suspicion of an
erosion, and cystourethroscopy should be done.
If there are no obvious abnormalities on physical exam and urine analysis, then the
PVR becomes the most important factor in determining how to proceed.
If PVR is significantly elevated (e.g., v 50% of bladder capacity) and this is new, then
obstruction must be suspected. As the possibility of obstruction is just recognized, a
period of drainage (preferably with intermittent self-catheterization) is warranted.
Symptoms and PVR can then be followed for a period of time (usually 2–6 wk) if neces-
sary. Only if self-catheterization is not possible should an indwelling catheter be placed.
If after adequate time has passed the patient continues to be symptomatic and emptying
is still impaired, then consideration to take down the sling by simple incision or urethro-
lysis (if necessary) is warranted. Both procedures have been effective for all types of slings
(4–10). If one has a definite understanding of the patient’s presling voiding and emptying
status and it has clearly changed for the worse, then there is little utility for urodynamic
studies (UDS).
We prefer the simpler sling incision or lysis to formal urethrolysis whenever possi-
ble (i.e., the sling can be clearly identified) as it is less invasive and has comparable
results. For synthetic slings, we feel that the sling must be cut to relieve obstruction
whether or not a formal urethrolysis is done as well. In the early postoperative period,
it is often possible to loosen a midurethral synthetic sling by pulling it down; however,
after 10–14 d this is usually not possible, and the tape must be cut. There are not many
data on the effectiveness of conservative therapy for OAB and, in particular, anticholin-
ergics, in the face of obstruction after incontinence surgery. In our experience, it does
not seem particularly effective if obstruction is not relieved.
If PVR is minimally elevated or unchanged, then uroflow may help to raise or lower
the suspicion of obstruction and proceed with aggressive treatment. However, unless
there are gross changes in uroflow, it is reasonable to treat the OAB symptoms with a
variety of conservative measures (e.g., pelvic floor exercises, anticholinergics, and so on)
Case 6 / De novo Overactive Bladder Symptoms After a Sling 367
if they are bothersome. It is also reasonable to consider watchful waiting if acceptable

to the patient. In many cases, OAB symptoms will resolve over time. If they do not or
if conservative therapy fails, then workup with UDS and cystoscopy is warranted.
It is in those cases for which obstruction is not obvious that UDS probably has its
highest yield. Although it is sometimes difficult to definitively rule in obstruction (e.g.,
the patient cannot void or has low-pressure/low-flow voiding dynamics), it can be ruled
out (e.g., the patient has low-to-normal pressure and normal-to-high-flow voiding
dynamics). Urethrolysis and sling incision have been effective in relieving symptoms
when obstruction is suspected but not urodynamically documented. However, there
are insufficient data regarding the outcomes of such procedures in patients who are
unequivocally unobstructed on UDS. If OAB symptoms persist after successful treatment
of obstruction, then the standard OAB treatments mentioned can be tried.
When OAB symptoms persist despite treatment with appropriate conservative meas-
ures, and obstruction/recurrent obstruction, other treatable causes of OAB, and recurrent
SUI have been excluded (e.g., sling erosion), then second-line therapies such as neuro-
modulation, botulinum type A toxin, and even bladder augmentation can be considered
depending on severity and degree of bother.
REFERENCES
1. Smith ARB, Daneshgari F, Dmochowski R, et al. Surgery for urinary incontinence in women. In
Incontinence (Edition 2005) Third International Consultation on Incontinence (Abrams P, Cardozo L,
Khoury S, Wein A, eds.), Health, Plymouth, UK, 2005, pp. 1297–1370.
2. Chaikin DC, Rosenthal J, Blaivas JG. Pubovaginal fascial sling for all types of stress urinary inconti-
nence: long-term analysis. J Urol 1998;160:1312–1316.
3. Morgan TO, Jr, Westney OL, McGuire EJ. Pubovaginal sling: 4-yr outcome analysis and quality of life
4. Klutke C, Siegel S, Carlin B, Paszkiewicz E, Kirkemo A, Klutke J. Urinary retention after tension-free
vaginal tape procedure: incidence and treatment. Urology 2001;58:697–701.
5. Amundsen CL, Guralnick ML, Webster GD. Variations in strategy for the treatment of urethral
obstruction after a pubovaginal sling procedure. J Urol 2000;164:434–437.
6. Nitti VW, Carlson KV, Blaivas JG, Dmochowski RR. Early results of pubovaginal sling lysis by mid-
line sling incision. Urology 2002;59:47–52.
7. Goldman HB. Simple sling incision for the treatment of iatrogenic urethral obstruction. Urology
2003;62:714–718.
tape for the treatment of refractory postoperative voiding dysfunction. Obstet Gynecol 2002;100:
898–902.
COMMENTARY BY CARL G. KLUTKE, MD AND TRAVIS L. BULLOCK, MD

The majority (30–60%) of women who present with complaints of urinary incontinence
are found to have mixed stress and urge incontinence. The true incidence of isolated
SUI in the general population is estimated to be between 10 and 20% (1,2). The patho-
physiology of SUI is not well understood; consequently, the surgical treatment of this
condition has undergone significant changes over many decades. In the last 100 yr, more
than 150 different surgical procedures have been described (2). All of these various
procedures have one thing in common: Voiding dysfunction is a commonly reported and
troublesome complication.
The idea of using a biological urethral sling for the surgical correction of SUI was
first proposed in 1910. Over the last several decades, the various sling procedures have
become among the most common and efficacious incontinence procedures performed,
with long-term success rates reported to be between 70 and 95% (3). In 1996, Ulmsten
first described the TVT. With the advent of this procedure, there was a paradigm shift
in the surgical treatment of SUI, with the placement of the sling moved more distally
into the midurethra in a tension-free manner (4). According to the original theory, leakage
is prevented when the urethra comes in contact with the mesh during periods of stress.
The procedure is attractive to both physicians and patients because of its effectiveness,
simplicity, short learning curve, minimally invasive nature, and low rates of intraoperative
complications and postoperative morbidity.
When a patient presents with complaints of new-onset frequency, urgency, urge
incontinence, or difficulty voiding after an antiincontinence procedure, it is of paramount
importance to first rule out obstruction, usually by determination of PVR urine and
occasionally by urodynamics. The incidence of true urinary retention after pubovaginal
sling and TVT is reported to be between 4 and 15% and between 2.5 and 19.7%, respec-
tively (1,3,5–7). Many of these cases resolve with either temporary clean intermittent
catheterization or short-term indwelling catheterization, but reoperation is sometimes
required in the form of loosening or cutting of the sling and in some cases formal
urethrolysis. In a series by Klutke et al., 2.8% of patients who underwent TVT required
reoperation to loosen or cut the sling. All voided freely without obstruction 24 h after
the procedure, and continence was maintained in 94% (8).
Once obstruction is effectively ruled out, one is left with de novo instability as the likely
cause of a patient’s complaints of urgency and urge incontinence. Postoperative OAB
symptoms following urethral sling surgery are historically unpredictable and often lead
to patient dissatisfaction. Urgency symptoms may worsen, resolve, or remain unchanged.
Voiding dysfunction, particularly de novo urgency or urge incontinence after pubovaginal
sling and TVT, range from 5 to 24% and from 4.3 to 12%, respectively (2,4,9). This lower
incidence of detrusor instability in the TVT literature as compared to traditional sling
procedures is thought to be primarily because of the tension-free placement of the tape.
There are several theories to explain why sling procedures may lead to new-onset
OAB symptoms. Placement of the sling may lead to bladder mucosal irritation or a foreign
body reaction. The procedure may also cause autonomic dysfunction within the nerves
to the pelvic floor, especially when the sling is placed in the neurologically important
bladder neck area. Others believe that changes in paraurethral collagen metabolism or
sclerosis around the tape may be involved in de novo voiding dysfunction. Postoperative
detrusor instability may also stem from excessive urethral compression, leading to partial
outflow obstruction, or increased outflow resistance may lead to the unmasking of existing
detrusor overactivity (2,5,10).
In a series of 62 women undergoing TVT, Haab et al. noted de novo OAB symptoms
in 4 patients (6.5%). Videourodynamics performed in these patients revealed an open
bladder neck at rest and during stress without evidence of obstruction. Based on these
findings, the researchers proposed that de novo urgency was related to the activation of
the voiding reflex by stimulation of afferent fibers in the proximal urethra (11). Similar
videourodynamic findings were found by Fulford et al., in a series of 85 patients under-
going pubovaginal sling; 41% of patients with urge symptoms had an open bladder neck
at rest (12). These two studies did differ, however, in that the TVT group showed normal
pressure/flow parameters on urodynamics, and the pubovaginal sling cohort showed a
significant degree of outflow obstruction (11,12).
Treatment of de novo OAB after urethral sling surgery should be managed similarly
to idiopathic OAB. Principle treatment options include fluid restriction, timed voiding,
Case 6 / De novo Overactive Bladder Symptoms After a Sling 369
pelvic floor exercises, physical therapy, and medications, specifically the antimuscarinic
family of drugs. Cross et al., reported a 19% incidence of de novo urgency in a series of
150 women undergoing pubovaginal sling with autologous rectus fascia. In all but four
(3%) of these women, postoperative OAB symptoms resolved within 3 mo with timed
voiding and anticholinergic medications (13).
In the TVT literature, Segal et al., reported a 9.1% incidence of de novo urge incon-
tinence and a 4.3% incidence of new-onset OAB symptoms. In this series, only 8.7% of
patients required anticholinergic medication for symptom relief (2). In marked contrast,
Jeffry et al., reported a 25.9% incidence of de novo urge symptoms in 112 consecutive
women undergoing TVT. Anticholinergic medications only provided effective symptom
relief in 51.7% of patients. Of the women developing OAB symptoms, only 37.9%
reported subjective cure of their stress incontinence, likely because of their new-onset
urge incontinence (14). Reports like this have led some to advocate sling release in an
attempt to relieve any component of underlying obstruction in all patients complaining
of de novo urgency (C. G. Klutke, personal communication, June 2005).
In conclusion, de novo OAB is a commonly reported and distressing complication
of sling procedures for the surgical correction of SUI. It often leads to patient dissatis-
faction with surgery and a decrease in subjective cure rates. It is of utmost importance
to counsel women preoperatively regarding the likelihood of new-onset urgency and
its various treatment options. Continued research is needed to elucidate the true etiology
of de novo urgency after sling surgery and to predict which patients are at risk for its
development.
In this particular case, with de novo urgency accompanied by evidence of outlet
obstruction because of elevated residuals and suggestive symptoms, we would advocate
sling release in an attempt to relieve any component of underlying obstruction. If de novo
symptoms persist, then a course of behavioral and pharmacological therapy would be
instructed; if no improvement was evident in 3–6 mo, then a test of sacral nerve stimu-
lation would be performed.
REFERENCES
1. Abouassaly R, Steinberg JR, Lemiuex M, et al. Complications of tension-free vaginal tape surgery:
a multi-institutional review. BJU Int 2004;94:110–113.
2. Segal JL, Vassallo B, Kleeman S, Silva A, Karram MM. Prevalence of persistent and de novo overactive
bladder symptoms after the tension-free vaginal tape. Obstet Gynecol 2004;104:1263–1269.
3. Minassian VA, Al-Badr A, Drutz HP, Lovatsis D. Tension-free vaginal tape, Burch, and slings: are
there predictors for early postoperative voiding dysfunction? Int Urogyn J 2004;15:183–187.
4. Wang KH, Neimark M, Davila GW. Voiding dysfunction following TVT procedure. Int Urogyn J
2002;13:353–358.
5. Gateau T, Faramarzi-Roques R, Normand LL, Glemain P, Buzelin JM, Ballanger P. Clinical and
urodynamic repercussions after TVT procedure and how to diminish patient complaints. Eur Urol
2003;44:372–376.
6. Levin I, Groutz A, Gold R, Pauzner D, Lessing JB, Gordon D. Surgical complications and medium-
term outcome results of tension-free vaginal tape: a prospective study of 313 consecutive patients.
7. Miller EA, Amundsen CL, Toh KL, Flynn BJ, Webster GD. Preoperative urodynamic evaluation
may predict voiding dysfunction in women undergoing pubovaginal sling. J Urol 2003;169:
2234–2237.
8. Klutke CG, Siegel S, Carlin B, Paszkiewicz E, Kirkemo A, Klutke JJ. Urinary retention after tension-
free vaginal tape procedure: incidence and treatment. Urology 2001;58:697–701.
9. Karram MM, Segal JL, Vassallo BJ, Kleeman SD. Complications and untoward effects of the tension-free
vaginal tape procedure. Obstet Gynecol 2003;101:929–932.
10. Deval B, Jeffry L, Al Najjar F, Soriano D, Darai E. Determinants of patient dissatisfaction after tension-
free vaginal tape procedure for urinary incontinence. J Urol 2002;167:2093–2097.
11. Haab F, Sananes S, Amarenco G, et al. Results of the tension-free vaginal tape procedure for the treatment
of type II stress urinary incontinence at minimum follow-up of 1 yr. J Urol 2001;165:159–162.
12. Fulford SC, Flynn R, Barrington J, Appanna T, Stephenson TP. An assessment of the surgical outcome
and urodynamic effects of the pubovaginal sling for stress incontinence and the associated urge
syndrome. J Urol 1999;162:135–137.
13. Cross CA, Duane CR, McGuire EJ. Our experience with pubovaginal slings in patients with stress
urinary incontinence. J Urol 1998;159:1195–1198.
14. Jeffry L, Deval B, Birsn A, Soriano D, Darai E. Objective and subjective cure rates after tension-free
vaginal tape for treatment of urinary incontinence. Urology 2001;58:702–706.

Drs. Nitti, Klutke, and Bullock have done an extremely nice job highlighting all of
the salient issues in this case. Certainly, a diagnosis of OAB in the setting of potential
bladder outlet obstruction is challenging at times. They have stated well that often the
temporal relationship of the symptoms to the patient’s previous surgery may be the
most telltale indication of the sling or bladder outlet procedure as the likely cause.
Nonetheless, urodynamics may play some role in helping elicit the proper diagnosis,
and ultimately sling incision may be the procedure of choice to manage this patient ini-
tially. Correctly, they have stated that some cases, especially ones that have long-standing
obstruction, may require adjuvant therapies, including neuromodulation, botulinum
toxin injections, or rarely bladder augmentation.
The overall incidence of de novo urge incontinence in the setting of recent TVT
procedures is overall low. Nonetheless, one should be prepared to manage these compli-
cated situations as they may, even though infrequent, be problematic. It should be
understood that patients who have undergone TVT procedures in which they eventually
developed de novo symptoms, quality of life was diminished. Furthermore, this adverse
effect on quality of life persisted if physicians prolonged the time to intervention in
cases of suspect bladder outflow obstruction. Accordingly, one should clinically follow
patients with suspect obstruction very closely and perhaps consider early evaluation to
avoid long-term detriment to quality of life.
7 Recurrent Pelvic Organ Prolapse
A 56-yr-old sexually active woman presents with a bothersome, large vaginal bulge.
She had a hysterectomy and cystocele repair 5 yr earlier. She voids well and does not
complain of incontinence. On exam, she has total procidentia. She desires treatment.
How would you evaluate her, and what are the treatment options—pros and cons?
How would you counsel her?
COMMENTARY BY CHRISTOPHER C. ROTH, MD

AND J. CHRISTIAN WINTERS, MD
This case of a sexually active woman who has developed procidentia following an
anterior colporrhaphy presents interesting diagnostic and therapeutic considerations.
One must understand the impact of this condition on her quality of life and identify all
anatomic defects and any present (or potential) pelvic floor dysfunction. Finally, treatment
options with the associated risks and benefits of these interventions must be discussed
openly with the patient.
A careful history and physical exam should target bowel, bladder, and sexual function,
as well as the patient’s goals and expectations of treatment. Widely available validated
questionnaires can provide input into the patient’s specific voiding or prolapse problems
and the effects on quality of life. In this scenario, there is no mention of urinary, bowel,
or sexual dysfunction.
A systematic pelvic exam, including inspection of urethral, anterior, apical, and
posterior support, is done with the prolapse reduced. Urethral mobility is determined by
observation or Q-tip test. A basic assessment of continence is performed by having the
patient Valsalva and observing for any leakage per urethra. Although the posterior com-
partment is reduced, the anterior compartment is assessed for both central and lateral
defects. The anterior compartment will be reduced to evaluate the posterior support.
Careful inspection of the apex will determine location of the vaginal cuff and any asso-
ciated enterocele. A rectal exam will determine anal sphincter tone and may help in the
diagnosis of enterocele. A clinical classification of the defects, for example, the Pelvic
Organ Prolapse Quantification system, can be useful to the clinician to compare the
severity of prolapse in each of the respective compartments.
Prior to repair, voiding function needs to be well understood. Obstructive symptoms
caused by prolapse should be carefully evaluated. Likewise, occult stress incontinence
can be seen once the prolapse is reduced. Urodynamics will provide the most information
and should be done with and without reduction of the prolapse via vaginal packing or
pessary. We assume that occult stress urinary incontinence was determined on urodynamic
testing, and the patient voids normally with the prolapse reduced without coexisting
fecal control abnormalities.

371
In the scenario of a middle-aged sexually active woman, aggressive management of

her condition will be needed. Pessaries are the mainstay of nonsurgical management.
Although not likely applicable in this scenario, patients should be informed of this non-
surgical option. Surgical management is likely to provide this patient with the best
results. This particular patient has recurrent prolapse following anterior colporrhaphy at
the time of hysterectomy and is likely going to be concerned with rates of future recurrence.
Counseling this patient will largely center on a careful discussion of the various surgical
techniques and their associated risks and benefits.
Either a vaginal or an abdominal approach can be considered. In general, vaginal
approaches offer less morbidity than abdominal approaches regarding hospital stay and
overall convalescence. In addition to supporting the apex, concomitant incontinence
procedures and measures to restore anterior and posterior support can be done through
the same approach. However, we disclose that, in our experience, the most durable and
successful correction of apical prolapse is achieved with an abdominal sacral colpopexy.
Even though a combined approach may be needed, the colpopexy ensures the most
definitive correction of the apical prolapse and enterocele, which is the major contributing
cause to the patient’s complex problem. In addition, we disclose that the vaginal axis
and length are consistently better following colpopexy. Ultimately, the patient chooses
the approach after reviewing the risks and benefits of each.
Our preference in the transvaginal approach to restoring apical support in this scenario
is the uterosacral ligament suspension. This procedure restores the apical anatomy by
reapproximating the vaginal cuff with proximal remnants of the uterosacral ligaments.
In this patient, who undoubtedly has a large enterocele, the enterocele sac is reduced
and ligated. In the same operative setting, an anterior-posterior repair and transobturator
sling procedure will be performed. The pubocervical and pararectal fascia are included
in the sutures that secure the apex of the vagina to the uterosacral ligament. This provides
an anatomically sound vagina, restoring adequate depth and axis. Disadvantages of this
technique include difficulty in identifying the proximal uterosacral ligaments and the
concern of reattaching the apex to an already-deficient structure.
Despite these limitations, we have been satisfied with this approach. The rate of
recurrence of apical prolapse after this procedure is approx 11% (1). Rates of sexual
dysfunction have been similar for vaginal and abdominal prolapse procedures, with an
incidence of 20% (2). However, our experience, as well that of others, points toward
increasing rates of dyspareunia with increasing numbers of vaginal procedures (3).
It is for these reasons that we prefer an abdominal sacral colpopexy and enterocele
repair. This technique restores apical vaginal support by fixing the vaginal cuff to the
sacral promontory with synthetic mesh. We are now performing this procedure laparo-
scopically, and this has eliminated the abdominal incision and shortened hospitalization.
This procedure can easily be performed in conjunction with a midurethral sling pro-
cedure. A limitation of this approach is the ability to correct distal pubocervical,
pararectal, and perineal body defects.
Some report completing all of the vaginal procedures prior to the colpopexy; however,
we have adopted a different approach. We initially perform the abdominal sacral
colpopexy and enterocele repair, followed by an assessment of the distal defects. If
these defects are not significant, then we have not been repairing them—particularly the
anterior compartment. In this particular patient, it is likely that the abdominal surgery
will be followed by a posterior and perineal body repair and a transobturator tape
procedure because in patients with total procidentia the levator hiatus is often severely
Case 7 / Recurrent Pelvic Organ Prolapse 373
widened and needs correction. With this selective approach, success rates of 97.5% are
achieved in correcting the apical defects and enterocele. Distal defects may occur as
often as 40% of the time, but most of these defects are minor, and over 80% of the
patients are satisfied with their outcome (4).
Thus, we would combine a laparoscopic abdominal sacral colpopexy and enterocele
repair with a posterior repair and TOT procedure. An anterior repair would be performed
if necessary after reduction of the apex.
REFERENCES
1. Sze EHM, Karram MM. Transvaginal repair of vault prolapse: a review. Obstet Gynecol 1997;89:466.
2. Maher CF, Qatawneh AM, Dwyer PL, Carey MP, Cornish A, Schluter PJ. Abdominal sacral colpopexy
or vaginal sacrospinous colpopexy for vaginal vault prolapse: a prospective randomized study. Am J
3. Nygaard IE, McCreery R, Brubaker L, et al. Abdominal sacralcolpopexy: a comprehensive review.
4. Blanchard K, Vanlangendonck R, Winters J. Abdominal sacral colpopexy and abdominal enterocele
repair for the correction of vaginal vault prolapse. J Urol 2005;174:V497(A).

Drs. Roth and Winters have given us a review of the various surgical treatment
options for total procidentia. Current outcomes data would seem to agree with their
approach as an abdominal sacrocolpopexy seems to have the fewest reoccurrences.
From the vaginal approach, another option besides the uterosacral ligament suspension
would be a sacrospinous fixation of the apex. There are data that show a higher rate of
cystocele formation, probably because of the change in the vaginal axis.
In the last few years, the number of transvaginal procedures utilizing nonnative materials
to supplement the prolapse repair has increased. There have been relatively good outcomes
utilizing cadaveric fascia for that purpose, and there have been a number of procedures
described using synthetic mesh for this purpose. With use of the synthetic mesh, one has
theoretically a permanent material that may help prevent recurrence. This mesh can be
used to treat both anterior and posterior components as well as the apex. At this point,
most seem to favor the use of a large-pore polypropylene-type material for these types
of procedures. Although there are some potential risks with this, including mesh extru-
sion and infection, to date these have not been too significant. The outcomes data and
the follow-up on these patients are minimal at this point, and certainly although many
have adopted this approach, more follow-up data are required before one can adequately
compare it to the existing procedures.
8 Recalcitrant Urinary Frequency
and Urgency
A 36-yr-old woman presents with a 7-yr history of worsening urgency and frequency.
She voids 20 times a day and awakens 5 times at night to void. She says that the force
of her stream is normal. Her physical exam is normal. Fluid diary reveals an average
volume of 60 cc per void. She has failed the standard anticholinergic treatments.
How would you evaluate and treat this woman? What are her treatment options?
COMMENTARY BY MICHAEL CHANCELLOR, MD

Although the general history and physical exam are reported as normal, I would ask
the patient again for specific symptoms that may suggest an occult neurological condition.
Specific questions include change in vision, numbness or weakness of the lower extrem-
ities, changes in sexual function such as erectile dysfunction or vaginal numbness, and
change in bowel function such as new onset of constipation. Essentially, I want to be
sure that she does not have an occult lumbosacral radiculopathy or multiple sclerosis.
If I am still not convinced, then I will refer her to a neurologist, who I trust would facil-
itate a workup of occult neurological conditions.
Before discussing treatment with the patient, I will make sure she has a normal
urinalysis and not be at risk for bladder carcinoma.
To try to help this patient, I would first offer the option of double-, or rarely triple-, dose
antimuscarinic agents. I have had good success using a double dose of antimuscarinic
agents such as 30 mg oxybutynin every 24 h or adding 15 mg oxybutynin and 4 mg
tolterodine or 40 mg tropsium every 24 h. For refractory cases, I often see improved
efficacy with greater dosage of overactive bladder (OAB) medications without doubling
side effects. With the “black box” labels slapped on all antidepressants, I do not recom-
mend imipramine anymore as a second- or third-line therapy. I would also recommend
pelvic floor biofeedback if she has not done this already, although I doubt biofeedback
alone will resolve the refractory OAB.
If an oral agent and biofeedback do not work, then I will offer sacral neuromodula-
tion or off-label use of bladder botulinum toxin injection. In my experience, when cost
is not an issue, most patients will choose cystoscopic botulinum toxin injection over the
invasive sacral stimulator implantation. In my personal experience, bladder botulinum
toxin has worked better than sacral neuromodulation. I have stopped performing bladder
augmentation in nonneurogenic detrusor overactivity as the results have not been as
satisfactory as in true neurogenic detrusor overactivity, and the patients often are not
willing to trade off frequency and incontinence with a big operation that can result in
retention and self-catheterization.

375
If the patient chooses bladder botulinum toxin injection and gives informed consent,
I typically use 200 U botulinum type A toxin (BTX-A; Allergan, Irvine, CA) dissolved in
20 mL sterile saline. I have mostly used a flexible cystoscope technique and a 27-French
Olympus flexible cystoscopy injection needle. Through a urethral Foley catheter, I
first instill 30–50 cc of 1% lidocaine anesthesia and leave the catheter clamped in
the bladder for approx 10 min. I focus on placing most of the injection directly into the
bladder base, and I have not avoided the trigone. I make a 1.0-cc submucosal bleb raised
at each site to maximize horizontal spread of BTX-A within the tissue.
I tell the patients that, in addition to the usual cystoscopic risks, the BTX-A bladder
injection is an off-label use of an agent approved by the Food and Drug Administration
(FDA) for muscle spasticity, and that unanticipated events may occur, and there is a risk
of urinary retention that may last weeks to months. Usually, patients will notice an
improvement, not immediately, but after about 1 wk, and then the efficacy will further
improve to a maximum at about a month. In my hands, the duration of response is com-
monly 6 mo. Most interesting and a nice observation is that subsequent injection lasts
longer than the first one. So, if the first injection lasts 6 mo, subsequent injections may
last 8 mo or longer.
COMMENTARY BY GAMAL M. GHONIEM, MD, FACS

This patient has chronic and refractory OAB. Her condition is consistent and progressive,
requiring careful evaluation. Her bladder capacity while awake is small and probably
true because of her nocturia; she may have a true contracted bladder. Another differen-
tial diagnosis may include neurogenic bladder. Approximately 10% of idiopathic OAB
patients show neurological symptomatology in 3–5 yr. A common finding with our
patient’s scenario is multiple sclerosis. Neurological evaluation is recommended.
Evaluation
Evaluation includes quality-of-life questionnaires like the short form of the Urogenital
Distress Inventory (UDI-6) and discussions with the patient about her expectations. The
patient is often frustrated at this point because of the long duration of her progressive
and severe symptoms in spite of previous anticholinergic treatments, which are signifi-
cantly interfering with her life. I would perform the following tests:
1. Urine: Urinalysis, including microscopic examination to rule out infection and micro-
hematuria, is the first step. Urine culture and urine cytology will be the second step if
the urine is positive. Special culture for acid-fast bacilli (to rule out tuberculosis) and
urine examination for ova and parasites (to rule out schistosomiasis) should be consid-
ered if there is pyuria, microhematuria, or history of foreign travel.
2. Urodynamics: Multichannel fluorourodynamics is indicated in this patient. Expected
abnormalities could be all or any combination of the following: small bladder capacity, low
bladder compliance, detrusor overactivity with early involuntary contractions, detrusor-
sphincter dyssynergia, bladder trabeculations, diverticuli. and vesicoureteral reflux.
3. Cystoscopy: Cystoscopy is performed to look for bladder tumor, carcinoma in situ,
bladder calculi, or foreign bodies. It is preferable to do cystoscopy under anesthesia to
determine the anesthetic bladder capacity and to perform a biopsy if needed.
4. Upper tract studies may be required with any abnormality. I like to use computed
tomography with genitourinary three-dimensional reconstruction.
Case 8 / Recalcitrant Urinary Frequency and Urgency 377
Treatment Options
If the patient was previously treated with anticholinergic medications, combinations
and maximum tolerable dosage are less likely to help. Biofeedback and bladder retraining
behavioral technique may help to a small extent. Before considering aggressive surgical
options, I would recommend the following:
1. Intravesical injection of botulinum toxin A (Botox®). I use 200–300 U in an office pro-
cedure. Botox is injected into the detrusor muscle, not submucosally. This treatment has
shown efficacy for treatment of either neurogenic detrusor overactivity or idiopathic
OAB in many publications, especially from Europe. At present, it is not FDA approved
for urological use.
2. Neuromodulation: Implantation of a unilateral S3 quadripolar lead for sacral stimula-
tion has shown efficacy up to 70% in refractory OAB. It is an FDA-approved device for
select indications, including frequency of urination. Because I suspect that this patient
may have a truly small bladder, I would do a staged implant. Approximately 2 wk after
the first stage, her bladder diary and quality of life are reviewed, and if there is signifi-
cant improvement, she will undergo the second stage; otherwise, the lead is removed.
Urinary diversion is considered if the evaluation and the first-line interventions
support this decision, especially if her bladder is end stage (small contracted bladder).
Augmentation cystoplasty or even continent diversion would also be valid options.

Drs. Chancellor and Ghoniem have demonstrated the evaluation as well as therapeutic
options for a patient who has what sounds to be severe overactive bladder. They have
both appropriately indicated the need to rule out occult neurological disease in many of
these patients. Certainly, minimally invasive therapy would include medications, but
often when this fails the patient may need more advanced therapy. Botulinum toxin
injections, although considered currently off-label use in the United States, is an option
and certainly one of the less-invasive refractory options for management of a patient
such as this. We do not know the long-term effects of Botox injections; however, the
patient needs to understand, especially at such a young age, that she is likely to require
this management for many years. Accordingly, one may consider neuromodulation as
first-line therapy in the refractory state of overactive bladder; however, this is a bit
more invasive. Neuromodulation may, however, give better single-treatment, long-term
management of her problem.
9 Difficulty Voiding and Overactive
Bladder Symptoms
A 23-yr-old woman presents with slow onset over the course of 2 yrs of worsening
hesitancy and slowing of urinary stream and recent onset of urgency and frequency. Her
physical exam is normal. Postvoid residual (PVR) is 100 cc. Urodynamics reveal a detrusor
pressure at maximum flow of 28 cc H2O and a peak flow of 4 cc/s. Electromyography
(EMG) of the external sphincter is normal (not shown on urodynamic studies tracing).
Magnetic resonance imaging (MRI) of the pelvis is normal.
How would you treat this patient? What else would you do to evaluate her?
COMMENTARY BY MICHAEL J. KENNELLY, MD, FACS

When meeting a patient on the initial visit, I have the patient verbalize not only which
specific issue they are trying to resolve but also their expectations. The response is critical
to the workup and evaluation. An elevated voiding pressure of 28 cm H2O and 100 cc
residual on an isolated urodynamic study does not warrant further evaluation unless the
patient is symptomatically bothered. Assuming that the patient would like to improve
her voiding stream and reduce her overactive bladder symptoms, I would begin an orderly
evaluation of female bladder outlet obstruction (BOO).
History would include questioning the time-course of symptoms with association of
any change in mobility, neurological function, bowel dysfunction, and psychosocial
issues. Complete medication review would look for agents that decrease detrusor function
(anticholinergics) and agents that increase urethral tone (F-agonist, norepinephrine/
serotonin reuptake inhibition). Past surgical history, including urological and obstetrical
history, would be reviewed specifically to look for potential effects on the lower urinary tract.
Beyond the stated physical exam findings, a focused neurourological exam of the S2
through S4 segments of the spinal cord provides insight into lower urinary tract dys-
functions. Various techniques would be done to ascertain if reflex activity, sensation, and
volitional control are present. Bulbocavernosus reflex, digital anal reflex, anocutaneous
reflex, pinprick and light touch sensation testing of S2–S4 dermatomes, and volitional
control of the external anal sphincter would be tested. Cutaneous abnormalities of the
lumbosacral back (dermal sinus tract, deep skin pimples, hairy tufts, and hemangiomas)
are often present in occult spinal dysraphism. In our office, urinary residual assessment is
typically performed with ultrasound. An elevated PVR would prompt urethral catheteri-
zation to obtain a true PVR and rule out a urethral stricture. The patient would be asked
to complete a 3-d frequency/volume diary to objectively document her symptoms.
Based on the clinical information, the patient appears to have BOO with etiologies
that can be neurogenic or nonneurogenic in origin.

379
Fig. 1.
Neurogenic
Positive neurological findings on the exam may indicate a neurogenic etiology for her
symptoms, such as multiple sclerosis, unrecognized occult spinal dysraphism, or develop-
ment of spinal cord pathology.
If I had a heightened suspicion for neurological etiology (despite a normal EMG), I would
order an MRI of the central nervous system and refer the patient to a neurologist for
evaluation. A patient with multiple sclerosis can have a variety of lower urinary tract
dysfunction, including detrusor overactivity, detrusor areflexia, and detrusor external
sphincter dyssynergia (DESD). In this patient, BOO may be secondary to DESD. Patients
with DESD are evaluated at least annually, monitoring the status of multiple sclerosis,
lower urinary tract symptoms, and PVR. Genitourinary complications (repeated urinary
tract infections, urinary incontinence, hematuria, and so on) warrant an upper urinary
tract (renal ultrasound or computed tomographic urogram) and lower urinary tract (uro-
dynamics and cystoscopy) investigations as appropriate.
Nonneurogenic
A normal physical exam and MRI of the pelvis ruled out many anatomic etiologies,
including an anterior vaginal wall cyst, Mullerian duct remnant, urethral diverticulum,
large ovarian cyst, uterine fibroids, and bladder foreign body.
If the patient has had prior lower urinary tract surgery/instrumentation or there is difficulty
in urethral catheterization, then cystoscopy would be performed. Urethroscopy allows
Case 9 / Difficulty Voiding and Overactive Bladder Symptoms 381
visual assessment, localization, and treatment implications of urethral fibrosis/stricture

if present. My initial management of a female urethral stricture would be cystoscopy
and coaxial dilation. Periodic follow-up office visits (initially 3–6 mo, then annually)
would monitor symptoms and PVR. Recurrent strictures would be managed with
dilation and self-obturation (less likely) vs urethral reconstruction, which has a more
durable effect.
With neurological etiologies excluded, videourodynamics would be performed specifically
looking for primary bladder neck obstruction and dysfunctional voiding (nonrelaxation
of the pelvic floor). The voiding cystourethrography part of the videourodynamics study
is critical in this patient to identify the specific anatomic area of obstruction. Video
images reveal a nonopening of the bladder neck in primary bladder neck obstruction
(i.e., smooth muscle dyssynergia). Nonrelaxation of the pelvic floor demonstrates
intermittent contraction along the midurethra area that may be missed on EMG.
Because of confounding variables (patient and catheter), the voiding cystourethrography
part of the study would be performed with and without a urethral catheter. Voiding
without a catheter often allows improved visualization of the obstruction site. Although
no absolute urodynamic criteria exist for differentiating BOO in women, most agree
that urodynamics are essential. Important urodynamic parameters are detrusor pressure
at peak flow, maximum flow rate (instrumented and uninstrumented), PVR, and radi-
ographically localizing obstruction. According to the Blaivas-Groutz nomogram (1),
this patient has mild obstruction (Zone 1) with a detrusor pressure at maximum flow
of 28 cm H2O and a peak flow of 4 cc/s.
In this patient, whether she had neurogenic or nonneurogenic etiologies of her voiding
dysfunction, urological management would be similar. Initially, multimodal conservative
management with behavioral therapy and medications would be prescribed. Our
Continence Care Center employs specialists who are experts in lower urinary tract
function. The behavioral methods they would utilize for this patient would include
pelvic physiotherapy, biofeedback, and emptying maneuvers (pelvic tilt, double void,
and deep breathing). The focus would be on identification and subsequent relaxation of
the pelvic floor muscles to assist in bladder emptying. Electrical stimulation would be
used to fatigue the muscle and assist in pelvic floor reeducation. In addition, they would
teach urge suppression techniques to help her overactive bladder symptoms.
Medications offered this patient may include F-adrenergic blocking agents (prazosin
[Minipress®], terazosin [Hytrin®], tamsulosin [Flomax®], and alfuzosin [Uroxatrol®])
and antispasticity agents (baclofen [Lioresal®], tizanidine hydrochloride [Zanaflex®],
and diazepam [Valium®]). In my experience, F-blockers are effective first-line therapy
and seem to be well tolerated. Recalcitrant patients would be offered botulinum toxin
injection (Botox®) into the external/internal sphincter or neuromodulation of the sacral
nerves with Interstim® or tibial nerve stimulation. My anecdotal experience with botu-
linum toxin injections has been promising. Unfortunately, the desired effect on the bladder
neck/pelvic floor (skeletal muscle) seems to taper off after 3– 4 mo, unlike the usual
6- to 9-mo duration of effect on detrusor smooth muscle injections. Patients with
primary bladder neck obstruction who respond to botulinum toxin injection are offered
bladder neck incision, which has provided a more durable response.
REFERENCE
1. Blavas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract sympto-
COMMENTARY BY DEBORAH LIGHTNER, MD

Her voiding dysfunction evaluation is incomplete without objective evidence of the
symptom impact beyond her subjective history. The symptoms should be further quanti-
fied by a bladder diary. The AUA symptom index, initially developed for male voiding
dysfunction, can also help evaluate the degree of bother and effect on quality of life that
these voiding symptoms cause in women (1).
A review of symptoms is critical in determining if she has other system complaints
often associated with voiding dysfunction. Many have a history of pelvic trauma; questions
regarding sexual abuse are most appropriate. Given the common association of voiding
symptoms with other pelvic organ dysfunction, particular attention to bowel and sexual
function, prolapse symptoms, and a neurological review of systems is also appropriate.
The physical examination includes an examination of sacral nerve roots, of light
touch sensation over the medial thigh and labia, of the patient’s ability to identify and
contract the pelvic floor, with palpation of the urethra for cysts, other masses, tenderness,
or expressible discharge; palpation of the levators; and Valsalva maneuver to briefly
assess that there is no high-grade prolapse. The rectal examination evaluates rectal tone,
anal wink, and a bulbocavernosus reflex, particularly important as the differential
includes several neurological diseases. This tailored brief exam then tailors the radi-
ographic and urodynamic evaluations. For example, the pelvic MRI is an expensive test
with low yield, particularly if the history and examination raise suspicions for a neuro-
logical lesion, but it rules out extrinsic urethral compression and extraluminal pathology
(2). Appropriate cultures for sexually transmitted disease are important in this initial
consultation.
The most helpful and cost-effective urodynamic test, not supplied to us, would be
uninstrumented free urinary flow, including the contour, peak, and average flow rates.
An uninstrumented free flow greater than 15 mL/s, a voided volume of greater than 100
cc with a low PVR volume would have been good screening evidence of no obstruction.
Here, we are given the results of the more expensive gold standard test: Her pressure
flow study reveals both a decrease in the flow rate (less than 15 mL/s is suspicious
for outlet obstruction) and an increase in the maximum voiding pressure (>20 cm
H2O water is highly suspicious); by all female pressure flow nomograms, the high-
pressure/low-flow combination is diagnostic of a degree of BOO. With a detrusor capable
of compensating, she remains able to empty adequately. Assuming that these urody-
namics values are obtained appropriately with the urodynamics catheter size sufficiently
small to reduce catheter artifact and that a multichannel system is used to adequately
subtract the influences of changing intraabdominal pressures, adding fluoroscopy to
the urodynamic study could be helpful in determining any possible anatomic sites
of obstruction.
Most urodynamic equipment is equipped only for patch electrode EMG studies;
hence, this screening patch EMG reported as normal does not rule out the possibility of
either a pseudodyssynergic or truly dyssynergic voiding pattern; both remain high in the
differential of a young woman with BOO.
A cystoscopic examination with careful attention to urethral distortion by compression
or intraluminal pathology and to bladder neck is necessary. Retroflexion of the cystoscope
to view the bladder neck should be included.
Treatment is predicated on the etiology of the outlet obstruction, which in this case may
still be either functional or anatomic. BOO occurs in the setting of voiding symptoms in
Case 9 / Difficulty Voiding and Overactive Bladder Symptoms 383
8% (3) to 23% (4). Studies of BOO in females suggest that voiding dysfunction, parti-
cularly in a young patient, is the most likely; anatomic causes, such as cystocele (unlikely
without high-grade prolapse on examination) and primary bladder neck obstruction
account for the majority of women who have not had prior antiincontinence surgery. If
she proves to have a dysfunction outlet on video studies, then she may report dyspareunia
and have inducible pelvic floor spasm on physical examination. Again, all women with
these complaints should be queried regarding risk for sexually transmitted diseases or
history of instrumentation or abuse. A truly dyssynergic outlet should be ruled out, with
careful determination if the patient has other signs or symptoms of a neurological disease.
Completion of this examination may necessitate a formal neurological evaluation.
Parenthetically, the presence of an overactive bladder and BOO are presumptive evidence
of a neurological lesion. However, detrusor overactivity on the urodynamic study is not
reported here. Hence, although there is nothing in provided urodynamic information is
highly suggestive of neurological etiology, noting that a patch EMG is not reliable evi-
dence for the lack of a dyssynergic outlet. Assuming a normal neurological examination
(no occult cord lesion or evidence of a demyelinating disorder), a normal videourodynamic
study and cystoscopy (e.g., no delayed or incomplete opening of the bladder represen-
tative of primary bladder neck obstruction, no strictures), we are left with the presumptive
diagnosis of dysfunctional voiding and hold discordant information that the presumably
abnormally high tone of the pelvic floor leading to the BOO and dysfunctional voiding
could not be detected by the high false-negative patch EMG.
Pelvic floor muscle relaxation and biofeedback may be helpful in patients with isolated
pelvic floor dysfunction. Often associated with a traumatic history or dysfunctional bowel
and sexual symptoms, these patients respond well to treatment of associated constipation,
pelvic floor relaxation exercises, biofeedback, and even physical therapy (5). Urethral
dilation plays no role in voiding dysfunction without a demonstrable anatomic stricture;
this form of BOO is uniquely rare in women. The use of F-adrenergic antagonists is
described, but the results are unimpressive in my hands. Failing these conservative and
less-costly treatments, the use of sacral neuromodulation can be curative of the voiding
dysfunction (6,7). Botulinum toxin injected into the external sphincter can also be tempo-
rarily curative, clinching both the diagnosis and an effective therapy (8).
REFERENCES
1. Scarpero HM, Fiske J, Xue X, Nitti VW. American Urological Association Symptom Index for lower
urinary tract symptoms in women: correlation with degree of bother and impact on quality of life.
Urology 2003;61:1118–1122.
2. Neitlich JD, Foster HE Jr, Glickman MG, Smith RC. Detection of urethral diverticula in women: com-
parison of a high resolution fast spin echo technique with double balloon urethrography. J Urol 1998;
159:408– 410.
3. Blaivas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract sympto-
4. Nitti VW, Tu LM, Gitlin J. Diagnosing bladder outlet obstruction in women. J Urol 1999; 161:1535–1540.
5. Weiss JM. Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-
frequency syndrome. J Urol 2001;166:2226 –2231.
6. Spinelli M, Bertapelle P, Cappellano F, et al. Chronic sacral neuromodulation in patients with lower
urinary tract symptoms: results from a national register. J Urol 2001;166:541–545.
7. MaLossi J, Chai TC. Sacral neuromodulation for the treatment of bladder dysfunction. Curr Urol Rep
2002;3:61–66.
8. Frenkl TL, Rackley RR. Injectable neuromodulatory agents: botulinum toxin therapy. Urol Clin North
Am 2005;32:89–99.

The treatment of women with bladder obstruction without an obvious anatomic site
of obstruction can be challenging. Our reviewers have summed up the basic evaluation
and management of women with such problems. For those who have primary bladder
neck obstruction, Botox or neuromodulation can be effective, but they can also be
expensive. A transurethral incision of the bladder neck is fairly easy with high efficacy
rates and only a small risk of stress incontinence; it should be discussed with the patient
in that setting.
10 Post-Hysterectomy Incontinence
A 54-yr-old woman presents for a second opinion concerning her urinary incontinence,
which started after an abdominal hysterectomy. She notes increased leakage with cough,
sneeze, and laugh but notes that she seems to have leakage even when still and at night
in bed. She cannot recall any time that she is actually completely dry. On exam, she has
urine in the vaginal vault but does leak per urethra with straining. She has significant
urethral hypermobility. An intravenous pyelogram is normal. A cystogram shows contrast
entering the vagina. Cystoscopy shows two small ostia in the bladder base away from the
ureteral orifices.
How would you proceed?
COMMENTARY BY COURTENAY K. MOORE, MD

With the history, the suspicion for a vesicovaginal fistula is extremely high. On physical
examination, the patient also has reproducible stress urinary incontinence per urethra. The
cystogram confirmed evidence of contrast entering the vagina, which confirms a fistulous
track at the apex of the vagina. Cystoscopy also confirmed the diagnosis, demonstrating
two small ostia at the bladder base. A pyridium pad test or methylene blue instillation in
the bladder and confirming evidence of blue dye effluxing the apex of the vagina would
also be suggestive of a vesicovaginal fistula. The intravenous pyelogram was done to
confirm the integrity of the upper urinary tracts, ruling out the possibility of a coexistent
ureterovaginal fistula. In the differential diagnosis, peritoneovaginal fistula should be
considered. A peritoneovaginal fistula could present with similar symptoms and physical
exam; however, both the pyridium pad test and cystogram would be negative.
Therapeutic options should then be discussed with the patient and may include initial
conservative management with urethral catheter if the leakage is minimal. Although
there are reports using fibrin glue and electrocauterization of the fistulous tract, these are
small series, and the data are inconclusive. Assuming that the leakage does not resolve
after a prolonged period of time (2 wk) of Foley catheter drainage, definitive surgical
correction (vaginal or abdominal) should be discussed. The time of repair remains some-
what controversial. Some surgeons will attempt to repair the fistula several days to a few
weeks after the injury. However, early intervention should not be attempted in the face
of active inflammation or infection.
The main determination of when and how to repair the fistula appears to be based on
surgeon comfort and anatomy. If there are one or two small adjacent ostia accessible
vaginally, a vaginal approach is desirable. Given the fistula is accessible vaginally, I would
perform a transvaginal vesicovaginal fistula repair with a peritoneal-based vascularized-
interposition graft covering the entire repair. Contraindications to performing a transvaginal
procedure would be active inflammation, obvious infection, evidence of healing early

385
in the postoperative period, and markedly diminished bladder capacity secondary to

radiation or other changes within the bladder. It is important to remember that the patient
also had evidence of leakage per urethra. One can contemplate a vaginal sling at the time
of the fistula repair. If a sling is done simultaneously, then it should be a tension-free
sling to minimize the risk of postoperative complications, such as postoperative urinary
retention. After performing a good apical vaginal fistula closure, one would not want to
place the repair under undue tension or stress, like voiding against a higher degree of
urethral resistance. Alternatively, the stress incontinence could be done in a staged
approach at a later date.
An abdominal approach to the vesicovaginal repair with interposition of either peri-
vesical or omental fat is another option. In these cases, it is best to bivalve the bladder
through the fistula tract, followed by closure of both the vagina and bladder. The bladder
is closed using interrupted sutures near the fistula tract, followed by a standard running
closure of the remainder of the bladder. At the time of an open abdominal vesicovaginal
fistula repair, it is important to identify the ureters. Intraoperative placement of 5-French
feeding tubes allows identification of the ureters to avoid iatrogenic injury.
Postoperative care in both cases involves a urethral Foley and suprapubic tube. The
urethral catheter can be removed prior to discharge, leaving the patient with a suprapubic
catheter to minimize postoperative bladder spasms. The use of postoperative anticholin-
ergics and antibiotics is prudent to prevent bladder spasms and infections, respectively.
A cystogram is obtained 2 wk postoperatively to confirm closure of this fistula site. The
suprapubic tube is removed if the cystogram is negative.

Dr. Moore thoroughly describes the treatment approaches for repair of a vesicovaginal
fistula. Ultimately, as noted, the timing of the repair as well as the approach are based
on both patient factors and surgeon preference. Treatment of the patient’s stress urinary
incontinence can be done at the same time as the fistula repair; however, as noted by
Dr. Moore, it is particularly important in a case like this not to cause outlet obstruction.
If one were to do an abdominal repair of the fistula, a Burch procedure certainly could
be considered, whereas with a vaginal approach, a nonobstructing midurethral sling,
which would be well away from the area of repair, would be a good choice.
11 Severe Incontinence
After Multiple Prior Procedures
A 72-yr-old active woman presents for evaluation of incontinence. She leaks with any
sort of activity and wears 11 pads per day. She rarely goes to the bathroom as the bladder
rarely fills—it all leaks out. The only time the bladder fills and she has the urge to void is
at night in bed, and as soon as she gets the urge, the bladder completely empties before
she even stands up. She has had an autologous fascial sling at the bladder neck and four
treatments with a bulking agent, all with minimal improvement. On exam, she has no pro-
lapse or urethral hypermobility. Urodynamics show no detrusor overactivity, a capacity of
245 cc, and a Valsalva leak-point pressure of 41 cm H2O.
Would you do anything else to evaluate her? What are the treatment options?
COMMENTARY BY ROGER DMOCHOWSKI, MD, FACS

The woman with mixed urinary incontinence (MUI) represents probably the most
common clinical scenario for women with bothersome incontinence who seek therapy.
This presentation is often confounded by prior surgical intervention for stress incon-
tinence, as in the case presented here for discussion.
No single paradigm can completely address the clinical evaluation and therapeutic
management in this scenario; however, several caveats and options do exist. It is our
preference to evaluate this woman as completely as possible. A subjective and objective
assessment of incontinence is crucial, as is a one-item assessment of the woman’s bladder
condition (PPBC). We prefer a combination of quality-of-life estimation, a PPBC, and
an assessment of those symptoms most bothersome to the individual. It is often difficult
for women to segregate their symptoms, but an early estimate of degree and magnitude
of stress and urge symptoms can at least frame the patient presentation.
From an objective standpoint, clinical evaluation should include history and physical
(with emphasis on vaginal examination to identify hypersuspension of the proximal ure-
thra, concomitant anterior vaginal compartment prolapse, and any other associated vaginal
compartment prolapse), and testing. We would perform urodynamic studies (UDS) in this
circumstance given the prior interventions and their associated failure. UDS are crucial
for identifying not only urethral dysfunction, but also associated storage abnormalities
(detrusor overactivity, bladder compliance abnormalities, and sensory changes, such as
either loss of or delay in normal sensation or, in contradistinction, sensory overactivity)
and pressure/flow aberrancies (low pressure or poorly sustained detrusor contractions, or
high-pressure/low-flow voiding, possibly indicating outlet obstruction).
We also feel that cystoscopy is a valuable adjunctive diagnostic tool. Cystoscopy
will exclude bladder pathologies such as foreign bodies and assist in the identification

387
Fig. 1.
Fig. 2.
Case 11 / Severe Incontinence After Multiple Prior Procedures 389
of subtle urethral obstruction (acute angulation of the urethra in relation to the bladder).
A bladder diary may be particularly beneficial for women with significant urgency and
frequency. We tend not to use pad testing but occasionally will do so in persistently
problematic diagnostic scenarios.
At this juncture, a reappraisal of the varying contributions of stress and urgency
symptoms is important, as is a frank discussion regarding patient expectations for therapy.
We prefer to frame the therapeutic discussion in the context of the degree and relative
contributions of MUI and realistic outcomes for the particular individual. The impor-
tance of conveying the concept of symptomatic improvement as opposed to resolution
cannot be overestimated during this discussion.
Assuming a substantial urgency component, a presumptive trial of anticholinergic agents
is reasonable and would be an early option in our paradigm. A degree of improvement may
be predictive of the need for these agents after intervention for any outlet dysfunction. In
the circumstance of predominant urgency, this trial will dictate further interventions aimed
at improving bladder storage abnormalities.
In those women with pure mixed symptoms (relative equal contributions) or with stress-
predominant MUI, outlet therapy almost certainly will be dictated to achieve symptomatic
improvement. In the scenario of this patient, we would offer either bulking therapy or
a sling. Many would also consider behavioral or pelvic floor exercise regimens, and
certainly this should be mentioned to the patient; however, in the case of prior surgical
failure, it is our impression that the overall benefit of these therapies is somewhat less
than in the woman who has not undergone prior therapies. Bulking offers a reasonable
option and often is our first treatment, especially if there is relatively depressed urethral
function, as measured by leak-point pressure evaluation (with or without urethral hyper-
mobility). It can also be used sequentially with secondary surgical therapy.
Surgical therapy for this case would be founded on some type of sling. Often, in our
hands, an autologous pubovaginal sling is used when surgical failure has occurred with
one of the newer sling modalities (i.e., alternative material or midurethral placement).
We will occasionally use a secondary midurethral tape if persistent hypermobility is
present, but in the circumstance of an immobile urethra or relative urethral fixation, we
prefer the autologous sling as the optimal salvage procedure.
We often find that this paradigm provides reasonably successful outcomes and patient
satisfaction. However, there is no substitute for patient education and a clear delineation
of patient expectations and reasonability of outcomes in the circumstances of prior
failed interventions.

The patient with severe incontinence who has already failed multiple treatments is a
challenging problem for the clinician. The patient in this case who goes through 11 pads
a day and has already has a bladder neck sling and treatment with bulking agents is one
such patient. During urodynamic evaluation, detrusor overactivity was noted; however,
given the severity of the stress incontinence, one cannot be totally sure how the bladder
will function when it is allowed to fill without almost continuous leakage because of an
incompetent sphincter. The fact that the patient does not leak while in bed at night and
only leaks on standing up gives some indication that it may not be abnormal detrusor
overactivity that is causing her problem. In this case, treatment of the bladder outlet first
would certainly be an appropriate option; however, the patient would need to understand
that treatment for overactive bladder symptoms may be necessary once she has adequate
sphincteric competence.
Certainly, another trial with a bulking agent is a good way to start treatment of this
patient; however, given that she has already failed multiple other bulking agent treatments,
the likelihood of success is perhaps diminished. She had already failed one autologous
fascial sling, although some of the failure may have been because of technical issues,
and one could try another fascial sling. However, another option that may give the best
chance of achieving adequate sphincteric resistance would be a synthetic midurethral
“wraparound” sling. These slings, which have recently been described and shown to be
effective, are formed by taking a long strip of synthetic mesh, then dissecting around the
urethra and passing the ends of the sling to the contralateral side above the urethra and
up and out through a prepubic incision. The success rates with these have been relatively
good; however, there certainly is a risk of requiring long-term intermittent catheteriza-
tion. Once the stress incontinence is addressed, any further issues related to overactive
bladder symptoms can be dealt with in the standard fashion.
Urinary Frequency and Pelvic Pain
12
A 41-yr-old woman complains of urinary frequency and pelvic pain. Three years
earlier, she began to have “recurrent urinary tract infections.” Cultures were always
negative. Since then, she has developed significant urinary frequency and pelvic pain that
seems to intensify when she needs to void. She also has significant dyspareunia and says
this is ruining her life. She has had a normal office cystoscopy, normal pelvic magnetic
resonance imaging (MRI), and urodynamic studies that show early sensation of need to
void but no detrusor overactivity or emptying problems. She has been on Elmiron, Atarax,
multiple anticholinergics, amitriptylene, and occasionally narcotics for the pain—all
without any significant improvement. On exam, she has no prolapse but does have diffuse
tenderness throughout the vagina and appears to have a tense pelvic floor by palpation.
How would you proceed with this patient?
COMMENTARY BY E. ANN GORMLEY, MD

Ideally, when a patient with this case history makes an appointment, they are asked to
send us all office notes from their primary care provider, other urologists, or gynecologists
and the results of all diagnostic tests pertaining to the diagnosis. The urodynamic tracings
and films are also obtained. After receiving and reviewing the appropriate records, a 30-min
visit is booked. With the information confirmed from our review of the correspondence,
the purpose of the first visit is to obtain more information from the patient and to begin
to treat the patient’s symptoms. In some cases, after a review of the records, additional
testing may need to be performed or repeated.
When the patient is first seen, a more detailed history is obtained. The following
questions are asked to add to the information that we already have:
1. Is her pain episodic or constant?
2. Does she have good days and bad days? How many bad days does she have per month?
3. How often does she void? What is the longest she can hold urine during the day and at
night when she is having a relatively good day?
4. Are her pain and or frequency at all related to her menstrual cycle?
5. More details are asked about previous treatments. Specifically, how long did she take
Elmiron and amitriptyline? Did she notice any improvement, and if so, was it her pain
or frequency or both that improved? Has she tried taking nonsteroidal antiinflammatory
drugs for the pain, and if so, have they helped?
6. Are her symptoms at all affected by diet, and if so, what foods are aggravating?
The physical exam is repeated to assess the patient’s ability to relax her pelvic floor.
This is done by asking the patient during the pelvic or rectal exam to first tighten and
then relax her pelvic floor.

391
The diagnosis is then explained to the patient. She is told that urinary tract infections,
urethral diverticulum, ovarian pathology, and bladder cancer have all been ruled out by
negative cultures and normal MRI and office cystography. The patient is told that the
most likely diagnosis is interstitial cystitis (IC). It is explained that the diagnosis is
based on her symptoms, the urodynamic finding of sensory urgency, and the lack of
other diagnosis. IC is described to the patient as a chronic inflammatory disease affect-
ing the lining of the bladder that waxes and wanes and that is rarely progressive. The
patient is advised that the goal of therapy is to control her symptoms, and like many
chronic diseases, the optimum treatment is long-term multimodality therapy. Further
explanation regarding what is and is not known about the disease is also provided.
Written patient information on the disease and treatment options, including the IC
Association patient education brochures on diet and sex, are also provided.
Treatment, based on the patient’s symptoms, is then prescribed. If she has noted that her
symptoms are affected by diet, the IC diet, published by the IC Association, is reviewed.
If the patient is unable to relax her pelvic floor, then she is offered a referral to
physical therapy to learn to relax her pelvic floor. Because pain is significant in this
patient, she is advised to take nonsteroidal antiinflammatory drugs daily, with 200 mg
feldene twice daily or 200 mg ibuprofen three times daily generally prescribed. If
ibuprofen is used, then additional ibuprofen, for a total of 800 mg three times a day, may
be taken during flares.
If amitriptyline was not tried for a minimum of 8 wk and was not given throughout
the day, then the patient is advised to try it again. Amitriptyline, with its anticholinergic
and antiinflammatory properties as well as its effect on neuropathic pain, is prescribed to
help pain, frequency, and sleep. Initially, 10 mg amitriptyline three times daily is prescribed
with a warning regarding severe fatigue for the first 2 wk. Patients who have not tolerated
the fatigue in the past are started with 10 mg at bedtime and then instructed to titrate the
drug by 10 mg when they are no longer tired. Once the patient has been on 10 mg three
times daily for 8 wk without adequate symptomatic relief, they are increased to 25 mg
three times a day.
If the patient fails amitriptyline as prescribed here, then neurontin is started. The
starting dose is 100 mg three times daily, and then the dose is titrated every 1–2 wk until
a maximum dose of 800 mg three times a day is reached.
Elmiron is restarted if the patient did not try it for at least 6 mo. Patients are
advised that Elmiron may take 6–12 mo before the full benefit is noted. Elmiron
instillations, consisting of 100 mg Elmiron mixed with a vial of sodium bicarbonate
and a vial of lidocaine, are used during flares for patients who describe good days and
bad days, or they may be used in patients who have chronic pain. Instillations are gen-
erally given three times per week for 2 wk, and patients can be taught to do their own
instillations.
A cystoscopy and hydrodistention under anesthesia are only performed when the out-
come will affect treatment or if the patient is going to undergo an anesthetic for some
other reason. Previously, hydrodistention was felt to be therapeutic; however, it rarely is,
and when it is, the results are often short-lived. A hydrodistention is often done prior to
considering dimethyl sulfoxide instillations or performing neuromodulation. The most
valuable piece of information that is obtained from the hydrodistention is the bladder
capacity. A good bladder capacity under anesthesia, more than 500–600 cc, bodes well
for the patient because long term if her pain can be controlled, then her frequency will
ultimately be controlled. Conversely, a poor bladder capacity under anesthesia (<200 cc)
Case 12 / Urinary Frequency and Pelvic Pain 393
is a poor prognostic sign because the patient will likely always have frequency even once
her pain is managed.
Bladder capacity can also be inferred by history and confirmed by having the patient
do a voiding diary in which she is asked to measure her output. The potassium sensitivity
test is not used because it is painful. The PUF score is administered at all office visits to
evaluate response to treatment.
Once patients are started or restarted on any or all of the drugs mentioned, plans are
made to see the patient in 3 mo. Patients are told to call prior to that if they would like
to consider Elmiron instillations or if their pain is poorly controlled. Patients who do not
get relief of pain with nonnarcotics are referred to a pain clinic prior to starting long-
term narcotic usage. If a patient has failed all of the behavioral and medical treatments
mentioned, sacral nerve stimulation may be considered. Patients are advised that sacral
neuromodulation with a sacral stimulator can be effective for patients with pain and
frequency from IC; however, little is known about the durability of the response. Pudendal
nerve stimulation has been shown to have an even greater improvement in frequency
and urgency than sacral nerve stimulation in IC patients, but even less is known about
durability. Dimethyl sulfoxide is offered to patients who have failed oral therapy prior
to consideration of sacral neuromodulation.
In conclusion, this patient with symptoms of IC would be offered combination
behavioral and medical therapy with a variety of drugs either alone or in combinations.
Efforts would be made to control her frequency and pain. She would be offered oral
therapies as well as intravesical agents before being offered neuromodulation. She would
be followed at 3-mo intervals both subjectively and objectively, with the final goal control
of symptoms so that she can lead a reasonably normal life.

Dr. Gormley has demonstrated well her evaluation as well as therapeutic options for a
patient with potential IC. She has correctly stated that numerous therapies have been used
and work in small series; however, no single treatment algorithm seems to have been able
to manage the majority of patients in this situation. Refractory therapies, neuromodulation,
and intravesical therapy have been only moderately successful. She is correct in her
statement that most patients will require some combined form of behavioral and medica-
tion therapy as well as potentially other more invasive therapeutic options for ultimate
management so they can resume a reasonable quality of life.
EDITOR’S NOTE
How would you manage this differently if the patients pain was not related to voiding?
COMMENTARY BY JEFFREY P. WEISS, MD

The history and evaluation presented is significant for having narrowed the long list
of possibilities of female pelvic pain to a disorder known as pelvic floor dysfunction
(PFD). Negative urine cultures rule out chronic cystitis; normal cystoscopy militates
against carcinoma in situ, although I would like to see normal urinary cytologies and
urine for acid-fast bacilli. Urethral swabs for chlamydia would be appropriate in the
course of the workup of this woman. An upper tract study to rule out hydronephrosis
or hydrocalyx should accompany the workup to exclude genitourinary tuberculosis.
High-pressure/neurogenic voiding dysfunction is excluded by the normal urodynamic

studies; the neurourologic exam was presumably normal.
Diffuse, as opposed to focal, vaginal tenderness plus a normal pelvic MRI and
absence of infection are taken to exclude the diagnosis of urethral diverticulum, which
are commonly associated with female lower urinary tract symptoms and dyspareunia.
IC often presents with pain relieved by voiding, which is not the case in our 41-yr-old,
who in any case did not respond to Elmiron. A 24-h voiding diary would be useful to
evaluate the typical volume of her voids and whether bladder capacity is better during
hours of sleep than day. If that were the case, then a functional as opposed to physical
explanation for her symptoms would exist. Urodynamic demonstration of a stable detrusor,
albeit with early sensation to void, along with diary evidence for small volume voids
suggest a diagnosis of sensory urge voiding dysfunction. However, the constellation of
detrusor hypersensitivity, pelvic pain/tenderness, and dyspareunia all point to the diagnosis
of PFD.
The pathogenesis of PFD is thought to be related to discoordination and excessive
tone of the pelvic floor musculature (PFM). Elements of PFM include the pubovaginalis,
puborectalis, iliococcygeus, as well as related anal sphincter, obturator internus, and
piriformis muscles. The PFM forms a hammock in the pelvis and acts as a sling for the
rectum, vagina, and urethra. Owing to the complex relationship between the various
components of these pelvic structures, it is not surprising that on occasion there is failure
of appropriate contraction and relaxation, as exemplified by inappropriate contraction
of the vaginal sling muscles during intended intercourse, at which point contraction of
both the urethral and anorectal hammocks is appropriate.
A theory regarding the etiology of pelvic pain has been proposed as caused by excessive
tension in relatively short pelvic floor muscles, the short pelvic floor. Related lower urinary
tract symptoms and dyspareunia may be treated by pelvic floor reeducation techniques,
which involve biofeedback-mediated recognition of pelvic muscle function/contraction
as well as local physiotherapy of the involved muscle bellies and their tendinous inser-
tions. These structures may be identified as excessively tense by experienced urologists
and physical therapists and may respond to therapy that emphasizes myofascial release
of trigger points identified during digital rectovaginal examination.
Administration of low-dose benzodiazepines (e.g., diazepam) as well as warm baths
may be useful adjuncts to massage-related therapy. Constipation should be identified
and treated in the standard fashion. Instructing patients to relax during micturition and
defecation will thwart the tendency to further tense pelvic floor structures, which have
a primary function of maintenance of continence. Transrectal administration of low-
intensity electrical stimulation is useful in patients who are not excessively sensitive to
such stimuli and can help create an awareness of their voluntary pelvic floor muscles to
teach contraction/relaxation, with emphasis on the latter. Bladder hydrodistension and
instillations, topical hormone creams, urethral dilatation, anticholinergics, and F-blockers
have not generally been helpful in treatment of these patients.
In summary, the emphasis in treatment of PFD is pelvic floor muscle relaxation to
match pelvic muscle tightness and spasm as its suspected pathophysiology.
REFERENCES
1. Fitzgerald MP, Kotarinos R. Rehabilitation of the short pelvic floor. I: Background and patient evalu-
ation. Int Urogynecol J 2003;14:261–268.
Case 12 / Urinary Frequency and Pelvic Pain 395
2. Fitzgerald MP, Kotarinos R. Rehabilitation of the short pelvic floor. II: Treatment of the patient with
the short pelvic floor. Int Urogynecol J 2003;14:269–275.
3. Weiss JM. Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the
urgency-frequency syndrome. J Urol 2001;166:2226–2231.
4. Butrick CW. Discordant urination and defecation as symptoms of pelvic floor dysfunction. In: Pelvic Pain.
Diagnosis and Management (Butrick CW, ed.), Lippincott, Williams, and Wilkins, Philadelphia, 2000.

Dr. Weiss has touched on a common issue that I think is often overlooked in the
majority of general urologic as well as female urological care and that is pelvic floor
dysfunction (PFD). One must realize that patients with PFD may present with a variety
of symptoms and complaints, and he has appropriately isolated this. In our experience one
should have access to a good physical therapist or other specialist to help in evaluating and
managing these patients as often this is our first line of therapy and can be successful. It
seems that many patients have never been treated appropriately for this, and I believe
that once this continues long term they do not respond quite as well to the simple thera-
peutic measures that he has described. In these cases, selectively they may require more
invasive management, including neuromodulation, as the next step in management.
13 Pelvic Organ Prolapse
A 55-yr-old woman presents with significant apical and anterior vaginal wall prolapse.
She had a hysterectomy 5 yr earlier and a cystocele and rectocele repair and uterosacral
vault suspension 2 yr ago. Currently, she is bothered by the prolapse, has difficulty voiding,
and has a postvoid residual (PVR) of 200 cc. She does not note any incontinence. She
is not interested in a pessary.
What further work-up is required? How would you treat her?
COMMENTARY BY SHLOMO RAZ, MD

AND MATTHEW P. RUTMAN, MD
A new patient presenting with voiding symptoms and prolapse would undergo a
complete evaluation. This would include a routine history and physical examination.
History should document any prior anti-incontinence procedure. Pelvic examination
would be evaluated by the Pelvic Organ Prolapse Quantification grading system. Urinalysis
and PVR would be checked.
With a history of previous surgery and elevated PVRs, this patient would undergo
evaluation with videourodynamics, magnetic resonance imaging (MRI) for prolapse,
and cystoscopy. Urodynamics evaluation would evaluate the patient for stress inconti-
nence, detrussor instability, obstructive voiding, and demonstrate the grade of cystocele
with the patient in standing position. In our experience, performing urodynamics is
critical in patients with prior surgery or voiding complaints. The MRI study provides
excellent anatomic pictures of the anterior, apical, and posterior vaginal wall and often
shows more prolapse than that seen on pelvic examination. Patients with severe anterior
wall prolapse develop obstructive uropathy in up to 5% of cases, and MRI includes
upper tract imaging. MRI also rules out any concomitant pelvic pathology, such as ovarian
disease. Cystoscopy is performed in patients with voiding symptoms and prior surgery
and is important to document absence of suture or foreign body.
Based on the patient’s desire to avoid a pessary, we would recommend surgical
correction. In a patient with significant apical and anterior vaginal wall prolapse, it is
rare not to have posterior wall and perineal body descent. If the patient has not had a
prior anti-incontinence procedure, then we place a prophylactic sling along with cystocele
repair. In our series of over 600 distal urethral polypropylene slings, no patients are in
retention. It is a 20-min procedure that adds no morbidity. No anti-incontinence procedure
is done if the patient had a prior bladder neck procedure and is obstructed clinically
or urodynamically.
Based on prior experience with failures of slings and cystocele repair without
surrogate materials, we now advocate total mesh reconstruction. This is based on the
premise that sewing attenuated tissues together will not provide a durable repair. This

397
mesh reconstruction includes a mesh sling, paravaginal mesh repair for the cystocele,
and a mesh reconstruction for vault/enterocele/rectocele, even in patients with no
prior failures.
The patient is placed in the lithotomy position and prepped in standard sterile fashion.
Intravenous antibiotics are administered, and a ring retractor is positioned. A distal urethral
polypropylene sling is placed as previously reported.
Attention is now turned to repair of the grade IV cystocele. The cuff of the vagina is
marked. A vertical incision is made from the bladder neck to the cuff of the vagina.
Dissection is performed around the perivesical fascia laterally to expose the obturator
fascia and distally to the bladder neck. Proximally, the enterocele sac is identified and
freed completely from the rectal wall posteriorly and bladder anteriorly. Two laparotomy
pads are inserted into the peritoneal cavity, and the bladder is retracted anteriorly. A soft
Prolene mesh in the shape of a T is prepared. The center segment is 3 × 7 cm with two
lateral segments of 4 × 1 cm.
To repair the vaginal vault, a 1-0 Vicryl suture is placed through the vaginal wall in
the area of the cuff. It is then passed into the peritoneal cavity, between the levator and
rectal wall, incorporating the perirectal fascia and the origin of the sacrouterine ligament
1–2 cm from the sacrum. After incorporating a strong bite of tissue, the transverse
arm of the mesh is included, and a second purchase of the sacrouterine ligament is taken.
The needle is brought out the vaginal wall 1 cm from the original entrance. The same
maneuver is performed on the contralateral side.
The enterocele sac is now closed. Two 1-0 Vicryl sutures are placed in a purse-string
fashion to incorporate prerectal fascia, the transverse segment of the mesh, lateral peri-
toneum, and perivesical fascia. The laparotomy pads are removed, and the purse-string
sutures are secured and left tagged. Attention is now turned to repair of the grade IV
cystocele. Interrupted sutures of 3-0 Vicryl are used to approximate the central defect.
This helps reduce the central defect to assist in the repair but does not provide strength
and durability. The obturator fascia is identified bilaterally, and 2-0 Vicryl sutures are
placed, incorporating a strong bite of the fascia on the side.
Cystoscopy is performed after injection of indigo carmine, and good excretion
from both ureters is confirmed. Suprapubic catheter position is confirmed, and blad-
der and urethral injury are excluded. The central defect sutures are tied. A 5 × 5 cm
disk of soft Prolene mesh is prepared. The base of the mesh is approximated to the
area of the sacrouterine ligament (enterocele suture). Laterally, the mesh is approxi-
mated to the obturator fascia and distally to the bladder neck. The vault suspension
sutures are tied, providing depth and support to the vaginal cuff. The excess vaginal
wall is excised, and the anterior vaginal wall closed with runs of 3-0 and 2-0 Vicryl
suture. Prior to closure, the vertical segment of mesh is transferred to the posterior
vaginal wall.
The rectocele is now repaired as previously reported. Dissection is carried out on
the prerectal fascia to the opening of the mesh at the vaginal cuff. A 1-cm rectangular
strip of posterior vaginal wall is excised to expose the prerectal fascia. The mesh is
applied over the prerectal area. The rectocele is repaired by incorporating anterior
vaginal wall and perirectal fascia with running and interrupted sutures. Interrupted
sutures of 2-0 Vicryl approximate the perineal membrane and the levator plate in the
midline in the distal 4 cm of the vagina, obtaining significant elevation and restoration
of the normal vaginal axis. A vaginal packing soaked with antibiotic is inserted in the
vagina, and the patient is discharged the following day.
Case 13 / Pelvic Organ Prolapse 399
COMMENTARY BY KATHLEEN C. KOBASHI, MD

History
Some aspects of the history should be clarified. Understanding of the patient’s
symptomatology can be important in directing proper counseling so that the patient has
appropriate expectations postoperatively.
How, specifically, is she bothered by the prolapse?
What would she like to have “fixed” or “changed” by undergoing surgery?
What specific difficulties is she having with voiding? Urgency? Frequency? Decreased
force of stream? Hesitancy? Sensation of incomplete voiding?
Any trouble with urinary tract infections?
Physical Examination
A physical examination should be performed to assess the following:
Components of prolapse.
Degree of pelvic prolapse.
Estrogen status.
Presence or absence of overt or occult stress urinary incontinence (SUI) (examination
with and without reduction of prolapse).
Position of urethra and urethral mobility.
Urodynamics
To obtain as much information as possible to facilitate proper counseling of the
patient about reasonable postoperative expectations, urodynamics should be performed
to evaluate the following:
1. Bladder function/stability/compliance.
Those patients who are found to have instability or decreased compliance should be
counseled on the possibility that they may experience no improvement or even
exacerbation of symptoms related to these findings (i.e., urinary frequency, urinary
urgency/urge incontinence). They may require further therapy or need to continue
preoperative therapy (e.g., medications, dietary or behavioral modification, bladder
training, and so on) to address these symptoms if they should persist or arise.
2. Bladder capacity.
Patients should be counseled that bladder capacity may or may not be affected by
pelvic floor reconstruction. For instance, in the patient who is experiencing symptoms of
urgency/frequency as a manifestation of mechanical bladder outlet obstruction caused
by kinking of the urethra secondary to the prolapse, reduction of the prolapse may
effectively increase bladder capacity by decreasing the obstructive urinary symptoms.
Conversely, in those who have primary symptoms of frequency/urgency (unrelated to
the prolapse), reconstruction may have no effect.
3. Bladder emptying.
With concomitant sling placement, subsequent incomplete bladder emptying or
complete urinary retention is always a possibility. In those who have baseline retention
of any degree, emptying ability may or may not be affected by reduction of the
prolapse.
4. Presence or absence of SUI with and without reduction of the prolapse.

Whether to place a sling concomitant with anterior compartment reconstruction
regardless of whether SUI is demonstrated is controversial. It is my practice to
proceed with sling even in those patients in whom SUI is not demonstrated in light
of the literature that suggests a relative and not insignificant risk of postoperative
SUI even when SUI is not demonstrated preoperatively (1). There are always
exceptions to this rule, and one must treat each patient on a case-by-case basis. One
exception to this practice includes the patient with a well-supported urethra from
previous antiincontinence surgery and no objective SUI or complaints of SUI, such
as in this case.
At my institution, Valsalva leak-point pressure (VLPP) measurements are used some-
what to guide the choice of sling material, sling placement technique/approach, and
sling tension. How VLPP affects the outcomes of various slings is currently under
evaluation.
5. Pressure flow analysis.
This measure can be somewhat difficult to interpret in women as females tend to void
with low detrusor pressures. It is important to note, for instance, the patient who has
low flow and low voiding detrusor pressures with or without baseline elevated PVRs.
This patient is at risk for postoperative urinary retention, perhaps requiring intermittent
self-catheterization, and she needs to be counseled on this preoperatively.
Cystoscopy
Cystoscopy should be performed to evaluate for
Trabeculation/cellules: The presence of trabeculation and cellules indicates some func-
tional pathology, such as detrusor overactivity or bladder outlet obstruction.
Other pathology (e.g., bladder tumors, stones): These findings must be addressed before
proceeding with pelvic floor reconstruction.
Foreign body (e.g., suture from previous surgery): Foreign body can contribute to
irritative voiding symptoms.
Treatment
Assuming that the patient is healthy, I would counsel her on the following options:
1. Open abdominal sacrocolpopexy (ASCP) with concomitant cystocele repair with or
without sling.
ASCP is considered by many to be the current gold standard for repair of vault
prolapse. It restores the vault with excellent depth and position without deviation
of the vagina to one side or another as seen with the sacrospinous ligament fixation.
Success rates reported in the literature are high (2,3), although the ASCP does involve
the morbidity of an abdominal incision and the prolonged recovery period associ-
ated with transperitoneal surgery. I use soft polypropylene mesh fashioned into a
Y configuration and sacral bone anchors to secure the repair to the sacrum.
Regardless of the graft material used to suspend the vault to the sacrum, there have
been reports of transvaginal extrusion of the material (4). In many cases, this requires
complete removal of the mesh and puts the patient at risk for failure of the repair and
intra-abdominal infection.
2. Laparoscopic sacrocolpopexy with concomitant cystocele repair with or without sling.

In the case presented here, assuming the patient has not undergone multiple abdominal
surgeries, laparoscopic sacrocolpopexy would be my choice. In my experience, patients
are typically discharged on postoperative day 1 (23-h observation). This patient
should be counseled on the risks of laparoscopic surgery, including possible conver-
sion to open surgery, in addition to the risks of infection or vaginal extrusion of the mesh
and infection or inflammation of the bone anchors, possibly requiring removal.
3. Transvaginal repair using levator myorraphy with concomitant cystocele repair with or
without sling.
This is an excellent option in those patients who do not wish to undergo abdominal
surgery or who are not candidates for such surgery. The success rate is not as high
as that seen with the sacrocolpopexy (5), but the transvaginal approach affords the
patient advantages over that seen with abdominal surgery, whether open or laparo-
scopic. In this case, I would use a segment of cadaveric fascia for the cystocele
repair, which would be secured apically by the levator myorraphy stitches prior to
their passage through the vaginal wall to provide reinforcement of the repair both
apically and anteriorly.
4. A recently introduced technique for a synthetic graft-reinforced transvaginal vault
suspension (6) is also an option.
This technique involves placement of a T-shaped polypropylene graft from the
sacroureterine cardinal ligament complex to just above the perineal body to support
the vault and the pelvic floor. The technique is new and is not currently employed
at my institution, with our biggest concern being placement of a considerable size
synthetic mesh intraperitoneally for the vault suspension and adjacent to the rectum
for the rectocele repair as described (although in this case a significant rectocele is not
presented). The concern is the risk of visceral adhesions prompted by the polypropylene
mesh and rectal erosion of the graft.
My current technique of choice for anterior compartment repair is a variation on the
CaPS technique (7), which incorporates a single piece of solvent-dehydrated, nonfrozen
cadaveric fascia lata in a simultaneous cystocele repair with sling. In my institution, this
technique has evolved to involve a polypropylene mesh sling placed pubovaginally,
transvaginally, or via the transobturator approach with concomitant fascial reinforcement
of the anterior compartment reconstruction. We continue to use cadaveric fascia for the
cystocele repair despite recent reports of less-than-optimal outcomes with cadaveric
fascial slings as our outcomes with the anterior compartment reconstruction have
continued to be favorable with continued follow-up.
This particular case presents a potential exception to my general practice to proceed
with a sling concomitant with repair of a large cystocele. In light of the fact that the patient
has undergone previous surgical repair of prolapse (although it is unclear regarding
whether she underwent a concomitant anti-incontinence procedure or what the current
position of the urethra is on physical examination) and that she is experiencing incomplete
bladder emptying and “difficulty voiding,” consideration of a concomitant sling poses
somewhat of a dilemma. Urodynamics, specifically the pressure flow analysis, should
be helpful in making this decision. In addition, further questioning regarding what she
means by difficulty voiding would be useful.
If the pressure flow analysis indicates outlet obstruction even with reduction of
the prolapse, then I would not proceed with sling and would counsel the patient that
she may likely continue to experience voiding difficulty and incomplete emptying
postoperatively despite repair of the prolapse. Unfortunately, she is also at risk for
development of SUI, although this may be less likely if she does not demonstrate any
change in her voiding or the presence of SUI with prolapse reduction.
If, on the other hand, she demonstrates SUI and complete bladder emptying with
reduction of the prolapse, then concomitant sling placement would be performed. The
method by which I currently determine sling material and technique is undergoing eval-
uation to determine its validity, but in short, if the VLPP is high, then she would be
offered a polypropylene sling placed transvaginally with bone anchors, pubovaginally,
or by the transobturator approach. If the VLPP is moderate to low, then the transob-
turator approach would not be considered. If the VLPP is excessively low, then she would
also be counseled on autologous fascia pubovaginal sling.
If SUI is seen in the face of a fixed urethra, concomitant partial (lateral) urethrolysis
may be considered to render the urethra “compressible” enough to benefit from a sling.
Detailed conversation regarding risks, benefits, and alternatives is imperative to
ensure that the patient’s expectations are realistic. In a patient with baseline retention,
exacerbation of the retention requiring intermittent catheterization is clearly a risk. In
addition, the risk of postoperative SUI, urgency, frequency, and slow stream, as well as
the risks inherent in placement of a foreign body (urinary tract erosion, vaginal extrusion,
infection, or inflammation of the mesh or bone anchors, if used) should be presented.
Finally, if she undergoes an autologous fascial sling, I would preferentially choose rectus
fascia over fascia lata to minimize morbidity. However, if she has reason to have poor
rectus fascia, such as pelvic radiation, steroids, multiple abdominopelvic surgeries, and
so on, then fascia lata would be considered. The risks associated with harvesting at the
selected site would be reviewed in detail with the patient.
REFERENCES
1. Gallentine ML, Cespedes RD. Occult stress urinary incontinence and the effect of vaginal vault
prolapse on abdominal leak point pressures. Urology 2001;57:40–44.
2. Maher C, Baessler K, Glazener CM, Adams EJ, Hagen S. Surgical management of pelvic prolapse in
women. Cochrane Database Syst Rev 2004;(4):CD004014.
3. Nygaard IE, McCreery R, Brubaker L, et al. Pelvic Floor Disorders Network: abdominal sacro-
colpopexy: a comprehensive review. Obstet Gynecol 2005;104:805–823.
4. Begley JS, Kupferman SP, Kuznetsov DD, et al. Incidence and management of abdominal sacro-
colpopexy mesh erosions. Am J Obstet Gynecol 2005;192:1956–1962.
5. Lemack GE, Blander DS, Margulis V, Zimmern PE. Vaginal vault fixation and prevention of entero-
cele recurrence by high midline levator myorraphy: physical examination and questionnaire-based
follow-up. Eur Urol 2001;40:648–651.
6. Rutman MP, Deng DY, Rodriguez LC, Raz S. Repair of vaginal vault prolapse and pelvic floor
relaxation using polypropylene mesh. Abstract presented at: SUFU 2005; Orlando, FL.
7. Kobashi KC, Mee SL, Leach GE. A new technique for cystocele repair and transvaginal sling: the
cystocele repair with sling (CaPS): Urology 2000;56(suppl 6):9–14.

The authors have done an excellent job summarizing the evaluation and treatment for
a patient with recurrent pelvic organ prolapse. It is debatable whether an MRI of the
pelvis is necessary in all patients, as it can significantly add to the cost of the evaluation
at most centers but may not ultimately change the operative approach or outcomes.
It does, however, benefit the surgeon in revealing occult defects and give additional
preoperative information. Concerning the treatment, both authors discussed the possibility
of doing a transvaginal technique utilizing a synthetic mesh. There are now commercially
available kits that can facilitate such a technique; however, the costs of the kits are signi-
ficantly higher than cutting one’s own mesh, as described by these authors. Long-term
outcomes are still not available.
14 Recurrent Pelvic Organ Prolapse After
Colpocleisis
A 72-yr-old woman presents with total pelvic prolapse. She also notes occasional
incontinence when she sneezes. She had a colpocleisis 3 yr ago. She is bothered by the
prolapse. Exam reveals a significant vault prolapse with an introitus that easily admits
four fingers.
How would you proceed?
COMMENTARY BY RAYMOND RACKLEY, MD

For this 72-yr-old woman who chose a previous surgical intervention consisting of a
vaginal obliterative procedure in the past, the option of a pessary or total vaginal length
restoration as part of her pelvic prolapse repair are less likely to match her needs and
expectations.
The finding of the pelvic organ prolapse recurrence in the setting of a large vaginal
hiatus suggests that a likely reason for failure of the previous colpocleisis was the failure
to provide a robust perineal body reconstruction, which often includes a distal rectocele
repair at the time of colpocleisis. Thus, a repeat colpocleisis procedure using a
biodegradable or absorbing synthetic mesh interposition with high perineal body repair
and distal rectocele repair with tension-free midline approximation of the levator muscle
surrounding the vaginal hiatus would be an excellent first choice for a reconstructive
option. If during the procedure the surgeon was not pleased with the quality of the tissue
for colpocleisis repair, then a unilateral sacrospinous fixation procedure with the same
attention to high perineal body and rectocele repair with levator approximation would
be an excellent second option as enough vaginal depth to reach the sacrospinous ligament
is suggested by the finding of recurrent “total” pelvic organ prolapse. A third choice
includes the use of the newer transvaginal tape procedures for vault suspensions, which
would provide adequate apical stabilization of the vagina, but poor vaginal depth.
However, vaginal depth is not needed in this case, but there is no extensive reported
experience in performing these vaginal tape procedures for failed pelvic organ prolapse
reconstruction.
In light of the symptoms of stress incontinence, urodynamic testing should confirm
the presence of the signs of the symptoms and determine the leak-point pressure that
guides the optimal sling intervention (platform transobturator sling for a high leak-point
pressure or low voiding detrusor pressure vs a suspending sling for low leak-point pressure
in the setting of normal voiding detrusor pressure). The timing of the chosen sling
procedure should precede the pelvic organ prolapse repair as exposure to the midurethra
and bladder neck will be limited after a robust posterior repair.

405
Fig. 1.
While waiting to perform the reconstructive procedure, the patient’s vaginal tissue
may be optimized for the surgical repair by instituting topical vaginal estrogen replacement
therapy for several months.

The finding of a 72-yr-old postcolpocleisis with recurrent prolapse is certainly rare.
Dr. Rackley has demonstrated that the appropriate type of repair usually is not simply
resuspending or support of the apical vaginal segments, but a robust distal vaginal
reconstruction in the form of the rectocele and perineal body to prevent further descent.
Furthermore, in our experience, it seems to be that many of these patients will require
some form of anti-incontinence procedure, and often they are subject to having voiding
dysfunction for which they may require longer term catheterization, or in many cases
we will simply place a suprapubic tube as the voiding dysfunction may be persistent for
some time. It becomes even more challenging to manage a patient with bladder outlet
obstruction that may be de novo after placing a sling in a colpocleisis patient as often
the vaginal canal is obliterated. Accordingly, one should be careful in placing sling
tension in these complex patients.
15 Stress Incontinence and Straining to Void
A 45-yr-old woman presents with stress urinary incontinence (SUI). On questioning,

she notes the need to strain to fully empty. A pressure flow study shows straining during
voiding but a Qmax of 21 mL/s. SUI is present on cystometrics with a Valsalva leak-point
pressure of 120 cm H2O. Exam shows a Q-tip test of 0–40° and no prolapse.
Is any further evaluation necessary? What would you recommend for treatment of
her SUI?
COMMENTARY BY STEVEN SIEGEL, MD

This case presentation demands an exploration of possible bladder outlet obstruction
(BOO) in conjunction with the presenting complaint of SUI. Although BOO in women
is relatively rare, the most common causes include iatrogenic obstruction from a prior
incontinence or prolapse repair, factors related to simultaneous pelvic prolapse, and
pelvic floor muscle spasticity with dysfunctional voiding. Less-common causes include
primary BOO, urethral stricture, malignancy, diverticulum, ectopic ureterocele, and
Fowler’s syndrome or pseudomyotonia of the external urethral sphincter.
Although the patient admits she must strain to empty, the history does not include
mention of any irritative voiding complaints. One would usually expect to find them in
women with BOO. There is no prior history of prolapse repair or antiincontinence surgery.
The physical exam indicates a degree of urethral hypermobility, but there is no prolapse
identified, which probably rules out prolapse as the cause. Finally, the urodynamic
exam demonstrates a normal filling phase, except for SUI with a relatively high leak-
point pressure. During the voiding phase, she develops a strong detrusor contraction
augmented by abdominal straining, a peak flow rate that is relatively normal, and evi-
dence of near-complete bladder evacuation. Is she obstructed? If so, what is the cause?
How do the answers impact the plan for treatment of her SUI?
First, is she obstructed? My gut sense is yes. I would rely on my clinical judgment
here and be careful to document the behavior of the pelvic floor musculature (PFM) on
physical exam. Does she relax adequately and contract efficiently, indicating a normal
range of motion of the PFM, or is there spasticity and tenderness even at rest, with
limited ability to isolate or further increase the muscles or effect the tone on command?
If these things were documented and a cystoscopy showed no visual evidence of an
obstruction, then I think I would not be tempted to do any additional evaluation and would
recommend a course of PFM electromyographic biofeedback to her, with the expecta-
tion that she could learn to void with relaxed PFM, and that the improved range of motion
from relaxation to coordinated contraction would be enough to resolve both the voiding
dysfunction and the SUI. If only the voiding dysfunction were to be improved, then the
treatment of the SUI would be greatly simplified.

407
Fig. 1.
Fig. 2.
Case 15 / Stress Incontinence and Straining to Void 409
Beyond clinical intuition, the objective determination of BOO in women is hard to

know. Using the Blaivas and Groutz nomogram (1), a Qmax of 21, and Pdet at Qmax of 45
puts her in the mildly obstructed zone. Nitti et al. (2) suggested that simultaneous video
imaging and pressure flow studies greatly aids the evaluation and diagnosis of BOO.
This is less likely to be true when there is adequate detrusor contractility, as in this
example. Radiographic imaging in the form of a videourodynamic study or fluoro-voiding
cystourethrography would be helpful to assess this complaint further if there was no
clear evidence of PFM dysfunction. An upright rest-stress cystogram would also be
helpful to rule out a significant degree of cystocele in the unlikely event that it was
missed on physical exam. In addition, the voiding phase of such a study may also elucidate
a diverticulum that was not otherwise identified. Finally, cystoscopy is essential to rule
out a local factor responsible for obstruction.
If a specific cause of obstruction were identified, then it would need to be resolved
prior to or as a part of her SUI management. I would be reluctant to recommend surgical
treatment for her SUI complaint unless the voiding dysfunction or other cause for her
emptying complaint is resolved because a midurethral sling is likely to compound the
difficulty whether done via a transobturator or retropubic route. An abdominal retropubic
bladder neck suspension such as a Burch procedure may offer less risk of obstruction,
but it is also less reversible should it prove unsatisfactory.
REFERENCES
1. Blaivas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract
symptomatology. Neurourol Urodyn 2000;19:553–554.
2. Nitti VW, Lefkowitz G, Ficazzola M, et al. Lower urinary tract symptoms in young men: videouro-
dynamic findings and correlation with noninvasive measures. J Urol 2002;168:135–138.

Dr. Siegel reviews all the pertinent points dealing with a woman with stress inconti-
nence who also may have BOO. The maximum flow rate of 21 cc/s, however, makes
one wonder the degree of obstruction, if any, that really exists. Care must be taken in
this subgroup of patients to ensure that one does not to anything that could potentially
increase the degree of obstruction. A midurethral transobturator sling may prove useful
in this case if she continues to have stress incontinence after various pelvic floor
relaxation and other potential treatments have been tried. There is some early evidence
that indicates that there may be less risk of urethral obstruction given the relatively
flatter position of the obturator slings than with the standard retropubic-type slings.
Nevertheless, good counseling of the patient at all steps of her evaluation and treatment
is crucial in a case like this.
16 Male With Post-Prostatectomy
Incontinence
A 64-yr-old man is 2 yr postradical retropubic prostatectomy for prostate cancer. He

currently leaks and uses two to three thick pads per day. He does not leak at night
while in bed and can sleep through the night without needing to urinate. Prostate-specific
antigen is undetectable.
What workup is necessary? What are the treatment options? What would you recom-
mend?
COMMENTARY BY CRAIG V. COMITER, MD

This gentleman suffers from postprostatectomy incontinence (PPI), which may be
caused by bladder or outlet dysfunction. Bladder causes of incontinence include detrusor
overactivity (DO), diminished vesical compliance, and overflow incontinence caused by
a noncontractile bladder. Outlet causes of leakage include intrinsic sphincter dysfunction
(ISD), and outflow obstruction (usually because of anastamotic stricture), which may lead
to DO or overflow incontinence. Because he is 2 yr out from surgery, his symptoms are
unlikely to improve spontaneously.
History and physical examination may not lead to a definitive diagnosis. Although
ISD is the most common finding in men with PPI (especially stress incontinence), bladder
dysfunction (detrusor overactivity or underactivity, diminished vesical compliance) is also
common. In addition, significant bladder outlet obstruction (BOO) should be ruled
out prior to consideration of pharmacological or surgical therapy. It is therefore essential
to evaluate patients suffering from PPI with multichannel urodynamics. Filling cysto-
metry is used to assess sensation, compliance, and the presence of unstable contractions.
Measurement of leak-point pressure (antegrade or retrograde) is useful for quantifying
the degree of ISD. Pressure flow study allows the examiner to rule out significant BOO.
Cystoscopy is indicated to rule out anastamotic stricture and urethral foreign body
(suture or clip).
DO is best treated with a combination of behavioral modification (pelvic floor exercises,
fluid restriction, timed voiding) and pharmacotherapy (antimuscarinic medication). BOO,
if significant, may be managed by dilatation or incision of any strictured area of the
vesical-urethral anastamosis, although this can result in new or worse stress inconti-
nence. ISD is often initially managed with a trial of pelvic floor exercises, fluid restriction,
and timed voiding. Unfortunately, evidence that pelvic floor exercises have any efficacy
for PPI outside the immediate postoperative period is generally lacking. In patients such
as this man, who is 2 yr out from his prostatectomy, surgery is usually required for the
successful treatment of significant stress incontinence.

411
The lack of supine leakage and absence of nocturia supports a diagnosis of ISD
without significant bladder dysfunction. One of the most important aspects of the man-
agement of PPI caused by ISD is to set realistic expectations of treatment outcome. For
milder cases of ISD, periurethral bulking agents may suffice. With more severe leakage,
injection therapy is unlikely to lead to a satisfactory outcome. Carbon-coated zirconium
beads in G-glucan gel (Durasphere, Boston Scientific, Natick, MA) and bovine glu-
taraldehyde crosslinked collagen (Contigen, Bard, Covington, GA) are the most popular
injectable agents for stress urinary incontinence caused by ISD in men. Cure rates with
transurethral retrograde collagen injection have generally been low for PPI, ranging
from 5 to 20%. Antegrade injection may be associated with slightly higher success rates.
Polydimethylsiloxane (Macroplastique, Uroplasty, Minneapolis, MN) is a newer agent
that has been shown to have moderate benefit for treating PPI, with success rates of 40%
at 1 mo but diminishing to 26% at 12 mo. In general, periurethral bulking agents fail to
provide satisfactory continence more than half the time.
The most successful surgical treatments for the management of PPI caused by ISD
are artificial urinary sphincter (AUS) surgery and male sling surgery. For the past
three decades, the AUS has proven to be the most effective long-term solution for male
stress urinary incontinence caused by ISD, with success rates between 75 and 90% in
most modern series and patient satisfaction rates of 85–95%, despite the frequent
necessity for surgical revision. Because of the circumferential compression of the ure-
thra, the corpus spongiosum invariably atrophies, and revision rates range from 17 to
21% at 5 yr to 65 to 80% at 10 yr. Complications requiring immediate reoperation
(infection, erosion) are generally less than 5% but can be as high as 10% in radiated or
reoperative patients.
Sling surgery has emerged as a viable alternative to AUS surgery, with similar satis-
faction rates and a lower incidence of infection and erosion. Based on the Berry prosthesis
described in 1961, multiple incarnations of the perineal sling have come in and out of
vogue. Such devices included the Kaufman prostheses from the 1970s and the North-
western abdominal-perineal sling from the 1990s. Perhaps the most significant innovation
affecting male sling surgery has been the use of bone screws. Bone fixation obviates the
abdominal incision, has transformed the surgery into a minimally invasive outpatient
procedure, and has led to a substantial reduction in perineal pain when compared to
suprapubic/rectus fascial fixation. Synthetic slings are associated with a substantially
higher success rate than are organic slings, with patient satisfaction and continence rates
generally as high as those achieved with AUS surgery.
Occasionally, certain patient factors dictate surgical therapy. If a patient lacks
adequate manual dexterity, then he may not be able to operate the AUS scrotal pump.
On the other hand, a patient must have adequate detrusor contractility to overcome the
fixed resistance of the perineal sling. In addition, in patients after full-course external
beam radiation therapy, AUS surgery is associated with more predictably favorable
outcomes than is sling surgery. Finally, in those who have had previous AUS implan-
tation, revision or reoperative AUS placement is more likely to succeed than is sling
surgery.
In this particular patient, if the urodynamics support the diagnosis of ISD with a
relatively normal bladder, I would recommend sling surgery. Although there is currently
insufficient data to support the superiority of one approach over the other, the bone-
anchored perineal sling is associated with fewer complications than the AUS, and the
revision rate for sling surgery is less than that for AUS surgery. In addition, unsuccessful
Case 16 / Male With Post-Prostatectomy Incontinence 413
Fig. 1.
sling surgery does not alter the difficulty or success rates of subsequent AUS placement.
On the other hand, failed AUS surgery may lead to urethral fibrosis, which may preclude
sling surgery in the future.
COMMENTARY BY FRED E. GOVIER, MD

As with most medical problems, we must begin with the history of present illness.
I would first want to know the timeline of the urinary leakage. Was leakage severe after
the prostatectomy, slowly improved, and now has not changed over the past year, or was
the leakage a lot better at some point after surgery and is now getting worse? What is
the character of the leakage? Is it stress incontinence, urge incontinence, or incontinence
without his knowledge? When he first arises in the morning, can he make it to the toilet,
or does he leak on the way? Once he gets to the toilet, is there any problem starting the
stream, does he have to use abdominal straining, how forceful is his stream, and does
he feel that he empties his bladder? Has he had radiation therapy, or has he had any
anastomotic strictures dilated since the prostatectomy?
Because erectile dysfunction is also common after this operation, I would want to know
about his function before the operation and at present. If the patient is not functional
now, what are his desires in the future? If he is not functional now and desires therapy,
then I would discuss which prior treatment options he has explored and the results he
has achieved.
Looking at his past medical history, I would want to know about any significant
medical or surgical issues that would affect placement of a male sling, AUS, or inflatable
penile prosthesis.
During the physical examination, I would conduct a brief neurological exam to ensure
he had the dexterity and strength to manipulate a sphincter. I would want to know about
any abdominal wall or inguinal hernias, any lymphadenopathy or rectal masses, and
whether the condition of the skin around the genitalia was healthy.
In my practice, this patient would undergo videourodynamic testing. I would start
by looking at his flow rate and urinalysis to rule out a urinary tract infection or hema-
turia. Next, I would examine his flow characteristics and residual urine. I would look
at his bladder capacity, his compliance and rule out detrussor overactivity. In most
cases, I would be able to reproduce his incontinence, know what type of detrussor
pressures he generated with voiding, and whether he used abdominal straining during
the voiding phase. Finally, I would get a dynamic, visual picture of the anastomosis
and urethra. If there were any concerns about the outlet or he had hematuria, I would
perform cystoscopy.
If I was considering him for a male sling, I believe a pressure flow study is mandatory
to rule out an areflexic bladder with abdominal straining. If I am considering him only
for an AUS, his health history was completely straightforward, and all of the above ques-
tions had been answered to my satisfaction, then I do not believe a urodynamic study is
mandatory, and a flow rate, urinalysis, residual urine, and cystoscopy would be an
acceptable workup.
The history given to us appears straightforward for anatomic sphincteric incontinence,
and unless something unexpected is discovered in the patient’s history, physical exami-
nation, or testing, he should be an excellent candidate for therapy. There is no effective
medical therapy, and I do not offer injection therapy to males. Therefore, we would be
considering a male sling or AUS, either of which may be done in conjunction with an
inflatable penile prosthesis (IPP). Before offering the patient a simultaneous IPP, I would
want to have explored other, less-invasive options for his erectile dysfunction, if not done
previously. Although I do an occasional male sling, my overall experience with this pro-
cedure has been less than satisfactory, and my experience mirrors the report by Castle et al.
(1). The male sling in my practice is offered primarily to those patients with less incon-
tinence, who have satisfactory voiding pressures and who desire a less-complicated but
in my hands a less-successful option. In those instances, I use only permanent mesh
products with bone anchors as opposed to allografts or xenografts.
My recommendation to this patient would be an AUS placed as far proximally on the
bulbar urethra as possible through a perineal incision. I would use a single cuff with a
61- to 70-cm pressure balloon filled with 24 cc of saline placed through a second lower
midline abdominal incision. The cuff would be sized so that it was snug but would rotate
with minimal tension around the urethra. Assuming the patient’s characteristics are
straightforward as presented, I would council him that he should expect to have a 50%
chance of getting out of pads completely and an additional 40– 45% chance of getting
down to one small pad a day. The patient would understand that, at 64 yr of age, he would
most likely require one or more revisions in his lifetime. In the unusual event that the
urethra was too small for adequate occlusion with a single cuff, we were not placing an
IPP, and he was impotent, he would be counseled preoperatively that I would place a
second cuff transcorporally. If we could not get occlusion with a single cuff and he were
potent or we were placing a simultaneous IPP, then I would place a second cuff more
Case 16 / Male With Post-Prostatectomy Incontinence 415
distally in the bulb. He would understand that simultaneously placing two cuffs would
carry up to a 10.5% risk of urethral erosion (2).
Placement of an AUS through a penile scrotal incision is a relatively straightforward
approach that saves a small amount of time and a second incision. The tradeoff is that the
cuff placement is more distal; therefore, the cuff is virtually always 4 cm, which limits
options later for dealing with atrophy. I use this approach only when I am placing a com-
bined AUS/IPP in an older individual with a limited life expectancy who is not physically
active. In the combined placement, I believe there is significant time-saving, and the entire
operation can be done through a single incision, both of which should theoretically lower
the infection rate. I believe these advantages outweigh the downside of the smaller, more
distal cuff in selected individuals.
As with all surgery, the key to good results and satisfied patients is to council the
patient realistically about expected results, complications, and any commonly encoun-
tered contingencies. For the surgeon, the time to plan for contingencies is before the
operation commences and not at the time one encounters an unexpected problem in
the operating room.
REFERENCES
1. Castle EP, Andres PE, Itano N, Novicki D, Swanson SK, Ferrigni RG. The male sling for post-
prostatectomy incontinence: mean follow-up of 18 mo. J Urol 2005;173:1657–1660.
2. Kowalczyk JJ, Spicer DL, Mulcahy JJ. Erosion rate of the double cuff AMS800 artificial urinary
sphincter: long-term follow-up. J Urol 1996;156:1300–1301.

Both Dr. Comiter and Dr. Govier have demonstrated the evaluation as well as man-
agement options, albeit the limited ones, that we have for a gentleman with PPI of a
mild-to-moderate nature. As many of us know, there is no good, sure way to quantitate
how severe incontinence is in most of our patient populations. We have used surrogate
markers of pad usage as well as sometimes pad weights to evaluate these patients pre-
operatively. Nonetheless, we are still in need of some form of a severity scale to help us
evaluate and follow patients before and after any interventions. I certainly agree with all
of the commentaries made about options, including the most definitive options of male
sling procedures as well as AUSs. Eventually we will obtain longer term data that may
give us more information so we are able to counsel our patients appropriately regarding
the success rates with the male sling. We certainly have these data with the AUS, and
patients certainly need to understand this as they are counseled on ultimate treatment
approaches to their problem.
17 Mixed Incontinence in an Elderly Woman
A 79-yr-old active woman complains of symptoms of mixed incontinence requiring

four thick pads per day. Exam reveals no prolapse, a postvoid residual (PVR) of 170 cc
and a Q-tip test of 0–30°. Urodynamics demonstrates a Valsalva leak-point pressure of
52 cm H2O, detrusor overactivity, and poor detrusor contraction during voiding.
Is further evaluation necessary? What are the treatment options?
COMMENTARY BY TOMAS L. GRIEBLING, MD, FACS FGSA

Mixed urinary incontinence in the elderly female patient can present a considerable
therapeutic challenge. This patient complains of significant mixed incontinence, which
can have major negative impacts on her physical activity, social interactions, and overall
quality of life.
The physical examination reveals no pelvic organ prolapse and no significant urethral
hypermobility (Q-tip test 0–30°). This information, combined with the positive leak-point
pressure of 57 cm H2O on pressure flow urodynamics, supports a diagnosis of intrinsic
sphincter deficiency (ISD) as the etiology of her stress incontinence.
However, her complaints of urinary urgency and urge incontinence complicate the
clinical situation. The filling cystometrogram reveals low-pressure detrusor overactivity
with associated urge sensations and urge incontinence at a volume of approx 200 mL.
This study was performed with a relatively fast infusion rate (80 mL/min), which could
artificially exacerbate involuntary detrusor contractions. Repeating the filling portion of
the study at a slower rate that more closely matches physiological parameters might
help to diminish potential artifact. However, in this particular case, the patient reports she
experiences urinary urgency and urge incontinence on a regular basis. This historical
information suggests that the observed urodynamic finding is clinically significant and is
more than just an artifact of the filling rate.
The clinical situation is also complicated by the poor detrusor contractility identified
on the pressure flow portion of the study and the elevated PVR volume of 170 mL. These
results, combined with the findings from the filling cystometrogram, support a diagnosis
of detrusor hyperactivity with impaired contractility (DHIC). This is a relatively common
disorder in older adults that presents as a combination of incomplete bladder emptying
and urinary urgency or urge incontinence (Griffiths et al., 2002; Malone-Lee, 1992).
Additional evaluation would include upper tract imaging and an assessment of renal
function. Some patients with detrusor overactivity and elevated postvoid residuals can
develop clinically significant hydronephrosis as a long-term complication. This can lead
to renal insufficiency in some cases. Renal ultrasonography and measurement of serum
urea nitrogen and creatinine would be useful in this patient. Videourodynamics or a
voiding cystourethrogram could also be considered to rule out associated vesicoureteral

417
Fig. 1.
Fig. 2.
Case 17 / Mixed Incontinence in Elderly Woman 419
reflux or a bladder diverticulum. A voiding diary with measurement of PVR volumes

would also be helpful in this patient. Although her PVR was elevated at 170 mL on the
urodynamic study, this measurement represents a single point in time. If the patient is
willing and able to perform intermittent self-catheterization, then measurements of PVR
over several days could provide useful information. If the patient does have consistently
elevated PVR volumes, then intermittent self-catheterization might also provide some
therapeutic relief of her urgency and frequency symptoms.
The choice of treatment options in this patient with combined ISD and DHIC presents
a significant clinical challenge. Combination therapy will likely be required given her
combined diagnoses. Because of her large-volume leakage (four thick pads daily), some
type of treatment will be needed to address the open bladder neck. However, many
common treatments for this condition may worsen her urgency or retention. In some
cases, intentional creation of urinary retention with subsequent institution of a self-
catheterization regimen may be preferred over urinary incontinence. In this case, therapies
can be targeted to maximally treat both the stress and the urge components without concern
for the risk of retention.
Conservative therapies could help both the urge and stress components of her incon-
tinence. Dietary modification should be recommended. Avoidance of known dietary
irritants, such as caffeine, carbonated beverages, artificial sweeteners, acidic foods, and
alcohol, may help diminish her urinary urgency and urge incontinence. Timed voiding
and double voiding may also be helpful. Many patients only experience urinary urgency
near bladder capacity. Timed voiding may help to preempt this occurrence by preventing
the bladder from reaching this volume. Double voiding might help reduce her overall
PVRs, which could also improve urinary frequency.
Pelvic floor muscle exercises may be helpful in this case, particularly in terms of the
patient’s urgency and urge incontinence. Targeted pelvic floor exercises may help to
reduce the duration and intensity of involuntary detrusor contractions. This could provide
additional time to reach the toilet and help alleviate urge incontinent episodes. Bio-
feedback therapy may help to localize muscle contractions correctly and enhance exercise
efficiency. Improved pelvic floor muscle tone may help with her stress incontinence,
although the improvement in patients with ISD will likely be less pronounced compared
to patients with urethral hypermobility.
Treatment of the stress incontinence component will be somewhat more difficult in
this patient because she also has DHIC. Many treatments for her stress incontinence
may worsen her urinary urgency or retention. Surgical therapy could be considered,
including either injection of periurethral bulking agents or a pubovaginal sling cysto-
urethropexy. Because the patient has ISD with no significant urethral hypermobility, a
traditional bladder neck sling would be preferable over a midurethral sling. However,
both injection therapy and sling cystourethropexy may worsen this patient’s urinary
urgency and urinary retention. A sling would likely provide better durability compared
to injection therapy, particularly if she requires intermittent self-catheterization.
Anticholinergic therapy could be considered for treatment of the urinary urgency and
urge incontinence. This may worsen urinary retention, which could necessitate intermittent
self-catheterization. The potential clinical benefits must also be balanced with associated
pharmacological side effects, including dry mouth, constipation, visual changes, and con-
fusion. The incidence of these side effects may be somewhat higher in elderly patients.
Sacral neuromodulation may also be useful in this patient to help treat both urinary
retention and urgency with associated urge incontinence. One benefit of this therapy is
that it can be tested in a staged fashion using an external generator prior to implantation
of the programmable generator. If the test is unsuccessful, then the lead is removed.
Treatment of combined ISD and DHIC in the elderly female patient can be challenging.
Therapeutic choices must be tailored carefully with input from the patient about her spe-
cific desires and preferences. Successful treatment can lead to substantial improvements
in overall quality of life.
REFERENCES
1. Malone-Lee J. A re-examination of detrusor hyperactivity with impaired contractile function.
2. Griffiths DJ, McCracken PN, Harrison GM, Gormley EA, Moore KN. Urge incontinence and impaired
detrusor contractility in the elderly. Neurourol Urodyn 2002;21:126–131.

Dr. Griebling correctly notes the potential presence of DHIC in this patient and the
difficulties that can ensue when trying to treat someone with this conditions. A trial of
conservative measures combined with anticholinergics may help reduce the bladder
overactivity, perhaps without impacting her ability to void. It is important to highlight
that one measurement of an elevated PVR does not necessarily mean that it is the
usual status of her bladder. Frequently, on a first visit to the doctor or perhaps under a
testing situation, patients may not empty as well as in their natural setting. For the stress
incontinence, a bulking agent would probably be a less-morbid and a potentially less-
obstructing treatment for this woman and is likely an appropriate first-line therapy given
her relatively low leak-point pressure.
18 Male With Post-Prostatectomy
Incontinence
Status Post-removal
of Eroded Artificial Sphincter
A 58-yr-old active man is 18 mo postradical retropubic prostatectomy for prostate

cancer, 6 mo post-artificial urethral sphincter placement for stress urinary incontinence,
and 3 mo postsphincter removal (all components) for cuff erosion and infection. He is
currently totally incontinent, requiring 10 thin pads per day. Cystoscopy shows no ure-
thral strictures and no bladder neck contracture. His prostate-specific antigen (PSA) has
started to rise. Metastatic evaluation is negative. No radiation is planned. Hormonal
ablation was discussed and may be instituted in the future if the PSA continues to rise.
The patient states that the incontinence is ruining his life.
How would you proceed with evaluation and treatment?
COMMENTARY BY AJAY SINGLA, MD, FACS, FRCS, FICS

This is a 58-yr-old gentleman who is 18 mo postradical retropubic prostatectomy for
prostate cancer who developed urinary stress incontinence and underwent an artificial
urinary sphincter placement. He developed cuff erosion 3 mo later, and the artificial urinary
sphincter was removed. The patient is currently totally incontinent, requiring 10 pads a
day. Cystoscopy showed no urethral stricture and no bladder neck contracture. The
patient did not receive radiation or any hormonal treatment. The PSA has started to rise
slightly. The patient is currently bothered by severe urinary incontinence. He is requesting
further treatment.
A detail urological history is taken from the patient to determine his urinary habits;
urinary frequency; any urge incontinence; whether the incontinence is caused by
pure stress; his voiding habits, which would include any history of incomplete bladder
emptying as well as history of any obstructive symptoms. I also ask if the patient’s
incontinence was resolved after the first artificial urinary sphincter placement and if the
patient was satisfied with this device. A past medical history will also be obtained,
which will include a neurological history, any history of diabetes, and any prior surgeries.
A complete physical examination, which will involve examination of genitalia, scrotum,
and a digital rectal examination as well as a focused neurological examination, will be
carried out. I will also order the operative report from his previous artificial urinary
sphincter implantation to check on a cuff size and measurement of the urethra.
A urinary analysis will be ordered, and I would also like to check his postvoid residual.
I will counsel the patient in detail regarding the need for the videourodynamic eval-
uation to assess the detrusor function, to rule out any poor compliance, and to check his
bladder capacity as well as any uninhibited detrusor overactivity. This will also help to

421
rule out any bladder outlet obstruction. After the urodynamic evaluation is completed,
I will have a detailed discussion with the patient regarding the treatment plan. If the
detrusor function is stable on the urodynamic evaluation, then I will discuss all the treat-
ment options in detail, which will include (1) role of bulking agent, (2) option of male
sling, and (3) a repeat implantation of artificial urinary sphincter.
Because this patient has severe urinary incontinence, he would be a good candidate
for artificial urinary sphincter placement, and it would provide him the best chances of
success. Based on our experience, I would counsel this patient that male sling can be
performed in this particular situation even though chance of complete continence is low.
The patient may have some improvement, but chances of failure would be high. Similarly,
the bulking agent would have no role in patients with severe urinary incontinence and
has almost zero success in patients who use 10 pads a day. If the patient agrees to have a
repeat implantation of artificial urinary sphincter, then I will inform him that the artificial
urinary sphincter is the only procedure that would provide him the highest satisfaction
and either complete dryness or significant improvement in his urinary incontinence. There
are reports in the literature that the male sling has not performed well in cases of severe
urinary incontinence (1). If the patient agrees with this approach, I will proceed with a
repeat artificial urinary sphincter implantation using either a single cuff or a tandem cuff.
REFERENCE
1. Onur R, Singla A, Rajpurkar A. New perineal bone-anchored male sling. Lessons learned. Urology
2004;64:58–61.

This patient is unlikely to respond well to either bulking agents or a male sling to
manage his, what sounds to be, severe urinary incontinence. He has certainly failed a
single artificial urinary sphincter alone in that he has developed cuff erosion and ultimately
explantation of this device. He should be counseled about other diversionary options to
manage his situation as he is at risk of developing complications from a subsequent
sling. One may consider a distal placement of the cuff or tandem cuff placements as well.
Others have considered these types of patients ideal candidates for transcorporeal cuffs
in a distal location. Nonetheless, he should be counseled that he is certainly a high-risk
patient for failure, and additional therapies may be required to manage him appropriately.
Index
A alternatives to, 252

cecum, 252–253, 256
A-adrenergic agonists, 89–90, 93
complications, 257–258
Abcesses
ileocecal segment, 253, 255
from slings, 168–169
ileum, 252, 256
transvaginal repair and, 312
indications/contraindications, 251–252
Abdomen, examination of, 34
jejunum, 252
Abdominal leak-point pressure, 42–45, 98, 99
overview, 251, 258
A-blockers, mechanism of action, 28, 29
port sites, 254
Acetylcholine
results, 256–257
in bladder control, 20, 24, 25, 180, 198
sigmoid colon, 253
inhibition of, 209
stomach, 253
ACT®, 105
surgical technique, 252–256
Actinomycosis, 169
Autologous fat, 97
Active continence, mechanism of, 11
AI fibers, 199
B
Adrenergic agonists, 28
Adrenergic antagonists, 28 Bartholin gland anatomy, 16
B3-Adrenergic receptor (G3-AR), 20 Behavioral treatments described, 63
B2–Adrenoceptor agonists/antagonists, 90 Benign prostatic hyperplasia, F-blocker treatment
Alcohol as bladder irritant, 65 of, 28
Amitriptyline, 392 Biofeedback therapy, 73–74, 373
Anogenital stimulation, 221–222 Bion® microstimulator
Anterior colporrhaphy described, 223–225
complications, 371–373 procedure, 229–232
outcomes, 270–273 Bladder
surgical techniques, 267–268 anatomy, 10
Anterior wall vaginal prolapse. See Cystoceles botulinum toxin injection techniques, 213, 214
Antibiotics and VVF, 312 in continence, 12
Anticholinergic medications, 126, 179, 187–191, examination of, 34
260. See also specific drug by name function, neurophysiological control
Antidiuretic hormone, 88 afferent pathway, 24–27
Antimuscarinic agents, 22, 177, 179–187. See also efferent pathway, 20–24
specific drugs by name micturition/storage, 26–29
Anus overview, 19–20, 30
anatomy, 16 histology, 19
EMG sensors, 73 injuries
sphincter, examination of, 285 augmentation cystoplasty, 258
Aorta, 7 by slings, 153, 161–163
Apical prolapse. See Enteroceles innervation
Arcus tendinous fascia pelvis (ATFP), 5 afferent, 199
Artificial sweeteners as bladder irritant, 65–66 efferent, 198
Artificial urinary sphincter surgery, 412, 422 overview, 12, 14
Aspartame as bladder irritant, 65–66 overactivity, radiation-induced, 54, 56
ATP in bladder control, 22–23, 25 sensory processing neurotransmitters, 25
Atrium, 117 uroepithelium, anatomy/function, 198
Atropine sulfate (DL-hyoscyamine), 180 Bladder neck slings
Augmentation cystoplasty complications, 132, 150–153
423
424 Index
history, 131–132 described, 192–193, 209

incisions, 148 for DO, 252
material selection injection techniques
autologous rectus fascia, 139, 159 bladder, 213, 214
bovine collagen-injected polyester, 147 urethra, 213–214
cadaveric dermis/acellular collagen matrix, mechanism of action, 209–210
144–145, 159 for OAB, 373–375
cadaveric fascia lata, 144, 159 vs. resiniferatoxin, 205
fascia lata, 139–140, 144, 159 side effects, 215
overview, 138, 159 Bowel
polyethylene terephthalate, 117, 118, 147 complications, augmentation cystoplasty, 258
polypropylene mesh (See Polypropylene function regularity, 66
mesh) injury, by slings, 162
polytetrafluoroethylene (PTFE; Gore-Tex) Broad ligaments, 13
(See Gore-Tex); Polytetrafluoroethylene Bulbocavernosus muscles, 16
(PTFE) Bulking agents
porcine dermis, 145, 159 complications, 103–104
porcine small intestinal submucosa, contraindications, 99
145–146, 159 Durasphere, 104–105
silicone-coated polyester, 147, 168 GAX (See Glutaraldehyde crosslinked (GAX)
synthetic materials, 146–147, 159 collagen)
method of suspension history, 97–98
bone anchors, 124, 148, 169 injection technique, 100–102
sutures, 147–148 overview, 107
outcomes, 149–152 patient selection, 98–100
patient selection, 132–133 results, 102–103
surgical technique Tegress®, 105–107
fascia lata harvest, 140, 148 Burch procedure, 112, 115
postoperative care, 137–138
C
pubovaginal slings (autologous rectus
fascia), 133–137, 139–141, 267 Cadaveric dermis/acellular collagen matrix
pubovaginal slings (urethral diverticula in bladder neck slings, 144–145, 159
repair), 137, 138 in rectocele repair, 293
vaginal wall sling, 140–141 Cadaveric fascia lata, 144, 149
variations, 142–143 Caffeine
suture selection, 147 consumption statistics, 65
tension, 148, 152 management, 66
VVF and, 313 and OAB/UI, 34, 65
Bladder outlet obstruction (BOO) Calcium in bladder control, 23
case studies, 379–384, 405–407 Caliculi formation, augmentation cystoplasty, 258
c-fiber activation in, 25 Capsaicin
neurophysiologic pathways, 24, 54, 58 administration, 205
treatment, 24, 411 c-fiber blockage by, 25
Bladder retraining (BT) chemical structure, 200
described, 68, 69 clinical results, 202–203
rationale, 63 complications, 205
recommendations, 64, 65 for OAB, 193–194, 197–198
Bleeding/hematoma complications, 160, 257 pharmacology, 199–202
Bone anchors, 124, 148, 169 Cardinal ligament anatomy, 6, 8, 13
Bony pelvic anatomy described, 3–5 Case studies
BOO. See Bladder outlet obstruction (BOO) bladder outlet obstruction, 379–384, 405–407
Botox®. See Botulinum toxin cystoceles, 371–373
Botulinum toxin (Botox®, Dysport®, MyoBloc®, interstitial cystitis, 391–395
NeuroBloc®) MS/voiding dysfunction, 361–364
contraindications, 215 MUI, 351–352, 385–388, 417–420
Index 425
overactive bladder, 236–237, 245, 365–370, bowel perforation, 162

373–375 fascia lata slings, 124
pelvic pain, 355–357, 391–395 infection/abcess, 124, 166, 168–169
post prostatectomy incontinence, 411–415, overview, 159–160, 169–170
421–422 polypropylene mesh slings, 123, 124,
prolapse, 343–346, 371–373, 397–404 161–168
sexual dysfunction, 391–395 retropubic midurethral slings, 121–122, 124, 165
SUI, 343–344, 383–384, 405–407 transobturator midurethral slings, 122–123,
urethral diverticula, 331–334, 355–357 161, 165, 168
UTI/pelvic pain, 355–357 urethral erosions, 123–124, 153, 165–168
UTI/prolapse, 343–346 urge incontinence, 153, 163–165
VVF, 383–384 urinary retention, 153, 163–164
Cecum, in augmentation cystoplasty, 252–253, 256 vaginal erosions, 123–124, 153, 165–168
Cervix anatomy, 13 vaginal extrusion, 168
C fibers, 25, 199, 201 voiding disturbance, 124–125, 162–165
Childbirth, 283 Computed tomographic (CT), 328
Children, botulinum toxin treatment, 210–211 Conjugated equine estrogens (CEEs), 87
Chronic constipation, 66 Conservative therapy
Clenbuterol, 90, 93 biofeedback therapy, 73–74
Clitoris, 10, 16 bladder irritants, influence of, 65–66
Coaptite®, 105 bladder retraining, 63–65, 68, 69
Coccygeus muscle, 5 bowel function regularity, 66
Coccyx anatomy, 16 fluid management, 64, 65
Cognitive impairment, antimuscarinic agents, lifestyle/behavior modifications, 63–67
180, 186 overview, 63
Colpectomy, 296 PFES, 75
Colpocleisis, 296, 403–404 PFMT, 63, 64, 69–75
Colporrhaphy recommendations, 64
anterior smoking and, 64, 66
complications, 371–373 toileting programs, 63, 67–69
outcomes, 270–273 urethral diverticula, 328
surgical techniques, 267–268 vaginal weights, 74–75
posterior, technique, 287–288 VVF, 311–312
Common iliac arteries, 7 Constipation, therapeutic reduction of, 66
Complications Contigen®, 105
anterior colporrhaphy, 371–373 Continence, mechanism of, 11–14, 20, 84–86
augmentation cystoplasty, 257–258 Cooper's (pectineal) ligament, 3, 4
bleeding/hematoma, 160, 257 Cough UPP, 46, 47
bulking agents, 103–104 CRF in bladder control, 28
capsaicin, 205 Cymbalta (Duloxetine), 29, 90–93
cystoceles, 273–274 Cystoceles
enteroceles, 274 case studies, 371–373, 397–403
GAX collagen, 103–104 complications, 273–274
prolapse, 274 evaluation, 266–267, 344, 345
rectoceles, 274 formation of, 6
resiniferatoxin, 205 mesh/tissue graft repair, 267–269
sacral neuromodulation, 244–245 outcomes
SPARC technique, 122, 124, 160, 164–165, 168 anterior colporrhaphy, 270–273
tined quadripolar leads, 244–245 paravaginal defect repair, 272–274
TVT, 121–126, 160, 164, 166–168 overview, 265
VVF, 323–325 surgical techniques
Complications, sling surgery anterior colporrhaphy, 267–268
bladder neck slings, 132, 150–153 overview, 267
bladder perforation, 161–163 paravaginal defect repair, 269–272
bleeding/hematoma, 160 Cystometrograms, 24, 35
426 Index
Cystoscopy, 36, 163, 267, 385–386 case studies, 397–403

Cystourethrography (video urodynamics), 53 complications, 274
nonsurgical management, 296
D
observation management, 295
Darifenacin, 183–186 overview, 293, 301
daVinci robot, 298 physical examination, 295
Defecating proctography, 285 predisposing factors, 294
Depression and urge incontinence, 28 preoperative evaluation, 293–295
Detrusor contractions, tibial nerve stimulation, vs. rectocele, 285
220–221 surgical management
Detrusor leak-point pressure (DLPP), 41–42 laparoscopic sacrocolpopexy, 298–301
Detrusor overactivity (DO) overview, 296
botulinum toxin treatment of, 210–211 transabdominal sacrocolpopexy, 297–298
case study, 361–364 transvaginal repairs, 296–298, 372
refractory, 210–211, 252 uterosacral ligament suspension, 296, 372
tibial nerve stimulation, 219–221 symptoms, 294–295
urodynamic evaluation of Ephedrine, 89
nonneurogenic findings, 54–57 Erosions
nonphasic, 55 midurethral slings, 123–124, 153, 165–168
phasic, 58 rectocele repair, 293
protocol, 53–54 Estrogens, 194–195, 260. See also Hormone
Detrusor smooth muscle signaling in bladder replacement therapy (HRT)
control, 20–24 for VVF, 311
Detrusor-sphincter dyssynergia (DSD) Excision technique, urethral diverticula, 329–330
botulinum toxin for, 211–212 External iliac artery, 7, 9
case study, 361–364 External pudendal artery, 8
neurogenic OAB and, 57–59 External sphincter, 11
Dexon, 117, 118 External urethral sphincter (rhabdosphincter),
Dicyclomine hydrochloride, 190 19, 28–29
Diverticula, urethral. See Urethral diverticula F
Diverticulectomy, endoscopic, 329
Dondren, 97 Fascia lata slings
Duloxetine (Cymbalta), 29, 90–93 cadaveric, 144, 149
Duraderm™, 117, 145 complications, 124
Durasphere, 104–105 described, 139–140
Dynamic MRI, 285, 286. See also Magnetic disadvantages of, 159
resonance imaging (MRI) history, 131
Dynamic UPP, 46, 47 types of, 117
Dyspareunia. See Sexual dysfunction Femoral artery, 7–8
Dysport®. See Botulinum toxin Fibrin therapy, for VVF, 312
Fistulas
E
augmentation cystoplasty, 257
Edema, fluid management, 65 bladder neck, 312
Elderly patients complex, 319
bladder contractility in, 22 fulguration of, 312
detrusor instability in, 98 infratrigonal, 312
fluid management, 65 perineovaginal, 383
midurethral slings, 114, 115 radiation-induced, 319
MUI in, 417–420 from slings, 166, 167
Electrical stimulation, anogential, 221–222 supratrigonal, 312
Electromyography (EMG), 73 ureterovaginal, 310, 311
Elmiron, 392 urethrovaginal, 330
Endometrium anatomy, 13 VVF (See Vesicovaginal fistula (VVF))
Endopelvic fascia, 6 Flavoxate hydrochloride, 190–191
Enteroceles Fluid management, 64, 65
Index 427
Foods as bladder irritant, 65–66 Inferior epigastric vein, 9

Frequency-urgency syndrome Inferior vesical artery, 9
case studies, 236 IntePro™ graft, 299, 300
pudendal neurostimulation, 225 Internal iliac artery, 7–9, 13
sacral neuromodulation, 238, 242, 243 Internal pudendal vessels, 9
tibial nerve stimulation, 220 Internal urethral sphincter, 19, 29
Fulguration, of fistulas, 312 Interstitial cystitis (IC)
ATP response, 23, 25
G
augmentation cystoplasty, 251
Genitals, examination of, 34 bladder afferent activity, clinical measures, 26
Genuine stress incontinence (GSI), 36 botulinum toxin for, 213
Glutamate, 85 case study, 391–395
Glutaraldehyde crosslinked (GAX) collagen c-fiber activation in, 25
complications, 103–104 sacral neuromodulation, 238, 243
described, 98 tibial nerve stimulation, 220, 221
injection technique, 100–102 vanilloid treatment of, 202, 204
patient selection, 98–100 Intravaginal slingoplasty (IVS), 112, 168
results, 102–103 Intravenous pyelography, 36
Gore-Tex, 117, 118, 146, 293 Intrinsic sphincter deficiency (ISD)
case study, 411–415
H
described, 98, 99
Habit training described, 67, 68 treatment, slings, 132
Heart and Estrogen/Progestin Replacement Study, 87 vaginal wall slings, 141
Hematoma complications, 160 VLPP readings, 133
Hormone replacement therapy (HRT) IPG implantation procedure, 241–243
for OAB, 194–195 Ischial spines, 4, 9
in postmenopausal women, 195 Ischiocavernosus muscles, 16
for SUI, 86–88, 93 Ischiopubic ramus, 3, 9
Hydrodistention, 392–393 ISD. See Intrinsic sphincter deficiency (ISD)
Hylagel®, 105
J
Hypersensitivity disorders, 202–203
Hypogastric nerve Jejunum, in augmentation cystoplasty, 252
in bladder innervation, 20, 24, 29, 84
K
in pelvic anatomy, 12, 14
Kegel exercises described, 70–73
I
Knack described, 71
IC. See Interstitial cystitis (IC)
L
Idiopathic detrusor overactivity, 52
Idiopathic nonobstructive urinary retention. Latzko operation, 318
See Bladder outlet obstruction (BOO) Lead migration, 244, 245
Ileocecal segment, in augmentation cystoplasty, Leak-point pressures (LPPs)
253, 255 abdominal, 42–45, 98, 99
Ileum, in augmentation cystoplasty, 252, 256 DLPP, 41–42
Iliococcygeus muscle, 5, 6 overview, 41
Ilioinguinal nerve, 10 VLPP, 42–45, 132–133
Imipramine vs. URP, 48
for OAB, 191 Levator ani group (LAG)
for SUI, 88–89, 93 anatomy of, 5–6, 8
Infections in biofeedback therapy, 74
augmentation cystoplasty, 257 in continence control, 12, 84
midurethral slings, 124, 166, 168–169 Levator hiatus, 6, 7
sacral neurostimulation, 244 Lower urinary tract symptoms (LUTS)
transvaginal repair and, 312 F-blocker treatment of, 28, 29
Inferior anal nerves, 10 urodynamic evaluation, 51, 52
Inferior epigastric artery, 8, 9 LPP. See Leak-point pressures (LPPs)
428 Index
M overview, 259
surgical outcomes, 261
Macroplastique®, 105 Monarc slings, 168
Magnetic resonance imaging (MRI), 285, 286, Movement disorders and DO, 57–58
327, 328, 332–334, 356 MRI (magnetic resonance imaging), 285, 286, 327,
Male sling surgery, 412, 422 328, 332–334, 356
Manometry described, 74 MUI. See Mixed urinary incontinence (MUI)
Marlex, 117, 118, 146, 293 Multidetector CT (MDCT), 328
Marshall-Marchetti-Krantz procedure, 112, 115 Multiple sclerosis (MS), 57, 203, 222, 361–364
Martius flap, 16 Muscarinic agonists, 24
Martius grafts, 319–320 Muscarinic receptors in bladder control, 20–25
MAUDE database statistics, 160, 162 MyoBloc®. See Botulinum toxin
Maximum urethral closure pressure, 46, 48, 133
N
Mayo culdoplasty, 296
Medroxyprogesterone acetate, 87 NeuroBloc®. See Botulinum toxin
Menopause, 86, 195 Neurogenic detrusor overactivity
Menstruation, 86 capsaicin, 203
Mersilene, 117, 118, 147 resiniferatoxin, 204–205
Methoxamine, 90 Neurological examination described, 34–35
Micturition/storage, CNS control of, 26–29, 198 Neuromodulation, nonsacral
Middle rectal artery, 9 electrical stimulation, anogential, 221–222
Midurethral slings overview, 219, 232
anesthetic requirements, 115 sacral (See Pudendal nerve electrical
complications stimulation; Sacral neuromodulation)
bladder perforation, 161–163 tibial nerve stimulation, 219–221
intraoperative, 121–123 Nocturia, 65
overview, 121, 159–160 Nocturnal polyuria, 65
postoperative, 123–126 Nonneurogenic detrusor overactivity, 205
history/background, 111–114 Norepinephrine, 29, 85, 88
materials, 117–118 NS-49, 90
for MUI/SUI, 261
O
overview, 111, 126
patient selection, 114 OAB. See Overactive bladder (OAB)
percutaneous Obesity, 67, 114
outcomes, 120–121 ObTape sling, 113, 116, 166, 168
technique, 116–117 Obturator artery, 9
retropubic Obturator canal, 8
complications, 121–122, 124, 165 Obturator foramen, 3, 4, 8
described, 112–113 Obturator muscle, 84
outcomes, 118–120 Obturator nerve, 8–9
technique, 115–116 O’Conor technique, 317–318
techniques, 115–117 Onuf’s nucleus, 26, 85
transobturator Osteitis pubis, 153
complications, 122–123, 161, 165, 168 Osteomyelitis, 124, 153, 169
described, 112–113 Ovarian artery, 12
outcomes, 120 Overactive bladder (OAB)
technique, 116 apical prolapse and, 294
VVF and, 313 caffeine and, 34
Mixed urinary incontinence (MUI) case studies, 236–237, 245, 365–370,
assessment, 259–262 373–375
behavioral/pharmacological therapy compliance loss in, 55
outcomes, 260 conservative therapy (See Conservative therapy)
case studies, 351–352, 385–388, 417–420 described, 197, 235
clinical presentation, 259–260 electrical stimulation, anogential, 221–222
defined, 259 fluid management, 65
Index 429
intravesical treatment Pelvic anatomy

capsaicin (See Capsaicin) bony, 3–5
overview, 197–198, 205–206 circulation, 7–10
resiniferatoxin (See Resiniferatoxin) lower urinary tract, 10–12
midurethral slings, 125–126, 164–165 (See also lymphatic drainage, 9
Midurethral slings) musculature/fascia, 5–8, 70, 71
pathophysiology, 22 nerves, 10
pharmacological therapy overview, 3, 282–283
anticholinergic agents, 126, 179, 187–191, 260 Pelvic diaphragm, 5
antimuscarinic agents, 22, 177, 179–187 Pelvic floor electrical stimulation (PFES), 75
atropine sulfate (DL-hyoscyamine), 180 Pelvic floor muscle exercises (PFMEs), 70–73
botulinum toxin, 192–193, 205 Pelvic floor muscle rehabilitation or training (PFMT)
capsaicin (See Capsaicin) vs. clenbuterol, 90
darifenacin, 183–186 described, 69–75
dicyclomine hydrochloride, 190 vs. duloxetine, 92
estrogens, 194–195 rationale, 63
flavoxate hydrochloride, 190–191 recommendations, 64
imipramine (See Imipramine) Pelvic nerve, in bladder innervation, 24, 29, 84
organ specificity, 179 Pelvic Organ Prolapse Quantification (POP-Q)
overview, 177–178, 195, 197 system, 285
oxybutynin chloride (See Oxybutynin chloride) Pelvic pain
propantheline bromide, 180–181 botulinum toxin for, 212–213
resiniferatoxin (See Resiniferatoxin) case studies, 355–357, 391–395
solifenacin, 183, 184, 186–187 diverticula and, 325
tolterodine tartrate, 181–184, 187, 189, 190, sacral neuromodulation, 238, 243
373 Percutaneous midurethral slings
tricyclic antidepressants, 191–193 outcomes, 120–121
trospium chloride, 182–184, 373 technique, 116–117
uroselectivity, 178–179 Periaqueductal gray (PAG), 26
refractory, 236–237, 373–375 Perineal body, 14, 285
sacral neuromodulation therapy, 242–243 (See also Perineal membrane, 5
Pudendal nerve electrical stimulation; Sacral Perineal membrane (urogenital diaphragm)
neuromodulation) anatomy, 14
stress-induced, 54, 56 Perineum anatomy, 14–17
tibial nerve stimulation, 220 Peripheral nervous system, 84–86
urodynamic evaluation Peritoneum anatomy, 10, 11
components of, 53–54 Periurethral fascia, 8
neurogenic findings, 57–58 Perivesical fascia, 8
nonneurogenic findings, 54–57 Phenylpropanolamine (PPA), 89, 90
overview, 51 Polyethylene terephthalate, 117, 118, 147
patient selection, 52–53 Polypropylene mesh slings
Oxybutynin chloride bone anchors, 148
intravesical, 197–199 complications, 123, 124, 161–168
overview, 53, 181, 183, 184, 187–189, 373 described, 146
transdermal, 189–190 types of, 117, 118
Polytetrafluoroethylene (PTFE; Gore-Tex),
P
117, 118, 146, 293
Paraffin, 97 Pontine micturition center (PMC), 26, 28
Paravaginal defect repair Porcine dermis slings, 145, 159
outcomes, 272–274 Porcine small intestinal submucosa slings,
retropubic approach, 269–271 145–146, 159
vaginal approach, 271–272 Positive pressure urethrography (PPU),
Parity, 7 323, 326–327, 356
Passive continence, mechanism of, 11 Posterior colporrhaphy technique, 287–288
Pectineal line, 3 Posterior triangle anatomy, 16
430 Index
Post prostatectomy incontinence (PPI), 411–415, R

421–422
Radiation-induced bladder overactivity, 54, 56
Pre-/pararectal fascia plication/levator reconstruction,
Radiation-induced fistulas, 319
288–290
Rectoceles
Pressure transmission ratio, 47
case studies, 397–404
Procidentia, 371–374
causes, 281, 283
Prolapse
complications, 274
anterior vaginal wall (See Cystoceles)
defecating proctography, 285
apical (See Enteroceles)
diagnosis, 283–286
case studies, 343–346, 371–373, 397–404
dynamic MRI, 285, 286
complications, 274
grading, 285
examination of, 34
natural history of, 281
posterior vaginal wall (See Rectocele)
overview, 294
vaginal, urodynamics, 266–267, 343–346, 397
rectovaginal septum breaks in, 17
Prolene, 117, 118, 146
risk factors, 281
Prompted voiding (PV) described, 67, 68
surgery, indications, 286–287
Propantheline bromide, 180–181
surgery, techniques
Propranolol, 90
laparoscopic, 293–294
ProteGen® sling, 147, 166, 167
posterior colporrhaphy, 287–288
Provocation test, 35
pre-/pararectal fascia plication/levator
Pseudodiverticula, 324, 330
reconstruction, 288–290
Pseudoephedrine, 89
repair, defect-directed, 284, 290–292
PTFE (polytetrafluoroethylene; Gore-Tex), 117,
repair with mesh, 292–293
118, 146, 293
symptoms, 283, 286
Pubic symphysis, 4
ultrasound, 285–286
Pubocervical fascia (vesicopelvic ligament), 6
Rectovaginal septum, 16–17
Pubococcygeus muscle, 5, 6
Rectum, 6, 282–283
Puborectalis muscle, 5, 6
Renal transplantation, augmentation cystoplasty
Pubourethral ligaments, 6, 11
and, 251
Pubovaginal slings. See also Midurethral slings
Repliform™, 117, 145
overview, 111
Resiniferatoxin
surgical technique
administration, 205
autologous rectus fascia, 133–137,
c-fiber blockage by, 25
139–141, 267
chemical structure, 200
urethral diverticula repair, 137, 138
clinical results, 202–205
Pudendal nerve
complications, 205
anatomy, 5, 9, 223
described, 194
in bladder innervation, 24, 28, 29, 85
pharmacology, 199–202
in continence, 12
Retropubic midurethral slings
Pudendal nerve electrical stimulation. See also
complications, 121–122, 124, 165
Sacral neuromodulation
described, 112–113
bion® microstimulator
outcomes, 118–120
technique, 115–116
procedure, 229–232
Retropubic urethral suspensions, surgical landmarks,
devices, 223–225
3, 4
overview, 222
Rho-rho-kinase pathway in bladder control, 23
patient selection, 224–225
Ro 115–1240, 90
tined quadripolar lead
S
procedure, 225–229 Sabre sling, 161
test stimulation, 240–241 Sacral neuromodulation. See also Pudendal nerve
P2X3/P2X2 purinergic receptors in bladder electrical stimulation
control, 25 complications, 244–245
Pyramidalis slings, 131 for DO, 252
Index 431
history, 237 pharmacologic treatment

indications, 238, 239 F-adrenergic agonists, 89–90, 93
IPG implantation procedure, 241–243 G2–adrenoceptor agonists/antagonists, 90
mechanism of action, 237–238 HRT, 86–88, 93
for OAB, 373, 375 imipramine, 88–89, 93
overview, 235, 245–246 overview, 93
results, 241–244, 373 serotonin/norepinephrine reuptake
test procedure, 238–241 inhibitors, 90–92
Sacrocolpopexy post-prolapse surgery, 273
laparoscopic, 298–301 surgical management guidelines, 41
transabdominal, 297–298 type II, 99
Sacrospinous ligaments, 4–5, 9 type III, 98, 99, 132
Sacrum, 3, 4 urodynamic testing
Sampson's artery, 12 LPPs, 41–45, 48
Scheduled toileting described, 67, 68 overview, 36, 53
Sensory urgency. See Detrusor overactivity (DO) role of, 48–49
Serotonin, 29, 85, 88 UPP, 45–48
Sexual dysfunction URP, 46
case study, 391–395 vaginal weights, 74–75
diverticula and, 325 VVF and, 313
midurethral slings, 126 xenografts, 118
post-rectocele repair, 288, 291 Substance P in bladder control, 24
vaginal prolapse, 266, 372 SUI. See Stress urinary incontinence (SUI)
Sigmoid colon, in augmentation cystoplasty, 253 Superior vesical arteries, 9
Silastic, 146 Suprapubic arc (SPARC) technique
Silicone-coated polyester slings, 147, 168 complications, 122, 124, 160, 164–165, 168
Silicone elastomer slings, 146 described, 112, 113
Simultaneous cystourethrography (video outcomes, 119
urodynamics), 53 technique, 115–116
Sling surgery, male, 412, 422
T
Smoking and UI/OAB/SUI, 64, 66
Sodium morrhuate, 97 Teflon, 117
Solifenacin, 183, 184, 186–187 Tegress®, 105–107
Sonography, 327 Tension-free vaginal tape (TVT)
SPARC. See Suprapubic arc (SPARC) technique anesthetic requirements, 115
Spinal cord injury (SCI) complications, 121–126, 160, 164, 166–168
botulinum toxin treatment, 210–212 described, 112–114, 161
DSD and, 59 materials, 117
tibial nerve stimulation, 219–220 outcomes, 118–121, 365
Spino-bulbo-spinal pathway issues, 58, 59 patient selection, 114
Stomach, in augmentation cystoplasty, 253 technique, 115–116
Stratasis, 117 Terminal detrusor overactivity, 54, 57
Stress urinary incontinence (SUI) Thigh nerves, 10
anogenital stimulation, 222 Tibial nerve stimulation, 219–221
apical prolapse and, 294, 296 Tined quadripolar lead
bladder neck slings (See Bladder neck slings) complications, 244–245
bulking agents (See Bulking agents) described, 223–224
case studies, 343–344, 383–384, 405–407 procedure, 225–229
causes of, 84, 265, 266 test stimulation, 240–241
described, 83 Toileting programs described, 63, 67–69
diverticula management, 330 Tolterodine tartrate, 53, 181–184, 187, 189, 190,
midurethral slings (See Midurethral slings) 373
patient history, 34 Transobturator midurethral slings
PFES, 75 complications, 122–123, 161, 165, 168
PFMT, 64 described, 112–113
432 Index
outcomes, 120 Urethral retroresistance pressure (URP), 46

technique, 116 Urge incontinence
Transobturator procedure, pelvic anatomy points, 9 anticholinergic therapy, 189–190
Transurethral suture cystorrhaphy, 318 apical prolapse and, 294
Tricyclic antidepressants, 191–193 case studies, 236
Trospium chloride, 182–184, 373 HRT, 194
Tutoplast, 117 oxybutynin vs. tolterodine, 181
TVT. See Tension-free vaginal tape (TVT) post-prolapse surgery, 273
post-sling surgery, 153, 163–165
U
pudendal neurostimulation, 225
Ultrasonography, 37, 285–286 sacral neuromodulation, 238, 241–243
Umbilical artery, 9 tibial nerve stimulation, 220
Uratape sling, 113, 116, 166 Urinary incontinence (UI)
Urecholine, 24 complicated, 35
Ureteropelvic ligaments, 6, 12 conservative therapy (See Conservative therapy)
Ureters described, 83
anatomy, 10–12 DO symptoms in, 54
obstruction of, post-prolapse surgery, 274 economic impact of, 83
Uretex slings, 168 etiologies, 98
Urethra fluid management, 65
afferent pathway, 29 HRT, 194–195
anatomy, 11 laboratory evaluation
botulinum toxin injection techniques, fluid intake/voiding diary, 34, 52
213–214 laboratory tests, 35
efferent pathway, 28–29 overview, 33
erosions, from slings, 123–124, 153, 165–168 patient history, 33–34
examination of, 34 physical examination, 34–35
function, neurophysiological control urodynamics, multichannel, 35–37
overview, 19 post-prolapse surgery, 273
histology, 13 Urinary retention
innervation, 12, 14 botulinum toxin for, 212
neural control of, 85 post-prolapse surgery, 273
pelvic support of, 6–8 post-sling surgery, 153, 163–164
resistance, characterizing, 45 pudendal neurostimulation, 225
in SUI etiology, 84 sacral neurostimulation, 243
Urethral closure pressure profile (UCPP), 46–48 tibial nerve stimulation, 220
Urethral diverticula Urinary system regulation, 12
case studies, 331–334, 355–357 Urinary tract imaging, 36
classification, 324 Urinary tract infections (UTIs)
conservative therapy, 328 case studies, 343–346, 355–357
etiology, 323–324 diverticula and, 325, 331–332
glandular sources of, 11 fluid management, 65
incidence, 325 Urination. See Micturition/storage
overview, 323, 331 Urodynamics
pathology, 330–331 OAB, 51–58
presentation/evaluation, 325–328 overview, 51
pseudodiverticula, 324, 330 SUI, 36, 41–49, 53
surgical techniques urinary incontinence, 35–37
complications, 330 vaginal prolapse, 266–267, 343–346, 397
endoscopic diverticulectomy, 329 video, 53
excision, 329–330 Uroepithelium, anatomy/function, 198
incision and drainage with packing, 328 Urogenital triangle anatomy, 16
open marsupialization, 329 Urothelial afferent signaling in bladder control,
pubovaginal slings, 137, 138 25–27
Urethral pressure profile (UPP), 45–48 Urovive®, 105
Index 433
Uterine arteries, anatomy, 9, 12, 13 laparoscopic, 318–319

Uterosacral ligament, 6 Latzko operation, 318
Uterosacral ligament suspension, 296, 372 Martius graft, 319–320
Uterus anatomy, 6, 12–13, 15 myocutaneous gracilis flap, 322–324
O’Conor technique, 317–318
V
omental interposition, 321–322
Vagina outcomes, 324
anatomy, 6–8, 13, 15, 265, 282–283 peritoneal flap, 320–321
anterior wall prolapse (See Cystoceles) preoperative considerations, 312–313
closure, Martius flap, 16 transabdominal repair, 316–317
EMG sensors, 73 transurethral suture cystorrhaphy, 318
erosions transvaginal repair, 312–316, 324
from rectocele mesh repair, 293 overview, 309, 325
from slings, 65–168, 123, 153 prevention, 310
examination of, 34 radiation-induced, 319
posterior wall prolapse (See Rectocele) symptoms/signs, 310–311
suburethral wall mass, differential diagnosis, Vicryl, 117, 118
356 Voiding, CNS modulation of, 85–86
VVF (See Vesicovaginal fistula (VVF)) Voiding cystourethrography (VCUG), 37,
Vaginal artery, 9, 12 326–328, 344, 345, 355–356
Vaginal weights, 74–75 Voiding dysfunction
Valsalva leak-point pressure, 42–45, 132–133 assessment of, 53, 266
Valsalva UPP, 46, 47 botulinum toxin for, 212
Vanilloid pharmacology, 199–202. See also case study, 361–364
specific drugs by name midurethral slings, 124–125
Vanilloid-receptor subtype 1, 194 pudendal neurostimulation, 225
VCUG (voiding cystourethrography), 37, 326–328, sacral neurostimulation, 252
344, 345, 355–356 slings generally, 162–165
Vesica™, 148 tibial nerve stimulation, 219–221
Vesicovaginal fistula (VVF) VVF. See Vesicovaginal fistula (VVF)
case study, 383–384 W
complex, 319
conservative management, 311–312 Women’s Health Initiative, 87–88
diagnosis, 311
X
etiology, 309–310
operative management Xenografts in slings, 118, 131, 145–146
Z
full-thickness labial flap, 322, 323
gluteal skin flaps, 322 Zuidex®, 105

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CURRENT CLINICAL UROLOGY

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Cover design by Karen Schulz.

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Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1

Female urology : a practical clinical guide / edited by Howard B.

15. Nonsacral Neuromodulation ......................................................................................... 221

12. Urinary Frequency and Pelvic Pain .............................................................................. 391

JOSEPH B. ABDELMALAK, MD • Section of Female Pelvic Medicine and Reconstructive

MELISSA FISCHER, MD • Department of Female Urology, Urodynamics and Pelvic

Color insert appears following p. 174

Color Plate 1. Fig. 1.4. See legend on p. 6 and discussion on p. 5.

Color Plate 2. Fig. 1.7. See legend on p. 8 and discussion on p. 6.

Color Plate 3. Fig. 1.8. See legend on p. 9 and discussion on p. 7.

Color Plate 4. Fig. 1.9. See legend on p. 10 and discussion on p. 9.

Color Plate 5. Fig. 11.1. See legend and discussion on p. 161.

Color Plate 6. Fig. 11.2. See legend and discussion on p. 162.

Color Plate 9. Fig. 11.5. See legend and discussion on p. 164.

Color Plate 2. Fig. 1.7. See legend on p. 8 and discussion on p. 6.

Color Plate 5. Fig. 11.1. See legend and discussion on p. 161.

Color Plate 9. Fig. 11.5. See legend and discussion on p. 164.

Melissa Fischer, MD, Priya Padmanabhan, MD,

From: Current Clinical Urology: Female Urology: A Practical Clinical Guide

Fig. 1. The bones of the pelvis. (From ref. 13.)

MUSCULATURE AND FASCIAE OF THE PELVIS

Fig. 6. Anterior vaginal fascial support. (From ref. 15.)

Fig. 7. Schematic of urethral and anterior vaginal wall support.

Fig. 8. Pelvic circulation. (From ref. 16.)

Fig. 9. Nerves of the female perineum. (From ref. 16.)

FEMALE PELVIC VISCERA

Fig. 10. Peritoneal cleavage planes. (From ref. 3.)

significant prolapse, and it is susceptible to injury during pelvic reconstruction. The

Fig. 11. Course of the ureter. (From ref. 3.)

Toby C. Chai, MD, FACS and Todd J. Lehrfeld, MD

From: Current Clinical Urology: Female Urology: A Practical Clinical Guide

Bladder Efferent Pathway

DETRUSOR SMOOTH MUSCLE SIGNALING

responsible for contractions measured in an organ bath (6,7). However, M2 receptors,

Bladder Afferent Pathway

UROTHELIAL AFFERENT SIGNALING

CLINICAL MEASURES OF BLADDER AFFERENT ACTIVITY

HIGHER LEVEL CENTRAL NERVOUS SYSTEM CONTROL

Adonis Hijaz, MD and Firouz Daneshgari, MD

From: Current Clinical Urology: Female Urology: A Practical Clinical Guide

neurological diseases such as multiple sclerosis, Parkinson’s disease, or stroke. Chronic

FLUID INTAKE/VOIDING DIARY

Kelly M. Maxwell, MD,

From: Current Clinical Urology: Female Urology: A Practical Clinical Guide

Abdominal Leak-Point Pressure (Valsalva Leak-Point Pressure)

Fig. 2. Multichannel urodynamic study demonstrating stress urinary incontinence.

METHOD OF OBSERVATION OF LEAKAGE

URETHRAL PRESSURE PROFILOMETRY

Relationship Between UPP and Urethral Anatomy

UPP and Urethral Closure Pressure Profile

Dynamic UPP: Cough and Valsalva

Pressure Transmission Ratio

URETHRAL RETRORESISTANCE PRESSURE

ROLE OF URODYNAMIC TESTING IN THE ASSESSMENT