How To Perform Ultrasonography in Endometriosis 2018
How To Perform Ultrasonography in Endometriosis 2018
How To Perform Ultrasonography in Endometriosis 2018
Ultrasonography in
Endometriosis
Stefano Guerriero
George Condous
Juan Luis Alcázar
Editors
123
How to Perform Ultrasonography
in Endometriosis
Stefano Guerriero
George Condous • Juan Luis Alcázar
Editors
How to Perform
Ultrasonography
in Endometriosis
Editors
Stefano Guerriero George Condous
Department of Obstetrics and Acute Gynaecology, Early Pregnancy
Gynecology and Advanced Endosurgery Unit
University of Cagliari Sydney Medical School Nepean
Cagliari University of Sydney
Italy Nepean Hospital
Sydney, Australia
Juan Luis Alcázar
Obstetrics and Gynecology Department
University of Navarra
Pamplona
Spain
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Preface
v
vi Preface
vii
viii Contents
Index�������������������������������������������������������������������������������������������������������� 191
List of Videos
ix
x List of Videos
Electronic supplementary material is available in the online version of the related chapter
on Springer Link: http://link.springer.com/
Endometriosis: Clinical
and Anatomical Considerations
1
Sukhbir S. Singh
symptoms in those who have developed central Extrapelvic endometriosis is a less common
sensitization [8]. variation of the disease but often seen in high-
Because of the identified need for an earlier volume referral centers. Endometriosis implants
diagnosis and understanding that surgery has its and invasive disease may be found throughout
limitations, there is growing support to provide the body with corresponding signs and symptoms
health-care providers with the tools necessary to as noted below:
help make a clinical diagnosis of endometriosis.
Site of disease Potential symptoms
When endometriosis is part of the differential
Lung/pleural cavity Catamenial pneumothorax
diagnosis, a thorough history, physical examina- or hemothorax
tion, and targeted imaging are key to guiding Diaphragm (Fig. 1.1a, b) Catamenial shoulder tip
management [9, 10]. Proper evaluation allows for pain
earlier targeted interventions including medical, Nerves (i.e., sciatic) Catamenial or non-
surgical, and/or fertility therapies. menstrual-related nerve
irritation (i.e., sciatica)
Past surgical incisions Catamenial swelling, pain
(i.e., Pfannenstiel for localized to incision site
1.2 How We Do It? cesarean section or
laparoscopy site)
Video 1.1: Scar
1.2.1 History Endometriosis
Bowel Intermittent obstruction,
On history, it is important to assess all aspects of hematochezia
the presenting complaint, related systemic
issues, past medical and surgical history, habits, A past surgical history confirming endometri-
and family history. A review of pain symptoms osis is helpful; however the quality of the surgical
with a focus on the four “D”s (dysmenorrhea, evaluation, documentation of the findings, and
dyspareunia, dyschezia, and dysuria) is impor- images (if available) should be reviewed.
tant. If a patient has more than one of these Misclassification of disease in inexperienced
symptoms, there is a greater likelihood of endo- hands may mislead clinicians, and as a result,
metriosis [11]. current history and examinations should help
While cyclic (catamenial) symptoms of pain guide next steps for evaluation.
prompt us to consider endometriosis, non- Family history is important as endometriosis has
menstrual pelvic pain (NMPP) should also be a genetic component as shown in twin and family
evaluated through history. A classic history of studies [12]. However, assessment for risk for ovar-
pain that began as cyclic in nature earlier in ian or breast cancer should also be considered as
reproductive life may turn into daily pelvic or treatment options may change in high-risk patients.
abdominal pain with catamenial exacerbation.
This finding may represent a shift from nocicep- 1.2.2 Key Historical Points
tive pain (pain due to inflammation and local tis-
sue damage) to centralized pain. Consider endometriosis in females with:
Systemic complaints in women with endome-
triosis are also commonly described. • Chronic pelvic pain (pain that persists for
Gastrointestinal or urinary tract symptoms greater than 3 months)
including bloating, constipation, nausea, or dys- • Catamenial (cyclic)-related pain symptoms
uria may be seen in women with endometriosis- including:
associated pain. However, systemic complaints –– Dysmenorrhea
may also require evaluation of comorbid condi- –– Dyspareunia
tions such as irritable or inflammatory bowel dis- –– Dysuria
ease and painful bladder syndrome [12]. –– Dyschezia
1 Endometriosis: Clinical and Anatomical Considerations 3
a b
Fig. 1.1 (a) Right diaphragm endometriosis lesions causing catamenial right shoulder tip pain for greater than 10
years. (b) Post resection of deep endometriosis of the diaphragm. (Courtesy of Dr. S. Singh)
• Infertility and pelvic pain nally and subsequently evaluating each aspect of
• Catamenial symptoms in other systems the patient’s experience. Pain that is elicited with
(extrapelvic) light touch only is termed allodynia, and pain
with deeper palpation but not in keeping with the
expected response is termed hyperalgesia.
1.3 Examination Allodynia and hyperalgesia are signs of central
sensitization or neuropathic pain and should be
An appropriate and targeted abdominal/pelvic documented separately.
examination will help evaluate the patient with Further evaluation of the pelvic floor and
suspected endometriosis-related pelvic pain. Many abdominal wall muscles is also extremely
with endometriosis may be asymptomatic, and important during the evaluation of the chronic
examination findings may be incidental. Females pain patient. Severe pelvic floor tension (hyper-
with infertility may or may not have pelvic pain. tonicity) is also a common finding among those
Rectal (or pelvi-rectal) examination may be who have suffered with long-standing pelvic
required in cases of suspected rectal pathology or pain, as a protective adaptive response, and
rectovaginal deep endometriosis (DE). should be documented and discussed.
Upon bimanual examination, the clinician Physiotherapy is often an important adjunct to
should attempt to distinguish the axis of the rest- treatment in these patients.
ing uterus (anteverted, retroverted), palpate for The importance of identifying allodynia,
nodularity, and map out regions of pain. hyperalgesia, and pelvic floor hypertonicity is
Figure 1.2 demonstrates a posterior vaginal for- key to effective multimodal treatment and also
nix nodule palpated and visualized on pelvic should be documented for and by the imaging
examination. expert who will be proceeding with transvaginal
An important consideration is to approach the ultrasound. Patients with extreme vulvodynia and
examination of a patient with “pain” in a step- pelvic floor hypertonicity may not tolerate or
wise manner that begins with light touch exter- may refuse transvaginal examination.
4 S. S. Singh
Fig. 1.2 Vaginal nodule (confirmed endometriosis) detected on physical examination. (Courtesy of Drs. S. Singh and
H. Stone)
a b
Fig. 1.3 (a) An example of superficial endometriosis (black deposits) along the vesicouterine peritoneum. (b) Post
excision of endometriosis and surrounding peritoneum. (Courtesy of Dr. S. Singh)
a b
Fig. 1.4 (a) Right pelvic sidewall superficial endometriosis deposits (white arrows). (b) Post peritoneum excision of
superficial disease. (Courtesy of Dr. S. Singh)
Positive
Response
Trial of Therapy
Change Therapy
Incomplete
or Referral
Reponse (Triage)
Clinical
Diagnosis
Chronic Pain
Management
Complex Pain or
Invasive Disease
Complex
Surgical
Managment
a b
Fig. 1.6 “Hidden disease.” While the cul-de-sac is ultrasound. (c) Illustrates the level of dissection required
reported as “open” on traditional imaging (a), there is (mid-surgery) to help excise the disease. (Courtesy of Dr.
deep invasive disease and anatomical distortion with nod- S. Singh)
ular disease (b) identified preoperatively on expert-guided
• Retropubic/Prevesical Space
1.7 Anatomical Considerations
• The retropubic space, also known as the space
for Pelvic Endometriosis
of Retzius, is a potential space lying immedi-
ately posterior to the pubic symphysis, with
The approach to endometriosis evaluation and
the urethra and urethrovesical junction
management should consider the relevant ana-
forming the floor and the obliterated umbilical
tomical relationships of the normal pelvic struc-
arteries forming the lateral boundaries.
tures that may assist with navigating the distorted
• Paravesical Space
pelvic anatomy. The pelvis may be considered in
• The prevesical space is contiguous with the
three anatomical compartments to assist with
right and left paravesical spaces, with the
approach to endometriosis involvement: anterior,
obliterated umbilical arteries serving as the
middle, and posterior compartment.
boundaries. Each paravesical space is bounded
The anterior compartment includes the blad-
laterally by the obturator internus muscle
der and vesicouterine peritoneum. Endometriosis
of this area may be present as superficial or deep
(Figs. 1.3a and 1.7).
The middle compartment would include the
ovaries, fallopian tubes, and uterus itself.
Endometriosis of this compartment is the most
expected and described forms of the disease
including ovarian endometriomas and peritubal
adhesions.
The posterior compartment describes the pos-
terior cul-de-sac including the rectum, pararectal
spaces, and presacral anatomy. Often, the DE
lesions are found here and often involving the Fig. 1.8 A deep endometriosis nodule obliterates the rec-
rectum (Fig. 1.8). tovaginal space. (Courtesy of Drs. S. Singh & H. Stone)
a b
Fig. 1.7 A deep endometriosis nodule invading the bladder at laparoscopy. (b) Endometriosis invading the bladder
mucosa at cystoscopy. (Courtesy of Dr. S. Singh)
8 S. S. Singh
along with the obturator nerve and vessels and internal iliac vessels (laterally). Further delin-
posteriorly by the endopelvic fascial sheath eation of a lateral (Latzko’s space) and medial
that encompasses the internal iliac artery, (Okabayashi’s space) pararectal space divided
vein, and its anterior branches. by the uterosacral ligament has been described
• Vesicovaginal Space to assist with the surgical approach to the rec-
• This is an avascular potential space that exists tovaginal nodule [15].
between the bladder and the vagina. • Presacral Space/Retrorectal Space
• Rectovaginal Space (Fig. 1.8) • While not often accessed during endometrio-
• The rectovaginal space is a potential space sis surgery, this space may be entered during
between the vagina anteriorly and rectum low anterior segmental bowel resection. The
posteriorly. space is an area of areolar connective tissue
• Pararectal Space (Fig. 1.9 and Video 1.3) between the rectum anteriorly, the sacrum and
• The pararectal spaces are also avascular poten- upper coccyx posteriorly, the peritoneal reflec-
tial spaces located posterior to the crossing of tion superiorly, the levator ani and coccygeal
the ureter with the uterine artery. They are muscle inferiorly, and the ureter and iliac ves-
bounded by the rectum (medially) and the sels laterally.
a b
Fig. 1.10 (a) Deposit of endometriosis along left pelvic (yellow line) with overlying peritoneum excised, avascu-
sidewall peritoneum (white arrow) with underlying ureter lar spaces (*), and the internal iliac vessels (IIA) and the
(yellow line). (b) Post excision demonstrating the “surgi- external iliac vein (EIV). (Courtesy of Dr. S. Singh)
cal” layers of the left sidewall beginning with the ureter
1 Endometriosis: Clinical and Anatomical Considerations 9
• 1st layer—ureter and overlying peritoneum the bowel. However, DE of the bowel is esti-
• 2nd layer—internal iliac vessels and their mated to occur in 8–12% of females with endo-
branches metriosis [17]. These complex patients require
• 3rd layer—pelvic sidewall musculature with experienced care providers and often a multidis-
overlying obturator nerve and external iliac ciplinary approach [17, 18].
vessels Any part of the bowel may be involved includ-
ing the appendix and small bowel [19] (Fig. 1.13a–
Between each surgical layer lies a potential c). However, the large bowel and especially the
avascular space to facilitate dissection.
Disease that involves the sidewall often
involves the ureter. Ureteric involvement may be
either superficial or in severe cases it can lead to
obstruction. Recent reports suggest that over half
of patients presenting with DE may have some
type of urinary tract endometriosis [16]. As a
result, in DE, urinary tract evaluation presurgery
should be performed (Figs. 1.11a, b, 1.12, and
Video 1.4: Excision of Bladder Endometriosis).
a b
Fig. 1.11 (a) Left ureteric nodule (arrow) that resulted in severe obstruction and left renal dysfunction. (b) Intraoperative
fluoroscopy with ureteroscopy confirming external ureteric obstruction. (Courtesy of Dr. S. Singh)
10 S. S. Singh
a b
Fig. 1.13 (a) Superficial vesicles of endometriosis over endometriosis invasion. (c) Small bowel surface endome-
the surface (arrow) of the appendix. (b) Classic “hockey triosis deposits (arrows). (Courtesy of Dr. S. Singh)
stick” sign (arrow) at tip of appendix associated with
rectosigmoid colon are most often involved. The and appropriate referral for treatment in many of
disease is seldom isolated, and hence a thorough these patients.
evaluation is required preoperatively.
One of the key considerations is that colonos- Acknowledgments Dr. S. Singh would like to acknowl-
copy may not detect disease of the colon unless it edge his local team for making it possible to provide great
multidisciplinary care that includes nursing support,
is invading through the mucosa (Fig. 1.14a–c). expert imaging, and great surgical care. Drs. Margaret
As a result, imaging is again necessary in the Fraser, Shauna Duigenan, and Vincent Della Zazzera pro-
evaluation to enhance appropriate management. vide local expert imaging for complex endometriosis
cases. Our fellows Drs. Michael Suen, Cici Zhu, and
Maris Yap-Garcia provide surgical and clinical care. Our
residents, Drs. Heather Stone and Devon Evans, worked
1.8 Summary on educational material to help advance our teaching of
surgical approaches. Shannen McDonald, Karen Deme,
Endometriosis is a common and debilitating dis- Kelly Lacombe, Monique Newman, and Ottawa Hospital
staff help support our patients through their journey. Our
ease affecting millions of women worldwide. surgical team includes Drs. Kristina Arendas, Innie Chen,
Many of those affected are often struggling with Karine Lortie, and Hassan Shenassa. Our interdisciplinary
pelvic pain and/or infertility. However, the diag- team of surgeons includes Drs. S. Gilbert (Thoracics),
nosis is often delayed likely due to the variable S. Tadros (General Surgery), and The Ottawa Hospital
Urology and Colorectal Services. Finally, our research
presentation of symptoms and disease states. team including Dr. Teresa Flaxman, Ms. Erica Nichols,
Thorough clinical evaluation, including focused Carly Cooke, Suzanah Wojcik, and Cairina Frank help
expert imaging, may help with a timely diagnosis with our endometriosis research program.
1 Endometriosis: Clinical and Anatomical Considerations 11
a b
Fig. 1.14 (a) Intraoperative colonoscopy is suggestive of Zazzera, Ottawa Hospital). (c) An example of pathology
a mass effect but not diagnostic of endometriosis (*). (b) specimen with an invasive intramural nodule (X) of endo-
Transvaginal expert-guided ultrasound completed preop- metriosis from a low anterior resection of the rectosig-
eratively identified a rectal nodule measuring 3 × 1.4cm to moid colon. (Courtesy of Dr. S. Singh)
aid in surgical planning (Image Courtesy of Dr. V. Della
13. Guerriero S, Condous G, van den Bosch T, Valentin 16. Knabben L, Imboden S, Fellmann B, Nirgianakis
L, Leone FP, Van Schoubroeck D, et al. Systematic K, Kuhn A, Mueller MD. Urinary tract endometrio-
approach to sonographic evaluation of the pelvis in sis in patients with deep infiltrating endometriosis:
women with suspected endometriosis, including prevalence, symptoms, management, and pro-
terms, definitions and measurements: a consensus posal for a new clinical classification. Fertil Steril.
opinion from the International Deep Endometriosis 2015;103(1):147–52.
Analysis (IDEA) group. Ultrasound Obstet Gynecol. 17. Abrao MS. Pillars for surgical treatment of
2016;48(3):318–32. bowel endometriosis. J Minim Invasive Gynecol.
14. Fraser MA, Agarwal S, Chen I, Singh SS. Routine vs. 2016;23(4):461–2.
expert-guided transvaginal ultrasound in the diagno- 18. Abrão MS, Petraglia F, Falcone T, Keckstein J,
sis of endometriosis: a retrospective review. Abdom Osuga Y, Chapron C. Deep endometriosis infil-
Imaging. 2015;40(3):587–94. trating the recto-sigmoid: critical factors to con-
15. Ceccaroni M, Clarizia R, Alboni C, Ruffo G, Bruni sider before management. Hum Reprod Update.
F, Roviglione G, et al. Laparoscopic nerve-sparing 2015;21(3):329–39.
transperitoneal approach for endometriosis infiltrating 19. Parr G, Leyland N. The hockey stick sign in appen-
the pelvic wall and somatic nerves: anatomical con- diceal endometriosis. J Obstet Gynaecol Can. 2010;
siderations and surgical technique. Surg Radiol Anat. 32(5):421.
2010;32(6):601–4.
Medical and Surgical Management
of Endometriosis
2
Errico Zupi, Lucia Lazzeri,
and Caterina Exacoustos
very young or premenopausal patients [7]. resulted in a shift of first-line treatment of endo-
Laparoscopic management of endometriosis metriosis from surgery to medical therapy.
should be individualized, maintaining an Hypoestrogenizing drugs induce atrophy of the
approach toward the disease which maximizes ectopic endometrium and possibly allow the con-
surgical cytoreduction while preserving and safe- trol of pain symptoms by reducing the intra- and
guarding function of pelvic structures [8]. peri-lesional inflammation of endometriotic nod-
Surgical excision of DE nodules is necessary ules. This diminishes the production of prosta-
when they cause bowel stenosis associated with glandins and cytokines and thus results in less
subocclusive symptoms and ureteral stenosis stimulation of pain fibers. However, since the dis-
causing hydronephrosis or in cases of symptom- continuation of hormonal medications for endo-
atic bladder DE nodules. In addition, surgery is metriosis is associated with the recovery of
necessary in approximately one in three women endometrial function under the influence of ovar-
in whom hormonal treatments fail [9]. ian steroids and thus with the recurrence of pain
The choice of medical versus surgical treat- symptoms, such medications need to be adminis-
ment of DE must be shared between the physician tered for long periods [12]. Therefore, provided
and the woman, after she has been adequately that the efficacy in the control of pain is compa-
informed of the risks and benefits associated with rable between all the available hormonal com-
both options. Each woman must have a clear pounds [13, 14], the choice of treatment is
understanding that DE lesions are benign and usu- primarily based on safety in the long term, side
ally not progressive [10], and therefore the choice effects, and costs. Based upon such principles,
of treatment should focus on her symptoms and progestins and estroprogestins in the form of oral
expectations rather than the eradication of the dis- contraceptives (OC) represent the first-line
ease. The information about the likelihood of pain choice for the medical treatment of endometrio-
relief after surgery or medical therapy should be sis [14–19]. In cases of endometrioma associated
as detailed as possible, and the rates of both inter- with pain symptoms, medical therapy should be
national and institutional surgical complications preferred to surgery when reassuring ultrasound
should be provided. Moreover, the woman’s age features are present. Surgery should be consid-
and the desire for pregnancy are two important ered only when medical treatment fails in con-
variables influencing the therapeutic plan. trolling pain symptoms, when the endometriotic
In women with endometriosis seeking preg- cyst undergoes a rapid growth, or if ultrasound
nancy, assisted reproductive technologies should features become less reassuring.
be considered because currently available hor-
monal treatments are all contraceptive. In case of
repeated IVFs, surgery is indicated [11]. The goal 2.2.1 Oral Contraceptives
of clinical management of endometriosis is to
individualize the timing of endometriosis treat- OC and progestins are considered as first-line
ment, integrating medical and surgical strategies, medical treatment for endometriosis-associated
to avoid repetitive surgery with the aim of chronic pelvic pain [20, 21]. OC inhibit the pro-
improving quality of life. duction of gonadal estrogen via a negative feed-
back mechanism. Moreover, by suppressing
ovarian activity, they also lead to a reduction in
2.2 Medical Treatment estrogen-induced production of prostaglandins,
of Endometriosis decreasing the inflammation associated with
endometriosis. The uninterrupted use of the oral
In the last decade, the substantial progress of contraceptive pill appears to be associated with a
diagnostic imaging has allowed a reliable nonin- greater pain score reduction [22]. Furthermore,
vasive diagnosis of DE, i.e., without the need for the continuous administration represents a valid,
surgical and histological confirmation. This has safe, and economical therapeutic coverage that
2 Medical and Surgical Management of Endometriosis 15
might be used in patients who have undergone nificant improvements in diarrhea, intestinal
conservative surgery for endometriosis [23, 24]. cramping, passage of mucus with stool, and cyclic
Moreover, different studies have demonstrated rectal bleeding [32]. In 2014, a 24-week open-
that women with rectovaginal endometriosis- label prospective study suggested that treatment
associated pain benefit from treatment with non- with dienogest might improve pain symptoms in
oral contraceptives such as the contraceptive women with rectovaginal endometriosis who had
vaginal ring and the contraceptive patch [25]. pain persistent after 6 months of NETA therapy
[33]. A recent study has shown that dienogest is as
effective as NETA in improving pain symptoms in
2.2.2 Progestins women with rectovaginal endometriosis. Because
the two molecules are similar and because all hor-
Progestins have been used in the treatment of monal therapies for endometriosis have been
endometriosis for over 30 years. Thanks to central proven effective without significant differences
and peripheral mechanisms, the mitogenic action among different drugs [13, 14], this outcome was
and estrogen-induced proliferation are lacking. expected. No major adverse side events were
Furthermore, the endometrium, firstly, undergoes recorded. Minor side effects were experienced by
a secretory transformation and then a decidualiza- 55% of women in the NETA group and 41% of
tion, and, finally, it becomes atrophic, thus creat- women in the dienogest group, the most frequent
ing a pseudopregnancy state [26, 27]. A recent being weight gain, vaginal spotting, and decreased
Cochrane review has shown that the use of libido. Overall tolerability was significantly better
medroxyprogesterone acetate (MPA) at a dose of in women using dienogest than in those using
100 mg/day is more effective in controlling pain if NETA. However, the overall effectiveness was
compared with placebo, but it is burdened by sev- higher with NETA, owing to limited compliance
eral side effects (menstrual irregularities, amenor- with dienogest therapy resulting from the high
rhea, weight gain, and breast tenderness) [28]. cost of this drug [34].
Norethindrone acetate (NETA) and dienogest are It has been suggested that the effectiveness of
the progestins that have been more extensively dienogest in the treatment of endometriosis
evaluated for the treatment of endometriosis. Both depends on its ability to create a hypoestrogenic
of them are 19-nortestosterone derivative proges- and hyperprogestinic endocrine environment,
tins, and the pharmacological differences between which, initially, causes the decidualization of
the two compounds are limited: NETA has ectopic endometrial tissue. Subsequently, for
“strongly effective” progestogenic activity and prolonged treatments, dienogest causes an atro-
androgenic activity, whereas dienogest has “effec- phy of the lesions. An open-label extension of
tive” progestogenic activity and antiandrogenic this study for up to 53 weeks showed that long-
activity [29, 30]. The only randomized controlled term dienogest has a favorable efficacy and safety
trial available, evaluating the medical treatment of profile, with progressive decrease in pain and
rectovaginal endometriosis, has compared oral bleeding irregularities [35]. Furthermore, the
NETA 2.5 mg daily with an oral contraceptive pill decrease of pelvic pain persisted for at least
containing ethinyl estradiol 0.01 mg and cyproter- 24 weeks after therapy discontinuation. These
one 3 mg [31]. In the NETA group, women who effects should be due to the multiple mechanisms
were free of symptom at 12-month follow-up of action of the drug that reduces the growth and
ranged between 74% for dyspareunia and 92% for the neoangiogenesis of the lesions and provides
dysmenorrhea. Comparable results were observed an anti-inflammatory activity [35].
in the estrogen-progestin combination group. In recent years, the use of the levonorgestrel-
Another study showed that after 12 months of releasing intrauterine device (LNG-IUD) has
treatment with NETA, 40 women with rectosig- aroused interest. Its use in the treatment of endo-
moid endometriosis, who were still symptomatic metriosis of the rectovaginal septum provides a
following non-radical surgery, experienced sig- significant reduction in dysmenorrhea, pelvic
16 E. Zupi et al.
pain and deep dyspareunia, as well as the size of administration after surgical treatment prolongs
the endometriotic implants, showing levels of the pain-free interval [45, 46]. The treatment for
efficacy comparable to gonadotropin-releasing 3 months with a GnRH-a may reduce the painful
hormone (GnRH) analogues [36, 37]. symptoms for about 6 months [45]. Among the
Furthermore, it appears to be effective in pre- limitations of their use, there are the high rate of
venting the recurrence of endometriosis after recurrence of pelvic pain (5 years after with-
surgical treatment [38]. Clinical trials that com- drawal of therapy is at 75%) and the side effects,
pared the use of LNG-IUD and depot medroxy- such as deterioration in the lipid profile, depres-
progesterone acetate (DMPA), administered for sion, flushes, urogenital atrophy, loss of libido,
a period of 3 years, showed better compliance in and bone mass decrease [47]. The latter may be
patients who used the IUD [39]. Moreover, bone avoided by an “add-back therapy” that involves
gain was observed with LNG-IUD, whereas the use of hormone replacement treatment (HRT)
bone loss was reported with DMPA [39]. alone or in combination with biphosphonates or
Danazol is a synthetic androgen derivative of other antiresorptive agents [48].
17α-ethinyltestosterone, commercially intro-
duced about 30 years ago with a specific indica-
tion for the treatment of endometriosis [40]. It 2.2.4 GnRH Antagonist
carries out a multifactorial biological action
inducing a hypoestrogenic-hyperandrogenic state, The use of GnRH antagonists in the treatment of
which is very hostile to the endometriotic tissue endometriosis has been recently introduced, with
growth. Several studies have demonstrated the optimistic results [49]. They reduce estrogen lev-
efficacy of danazol in reducing the pain associ- els in order to inhibit the pain symptoms but with-
ated with endometriosis [41]. However, its oral out triggering side effects as a result of estrogen
use is limited by significant side effects such as deprivation. Furthermore, in contrast to GnRH-a,
weight gain, muscle cramps, acne, seborrhea, they do not determine the initial stimulation of the
decreased breast size, hirsutism, and deepening of pituitary-ovarian axis with the resulting gonado-
the voice, all strongly related to the androgenic tropic peak [50]. A recent phase 2, randomized,
action [42]. The vaginal administration, through a double-blind, placebo-controlled study has shown
vaginal ring or gel or intrauterine device extended- that a new GnRH antagonist (elagolix) has an
release, has been tested in patients with DE with acceptable efficacy and safety profile [51]. More
encouraging results [43]. clinical trials are required before such agents
should be introduced into clinical practice.
2.2.3 Gonadotropin-Releasing
Hormone Analogues 2.2.5 Nonsteroidal Anti-
inflammatory Drugs
GnRH analogues (GnRH-a) suppress estrogen
ovarian production through a downregulation of Nonsteroidal anti-inflammatory drugs (NSAIDs)
GnRH receptors at pituitary level, causing a pro- are the most commonly used first-line treatment
found hypoestrogenism and consequently amen- for endometriosis [20, 21]. However, there is
orrhea and a hypoatrophic regression of the inconclusive evidence to show whether or not they
heterotopic endometrium. This effect is readily are effective in relieving pain associated with
reversible after stopping GnRH-a administration. endometriosis [52]. Furthermore, there is no evi-
They are considered as a second-line treatment in dence on whether any individual NSAID is more
case of failure of therapy with oral contraceptives effective than another [52]. NSAIDs interfere with
or progestins or when they are not tolerated or the function of the enzymes COX-1 and COX-2,
contraindicated. GnRH-a provide a reduction of inhibiting the production of prostaglandins, mole-
symptoms in about 50% of cases [44], and their cules involved in the genesis of endometriosis-
2 Medical and Surgical Management of Endometriosis 17
associated pain [53]. Specific inhibitors of COX-2, these drugs favors the onset of bone fractures,
as rofecoxib, have also the property to block the osteopenia, and osteoporosis [62]. The combina-
growth of ectopic cells and induce apoptosis, with tion of conventional therapy and aromatase
equivalent result to one achieved with GnRH-a inhibitors determines the block of the production
[54]. To date, there are no sufficient clinical data to of estrogens both in ovarian and extraovarian
prove the NSAIDs are as effective in the treatment endometriotic foci, reducing the painful symp-
of endometriosis-associated pain. toms. They have been used in a pilot study evalu-
ating 12 women with rectovaginal endometriosis,
who had pelvic pain resistant to conventional
2.2.6 elective Estrogen Receptor
S treatments: after 6 months of treatment with
Modulators letrozole (2.5 mg/day), norethisterone acetate
(2.5 mg/day), calcium citrate, and vitamin D,
Selective estrogen receptor modulators (SERMs) there have been a significant reduction in abdom-
interact with estrogen receptors as agonists or inal-pelvic pain and the disappearance of endo-
antagonists depending on the target tissue [55]. metriotic lesions at second-look surgery [63]. A
In patients with endometriosis, the rationale for subsequent study, from the same group, showed
their use is related to the estrogen-antagonistic that the association of letrozole with norethister-
activity at endometrial level and estrogen-agonis- one acetate provides pelvic pain control more
tic activity on bone and plasma lipoproteins [55]. effectively than norethisterone acetate alone [64].
Although studies on animals looked very promis-
ing [56, 57], currently available data in humans
on SERMs do not support their clinical use. In 2.2.8 Immunomodulators
fact, a double-blind prospective study comparing
raloxifene with placebo was halted early because Tumor necrosis factor-a (TNF-a), a proinflamma-
the raloxifene group had statistically significantly tory cytokine able to initiate inflammatory cas-
earlier pain and necessity of a second surgery cades, is increased in the peritoneal fluid and
[58]. serum of women with endometriosis. It has been
implicated in the pathogenesis of endometriosis
[65]. Clinically, a small randomized controlled
2.2.7 Aromatase Inhibitors trial of infliximab, another TNF-a blocker, was
shown to have no effect on endometriosis-related
An overexpression of the aromatase enzyme, the pain [66]. In a systematic review, the effective-
main responsible factor for estrogen synthesis in ness and safety of anti-TNF-a treatment in the
the ectopic endometrium, has been demonstrated management of endometriosis in premenopausal
in endometrial tissue [59]. Aromatase catalyzes women were evaluated. Only 1 trial of 21 patients
the conversion of the steroidal precursors into was included where infliximab (a monoclonal
estrogens, which stimulate the expression of the anti-TNF-a antibody) was compared with pla-
enzyme COX-2. The estrogens produced in the cebo. The reviewer concluded that there is not
endometrial tissue through aromatase promote enough evidence to support the use of anti-TNF-a
the growth and invasion of endometrial lesion drugs in the management of women with endo-
and favor the onset of pain and prostaglandin- metriosis for the relief of pelvic pain [66].
mediated inflammation [60]. The third-genera-
tion aromatase inhibitors, including letrozole,
anastrozole, and exemestane, are triazole deriva- 2.2.9 Antiangiogenic Agents
tives and have a selective, potent, and reversible
action [61]. Their side effects are represented Neoangiogenesis is essential for the initiation,
mainly by headache, stiffness or joint pains, nau- growth, invasion, and recurrence of endometrio-
sea, diarrhea, and flushing. The long-term use of sis. A wide variety of antiangiogenic agents have
18 E. Zupi et al.
been evaluated in vitro as potential treatments for “combined” technique [85, 86], have been pro-
endometriosis. Different members of the statin posed. The “three-stage” technique consists of a
family have been shown to be effective in vitro in first operative laparoscopy, where fenestration
reducing angiogenesis and endometriotic implant and drainage of the endometrioma are performed;
size in mice [67–69], rats [70], and human cells a second stage, consisting of a 3-month GnRH
in vitro [71, 72]. Multiple dopaminergic agonists analogue treatment; and a second laparoscopy,
also exhibit antiangiogenic activities. Cabergoline representing the third stage, where CO2 laser
was shown to decrease VEGF and VEGFR-2 pro- ablation of the cyst wall is performed. In a ran-
tein expression in cabergoline-treated mice [73]. domized controlled trial comparing the “three-
In addition, cabergoline and quinagolide have an stage” technique to the conventional stripping
equal effect in reducing endometriotic lesions as technique, better results in terms of ovarian
antiangiogenic agents [74]. Moreover, cabergo- reserve, evaluated both with antral follicle count
line and bromocriptine were comparable to (AFC) [83] and anti-Mullerian hormone (AMH)
GnRH agonist in reducing endometriotic lesion [84], have been reported with the “three-stage”
size in one human study [75]. technique. The small sample size (ten patients
per arm), the higher recurrence rate in the “three-
stage” arm (20 vs. 0% in the excision arm), and
2.3 Surgical Management the higher costs of a repeat surgical procedure do
of Endometriosis not sufficiently support the “three-stage” tech-
nique as a validated alternative to the stripping
2.3.1 Ovarian Endometrioma technique.
The “combined technique” has been recently
Since endometriomas often do not respond to proposed [85, 86] as an alternative to the strip-
medical therapy, surgical excision is generally ping technique, in the attempt to combine the
considered the treatment of choice in large endo- advantages of the two standard techniques (strip-
metriomas, especially when associated symp- ping and fenestration with coagulation/ablation),
toms are present [17–19, 76, 77]. Surgery may be avoiding the disadvantages of both. The excision
indicated in particular when pain persists despite technique is in fact associated with better results
medical treatment or in case of enlarging or sus- in terms of subsequent fertility and pain recur-
pect endometriotic cysts. The surgical approach rence, whereas the fenestration with coagulation/
to an ovarian endometrioma can be either com- ablation technique may be more respectful of the
plete excision of the cyst wall (the so-called strip- ovarian reserve. In the combined technique, strip-
ping technique, by which the plane of cleavage ping is performed for most of the surgical proce-
between the cyst wall and the ovarian paren- dure, whereas the coagulation/ablation technique
chyma is developed by traction and countertrac- is performed in the final part near the hilus, to
tion with two atraumatic forceps) or fenestration decrease the possible damage to the tissue.
and subsequent ablation or coagulation of the However, a recent randomized controlled trial
cyst wall. Three randomized controlled trials [87], comparing the stripping technique with the
[78–80] and a Cochrane meta-analysis [81] dem- combined technique in bilateral endometriomas,
onstrated that laparoscopic excision of the ovar- did not report significant differences between the
ian endometrioma yields better results in terms of two techniques in terms of recurrence rates and
subsequent pregnancy rates, pain control rates, ovarian reserve (evaluated with AFC). Ovarian
and cyst recurrence rates, compared with fenes- endometrioma ablation using plasma energy
tration and coagulation/ablation of the cyst wall. appears to be a valuable alternative to cystec-
Due to concerns that recently emerged on the tomy, because it could spare the underlying ovar-
possibility that surgical excision may damage the ian parenchyma. Recent studies [88, 89] reported
ovarian reserve [82], alternative surgical tech- high spontaneous conception rate after this abla-
niques, such as the “three-stage” [83, 84] and the tion technique and suggest ovarian endometri-
2 Medical and Surgical Management of Endometriosis 19
oma ablation using plasma energy as a valuable and size of the infiltrative lesion. Careful dissec-
alternative to cystectomy in patients presenting tion using a skinning technique removing super-
with endometriosis and pregnancy intention. ficial endometriosis of the bladder peritoneum
Other alternative techniques have been can be performed, followed by closure of the
reported [90–92], but none has been proven supe- defect with interrupted 3-0 monofilament suture.
rior to the standard excisional technique in ran- Infiltrative lesions with involvement of the blad-
domized controlled trials. Therefore, there is still der mucosa situated in the bladder dome can be
insufficient evidence to recommend any alterna- managed with partial cystectomy. Closure of the
tive technique instead of the stripping technique bladder with a single- or double-layer monofila-
as the procedure of choice for the surgical treat- ment is recommended, and methylene blue test
ment of endometriomas. Whichever the tech- should be performed to ensure integrity of the
nique, surgery should be performed by expert suture line. In cases of more complex lesions
operators, since it has been demonstrated that involving the posterior wall of the bladder or the
damage to the ovary is inversely correlated with trigone, cystoscopy and insertion of double J
surgeon’s experience [93]. stents may be considered. Adhesions between the
anterior uterine wall and the vesicouterine fold
should be divided prior to performing partial cys-
2.3.2 Deep Endometriosis tectomy. Removal of double J stents should be
delayed by 6–8 weeks postoperatively and a uri-
2.3.2.1 Anterior Compartment nary catheter left in situ for a minimum of 7 days.
In our practice, a urinary catheter is more often
Urinary Tract Endometriosis left in place for a minimum of 10 days. Low-
Endometriosis of the urinary tract is generally pressure cystography can also be performed prior
reported as affecting approximately 1% of to removal of the catheter to verify adequate
women with endometriosis; however, the inci- repair and healing of the bladder.
dence varies between centers and has been
reported to be as high as 20% [94, 95]. Of these Ureteral Endometriosis
cases, 85% involve the bladder, 10% ureter, 4% Ureteric involvement can be categorized into
kidney, and 2% urethra [96]. Bladder endometri- intrinsic or extrinsic and although rare can cause
osis is more commonly associated with other significant morbidity with silent loss of renal
lesions of the pelvis. function. Extrinsic disease accounts for 85% of
cases and causes infiltration of the overlying peri-
Bladder Endometriosis toneum, which can cause compression of the ure-
Bladder endometriosis is defined as the presence ter resulting in hydronephrosis and, if left
of endometrial glands infiltrating the detrusor untreated, renal impairment [96, 98]. Intrinsic dis-
muscle. It is associated with a myriad of nonspe- ease occurs in 15% of cases leading to fibrosis of
cific urinary symptoms such as urinary frequency, the muscularis and, in some instances, the mucosa.
dysuria, urgency, and, rarely, hematuria, which Ureteric endometriosis is more prevalent on the
can delay diagnosis. Cyclical pain related to left-hand side, which may be attributed to the
menses may confirm a clinical suspicion of endo- menstrual reflux theory and anatomical differ-
metriosis [94, 97]. The gold standard for diagno- ences of the right and left hemi pelvis [99]. The
sis of bladder endometriosis is direct visualization main aim of surgical treatment is to relieve
of lesions at cystoscopy or laparoscopy. obstruction, if present, while preserving renal
Transvaginal ultrasonography (see Chap. 8) and function and preventing recurrence. Surgical
MRI (see Chap. 15) may be useful in diagnosis; treatment options include ureterolysis, ureteral
however, small lesions may be missed. resection with end-to-end anastomosis, or ure-
Laparoscopic management of bladder endome- teroneocystostomy, and in cases of complete loss
triosis is dependent on the anatomical position of kidney function, ureteronephrectomy can be
20 E. Zupi et al.
considered [96, 100]. Placement of a double J result in infiltration of the cardinal ligament and
stent should be considered in cases of urinary may lead to ureteric involvement by means of
obstruction and hydronephrosis or where signifi- extrinsic compression [105]. In 16.8% of cases,
cant ureteric stenosis has been diagnosed preop- uterosacral disease was associated with additional
eratively. Due to the inflammatory nature of lesions, most commonly of the vagina, followed
endometriosis, the double J stent should be left in by intestinal and lastly bladder lesions [104].
place for approximately 6 weeks. At laparoscopy, Surgical excision of uterosacral endometriosis has
the ureter should be identified above the level of been demonstrated to be effective in the manage-
disease. This is more easily done at the level of the ment of pelvic pain symptoms with a 0.8% risk of
pelvic brim where the retroperitoneal space can major intraoperative complications [104]. Surgical
be opened and the course of the ureter followed. strategy for the management of isolated uterosac-
In ureteric endometriosis, ureterolysis should be ral lesions typically involves ureterolysis, with dis-
performed with care taken to avoid devasculariza- section medial to the ureter so it can be lateralized.
tion by preserving the adventitial layer and corre- During dissection, care should be taken to avoid
sponding vascular branches. Fibrosis secondary damage to the hypogastric nerve, which is closely
to endometriosis often leads to medial displace- related to the uterosacral ligaments as it attaches to
ment of the ureter, and care should be taken dur- the posterolateral aspect of the uterus [106].
ing its dissection. In cases of critical stenosis of
the ureter or intrinsic disease, a ureteral resection Bowel Endometriosis
with end-to-end anastomosis can be performed. Endometriosis involving the bowel occurs in
Studies have shown promising results with mini- 3–37% of cases, commonly affecting the rectum,
mal complications and recurrence rates [98, 101, rectosigmoid junction, or sigmoid colon in up to
102]. Ureteroneocystostomy is recommended 90% of cases [107]. This type of DE is complex
when a long ureteric segment requires resection with distortion of pelvic anatomy which often
or if the disease is near the level of the uretero- requires a multidisciplinary team approach with
vesical junction. Reimplantation of the ureter involvement of colorectal surgeons. Different
allows the fibrotic area of disease to be bypassed, surgical techniques exist, ranging from less radi-
minimizing the risk of recurrence [96]. A tension- cal excision by means of “shaving” or discoid
free anastomosis should always be observed, and resection to more aggressive surgical treatment,
if more length is required, a psoas hitch can be namely, bowel segmental resection with some
considered. Due to the rarity of this condition, studies reporting no relapses [98]. Shaving, or
there is limited evidence regarding treatment of mucosal skinning, involves careful dissection of
ureteral endometriosis. Most studies involve the endometriotic nodule freeing it from the
observational case series; however, the results are bowel wall without breaching the bowel lumen.
promising and in terms of patient morbidity are Areas of exposed mucosa are then sutured to
comparable to those treated by laparotomy. The maintain integrity and avoid postoperative perfo-
overall incidence of complications has been ration. This shaving technique has had promising
reported as 12% with some studies illustrating no results with low complication rates. Donnez and
long-term consequences and low recurrence rates Squifflet reported a 1.4% rate of rectal perfora-
[103]. Similarly, recurrence rates have been tion in a series of 500 patients and a recurrence
reported ranging from 5 to 15%. rate of approximately 7% [108]. The overall
pregnancy rate was 84%, with a natural concep-
2.3.2.2 Posterior Compartment tion rate of 78% [108]. Similar studies have
DE commonly affects the posterior compartment, reported low complication rates and recurrence
with involvement of the uterosacral ligaments rates of approximately 19%. This conservative
most frequently found. Isolated uterosacral lesions approach allows preservation of nerves and blood
occur in up to 83% of cases [104]. Lateral exten- supply, minimizing the risk of postoperative
sion of lesions from the uterosacral ligament can functional bowel and bladder complications.
2 Medical and Surgical Management of Endometriosis 21
Discoid excision involves removal of disease tion for endometriosis, postoperative digestive
with full-thickness resection of the anterior rectal symptoms may persist or de novo symptoms may
wall and subsequent laparoscopic repair in 1–2 develop. A recent systematic review of outcomes
layers or by using a transanal circular stapler associated with different surgical treatments of
[109]. An initial shaving of the nodule may be bowel endometriosis described an overall com-
necessary for debulking purposes. A guide suture plication rate of 13.9% [118] This varied from
is then placed at the level of the nodule and a cir- 2.8% in the shaving group to 29.6% in the resec-
cular stapler is inserted transanally. This tech- tion group [118].
nique is suitable for bowel lesions up to 2–3 cm in
size. For larger lesions up to 5 cm, a double dis-
coid technique can be used. Two circular stapling 2.4 Future Perspectives
lines are formed, the first above the lesion and the
second more distal including the initial suture line Endometriosis is a benign complex clinical con-
from the first firing [110]. Anterior discoid resec- dition, associated with chronic pelvic pain, which
tion has been shown as effective in reducing a can adversely affect women’s quality of life, sex-
patient’s symptoms with low complication rates ual satisfaction, and the possibility to conceive.
ranging from 0 to 12.5% [109, 111, 112]. Future improvements in imaging modalities and
Radical excision is unavoidable, specifically their interpretation in the context of endometrio-
in cases where the nodule is greater than 3 cm in sis and pelvic nerve involvement may help in
length and where there is sigmoid involvement, defining preoperative assessment and surgical
more than 50% circumferential disease or con- planning. This approach would not only aid the
current bowel stenosis, and multicentric disease surgeon but also provide more accurate informa-
[113, 114]. Studies have demonstrated that com- tion for the patient with regard to the length, type
plete excision of bowel lesions, including seg- of surgery, subsequent recovery, and risk of com-
mental resection, are associated with significant plications. Nowadays, the surgical approach is
improvement in pain symptoms and subsequent progressively changing its direction with the
quality of life [115, 116]. Surgical excision of most aggressive procedures being replaced by
bowel and rectovaginal endometriosis can be more conservative surgeries. Maintaining a bal-
associated with major complications such as ance between high success rates of treatment,
bowel perforation and peritonitis. Segmental minimal risk of recurrence, and low complication
bowel resection may be indicated where endome- rates drive the need for a more conservative sur-
triosis is found to be infiltrating both serosal and gical approach. At the same time, significant
mucosal layers. In these cases, we advocate seg- research has been focused on new drugs specifi-
mental bowel resection to be as economic as pos- cally designed for the treatment of endometriosis.
sible. The bowel is dissected at the edge of the Although current medical treatments are helpful
mesentery respecting all the vascular branches. for many women with endometriosis, these treat-
Once the diseased segment has been adequately ments have limitations that include side effects in
dissected, the bowel is divided caudal to the some women and contraceptive action for those
lesion using a linear stapler device. An endo- desiring pregnancy. Emerging medical treat-
scopic linear stapler is used to resect the bowel ments range from GnRH antagonists, aromatase
above the nodule. A minilaparotomy incision can inhibitors, and immunomodulators to antiangio-
be used to cut the rectum and place the anvil in genic drugs. More research into local neurogen-
the proximal bowel; alternatively, a transvaginal esis, central sensitization, and the genetics of
or transanal approach can be used [114]. A circu- endometriosis may provide future targets. The
lar stapler is inserted through the caudal portion role of the physician is to guide the woman
of the rectum and an end-to-end anastomosis per- through all therapeutic possibilities in order to
formed [117]. Despite a significant improvement resolve or minimize the impact of the disease
in pelvic pain following segmental bowel resec- while managing her expectations.
22 E. Zupi et al.
28. Brown J, Kives S, Akhtar M. Progestagens and 40. Greenblatt RB, Dmowski WP, Mahesh VB, Scholer
anti-progestagens for pain associated with endo- HF. Clinical studies with an antigonadotropin-Dan-
metriosis. Cochrane Database Syst Rev. 2012; azol. Fertil Steril. 1971;22:102–12.
3:CD002122. 41. Crosignani P, Olive D, Bergqvist A, Luciano
29. Hapgood JP, Africander D, Louw R, Ray RM, A. Advances in the management of endometrio-
Rohwer JM. Potency of progestogens used in sis: an update for clinicians. Hum Reprod Update.
hormonal therapy: toward understanding dif- 2006;12:179–89.
ferential actions. J Steroid Biochem Mol Biol. 42. Vercellini P, Somigliana E, Viganò P, Abbiati A,
2013;142:39–47. Barbara G, Crosignani PG. Endometriosis: current
30. Stanczyk FZ, Hapgood JP, Winer S, Mishell DR Jr. therapies and new pharmacological developments.
Progestogens used in postmenopausal hormone ther- Drugs. 2009;69:649–75.
apy: differences in their pharmacological properties, 43. Igarashi M, Iizuka M, Abe Y, Ibuki Y. Novel vagi-
intracellular actions, and clinical effects. Endocr Rev nal danazol ring therapy for pelvic endometriosis,
2013;34:171–208. in particular deeply infiltrating endometriosis. Hum
31. Vercellini P, Pietropaolo G, De Giorgi O, Pasin Reprod. 1998;13:1952–6.
R, Chiodini A, Crosignani PG. Treatment of 44. Shaw RW. GnRH analogues in the treatment of
symptomatic rectovaginal endometriosis with endometriosis-rationale and efficacy. In: Thomas EJ,
an estrogen-progestogen combination versus Rock JA, editors. Modern approaches to endome-
low-dose norethindrone acetate. Fertil Steril. triosis. London: Kluwer Academic Publishers; 1990.
2005;84(5):1375–87. p. 257–74.
32. Ferrero S, Camerini G, Ragni N, et al. Norethisterone 45. Hornstein MD, Yuzpe AA, Burry KA, Heinrichs LR,
acetate in the treatment of colorectal endometriosis: Buttram VL Jr, Orwoll ES. Prospective randomized
a pilot study. Hum Reprod. 2010;25:94. double-blind trial of 3 versus 6 months of nafare-
33. Morotti M, Sozzi F, Remorgida V, Venturini PL, lin therapy for endometriosis associated pelvic pain.
Ferrero S. Dienogest in women with persistent endo- Fertil Steril. 1995;63:955–62.
metriosis-related pelvic pain during norethisterone 46. Surrey ES, Hornstein MD. Prolonged GnRH ago-
acetate treatment. Eur J Obstet Gynecol Reprod nist and add-back therapy for symptomatic endo-
Biol. 2014;183:188–92. metriosis: long-term follow-up. Obstet Gynecol.
34. Vercellini P, Bracco B, Mosconi P, Roberto A, 2002;99:709–19.
Alberico D, Dhouha D, Somigliana E. Norethindrone 47. Prentice A. Regular review: endometriosis. BMJ.
acetate or dienogest for the treatment of symptom- 2001;323:93–5.
atic endometriosis: a before and after study. Fertil 48. Surrey ES. Gonadotropin-releasing hormone agonist
Steril. 2016;105:734–43. and add-back therapy: what do the data show? Curr
35. Petraglia F, Hornung D, Seitz C, et al. Reduced Opin Obstet Gynecol. 2010;22:283–8.
pelvic pain in women with endometriosis: efficacy 49. Küpker W, Felberbaum RE, Krapp M, Schill T,
of long-term dienogest treatment. Arch Gynecol Malik E, Diedrich K. Use of GnRH antagonists in
Obstet. 2012;285:167–73. the treatment of endometriosis. Reprod Biomed
36. Fedele L, Bianchi S, Zanconato G, Portuese A, Online. 2002;5:12–6.
Raffaelli R. Use of a levonorgestrel-releasing intra- 50. Finas D, Hornung D, Diedrich K, Schultze-Mosgau
uterine device in the treatment of rectovaginal endo- A. Cetrorelix in the treatment of female infertil-
metriosis. Fertil Steril. 2001;75:485–8. ity and endometriosis. Expert Opin Pharmacother.
37. Bayoglu Tekin Y, Dilbaz B, Altinbas SK, Dilbaz 2006;7:2155–68.
S. Postoperative medical treatment of chronic 51. Diamond MP, Carr B, Dmowski WP, et al. Elagolix
pelvic pain related to severe endometriosis: levo- treatment for endometriosis-associated pain: results
norgestrel-releasing intrauterine system versus from a phase 2, randomized, double-blind, placebo-
gonadotropin-releasing hormone analogue. Fertil controlled study. Reprod Sci. 2014;21:363–71.
Steril. 2011;95:492–6. 52. Allen C, Hopewell S, Prentice A, Gregory
38. Abou-Setta AM, Houston B, Al-Inany HG, Farquhar D. Nonsteroidal anti-inflammatory drugs for pain in
C. Levonorgestrel-releasing intrauterine device women with endometriosis. Cochrane Database Syst
(LNG-IUD) for symptomatic endometriosis fol- Rev. 2009;2:CD004753.
lowing surgery. Cochrane Database Syst Rev. 53. Hayes EC, Rock JA. COX-2 inhibitors and their
2013;1:CD005072. role in gynecology. Obstet Gynecol Surv. 2002;57:
39. Wong AY, Tang LC, Chin RK. Levonorgestrel- 768–80.
releasing intrauterine system (Mirena) and Depot 54. Dogan E, Saygili U, Posaci C, et al. Regression
medroxyprogesterone acetate (Depoprovera) as of endometrial explants in rats treated with the
long-term maintenance therapy for patients with cyclooxygenase-2 inhibitor rofecoxib. Fertil Steril.
moderate and severe endometriosis: a randomised 2004;82:1115–20.
controlled trial. Aust N Z J Obstet Gynaecol. 55. Buelke-Sam J, Bryant HU, Francis PC. The selec-
2010;20:273–9. tive estrogen receptor modulator, raloxifene: an
24 E. Zupi et al.
overview of nonclinical pharmacology and repro- 70. Esfandiari N, Khazaei M, Ai J, Bielecki R, Gotlieb
ductive and developmental testing. Reprod Toxicol. L, Ryan E, et al. Effect of a statin on an in vitro
1998;12:217–21. model of endometriosis. Fertil Steril. 2007;87:
56. Swisher DK, Tague RM, Seyler DE. Effect of the 257–62.
selective estrogen receptor modulator raloxifene 71. Sharma I, Dhawan V, Mahajan N, Saha SC, Dhaliwal
on explanted uterine growth in rats. Drug Dev Res. LK. In vitro effects of atorvastatin on lipopolysac-
1995;36:43–5. charide-induced gene expression in endometriotic
57. P. Fanning, T. J. Kuehl, R. Lee et al., Video mapping stromal cells. Fertil Steril. 2010;94:1639–46.e1.
to assess efficacy of an antiestrogen (raloxifene) on 72. Novella-Maestre E, Carda C, Ruiz-Sauri A, Garcia-
spontaneous endometriosis in the rhesus monkey, Velasco JA, Simon C, Pellicer A. Identification and
Macaca mulatta. In TJ Kuehl, editor. Bunkley Day quantification of dopamine receptor 2 inhuman
Proceedings. 1996; pp. 51–6. eutopic and ectopic endometrium: a novel molecu-
58. Stratton P, Sinaii N, Segars J, et al. Return of chronic lar target for endometriosis therapy. Biol Reprod.
pelvic pain from endometriosis after raloxifene treat- 2010;83:866–73.
ment: a randomized controlled trial. Obstet Gynecol. 73. Delgado-Rosas F, Gomez R, Ferrero H, Gaytan F,
2008;111:88–96. Garcia-Velasco J, Simon C, et al. The effects of
59. Meresman GF, Bilotas M, Abello V, Buquet R, ergot and non-ergot-derived dopamine agonists in
Tesone M, Sueldo C. Effects of aromatase inhibitors an experimental mouse model of endometriosis.
on proliferation and apoptosis in eutopic endome- Reproduction. 2011;142:745–55.
trial cell cultures from patients with endometriosis. 74. Ercan CM, Kayaalp O, Cengiz M, Keskin U,
Fertil Steril. 2005;84:459–63. Yumusak N, Aydogan U, et al. Comparison of effi-
60. Velasco I, Rueda J, Acién P. Aromatase expres- cacy of bromocriptine and cabergoline to GnRH
sion in endometriotic tissues and cell cultures of agonist in a rat endometriosis model. Arch Gynecol
patients with endometriosis. Mol Hum Reprod. Obstet. 2015;291:1103–11.
2006;12:377–81. 75. Yap C, Furness S, Farquhar C. Pre and post opera-
61. Pavone ME, Bulun SE. Aromatase inhibitors tive medical therapy for endometriosis surgery.
for the treatment of endometriosis. Fertil Steril. Cochrane Database Syst Rev. 2004;(3):CD003678.
2012;98:1370–9. 76. Kennedy S, Bergqvist A, Chapron C, et al; ESHRE
62. Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Special Interest Group for Endometriosis and
Rubin SD, Bulun SE. Anastrazole and oral contra- Endometrium Guideline Development Group.
ceptives: a novel treatment for endometriosis. Fertil ESHRE guideline for the diagnosis and treatment of
Steril. 2005;84:300–4. endometriosis. Hum Reprod. 2005;20:2698–704.
63. Remorgida V, Abbamonte HL, Ragni N, Fulcheri 77. Beretta P, Franchi M, Ghezzi F, Busacca M, Zupi
E, Ferrero S. Letrozole and norethisterone ace- E, Bolis P. Randomized clinical trial of two lapa-
tate in rectovaginal endometriosis. Fertil Steril. roscopic treatments of endometriomas: cystec-
2007;88:724–6. tomy versus drainage and coagulation. Fertil Steril.
64. Ferrero S, Camerini G, Seracchioli R, Ragni N, 1998;70:1176–80.
Venturini PL, Remorgida V. Letrozole combined with 78. Alborzi S, Momtahan M, Parsanezhad ME, Dehbashi
norethisterone acetate compared with norethisterone S, Zolghadri J, Alborzi S. A prospective, randomized
acetate alone in the treatment of pain symptoms caused study comparing laparoscopic ovarian cystectomy
by endometriosis. Hum Reprod. 2009;24:3033–41. versus fenestration and coagulation in patients with
65. Lu D, Song H, Shi G. Anti-TNF-α treatment for pel- endometriomas. Fertil Steril. 2004;82:1633–7.
vic pain associated with endometriosis. Cochrane 79. Carmona F, Martínez-Zamora MA, Rabanal A,
Database Syst Rev. 2013;3:CD008088. Martínez-Román S, Balasch J. Ovarian cystectomy
66. Becker CM, Sampson DA, Short SM, Javaherian versus laser vaporization in the treatment of ovarian
K, Folkman J, D’Amato RJ. Short synthetic end- endometriomas: a randomized clinical trial with a
ostatin peptides inhibit endothelial migration in vitro five-year follow-up. Fertil Steril. 2011;96:251–4.
and endometriosis in a mouse model. Fertil Steril. 80. Hart RJ, Hickey M, Maouris P, Buckett
2006;85:71–7. W. Excisional surgery versus ablative surgery for
67. Jiang HQ, Li YL, Zou J. Effect of recombinant ovarian endometriomata. Cochrane Database Syst
human endostatin on endometriosis in mice. Chin Rev. 2008;16:CD004992.
Med J. 2007;120:1241–6. 81. Raffi F, Metwally M, Amer S. The impact of excision
68. Dabrosin C, Gyorffy S, Margetts P, Ross C, Gauldie of ovarian endometrioma on ovarian reserve: a sys-
J. Therapeutic effect of angiostatin gene transfer tematic review and meta- analysis. J Clin Endocrinol
in a murine model of endometriosis. Am J Pathol. Metab. 2012;97:3146–54.
2002;161:909–18. 82. Pados G, Tsolakidis D, Assimakopoulos E,
69. Oktem M, Esinler I, Eroglu D, Haberal N, Bayraktar Athanatos D, Tarlatzis B. Sonographic changes after
N, Zeyneloglu HB. High- dose atorvastatin causes laparoscopic cystectomy compared with three-stage
regression of endometriotic implants: a rat model. management in patients with ovarian endometrio-
Hum Reprod. 2007;22:1474–80.
2 Medical and Surgical Management of Endometriosis 25
mas: a prospective randomized study. Hum Reprod. metriosis. Two different clinical entities shar-
2010;25:672–7. ing the same pathogenesis. Obstet Gynecol Surv.
83. Tsolakidis D, Pados G, Vavilis D, et al. The impact 2009;64:830–42.
on ovarian reserve after laparoscopic ovarian cys- 96. Maccagnano C, Pellucchi F, Rocchini L, et al.
tectomy versus three-stage management in patients Diagnosis and treatment of bladder endometriosis:
with endometriomas: a prospective randomized state of the art. Urol Int. 2012;89:249–58.
study. Fertil Steril. 2010;94:71–7. 97. Schneider A, Touloupidis S, Papatsoris
84. Muzii L, Panici PB. Combined technique of excision AG, Triantafyllidis A, Kollias A, Schweppe
and ablation for the surgical treatment of ovarian KW. Endometriosis of the urinary tract in women of
endometriomas: the way for- ward? Reprod Biomed reproductive age. Int J Urol. 2006;13:902–4.
Online. 2010;20(2):300–2. 98. Vercellini P, Pisacreta A, Pesole A, Vicentini S,
85. Donnez J, Lousse JC, Jadoul P, Donnez O, Stellato G, Crosignani PG. Is ureteral endometriosis
Squifflet J. Laparoscopic management of endome- an asymmetric disease? BJOG. 2000;107:559–61.
triomas using a combined technique of excisional 99. Scioscia M, Molon A, Grosso G, Minelli
(cystectomy) and ablative surgery. Fertil Steril. L. Laparoscopic management of ureteral endome-
2010;94:28–32. triosis. Curr Opin Obstet Gynecol. 2009;21:325–8.
86. Muzii L, Achilli C, Bergamini V, et al. Comparison 100. Ghezzi F, Cromi A, Bergamini V, Serati M, Sacco
between the stripping technique and the combined A, Mueller MD. Outcome of laparoscopic ure-
excisional/ablative technique for the treatment of terolysis for ureteral endometriosis. Fertil Steril.
bilateral ovarian endometriomas: a multicentre 2006;86:418–22.
RCT. Hum Reprod. 2016;31:339–44. 101. Mereu L, Gagliardi ML, Clarizia R, Mainardi P,
87. Mircea O, Puscasiu L, Resch B, Lucas J, Collinet Landi S, Minelli L. Laparoscopic management of
P, von Theobald P, Merviel P, Roman H. Fertility ureteral endometriosis in case of moderate–severe
outcomes after ablation using plasma energy versus hydroureteronephrosis. Fertil Steril. 2010;93:46–51.
cystectomy in infertile women with ovarian endome- 102. Smith IA, Cooper M. Management of ureteric
trioma: a multicentric comparative study. J Minim endometriosis 59 associated with hydronephrosis:
Invasive Gynecol. 2016;23:1138–45. an Australian case series of 13 patients. BMC Res
88. Motte I, Roman H, Clavier B, Jumeau F, Chanavaz- Notes. 2010;3:45.
Lacheray I, Letailleur M, Darwish B, Rives N. In 103. Chapron C, Fauconnier A, Vieira M, et al.
vitro fertilization outcomes after ablation of endome- Anatomical distribution of deeply infiltrating endo-
triomas using plasma energy: a retrospective case- metriosis: surgical 60 implications and proposition
control study. Gynecol Obstet Fertil. 2016;44:541–7. for a classification. Hum Reprod. 2003;18:157–61.
89. Roman H, Auber M, Mokdad C, et al. Ovarian 104. Mmm Kondo W, Bourdel N, Tamburro S, et al.
endometrioma ablation using plasma energy versus Complications after surgery for deeply infiltrating
cystectomy: a step toward better preservation of the pelvic endometriosis. BJOG. 2011;118:292–8.
ovarian parenchyma in women wishing to conceive. 105. Azaïs H, Collinet P, Delmas V, Rubod C. Uterosacral
Fertil Steril. 2011;96:1396–400. ligament and hypogastric nerve anatomical relation-
90. Angioli R, Muzii L, Montera R, et al. Feasibility of ship. Application to deep endometriotic nodules sur-
the use of novel matrix hemostatic sealant (FloSeal) gery. Gynecol Obstet Fertil. 2013;41:179–83.
to achieve hemostasis during laparoscopic exci- 106. Campagnacci R, Perretta S, Guerrieri M, et al.
sion of endometrioma. J Minim Invasive Gynecol. Laparoscopic colorectal resection for endometriosis.
2009;16:153–6. Surg Endosc. 2005;19:662–4.
91. Ghafarnejad M, Akrami M, Davari-Tanha F, Adabi 107. Donnez J, Squifflet J. Complications, pregnancy and
K, Nekuie S. Vasopressin effect on operation time recurrence in a prospective series of 500 patients
and frequency of electro- cauterization during lapa- operated on by the shaving technique for deep rec-
roscopic stripping of ovarian endometriomas: a ran- tovaginal endometriotic nodules. Hum Reprod.
domized controlled clinical trial. J Reprod Infertil. 2010;25:1949–58.
2014;15:199–204. 108. Fanfani F, Fagotti A, Gagliardi ML, et al. Discoid
92. Muzii L, Marana R, Angioli R, et al. Histologic anal- or segmental rectosigmoid resection for deep
ysis of specimens from laparoscopic endometrioma infiltrating endometriosis: a case–control study.
excision performed by different surgeons: does the Fertil Steril. 2010;94:444–9.
surgeon matter? Fertil Steril. 2011;95:2116–9. 109. Oliveira MA, Crispi CP, Oliveira FM, Junior PS,
93. Kovoor E, Nassif J, Miranda-Mendoza I, Wattiez Raymundo TS, Pereira TD. Double circular sta-
A. Endometriosis of bladder: outcomes after pler technique for bowel resection in rectosig-
laparoscopic surgery. J Minim Invasive Gynecol. moid endometriosis. J Minim Invasive Gynecol.
2010;17:600–4. 2014;21:136–41.
94. Yohannes P. Ureteral endometriosis. J Urol. 110. Koh CE, Juszczyk K, Cooper MJ, Solomon
2003;170:20–5. MJ. Management of deeply infiltrating endome-
95. Berlanda N, Vercellini P, Carmignani L, Aimi G, triosis involving the rectum. Dis Colon Rectum.
Amicarelli F, Fedele L. Ureteral and vesical endo- 2012;55:925–31.
26 E. Zupi et al.
111. Moawad NS, Guido R, Ramanathan R, Mansuria S, 115. Keckstein J, Wiesinger H. Deep endometriosis,
Lee T. Comparison of laparoscopic anterior discoid including intestinal involvement – the interdisciplin-
resection and laparoscopic low anterior resection of ary approach. Minim Invasive Ther Allied Technol.
deep infiltrating rectosigmoid endometriosis. JSLS. 2005;14:160–6.
2011;15:331–8. 116. Leroy J, Costantino F, Cahill RA, et al. Laparoscopic
112. Koninckx PR, Ussia A, Adamyan L, Wattiez A, resection with transanal specimen extraction for sig-
Donnez J. Deep endometriosis: definition, diagnosis, moid diverticulitis. Br J Surg. 2011;98:1327–34.
and treatment. Fertil Steril. 2012;98:564–71. 117. Moustafa MM, Elnasharty MAA. Systematic review
113. Wattiez A, Puga M, Albornoz J, Faller E. Surgical of the outcome associated with different surgical
strategy in endometriosis. Best Pract Res Clin Obstet technique of bowel and rectovaginal endometriosis.
Gynaecol. 2013;27:381–92. Gynaecol Surg. 2014;11:37–52.
114. Kavallaris A, Banz C, Chalvatzas N, et al. 118. Koninckx P, Craessaerts M, Timmerman D, Cornillie
Laparoscopic nerve-sparing surgery of deep infil- F, Kennedy S. Anti- TNF-a treatment for deep endo-
trating endometriosis: description of the technique metriosis-associated pain: a randomized placebo-
and patients’ outcome. Arch Gynecol Obstet. controlled trial. Hum Reprod. 2008;23:2017–23.
2011;284:131–5.
Standardized Ultrasonographic
Diagnostic Protocol to Diagnose
3
Endometriosis Based on the
International Deep Endometriosis
Analysis (IDEA) Consensus
Statement
Table 3.1 Four basic sonographic steps, which can be adopted in this or any order as long as all four steps are per-
formed to confirm/exclude the different forms of endometriosis
Routine evaluation of the uterus and adnexa (+ sonographic signs of adenomyosis/presence or
First step absence of endometrioma)
Second step Evaluation of transvaginal sonographic “soft markers” (i.e., site-specific tenderness and ovarian
mobility)
Third step Assessment of status of POD using real-time ultrasound-based “sliding sign”
Fourth step Assessment for DE nodules in anterior and posterior compartments
POD pouch of Douglas, DE deep endometriosis
should then be positioned and draped Next the adnexa should be evaluated. Ovarian
appropriately. A wedged cushion or medical
size and characteristics should be documented.
couch, with stirrups or lowering bottom section, The presence or absence of endometriomas
can be used to ensure adequate mobility with the should be noted. The following three elements
transvaginal probe. After sanitary protocols have are critical when assessing endometriomas. First,
been followed for probe cleaning, ultrasound gel the size, measured in three orthogonal planes. To
should be placed on the tip of the probe. A probe achieve appropriate orthogonal plane measure-
cover can then be placed overtop, followed by ments, the length is obtained in the midsagittal
lubricating gel to ease insertion of the probe into plane, thickness in the anteroposterior plane, and
the patient’s vagina. The scan can then begin. It is transverse diameter in the transverse plane.
recommended to implement a local protocol to Second, the number of endometriomas should be
ensure all steps are completed, though they may noted. Third and lastly, the sonographic charac-
differ in order than that presented here. Most teristics should be described according to termi-
importantly, the operator needs to be experienced nology published by the International Ovarian
in the evaluation of patients with potential deep Tumor Analysis (IOTA) group [7]. When an
endometriosis (DE). endometrioma is visualized, there is significantly
higher likelihood of multiple lesions of DE [8].
Though the IDEA consensus statement recom-
3.2.1 First Step mends all four steps in all patients with suspected
endometriosis, operators performing the ultra-
The first structure often identified is the uterus. sound should be more vigilant for DE when an
The orientation (anteverted, retroverted, or axial) endometrioma is diagnosed.
should be noted. Any uterine abnormalities The Fallopian tubes, though not usually visi-
should be noted. Specifically with endometriosis ble on ultrasound in a normal state, may be dis-
in mind, one should inspect carefully for signs of torted or blocked by adhesions in patients with
adenomyosis as there is significant correlation endometriosis. If a hydrosalpinx or hematosal-
between the two processes [4]. These findings pinx is seen on ultrasound, endometriosis should
should be described using the terms and defini- be considered as an etiology.
tions published in the Morphological Uterus
Sonographic Assessment (MUSA) consensus
opinion [5]. Though not included in the MUSA 3.2.2 Second Step
group’s opinion, the “question mark sign” should
be noted when seen as this can represent adeno- The next element of the scan is a dynamic assess-
myosis and/or endometriosis [5, 6]. In the context ment of “soft markers” – site-specific tenderness
of endometriosis, this sign generally signifies a (SST) and ovarian mobility [2]. “Soft markers” are
fixed (i.e., nonmobile) anteverted/retroflexed defined as sonographic features that indirectly
uterus with the fundus adhered posteriorly to the suggest the presence of endometriosis, specifically
rectum and/or sigmoid colon. superficial endometriosis and intra-abdominal
3 Endometriosis Ultrasound Protocol based on IDEA Consensus Statement 29
adhesions, neither of which can be directly visual- may be adhered to each other, known as “kissing”
ized [9, 10]. These “soft markers” are elicited ovaries (Fig. 3.1). Not only does this particular
using the transvaginal probe [10]. ultrasound sign indirectly indicate intra-abdomi-
Firstly, before evaluating for SST, it is important nal adhesions, but it may also represent underlying
to inform the patient that he or she may experience DE of the Fallopian tubes and/or bowel [11].
discomfort or pain. Their feedback to the operator
performing the scan is essential to this step. The
key anatomic locations to assess in this component 3.2.3 Third Step
of the scan include the uterus, adnexa, uterosacral
ligaments (USL), and pouch of Douglas (POD). The third step is another dynamic, real-time
No scoring system has been validated as yet for ultrasound technique involving assessment of the
SST. Currently, the IDEA group recommends a status of the POD called the “sliding sign.” When
scoring system of 0 or 1: 0 for no pain and 1 for the uterus and cervix move independently (i.e.,
pain. It may be prudent to complete this aspect of slide) along the anterior rectum and sigmoid, the
the ultrasound at the very end to prevent interrup- test is positive and the POD is not obliterated.
tion or termination of the scan secondary to pain. When the uterus and cervix move in unison with
Secondly, ovarian mobility should be judged by the anterior rectum and sigmoid, the test is nega-
applying pressure to the ovaries using the trans- tive and the POD is thought to be obliterated [12,
vaginal probe. The ovaries may be fixed laterally 13]. Depending on the orientation of the uterus,
to the pelvic side wall, medially to the uterus, or the method to test for POD obliteration is slightly
inferiorly to the USLs. In some cases, the ovaries different (Table 3.2).
Table 3.2 Pouch of Douglas assessment for obliteration using “sliding sign”
Anteverted Retroverted
Step 1 Place gentle pressure against the retro-cervix using Place gentle pressure against the posterior upper
the transvaginal probe. Observe whether the uterine fundus with the transvaginal probe. Observe
anterior rectum glides freely across the posterior whether the anterior rectum glides freely across the
aspect of the cervix and posterior vaginal wall posterior upper uterine fundus
Step 2 Place one hand over lower anterior abdominal wall Place one hand over lower anterior abdominal wall
and ballot the uterus between the palpating hand and ballot the uterus between the palpating hand
and the transvaginal probe. Assess whether the and transvaginal probe. Assess whether the anterior
anterior bowel glides freely over the posterior sigmoid glides freely over the anterior lower uterine
aspect of the upper uterine fundus segment
30 M. Leonardi and G. Condous
URETHRA
COMPARTMENT
UTERINE OVARY
ANTERIOR
ARTERY
TER
URE
BLADDER
DE
TRIGONE VESICAL DOME URETER UTERO-VESICAL OBLITERATION
2
SEPTUM VAGINAL RECTAL VAGINA
ONLY WALL WALL & RECTUM 3
COMPARTMENT
POSTERIOR
RECTOVAGINAL
SEPTUM 1- LOWER (RETROPERITONEAL)
ANTERIOR RECTUM
2- UPPER (VISIBLE)
ANTERIOR RECTUM
POSTERIOR VAGINAL FORNIX ‘DIABOLO-LIKE’ NODULE 3- RECTO-SIGMOID
Vagina
Bladder
Peritoneal cavity
Uterus
Endometriotic nodule
Uterosacral ligaments
Anal sphincter
Adhesions
Fig. 3.2 Overview schematic demonstrating various sites of endometriotic nodules and adhesions in the anterior and
posterior compartments, with associated legend. Reprinted with permission from Wiley Publishers [2]
32 M. Leonardi and G. Condous
sagittal
transverse
Fig. 3.3 Schematic drawing demonstrating method of obtaining orthogonal measurements, i.e., midsagittal, anteropos-
terior, and transverse. Reprinted with permission from Wiley Publishers [2]
Fig. 3.4 Schematic drawing demonstrating ultrasound (space between the blue line and the red line). Reprinted
definition of the rectovaginal septum (RVS) (double- with permission from Wiley Publishers [2]
headed green arrow) and the posterior vaginal fornix
3 Endometriosis Ultrasound Protocol based on IDEA Consensus Statement 33
SEROSA
a Longitudinal muscle
MUSCULARIS EXTERNA
b
Circular muscle
SUBMUCOSA
Muscularis mucosa
Lamina propria
MUCOSA
Epithelium
Lumen
Blood vessels
Gland in
submucosa
Fig. 3.7 Schematic image showing the histological layers of the rectum (a), which can be seen on the adjacent ultra-
sound image (b); a DE nodule can be seen as labeled. Reprinted with permission from Wiley Publishers [34]
examine the pelvis in patients with suspected 9. Guerriero S, Ajossa S, Lai MP, Mais V, Paoletti
AM, Melis GB. Transvaginal ultrasonography in
endometriosis. The published defined anatomical the diagnosis of pelvic adhesions. Hum Reprod.
terms and measurements used to describe the 1997;12(12):2649–53.
appearances of all endometriosis phenotypes 10. Okaro E, Condous G, Khalid A, Timmerman D,
should represent the benchmark standard for Ameye L, Huffel SV, et al. The use of ultrasound-based
“soft markers” for the prediction of pelvic pathology
endometriosis ultrasound henceforth. This in turn in women with chronic pelvic pain - can we reduce
will not only raise the standard of diagnostic the need for laparoscopy? BJOG. 2006;113(3):251–6.
ultrasound in this field but also ensure that expe- 11. Ghezzi F, Raio L, Cromi A, Duwe DG, Beretta P,
rienced operators, regardless of country of origin, Buttarelli M, et al. “Kissing ovaries”: a sonographic
sign of moderate to severe endometriosis. Fertil Steril.
describe the location and extent of disease in a 2005;83(1):143–7.
way which is uniform and easily interpretable. 12. Reid S, Lu C, Casikar I, Reid G, Abbott J, Cario G, et al.
Prediction of pouch of Douglas obliteration in women
with suspected endometriosis using a new real-time
dynamic transvaginal ultrasound technique: the sliding
References sign. Ultrasound Obstet Gynecol. 2013;41(6):685–91.
13. Hudelist G, Fritzer N, Staettner S, Tammaa A, Tinelli
1. Sandler M, Karo J. The spectrum of ultrasonic findings A, Sparic R, et al. Uterine sliding sign: a simple
in endometriosis. Radiology. 1978;127(1):229–31. sonographic predictor for presence of deep infiltrat-
2. Guerriero S, Condous G, van den Bosch T, Valentin ing endometriosis of the rectum. Ultrasound Obstet
L, Leone FPG, Van Schoubroeck D, et al. Systematic Gynecol. 2013;41(6):692–5.
approach to sonographic evaluation of the pelvis in 14. Chapron C, Chopin N, Borghese B, Foulot H, Dousset
women with suspected endometriosis, including B, Vacher-Lavenu MC, et al. Deeply infiltrating endo-
terms, definitions and measurements: a consensus metriosis: pathogenetic implications of the anatomi-
opinion from the International Deep Endometriosis cal distribution. Hum Reprod. 2006;21(7):1839–45.
Analysis (IDEA) group. Ultrasound Obstet Gynecol. 15. Hudelist G, Ballard K, English J, Wright J, Banerjee
2016;48(3):318–32. S, Mastoroudes H, et al. Transvaginal sonography vs.
3. Piketty M, Chopin N, Dousset B, Millischer- clinical examination in the preoperative diagnosis of
Bellaische AE, Roseau G, Leconte M, et al. deep infiltrating endometriosis. Ultrasound Obstet
Preoperative work-up for patients with deeply infil- Gynecol. 2011;37(4):480–7.
trating endometriosis: transvaginal ultrasonography 16. Fedele L, Bianchi S, Raffaelli R, Portuese A. Pre-
must definitely be the first-line imaging examination. operative assessment of bladder endometriosis. Hum
Hum Reprod. 2009;24(3):602–7. Reprod. 1997;12(11):2519–22.
4. Kunz G, Beil D, Huppert P, Noe M, Kissler S, 17. Guerriero S, Ajossa S, Gerada M, Virgilio B, Angioni
Leyendecker G. Adenomyosis in endometriosis--prev- S, Melis GB. Diagnostic value of transvaginal “ten-
alence and impact on fertility. Evidence from magnetic derness-guided” ultrasonography for the prediction
resonance imaging. Hum Reprod. 2005;20(8):2309–16. of location of deep endometriosis. Hum Reprod.
5. Van Den Bosch T, Dueholm M, Leone FPG, Valentin 2008;23(11):2452–7.
L, Rasmussen CK, Votino A, et al. Terms, definitions 18. Guerriero S, Ajossa S, Gerada M, D’Aquila M, Piras
and measurements to describe sonographic features B, Melis GB. “Tenderness-guided” transvaginal ultra-
of myometrium and uterine masses: a consensus sonography: a new method for the detection of deep
opinion from the Morphological Uterus Sonographic endometriosis in patients with chronic pelvic pain.
Assessment (MUSA) group. Ultrasound Obstet Fertil Steril. 2007;88(5):1293–7.
Gynecol. 2015;46(3):284–98. 19. Abrao MS, Gonçalves MODC, Dias JA, Podgaec S,
6. Di Donato N, Bertoldo V, Montanari G, Zannoni L, Chamie LP, Blasbalg R. Comparison between clinical
Caprara G, Seracchioli R. Question mark form of examination, transvaginal sonography and magnetic
uterus: a simple sonographic sign associated with resonance imaging for the diagnosis of deep endome-
the presence of adenomyosis. Ultrasound Obstet triosis. Hum Reprod. 2007;22(12):3092–7.
Gynecol. 2015;46(1):126–7. 20. Bazot M, Thomassin I, Hourani R, Cortez A, Darai
7. Timmerman D, Valentin L, Bourne TH, Collins WP, E. Diagnostic accuracy of transvaginal sonography
Verrelst H, Vergote I. Terms, definitions and measure- for deep pelvic endometriosis. Ultrasound Obstet
ments to describe the sonographic features of adnexal Gynecol. 2004;24(2):180–5.
tumors: a consensus opinion from the International 21. Savelli L, Manuzzi L, Pollastri P, Mabrouk M,
Ovarian Tumor Analysis (IOTA) group. Ultrasound Seracchioli R, Venturoli S. Diagnostic accuracy and
Obstet Gynecol. 2000;16(5):500–5. potential limitations of transvaginal sonography for
8. Chapron C, Pietin-Vialle C, Borghese B, Davy C, bladder endometriosis. Ultrasound Obstet Gynecol.
Foulot H, Chopin N. Associated ovarian endometri- 2009;34(5):595–600.
oma is a marker for greater severity of deeply infiltrat- 22. Moro F, Mavrelos D, Pateman K, Holland T, Hoo
ing endometriosis. Fertil Steril. 2009;92(2):453–7. WL, Jurkovic D. Prevalence of pelvic adhesions on
36 M. Leonardi and G. Condous
ultrasound examination in women with a history 29. Deura I, Harada T. Surgical management of endome-
of Cesarean section. Ultrasound Obstet Gynecol. triosis. In: Endometriosis: pathogenesis and treat-
2015;45(2):223–8. ment. New York: Springer; 2014. p. 385–98.
23. Pateman K, Holland TK, Knez J, Derdelis G, Cutner 30. Holland TK, Cutner A, Saridogan E, Mavrelos D,
A, Saridogan E, et al. Should a detailed ultrasound Pateman K, Jurkovic D. Ultrasound mapping of pel-
examination of the complete urinary tract be routinely vic endometriosis: does the location and number of
performed in women with suspected pelvic endome- lesions affect the diagnostic accuracy? A multicentre
triosis? Hum Reprod. 2015;30(12):2802–7. diagnostic accuracy study. BMC Womens Health.
24. Pateman K, Mavrelos D, Hoo WL, Holland T, Naftalin 2013;13(1):43.
J, Jurkovic D. Visualization of ureters on standard 31. Menakaya U, Reid S, Infante F, Condous G. Systematic
gynecological transvaginal scan: a feasibility study. evaluation of women with suspected endometriosis
Ultrasound Obstet Gynecol. 2013;41(6):696–701. using a 5-domain sonographically based approach. J
25. León M, Vaccaro H, Alcázar JL, Martinez J, Gutierrez Ultrasound Med. 2015;34(6):937–47.
J, Amor F, et al. Extended transvaginal sonography in 32. Nisenblat V, Bossuyt PMM, Farquhar C, Johnson
deep infiltrating endometriosis: use of bowel prepara- N, Hull ML. Imaging modalities for the non-inva-
tion and an acoustic window with intravaginal gel: pre- sive diagnosis of endometriosis. Cochrane Database
liminary results. J Ultrasound Med. 2014;33(2):315–21. Syst Rev. 2016;(2):Art. No.: CD009591. https://doi.
26. Carmignani L, Vercellini P, Spinelli M, Fontana E, org/10.1002/14651858.CD009591.
Frontino G, Fedele L. Pelvic endometriosis and hydro- 33. Tammaa A, Fritzer N, Strunk G, Krell A, Salzer
ureteronephrosis. Fertil Steril. 2010;93(6):1741–4. H, Hudelist G. Learning curve for the detection of
27. Knabben L, Imboden S, Fellmann B, Nirgianakis K, pouch of Douglas obliteration and deep infiltrat-
Kuhn A, Mueller MD. Urinary tract endometriosis in ing endometriosis of the rectum. Hum Reprod.
patients with deep infiltrating endometriosis: preva- 2014;29(6):1199–204.
lence, symptoms, management, and proposal for a new 34. Reid S, Winder S, Condous G. Sonovaginography:
clinical classification. Fertil Steril. 2015;103(1):147–52. redefining the concept of a “normal pelvis” on
28. Squifflet J, Feger C, Donnez J. Diagnosis and imaging transvaginal ultrasound prelaparoscopic interven-
of adenomyotic disease of the retroperitoneal space. tion for suspected endometriosis. AJUM. 2011;
Gynecol Obstet Investig. 2002;54(Suppl 1):43–51. 14(2):21–4.
Uterine Evaluation Using
a Diagnostic Protocol Based
4
on MUSA
Asymmetrical thickening
Hyperechoic subendometrial
lines and buds
Cysts
Translesional vascularity
Interrupted or ill-defined
junctional zone
Fig. 4.2 Ultrasound features of adenomyosis (From Van den Bosch et al. [2])
pendicular to the endometrium) and the total all myometrial echogenicity may be heteroge-
uterine wall thickness (measured perpendicular neous, making the reference echogenicity less
to the endometrium). Both should be measured reliable. The subjectivity of the scoring system
on the same image. had to be taken into account in the interpretation
The extent of an ill-defined lesion is reported of the report.
as localized, if less than 50% of the total uterine Shadowing originating from the myometrium
is involved, or as diffuse, if at least half of the may present as edge shadows, internal shadows,
uterine volume is involved. The extent may also or fan-shaped shadowing (Fig. 4.8). The degree
be recorded as the percentage of the myome- of shadowing is recorded as slight, moderate, or
trium involved. The estimation of ill-defined strong (Fig. 4.9).
lesions is a rough subjective estimation and is Myometrial cysts may be present. Cyst may
deemed difficult and probably not optimally be caused by adenomyosis, atrophy, and necrosis
reproducible. or may be drug induced (e.g., tamoxifen). The
The echogenicity of a myometrium lesion is cyst fluid may be anechogenic and have a low
reported as uniform or nonuniform. A uniform level echogenicity, a ground-glass appearance,
lesion may be hypo-, iso-, or hyperechogenic as or a mixed echogenicity. The cyst size may vary
compared with the surrounding (unaffected) considerably. At least in the presence of larger
myometrium. For research purposes, the rela- cysts, the number of cysts and the maximal
tive echogenicity can be scored as very
hypoechogenic (−−), hypoechogenic (−),
isoechogenic, hyperechogenic (+), or very
hyperechogenic (++). As stated before, the over-
Fig. 4.7 Penetration of ill-defined lesions (From Van den Fig. 4.9 Ultrasound image of a calcified fibroid causing
Bosch et al. [2]) intense internal shadows
Present Present
Fig. 4.8 Shadowing caused by fibroids (From Van den Bosch et al. [2])
4 Uterine Evaluation Using a Diagnostic Protocol Based on MUSA 41
the color score of the most vascularized part may The vessel morphology can further be
be reported using the same color score ranging described as to vessel number, size, branching,
from 1 to 4, and the percentage of solid tissue and direction. The number of vessels is recorded
with color signal can be specified (0–100%). The as single or multiple. The vessel size may be
vascularity within the lesion may be compared to large and equal, small and equal, or unequal.
the adjacent myometrium and reported as iso-, Vessels may exhibit regular or irregular branch-
hypo-, or hyper-vascularization. ing, or no branching. The direction of the vessels
The location of vessels is reported as circum- is recorded as perpendicular or not perpendicu-
ferential, intralesional, or translesional lar to the uterine cavity.
(Fig. 4.13). Circumferential flow is typical for
fibroids, whereas translesional vascularity is
characteristic for adenomyosis (Fig. 4.14). The 4.3 Technical Tips
vessel spread within a lesion may be uniform or
not uniform. In the latter case, there are areas Using 2D, the uterus is scanned in sagittal and
with increased or decreased vascularity within transverse plane to assess its position, shape, and
the lesion. volume. In transverse plane, a section high in the
a b
Fig. 4.13 Color imaging: circumferential (a), intralesional (b), and translesional (c) vascularization (adapted from Van
den Bosch et al. [2])
4 Uterine Evaluation Using a Diagnostic Protocol Based on MUSA 43
a b
Fig. 4.14 Ultrasound image of a fibroid with circumferential flow (a) and adenomyosis with translesional flow (b)
(Fig. 4.16). It is important to ask the patient if she ultrasound images of the JZ [11] (Fig. 4.17). If
experiences some discomfort or pain during the the endometrium is not clearly visible, the junc-
scanning. Site-specific tenderness [10] when tional zone cannot be evaluated neither. In those
applying some pressure on the uterus may be cases, fluid instillation may be helpful.
caused by, e.g., adenomyosis or infection. To detect vessels of lower velocity, the pulse
It is not always easy to identify the JZ on rate frequency (PRF) should be set low enough
ultrasound examination. The use of volume con- (e.g., 0.3). In most cases, the arcuate and the radial
trast imaging (VCI) set at 2 mm after 3D volume vessels are visible, providing an appropriate set-
acquisition has been reported to yield the best ting (Fig. 4.18). However, the vessels in the myo-
metrial wall nearest to the ultrasound probe are
more readily detectable than in the opposite wall.
An apparent asymmetrical vascularity between
anterior and posterior myometrium is mostly due
to a difference in focal depth and acoustic attenua-
tion. Transient myometrial contractions may cause
a temporary disappearance of the blood flow [12].
Arcuate artery
Radial arteries
Fig. 4.16 Examining the sliding sign (From Guerriero
et al. [9]) Fig. 4.18 Vascularization of the uterus
Fig. 4.17 Ultrasound image of adenomyosis using VCI and TUI: irregular junctional zone
4 Uterine Evaluation Using a Diagnostic Protocol Based on MUSA 45
Fig. 5.3 Small ovarian endometrioma with hyperecho- Fig. 5.6 Two ovarian endometriomas with low-level
genic foci located close to ovarian surface echogenicity, but not a ground-glass appearance
Fig. 5.8 Transvaginal ultrasound showing a “septate” Fig. 5.10 Transvaginal ultrasound showing an atypical
endometrioma. In fact, this is two different endometrio- endometrioma containing a solid area (S) arising from
mas (E) separated by ovarian parenchyma (S). Arrows internal surface of cyst’s wall
show the so-called “lambda sign”
Another very specific feature proposed for A recent study has shown that ultrasound fea-
ovarian endometrioma is the so-called acoustic tures of ovarian endometriomas change with the
streaming. Acoustic streaming is defined as the patient’s age [21]. For example, ground-glass
bulk movement of fluid due to the effect of a echogenicity appears in 75% of endometriomas
sound field caused by energy transfer from an in premenopausal women but only in 62% of
ultrasound beam to the fluid. In other words, endometriomas in peri-/postmenopausal women.
the energy of the ultrasound beam “pushes” the Anechoic cysts are uncommon in premenopausal
particles of the fluid away from the transducer women (3%) but may appear in up to 11% of
(Video 5.1). Clarke et al. supported the concept peri-/postmenopausal women.
that ovarian endometrioma never show acous- There are two clinical entities that deserve partic-
tic streaming [17]. However, a subsequent ular mention: decidualization of an e ndometrioma
study in a much large series demonstrated that and ovarian cancer arising from an endometrioma.
acoustic streaming occurs in 9% of endome- Endometrioma decidualization is a phenomenon
triomas, and, therefore, this feature cannot be characterized by the thickening of the ectopic endo-
considered as 100% specific for ovarian endo- metrium due to the effect of progesterone during
metrioma [18]. pregnancy. When decidualization occurs, endome-
The inherent dynamic nature of ultrasound triomas may mimic an ovarian cancer during ultra-
evaluation allows the evaluation of two additional sound evaluation. Typical findings are the presence
signs [1]. The assessment of ovarian cyst mobil- of one to several vascularized solid papillary projec-
ity is important. The lack of mobility is due to tions arising from the internal surface of the cyst’s
the formation of adhesions to the uterus, to the wall [22, 23] (Video 5.4). The knowledge of past
pelvic wall, or to the contralateral ovary, the so- history of endometriosis observing the “suspicious”
called kissing ovaries (Fig. 5.13). The presence lesion in the same ovary where endometrioma had
of ovarian adhesion to the uterus, pelvic wall, or been diagnosed prior to pregnancy may give clues
contralateral ovary is highly predictive of ovar- for considering decidualization. Another important
ian endometrioma [19] (Video 5.2), but it is not tip is paying attention to the surface of the papillary
always present (Video 5.3) [2]. The presence of projection. In decidualized endometriomas surface
site-specific tenderness (see Chap. 3) when mov- uses to be smooth [22], whereas in malignancy
ing the ultrasound probe against particular struc- surface uses to be irregular. Serial evaluation dur-
tures is also very suggestive of endometriosis [20]. ing pregnancy can be advised in cases of suspected
decidualized endometriomas [24].
Although there is a clear association between
endometriosis and ovarian cancer [25], the risk of
developing a malignancy from ovarian endome-
trioma is low [7]. Testa et al. reported a retrospec-
tive study comprising 15 malignancies arising
from ovarian endometrioma [26]. They found
that all malignancies were characterized by the
presence of solid tissue, as compared to 16% of
benign endometriomas. Blood flow within the
solid component was observed in 92% of malig-
nancies and only in 8% of benign endometriomas
with solid areas. Both mean size of the lesion and
mean size of the solid areas were significantly
Fig. 5.13 Transvaginal ultrasound showing the two ova-
larger in malignancies. Figure 5.14 shows a case
ries containing several ovarian endometriomas (E) and
adhered one to each other (A), the so-called kissing of ovarian malignancy arising from an ovarian
ovaries endometrioma.
52 J. L. Alcázar
Alcazar et al. evaluated the use of the so-called 5.3 Important Technical Tips
mean gray value (MGV) of the cyst’s content for
discriminating endometrioma from other benign There are several important technical tips to be
unilocular cysts [34]. MGV represents the mean considered when evaluating the ovary and ovarian
intensity of grayscale voxels contained in a given endometriomas. These technical tips are basically
3D region of interest and can be calculated using related to the ultrasound machine settings and
the virtual organ computer-aided analysis depth. The objective of the examination from the
(VOCAL™) software (Fig. 5.15); the more technical point of view is trying to get the maxi-
anechoic the content, the lower MGV, and the mum possible resolution. This is the main reason
more echogenic content, the higher MGV. They why TVS should be performed whenever possi-
found that MGV in endometriomas was signifi- ble, and the use of transrectal ultrasound is the
cantly higher as compared with other cysts (sim- best alternative when TVS cannot be performed.
ple cysts, hemorrhagic cysts, and mucinous cysts).
However, Huang et al. found the opposite
findings; MGV was significantly lower in ovarian 5.3.1 Depth
endometrioma [35]. These controversial results
can be explained by two facts: first, Huang’s The distance between the transducer and any
study included dermoid cysts, which tend to structure under examination is a very relevant
show highly echogenic areas. Second, MGV is issue, especially if Doppler is used, since Doppler
highly affected by some machine settings (espe- signal is heavily affected by attenuation. If the
cially gain), so different machine settings used ovary and/or uterus are far from the transducer
render different MGV values. Due to the paucity (>5 cm), gentle pressure with the hand over the
of studies and their controversial results, it could abdomen while performing the ultrasound exam-
be stated that the role of 3D ultrasound still needs ination may get these structures closer to the
to be determined. transducer favoring image resolution.
Fig. 5.15 Three-dimensional ultrasound showing mean gray value calculation from the cyst content in a case of ovar-
ian endometrioma
54 J. L. Alcázar
Ultrasound machine settings are also important Several areas in the ultrasound evaluation and
for achieving a good resolution image. The trans- follow-up of endometriomas should be evaluated
ducer’s frequency is the most important machine in the future research studies. These include:
setting. It should not be less than 5 MHz and even
higher frequency (8–9 MHz) is advisable. If 1. Assessment of diagnostic performance of
Doppler is used, 5 MHz is an optimal frequency. ultrasound in hands of non-expert examiners.
Gain is another important ultrasound machine 2. Assessment of reproducibility on ultrasound
setting to be considered, especially for grayscale diagnosis of ovarian endometrioma among
ultrasound. Gain significantly affects the echo- non-expert examiners.
genicity of the structures. Thus, using adequate 3. Define the role of 3D ultrasound.
gain is essential for avoiding confusion between 4. Long-term prospective studies based on
different cyst’s content echogenicity. For gray- expectant management for determining the
scale evaluation, mid gain is initially advisable, risk of developing ovarian cancer from ovar-
increasing or lowering it until good quality image ian endometrioma.
is obtained. Very low gain may render an endo- 5. Prospective studies to determine if expectant
metrioma as an anechoic cyst, whereas high gain management of decidualized endometriomas
may render it as an echogenic cyst, both resulting during pregnancy is safe and what criteria
in potential to miss ground-glass echogenicity. should be used for advising expectant
For color/power Doppler assessment, it is rec- management.
ommended to increase gain until saturation and
then reduce gain reaching sub-noise gain level.
Harmonics increases image resolution, but References
penetration is lower. This can also affect cyst
content, and one should bear this in mind. If the 1. Redwine DB. Ovarian endometriosis: a marker for
more extensive pelvic and intestinal disease. Fertil
ovary is very close to the transducer, the use of Steril. 1999;72:310–5.
harmonics is advised. 2. Sokalska A, Timmerman D, Testa AC, Van Holsbeke
Other ultrasound machine settings such as C, Lissoni AA, Leone FP, Jurkovic D, Valentin
persistence, contrast, and enhancement power L. Diagnostic accuracy of transvaginal ultrasound
examination for assigning a specific diagnosis
do not usually need to be modified for improving to adnexal masses. Ultrasound Obstet Gynecol.
image quality or resolution in most circumstance. 2009;34:462–70.
For Doppler assessment, other important 3. Alcázar JL, Guerriero S, Laparte C, Ajossa S, Ruiz-
parameters are: Zambrana A, Melis GB. Diagnostic performance of
transvaginal gray-scale ultrasound for specific diag-
nosis of benign ovarian cysts in relation to meno-
• Pulse repetition frequency (PRF). Since blood pausal status. Maturitas. 2011;68:182–8.
flow within the ovary and endometrium uses 4. Al-Fozan H, Tulandi T. Left lateral predisposition of
to be slow and the vessels are small, low PRF endometriosis and endometrioma. Obstet Gynecol.
2003;101:164–6.
is advised (0.6–0.3 kHz). 5. Nisolle M, Donnez J. Peritoneal endometriosis, ovar-
• Wall filter should be low (50 Hz). ian endometriosis, and adenomyotic nodules of the
• Sample volume should cover the whole ovary. rectovaginal septum are three different entities. Fertil
• Insonation angle is not relevant for assessing Steril. 1997;68:585–96.
6. Chapron C, Pietin-Vialle C, Borghese B, Davy C,
ovarian vascularization since the vessels are Foulot H, Chopin N. Associated ovarian endometri-
so small that it is virtually impossible to ascer- oma is a marker for greater severity of deeply infiltrat-
tain vessel orientation. ing endometriosis. Fertil Steril. 2009;92:453–7.
• Pulsed Doppler sample volume size should be 7. Nishida M, Watanabe K, Sato N, Ichikawa
Y. Malignant transformation of ovarian endometriosis.
adjusted to vessel caliber as better as possible. Gynecol Obstet Investig. 2000;50(Suppl 1):18–25.
If not possible, sample volume size of 0.7– 8. Alcázar JL, Olartecoechea B, Guerriero S, Jurado
1.0 mm is advisable. M. Expectant management of adnexal masses in
5 Ovarian Endometriosis 55
6.1 Update on Soft Markers [2, 3]. The most common sites for ovarian adhe-
sions to form are with the neighbouring uterus
Transvaginal sonography (TVS) soft markers for (Fig. 6.1) or pelvic sidewall; however, the
endometriosis include ovarian immobility and bowel and uterosacral ligaments (USL) can
site-specific tenderness (SST). In the recently also be involved. Okaro et al. found that preop-
published consensus statement entitled erative TVS ‘soft markers’ (i.e. site-specific
‘Systematic approach to sonographic evaluation tenderness, reduced ovarian mobility) and ‘hard
of the pelvis in women with suspected endome- markers’ (i.e. endometrioma, hydrosalpinx) in
triosis, including terms, definitions and measure- women with a history of CPP correlated with
ments: a consensus opinion from the International the presence or absence of disease at laparos-
Deep Endometriosis Analysis (IDEA)’, the eval- copy [4]. Pre-operative TVS and transrectal
uation of soft markers is recommended as a com- ultrasound have also been used to predict endo-
ponent of the ultrasound evaluation of women metriosis stage (including pelvic adhesions) at
with suspected pelvic deep endometriosis (DE)
[1].
laparoscopy, with a sensitivity and specificity of indicating a high false-positive rate [9]. This
86% and 82%, respectively, for Stage III and 76% study did not find SST was predictive of superfi-
and 91%, respectively, for Stage IV disease [5]. cial endometriosis location.
In a recent study by Marasinghe et al., the With regard to posterior compartment DE,
combination of ovarian immobility and clinical some studies have found that tenderness-guided
findings (i.e. dyspareunia, dysmenorrhea and vag- TVS may aid in the prediction of specific locations
inal examination) was able to demonstrate a sen- of posterior compartment DE [10, 11]. A recent
sitivity/specificity of 92%/61% for the detection study from our group showed that TV probe ten-
of endometriosis at laparoscopy [6]. More specifi- derness in the posterior pelvic compartment (left
cally, ovarian immobility at TVS is strongly asso- USL, POD and right USL) was significantly asso-
ciated with the presence of endometrioma [2, 7] ciated with both deep and superficial endometrio-
and POD obliteration [8]. The identification of ses in the posterior pelvic compartment (p < 0.05)
ovarian immobility at TVS may improve our abil- [12]. SST appears to be a useful soft marker for the
ity to stage endometriosis severity preoperatively, prediction of the presence/absence of endometrio-
allowing for improved surgical planning. sis at laparoscopy [4, 9] and should be included in
The diagnostic accuracy of ovarian immobility the sonographic evaluation of the pelvis in women
at TVS has been reported in previous studies, usu- with suspected endometriosis [1].
ally in the presence of endometriomas. In a study
by Guerriero et al., women undergoing surgery for
endometrioma were assessed for ovarian mobility 6.4 How We Do It
in relation to the uterus. The sensitivity and speci-
ficity of the fixation to the uterus of at least one 6.4.1 Assessment of Ovarian
ovary were, respectively, 89% and 90% [2]. Mobility
Holland et al. also evaluated TVS accuracy for
ovarian adhesions in women with proven/sus- In order to assess for ovarian mobility, the exam-
pected endometriosis by classifying adhesions as iner places gentle pressure with TV probe toward
minimal, moderate or severe in accordance with the ovary of interest in order to mobilize the
the rASRM classification. For severe ovarian ovary. The examiner assesses whether the ovary
adhesions, the sensitivity and specificity of TVS glides freely along (1) the corresponding pelvic
was 83.5% and 93.5%, respectively. In another sidewall and (2) the neighbouring uterine sur-
study by our group, ovarian immobility was face. This is the same concept that is applied to
assessed as a sonographic ‘soft marker’ of DE and the assessment of the POD for obliteration using
was found to perform better in the presence of the uterine sliding sign, where a negative sliding
endometriomas compared with normal ovaries [7]. sign indicates adhesions are present causing lim-
ited mobility [13, 14]. Ovarian mobility is
assessed in both the sagittal and transverse planes
6.3 Site-Specific Tenderness for each location (i.e. pelvic sidewall and uterine
(SST) surface). If the ovary glides smoothly along the
surface of the uterus and pelvic sidewall, the
A relationship between SST at TVS and endome- ovarian sliding sign is considered positive and the
triosis at laparoscopy has also been demonstrated ovary is recorded as mobile in these regions.
in previous studies. In a study that evaluated ten- Video 6.1 displays a mobile right ovary (positive
derness during a combination of vaginal and TVS ovarian sliding sign) along the right pelvic side-
examination, Yong et al. found that SST may be wall, in the transverse plane. Video 6.2 displays
helpful in predicting abnormal laparoscopy and ovarian mobility along the lateral uterus (positive
the presence of superficial endometriosis; how- ovarian sliding sign), as well as the pelvic side-
ever, the specificity of this study was low (22%), wall, in the transverse plane.
6 Soft Marker Evaluation 59
2. The external iliac vessels can be used to help In a recent study by our group, ovarian mobility
orientate the examiner to the pelvic sidewall and SST were included in the evaluation of an
when assessing ovarian mobility in this region. ultrasound-based endometriosis staging system
The colour Doppler function is used to confirm (UBESS) for the prediction of level of complexity
the location of the external iliac vessels. of laparoscopic surgery for endometriosis. The
3. The ovaries can be difficult to locate in the accuracy, sensitivity, specificity and positive and
presence of complex endometriotic disease, as negative predictive values of UBESS I for predict-
the anatomy can be severely distorted. Try to ing a requirement for Level 1 laparoscopic surgery
be systematic in the assessment of each ovary, were 87.5%, 83.3%, 91.7%, 90.9% and 84.6%;
carefully identifying each structure that is those of UBESS II for predicting Level 2 surgery
adherent to the ovary. These difficult scans were 87.0%, 73.7%, 90.3%, 65.1% and 93.3%;
take more time to perform as several struc- and those of UBESS III for predicting Level 3 sur-
tures may be involved, particularly in the pres- gery were 95.3%, 94.8%, 95.5%, 90.2% and
ence of endometriomas. 97.7%, respectively. This study demonstrated that
4. The addition of ultrasound gel (15–20 ml) in UBESS has the potential to facilitate the triage of
the posterior vaginal fornix (i.e. sonovaginog- women with suspected endometriosis to the most
raphy) may improve the view of the structures appropriate surgical expertise required for laparo-
in the posterior pelvic compartment, thereby scopic endometriosis surgery [12]. External vali-
helping the examiner to identify structures dation of UBESS is currently being performed to
that are associated with ovarian adhesions. determine the applicability of this system for plan-
ning laparoscopic endometriosis surgery.
5. Exacoustos C, Zupi E, Carusotti C, Rinaldo D, 10. Guerriero S, Ajossa S, Gerada M, D'Aquila M, Piras
Marconi D, Lanzi G, et al. Staging of pelvic endo- B, Melis GB. “Tenderness-guided” transvaginal ultra-
metriosis: role of sonographic appearance in sonography: a new method for the detection of deep
determining extension of disease and modulating endometriosis in patients with chronic pelvic pain.
surgical approach. J Am Assoc Gynecol Laparosc. Fertil Steril. 2007;88(5):1293–7.
2003;10(3):378–82. Epub 2003/10/22 11. Saba L, Guerriero S, Sulcis R, Pilloni M, Ajossa S,
6. Marasinghe JP, Senanayake H, Saravanabhava N, Melis G, et al. MRI and “tenderness guided” trans-
Arambepola C, Condous G, Greenwood P. History, vaginal ultrasonography in the diagnosis of recto-
pelvic examination findings and mobility of ova- sigmoid endometriosis. J Magn Reson Imaging.
ries as a sonographic marker to detect pelvic adhe- 2012;35(2):352–60. Epub 2011/10/29
sions with fixed ovaries. J Obstet Gynaecol Res. 12. Menakaya U, Reid S, Lu C, Gerges B, Infante F,
2014;40(3):785–90. Epub 2014/04/17 Condous G. Performance of an Ultrasound Based
7. Gerges BLC, Reid S, Menakaya U, Nadim B, Condous Endometriosis Staging System (UBESS) for pre-
G. “Soft marker” evaluation of ovarian mobility in the dicting the level of complexity of laparoscopic sur-
normal and endometriotic ovary. Ultrasound Obstet gery for endometriosis. Ultrasound Obstet Gynecol.
Gynecol. 2015. https://doi.org/10.1002/uog.15990. 2016;48(6):786–95. Epub 2016/01/15
8. Reid S, Lu C, Condous G. Can we improve the predic- 13. Holland TK, Yazbek J, Cutner A, Saridogan E, Hoo
tion of pouch of Douglas obliteration in women with WL, Jurkovic D. Value of transvaginal ultrasound in
suspected endometriosis using ultrasound-based mod- assessing severity of pelvic endometriosis. Ultrasound
els? A multicenter prospective observational study. Obstet Gynecol. 2010;36(2):241–8.
Acta Obstet Gynecol Scand. 2015;94(12):1297–306. 14. Reid S, Winder S, Reid G, Condous G. Can we pre-
Epub 2015/09/25 dict pouch of Douglas (POD) obliteration using a new
9. Yong PJ, Sutton C, Suen M, Williams C. Endovaginal real-time ultrasound technique: the “sliding sign”.
ultrasound-assisted pain mapping in endometrio- 21st World Congress on Ultrasound in Obstetrics and
sis and chronic pelvic pain. J Obstet Gynaecol. Gynecology. Los Angeles: Wiley-Blackwell; 2011.
2013;33(7):715–9. Epub 2013/10/17 p. 1–55.
Ultrasound in the Evaluation
of Pouch of Douglas Obliteration
7
Shannon Reid
a b
c d
Fig. 7.1 Examples of complete POD obliteration at trans- level of the posterior cervix to the posterior uterine fundus.
vaginal ultrasound (sagittal plane). (a) The anterior rectum (c) The anterior rectum contains a DE nodule (N) that infil-
contains a DE nodule (N) and is adherent posteriorly to the trates the posterior cervix (C) and rectovaginal septum
uterine cervix. (b) The anterior rectum/rectosigmoid bowel posteriorly. (d) The rectosigmoid bowel contains a DE
contains a DE nodule (N) that forms an adhesion from the nodule (N) that is adherent to the posterior uterine fundus
Given the strong relationship between POD The “sliding sign” has also been demon-
obliteration and ovarian endometrioma/posterior strated to have substantial to almost perfect
compartment DE, our group developed and vali- inter- and intra-observer agreement among
dated two mathematical TVS models to deter- sonologists/sonographers experienced in gyne-
mine whether a combination of TVS markers cological ultrasound [5] and is an easily learned
could improve the prediction of POD obliteration technique for those with previous experience in
as compared with the uterine “sliding sign” alone. gynecological ultrasound. Tammaa et al. deter-
These models included TVS findings such as mined the learning curve to be ~40 scans in
posterior compartment DE, ovarian fixation, and order to achieve competency in predicting POD
ovarian endometrioma, in addition to a negative obliteration using the uterine “sliding sign” [6].
uterine “sliding sign.” This study found that the Another study found similar results, with 38
incorporation of additional TVS markers did not scans required to reach competency for predic-
improve the prediction of POD obliteration as tion of POD obliteration using the “sliding
compared to the “sliding sign” alone [2]. sign” [7].
7 Ultrasound in the Evaluation of Pouch of Douglas Obliteration 65
colorectal input. Given the significant relation- niques to assess POD obliteration: a systematic
review and meta-analysis. In: Gynecol UO, editor.
ship between rectal DE and POD obliteration, a 26th World Congress on Ultrasound in Obstetrics
negative uterine “sliding sign” is an important and Gynaecology; September 2016; Rome. 2016.
red flag for the increased risk of bowel DE [8]. p. 165.
The ability to predict POD obliteration preopera- 4. Reid S, Lu C, Casikar I, Reid G, Abbott J, Cario G,
et al. Prediction of pouch of Douglas obliteration in
tively is therefore essential for appropriate women with suspected endometriosis using a new
specialist referral, surgical planning, and coun- real-time dynamic transvaginal ultrasound tech-
seling for these high-risk women. nique: the sliding sign. Ultrasound Obstet Gynecol.
As recommended in the recent consensus 2013;41(6):685–91. Epub 2012/09/25
5. Reid S, Lu C, Casikar I, Mein B, Magotti R, Ludlow
statement by the International Deep Endometriosis J, et al. The prediction of pouch of Douglas oblit-
Analysis group [9], women with pelvic pain/sus- eration using offline analysis of the transvaginal
pected endometriosis, should ideally undergo a ultrasound ‘sliding sign’ technique: inter- and intra-
standardized TVS examination for pelvic DE, observer reproducibility. Hum Reprod. 2013.; Epub
2013/03/14
including assessment for POD obliteration with 6. Tammaa A, Fritzer N, Strunk G, Krell A, Salzer H,
the uterine “sliding sign.” Although the “sliding Hudelist G. Learning curve for the detection of pouch
sign” has a high accuracy for the prediction of of Douglas obliteration and deep infiltrating endome-
POD obliteration and is an easily learned tech- triosis of the rectum. Hum Reprod. 2014;29(6):1199–
204. Epub 2014/04/30
nique, very few ultrasound centers currently per- 7. Piessens S, Healey M, Maher P, Tsaltas J, Rombauts
form an assessment for POD obliteration. Future L. Can anyone screen for deep infiltrating endometri-
gynecological ultrasound training programs will osis with transvaginal ultrasound? Aust N Z J Obstet
benefit from the integration of this important Gynaecol. 2014;54(5):462–8. Epub 2014/10/08
8. Hudelist G, Fritzer N, Staettner S, Tammaa A, Tinelli
technique into their curriculum for the ultrasound A, Sparic R, et al. Uterine sliding sign: a simple
assessment of women with suspected sonographic predictor for presence of deep infiltrat-
endometriosis. ing endometriosis of the rectum. Ultrasound Obstet
Gynecol. 2013;41(6):692–5. Epub 2013/02/13
9. Guerriero SCG, Van den Bosch T, Valentin L, Leone
F, Van Schoubroeck D, Exacoustos C, AJF I, Martins
References WP, Abrao MS, Hudelist G, Bazot M, Alcazar J,
Gonçalves MO, Pascual MA, Ajossa S, Savelli L,
1. Khong SY, Bignardi T, Luscombe G, Lam A. Is pouch Dunham R, Reid S, Menakaya U, Bourne T, Ferrero
of Douglas obliteration a marker of bowel endome- S, Leon M, Bignardi T, Holland T, Jurkovic D,
triosis? J Minim Invasive Gynecol. 2011;18(3):333–7. Benacerraf B, Osuga Y, Somigliana E, Timmerman
2. Reid S, Lu C, Condous G. Can we improve the predic- D. Systematic approach to evaluate the pelvis in
tion of pouch of Douglas obliteration in women with women with suspected endometriosis including
suspected endometriosis using ultrasound based mod- terms, definitions and measurements to describe the
els? A multicenter prospective observational study. sonographic features of deep infiltrating endometrio-
Acta Obstet Gynecol Scand. 2015;94(12):1297–306. sis: a consensus opinion from the International Deep
3. Shakeri B, Nadim B, Reid S, Martins WP Condous Endometriosis Analysis (IDEA) group. Ultrasound
G OP34.04: Accuracy of different imaging tech- Obstet Gynecol. 2016;48(3):318–32.
Anterior Compartment Including
Ureter
8
Luca Savelli and Maria Cristina Scifo
8.4 Important Technical Tips (or the three orthogonal diameters), mobility with
regard to the anterior uterine wall, and pain at
All scans should be performed both via transab- pressure with the probe should be recorded.
dominal (TAS) and transvaginal ultrasound Moreover, the relationship of the DE with the tri-
(TVS). The investigator must be aware of the gonus and the internal ureteral orifices should be
patients’ clinical and surgical history, symptoms evaluated, eventually waiting for the ureteral jet
(dysmenorrhea, dyspareunia, chronic pelvic to appear (Video 8.3). Assessment of vasculariza-
pain, dysuria, urgency, frequency, suprapubic tion of the nodule by means of color/power
pain, vesical tenesmus, infertility), and the Doppler does not seem to be crucial, but it might
results of a physical bimanual examination of be of help in the differential diagnosis with a
the patient. The optimal situation would be the bladder neoplasm (which is usually more vascu-
case in which the same physician performing larized than DE).
TAS and TVS is expert in bimanual exploration Pelvic sections of the ureter should be rou-
of the female pelvis (gynecologic examination) tinely evaluated at TVS [19] both at rest and
in order to obtain the best from both exams. The during peristalsing to identify any evidence of
ultrasound examinations must be performed in a ureteric dilatation, abnormal bending, or dif-
standardized manner using ultrasound machine ferences in peristalsis frequency between the
equipped with broadband abdominal and vagi- ureters [19]. In women with evidence of ure-
nal probes. teric obstruction, the distance between the nod-
At first, an accurate examination of the pelvis ule and the ureteric orifice should be measured.
should be undertaken to evaluate the anatomy of As already discussed, the operator must be
the uterus and the ovaries. The transvaginal trans- aware of the fact that nodules involving the
ducer should then be positioned in the anterior ureter are most often large nodules of the pos-
vaginal fornix and tilted upward to visualize the terior pelvic compartment extending laterally
vesicouterine space and the bladder, on a longitu- toward the parametrium (Figs. 8.11 and 8.12),
dinal and on a transverse section. In these planes, at the level of the uterine cervix, thus reaching
the bladder wall can easily be visualized if a the ureter either directly or as an involvement
moderate amount of urine is present. The sliding caused by the fibrotic reaction (collagen fibers,
of the normal bladder wall toward the anterior smooth muscle cells) surrounding the
wall of the uterus should be evaluated by gently DE. Thus, it is mandatory to perform a com-
pushing with the transvaginal probe (Video 8.1). plete evaluation of the posterior pelvic com-
The physician must be familiar with the normal partment. As previously recommended, TVS
anatomy of the bladder, in order to recognize the should be performed in a dynamic and interac-
peritoneum covering the intra-abdominal portion tive manner, while asking the patient about
(dome) of the bladder, the muscle layer, and the possible complaints and looking for painful
mucosa. site (pain mapping). A normal pelvis will show
Diagnostic criteria indicative of a bladder the sliding of the rectum toward the posterior
endometriotic nodule are the following [14, 18]: uterine wall (Video 8.2).
The examination is completed only after a
1. The presence of a hypo- or isoechogenic nod- TAS is done (which can be even done before
ule in the bladder wall TVS) by means of a 3.5–5.0 MHz curvilinear
2. The presence of a nodule with a heteroge- probe. Kidneys are easy to be evaluated by posi-
neous echostructure containing numerous tioning the woman on a lateral decubitus position
anechoic (“bubble-like”) areas (Fig. 8.14). with the probe in the lower intercostal space at
the level of the midaxillary line. Kidneys are
Whenever a bladder endometriotic nodule is scanned on a longitudinal (long axis) and trans-
seen at TVS, its location, shape, mean diameter verse (short axis) views.
74 L. Savelli and M. C. Scifo
Fig. 8.14 Transvaginal scan of a bladder endometriotic tom right) shows the distortion of bladder anatomy and
nodule (multiplanar image plus 3D reconstruction). The indenting of the bladder lumen. The nodule does not infil-
nodule appears as hypoechoic mass containing small cys- trate the mucosal layer which is smooth and has a normal
tic spaces (bubble-like). Three-dimensional image (bot- appearance
Hydronephrosis is diagnosed and graded junction with the hyperechoic fibrous layer sur-
using commonly accepted ultrasound criteria rounding the ureter [19].
[20]. When the cranial portion of the ureter
appears dilated (Figs. 8.1 and 8.2), it should be
followed on its abdominal and pelvic portions to References
the level of obstruction if not already seen vagi-
nally [19]. 1. Koninckx PR, Martin D. Treatment of deeply infil-
trating endometriosis. Curr Opin Obstet Gynecol.
The course of the ureter at TVS can be easily 1994;6:231–41.
followed starting from the trigonus up to the pel- 2. Chapron C, Fauconnier A, Dubuisson JB, Barakat
vic brim and to the crossing of the common iliac H, Viera M, Breart C. Deep infiltrating endometrio-
vessels. Color Doppler may help in differentiat- sis: relation between severity of dysmenorrhoea and
extent of disease. Hum Reprod. 2003;18:760–6.
ing the ureter from a blood vessel. Another fea- 3. Berlanda N, Vercellini P, Carmignani L, Aimi G,
ture which can help is the presence of peristalsis, Amicarelli F, Fedele L. Ureteral and vesical endome-
which can be seen in the ureter keeping the probe triosis. Two different clinical entities sarin the same
still for up to 180 s. The diameter of the ureter pathogenesis. Obstet Gynecol Surv. 2009;64:830–42.
4. Gabriel B, Nassif J, Trompoukis P, Barata S,
can be measured both at rest and during peak of Wattiez A. Prevalence and management of urinary
dilatation during peristalsis by placing the cali- tract endometriosis: a clinical case series. Urology.
pers on the outer edge of muscularis layer at the 2011;78:1269–74.
8 Anterior Compartment Including Ureter 75
acoustic window between the transvaginal probe The probe can be positioned either in the anterior
and the surrounding vaginal structures, combined or in the posterior vaginal fornix.
with an active role of the patient, who indicates The color and power Doppler box should
the site of any tenderness experienced during the include the nodule with the surrounding fat and
pelvic scan [9, 10]. Then, the image is magnified structures. Magnification and settings should be
to contain only the upper vagina, cervix, and adjusted to ensure maximal sensitivity for blood
lower uterus, to be assessed in the sagittal plane flow:
of the cervix from uterine artery to uterine artery
and in the transverse plane from the external to (a) Ultrasound frequency “normal” (at least
the internal cervical os. The magnification should 5.0 MHz)
be as large as possible, focusing on the area of (b) Pulse repetition frequency 0.6 kHz
interest. Furthermore, in order to obtain a high- (0.3–0.9 kHz)
quality image, a proper setting of the following is (c) Wall filter “low” 40 Hz (30–50 Hz)
of paramount importance: (d) Color and power Doppler gain (reduced until
all color artifacts disappear)
(a) Depth (the complete cervix on the screen
after whole pelvic assessment) The color content in the DE nodule may be
(b) Gain (setting also overall time gain scored using the standardized color score (CS), a
compensation) subjective semiquantitative assessment of the
(c) Dynamic range (less relevant for cervical amount of blood flow present: CS 1, no color
assessment) flow; CS 2, only minimal color; CS 3, moderate
(d) Focus (single enough, below the cervix) color; and CS 4, abundant color.
(e) Zoom (better high definition (HD) zoom) Normal USLs are usually not visible on ultra-
sound. USL DE lesions appear as hypoechoic
However, difficulties may arise from varia- thickening with regular, smooth outline, or irreg-
tions in uterine position (particularly when axial) ular, stellate margins, within the hyperechoic
or with uterine rotation (endometriosis or previ- peritoneal fat surrounding the USLs, with homo-
ous surgery-related adhesions). This problem geneous or heterogeneous echogenicity
may be overcome in some cases by pressing (Fig. 9.1) [2]. USL DE nodule can be seen in the
on the abdomen with the non-scanning hand. parasagittal view of the cervix (Fig. 9.2):
Fig. 9.1 USL DE lesion may appear as an hypoechoic, homogeneous thickened nodule with regular, smooth outline
(left) or as an hypoechoic, heterogeneous thickened nodule with irregular, stellate margins (right)
9 Uterosacral Ligament Endometriosis 79
a b
Fig. 9.2 (a) Sagittal image of the cervix with an imagi- the cervix, medial to the uterine artery, with an imaginary
nary line passing through the cervical internal os. (b) line passing at the level of the hypoechoic USL DE
Lateral sagittal image of the cervix with an imaginary line nodule
passing at the level of uterine artery. (c) Sagittal image of
(a) Place the transvaginal probe in the anterior or (b) Obtain the transverse plane of the cervix.
in the posterior vaginal fornix. (c) Sweep the probe cranially up to the internal
(b) Obtain the sagittal plane of the cervix and cervical os, and the USL DE nodule appears
select the midline (passing through the cervi- as a hypoechoic lesion.
cal canal).
(c) Trace an imaginary line passing through the The USL lesion may be isolated or may be
internal cervical os. part of a larger nodule extending into the vagina
(d) Sweep the probe laterally up to the uterine or into other surrounding structures (rectosig-
artery. moid, ovary) (Fig. 9.4). If the nodule is seen as a
(e) Sweeping back medially to the uterine artery, central block of hypoechoic tissue of the retrocer-
the USL DE nodule appears as a hypoechoic vical area (arciform abnormality), it should be
lesion. considered a DE lesion of the torus uterinus [2].
In the presence of an extended nodule, a posterior
Similarly, USL DE nodule can be seen in the negative “sliding sign” (i.e., pouch of Douglas
transverse view of the cervix (Fig. 9.3): obliteration) is usually observed [11, 12].
The thickness of the USL nodule should be
(a) Place the transvaginal probe in the anterior or measured systematically in three orthogonal
in the posterior vaginal fornix. planes by sagittal and transverse scans, to obtain
80 F. P. G. Leone
a b
Fig. 9.3 (a) Transverse image of the cervix with the vagi- Cranial transverse image of the uterine isthmus with the
nal bright edge. (b) Cranial transverse image of the upper hypoechoic left USL DE nodule adherent to a rectosig-
cervix with the hypoechoic left USL DE nodule. (c) moid bowel DE nodule
9.2.4 Sonovaginography
with Saline or Gel
of the condom fulfilled with gel is that it lasts selected cases or if TVS is impossible or inap-
longer, with no backflow and no need of a spe- propriate (virgo intacta) [15].
cific set (catheter, syringe). SVG should be
always performed when the clinical interview
and the preliminary pelvic exam suggest the pres- 9.2.6 3D-Transvaginal Sonography
ence of posterior DE nodules, permitting to iden-
tify isolated (Fig. 9.5) or extended lesions In the last decades, a large number of papers
(Fig. 9.6). As well as above, the whole procedure referred the usefulness of 3D-TVS in gynecolog-
should be digitally recorded for second opinion ical investigations, mainly focused on uterine
(videoclips) and the selected diagnostic images congenital anomalies and adenomyosis but
stored and/or printed. poorly on DE [16].
3D-TVS should always be performed after a
detailed tenderness-guided and dynamic trans-
9.2.5 Transrectal Sonography vaginal exam, useful to adequately report the
USL DE lesion on the three orthogonal planes
Transrectal sonography using transvaginal probe and its relationship with surrounding structures,
should be used if necessary to support TVS in thus easily permitting to distinguish isolated and
extended lesions (Fig. 9.7).
In order to obtain a high-quality 3D image, it is
of paramount importance to acquire an excellent
volume by a high-quality 2D image. Therefore:
a b
Fig. 9.6 Extended USL DE lesion, hypoechoic with smooth outline (a) and CS1 (b), at gel sonovaginography, strictly
adherent to a retrocervical DE hypoechoic lesion
82 F. P. G. Leone
(e) Choose the sagittal and/or transverse plane, In particular, the following steps after volume
being sure to include the whole nodule and acquisition of the USL DE lesion at 3D-TVS
surrounding structures. should be performed:
(f) Hold still, avoid pressure with the probe, ask
the patient to remain still during the acquisi- (a) Identify and magnify the selected image of
tion, acquire the volume, and store it elec- the USL DE lesion, in the multiplanar dis-
tronically for later analysis. play mode and add VCI.
(g) Magnification over 70% of the screen and (b) Shift the selected plane forward and back-
virtual navigation on the multiplanar display, ward to identify the plane containing the
referring to the fulcrum (dot of interest) and largest diameter of the DE lesion and evalu-
by rotating the three orthogonal planes on the ate involvement of surrounding structures.
rotational axis X, Y, and Z. (c) Rotate the DE lesion on its ideal center (“ful-
(h) Assessment and measurements of the USL crum”) on the Z-axis until the line passes
DE findings, by adding post-processing tools through the center of the nodule and assess
(volume contrast imaging (VCI), rendering extension to surrounding structures
mode, tomographic ultrasound imaging (Fig. 9.10).
(TUI)). (d) Report images adding TUI or rendering
mode if potentially useful to discuss in a clin-
Volume contrast imaging (VCI) is a technol- ical multidisciplinary setting.
ogy based on a volume acquisition technique that
leads to contrast enhancement and speckle sup- 3D volumes can be stored and analyzed later
pression in the two-dimensional ultrasound as many times as needed, permitting a second
image, by offering to increase resolution and to opinion by sending volumes by internet, offer-
reduce noise and artifacts. Hence, the result of ing the possibility of studying an infinite num-
VCI is a thin surface-rendered image of the DE ber of sections through the lesions. This latter
nodule, which thickness usually set at 2 mm by feature is particularly relevant when discussing
the sonographer (Fig. 9.7). with surgeons the surgical strategy (Figs. 9.11
Volume rendering analysis is based on the and 9.12).
selection of the region of interest (ROI) and of
the observation plane of the acquired volume of
the nodule, thus obtaining a thick slice of the 9.3 Future Perspectives
lesion (Fig. 9.8).
Tomographic ultrasound imaging (TUI) is a TVS should remain the first-line method in the
technology which leads to multiple planes dis- evaluation of patients with suspicion of DE. The
played at the same time, with the option of con- future uptake of the recent IDEA consensus on
comitant use of VCI. Similarly, the number of terms, definitions, and measurements of DE
images and the thickness might be selected by the lesions may improve standardization of scanning
sonographer, with differences depending on the and reporting and in turn potentially reduce the
plane used for analysis. I would suggest the operator dependency. This may optimize the pre-
option with three or nine images with distances operative triage and potentially improve surgical
of 0.5–3.5 mm depending on USL lesion (iso- outcomes. Furthermore, it may lead to large mul-
lated or extended) and involved surrounding ticentric studies and proper meta-analyses on
structures (Fig. 9.9). ultrasound diagnosis of endometriosis.
9 Uterosacral Ligament Endometriosis 83
Fig. 9.7 Multiplanar images with VCI analysis (2 mm) of an isolated (a) and an extended nodule (b) infiltrating the
rectosigmoid
84 F. P. G. Leone
Fig. 9.8 Multiplanar images with VCI (a) and Volume neous USL DE nodule, compared to the macroscopic sur-
Rendering Analysis (b), with the selection of the curved gical specimen (c)
render ROI, of an isolated hypoechoic smooth homoge-
9 Uterosacral Ligament Endometriosis 85
Fig. 9.9 TUI images (nine images with distance of 3.5 mm) with VCI analysis (2 mm) of an isolated hypoechoic
smooth homogeneous isolated USL DE nodule
Fig. 9.10 Multiplanar images with VCI analysis (2 mm) of an extended irregular hypoechoic homogeneous USL DE
nodule adherent to an ovarian endometrioma and to the sigmoid serosa
86 F. P. G. Leone
a b
Fig. 9.11 Extended hypoechoic homogeneous USL DE sigmoid nodule at 2D-TVS (a), with CS1 (b), and at
lesion with irregular outline, strictly adherent to a retro- 3D-TVS with multiplanar images and VCI analysis
cervical DE hypoechoic lesion and to an infiltrating recto- (2 mm) (c)
9 Uterosacral Ligament Endometriosis 87
a b
Fig. 9.12 Bilateral extended hypoechoic heterogeneous 2D-TVS on a transverse plane (a) and at 3D-TVS with
USL DE lesions with irregular outline, strictly adherent to multiplanar images and VCI analysis (2 mm) (b, c)
an arciform retrocervical DE hypoechoic lesion at
derness-guided’ ultrasonography for the prediction and magnetic resonance imaging in the diagnosis of
of location of deep endometriosis. Hum Reprod. posterior deep infiltrating endometriosis. Ultrasound
2008;23(11):2452–7. Obstet Gynecol. 2012;40:464–9.
11. Reid S, Lu C, Casikar I, Reid G, Abbott J, Cario 14. Reid S, Lu C, Hardy N, Casikar I, Reid G, Cario G,
G, Chou D, Kowalski D, Cooper M, Condous Chou D, Almashat D, Condous G. Office gel sono-
G. Prediction of pouch of Douglas obliteration in vaginography for the prediction of posterior deep
women with suspected endometriosis using a new infiltrating endometriosis: a multicenter prospective
real-time dynamic transvaginal ultrasound tech- observational study. Ultrasound Obstet Gynecol.
nique: the sliding sign. Ultrasound Obstet Gynecol. 2014;44:710–8.
2013;41(6):685–91. 15. Koga K, Osuga Y, Yano T, Momoeda M, Yoshino O,
12. Reid S, Lu C, Casikar I, Mein B, Magotti R, Ludlow Hirota Y, Kugu K, Nishii O, Tsutsumi O, Taketani
J, Benzie R, Condous G. The prediction of pouch Y. Characteristic images of deeply infiltrating recto-
of Douglas obliteration using offline analysis of the sigmoid endometriosis on transvaginal and transrectal
transvaginal ultrasound ‘sliding sign’ technique: inter- ultrasonography. Hum Reprod. 2003;18:1328–33.
and intra-observer reproducibility. Hum Reprod. 16. Pascual MA, Guerriero S, Hereter L, Barri-Soldevila
2013;28(5):1237–46. P, Ajossa S, Graupera B, Rodriguez I. Three-
13. Saccardi C, Cosmi E, Borghero A, Tregnaghi A, dimensional sonography for diagnosis of rectovagi-
Dessole S, Litta P. Comparison between transvagi- nal septum endometriosis: interobserver agreement. J
nal sonography, saline contrast sonovaginography Ultrasound Med. 2013;32(6):931–5.
Forniceal-Vaginal Deep
Endometriosis
10
Stefano Guerriero, Gil Cohen, Silvia Ajossa,
Ornella Comparetto, Camilla Ronchetti,
Bruno Piras, Alba Piras, and Valerio Mais
Fig. 10.1 A drawing of the three different localizations of forniceal-vaginal endometriotic lesions, previously called
“retroperitoneal or retrocervical lesion” proposed by Donnez et al. [10]
Type III: hourglass-shaped or diabolo-like DE that the presence of vaginal infiltration by the
nodules (25% of cases). These lesions occur posterior DE was related to the severity of dys-
when posterior fornix lesions extend cranially menorrhea, while this correlation was not
to the anterior rectal wall. The part of the observed by Vercellini et al. study [15].
adenomyotic lesion situated in the anterior
Several studies evaluated the sensitivity and
rectal wall is in the same size as the part situ- specificity of transvaginal ultrasound (TVS) for
ated near the posterior fornix. A small but vaginal DE lesions. Guerriero et al. [2] in their
well-observed continuum exists between these meta-analysis found a sensitivity of 58% and a
two parts of the lesion. These lesions always specificity of 96%. Nisenblat et al. [16] in a
occur under the peritoneal fold of the recto- Cochrane review found a mean sensitivity of
uterine pouch or pouch of Douglas and were 57% and a mean specificity of 99%. Noventa
found to be large (their average size estimated et al. [17] in their meta-analysis found a sensitiv-
to be 3 cm by clinical examination) [10]. ity of 50% with a specificity of 88.7%.
The present chapter is focused on types II and
III. Type I or rectovaginal septum DE is
described in Chap. 11. 10.2 How We Do It
Fauconnier et al. [13] found an association As suggested by IDEA consensus [5], an optimal
between the presence of vaginal DE and painful sonographic evaluation starts with a detailed clin-
defecation during menstruation and other gastro- ical history evaluation [5, 18–20]. It is mandatory
intestinal symptoms. Chapron et al. [14] found to do a vaginal examination in women with a
10 Forniceal-Vaginal Deep Endometriosis 91
CERVIX
Posterior Anterior
Posterior Anterior
Posterior Anterior
CERVIX CERVIX
UTERUS
UTERUS
CERVIX
Fig. 10.7 A solid forniceal nodule as visualized using Fig. 10.10 A solid forniceal nodule as visualized using
transvaginal ultrasonography transvaginal ultrasonography and power Doppler
CERVIX
Posterior Anterior
UTERUS
Anterior Posterior
UTERUS
CERVIX
Fig. 10.8 A solid forniceal nodule as visualized using Fig. 10.11 A solid forniceal nodule as visualized using
transvaginal ultrasonography transvaginal ultrasonography and power Doppler
probe back and forth from the vaginal introitus wall where a nodule is present at the level of
along the rectovaginal septum. muscularis mucosa (further details in Chap.
In vaginal DE cases which are hourglass- 12) (Figs. 10.13 and 10.14). In such cases,
shaped or diabolo-like in appearance, the both DE nodules should be measured in the
lesions extend cranially to the anterior rectal three planes.
10 Forniceal-Vaginal Deep Endometriosis 93
Posterior Anterior
CERVIX
b
Fig. 10.12 A solid forniceal nodule as visualized using
transvaginal ultrasonography and power Doppler
Posterior Anterior
Fig. 10.16 A three-dimensional visualization of a diabolo-like nodule. The straight arrow indicates the rectosigmoid
lesion and the curved arrow the forniceal nodule
a sagittal plane). Typically these lesions appear as fornix. In the assessment for DE lesions in the
small irregular nodules [22] (Fig. 10.16). posterior compartment, our advice is to include
In the presence of suspected vaginal DE, the the following information:
final recommended step for forniceal-vaginal
evaluation is to perform a TVS combined with 1. The size of DE lesion (measured in three
the use of either saline [23, 24] or gel [25–27] orthogonal planes)
sonovaginography (see Chap. 14). Using gel son- 2. The anatomical relationship with contiguous
ovaginography, before the insertion of the trans- structures
vaginal probe, approximately 20–50 mL of 3. The possible mobility or fixation of the sur-
ultrasound gel is inserted into the posterior vagi- rounding organs
nal fornix by using a 20 mL plastic syringe [25– 4. The presence or absence of flow using color
27]. The gel creates an acoustic window that Doppler
allows a “standoff” view of the structures of the
posterior compartment. It has been reported that The following recommendations might also
using this modality gives better visualization of be useful:
the lesion [25–27] (see Videos 10.3 and 10.4).
1. Perform a gradual introduction of the trans-
vaginal probe using gentle movements and the
10.3 Important Technical Tip possible addition of gel with lidocaine on the
cover probe.
Our advice is to use the four basic sonographic 2. Remember the synergy between the operator
steps proposed by the IDEA consensus [5], tak- and the patient especially when assessing ten-
ing note of site-specific tenderness and the derness-guided ultrasound.
dynamic evaluation of the relationship between 3. Explore suspected vaginal DE by using gel
the anterior rectal wall and the posterior vaginal sonovaginography. When compared to saline
10 Forniceal-Vaginal Deep Endometriosis 95
6. Koninckx PR, Meuleman C, Demeyere S, Lesaffre E, 20. Hudelist G, Ballard K, English J, Wright J, Banerjee
Cornillie FJ. Suggestive evidence that pelvic endome- S, Mastoroudes H, Thomas A, Singer CF, Keckstein
triosis is a progressive disease, whereas deeply infil- J. Transvaginal sonography vs. clinical examina-
trating endometriosis is associated with pelvic pain. tion in the preoperative diagnosis of deep infiltrat-
Fertil Steril. 1991;55:759–65. ing endometriosis. Ultrasound Obstet Gynecol.
7. Vercellini P, Frontino G, Pietropaolo G, Gattei U, 2011;37(4):480–7.
Daguati R, Crosignani PG. Deep endometriosis: defi- 21. Guerriero S, Ajossa S, Gerada M, D’Aquila M, Piras
nition and clinical management. J Am Assoc Gynecol B, Melis GB. “Tenderness-guided” transvaginal ultra-
Laparosc. 2004;11:153–61. sonography: a new method for the detection of deep
8. Anaf V, El Nakadi I, De Moor V, Chapron C, Pistofidis endometriosis in patients with chronic pelvic pain.
G, Noel JC. Increased nerve density in deep infiltrat- Fertil Steril. 2007;88(5):1293–7.
ing endometriotic nodules. Gynecol Obstet Investig. 22. Guerriero S, Saba L, Ajossa S, Peddes C, Angiolucci
2011;71(2):112–7. M, Perniciano M, Melis GB, Alcazar JL. Three-
9. Matsuzaki S, Houlle C, Botchorishvili R, Pouly JL, dimensional ultrasonography in the diagnosis of deep
Mage G, Canis M. Excision of the posterior vaginal endometriosis. Hum Reprod. 2014;29:1189–98.
fornix is necessary to ensure complete resection of 23. Dessole S, Farina M, Rubattu G, Cosmi E, Ambrosini
rectovaginal endometriotic nodules of more than 2 cm G, Nardelli GB. Sonovaginography is a new tech-
in size. Fertil Steril. 2009;91(4 Suppl):1314–5. nique for assessing rectovaginal endometriosis. Fertil
10. Donnez J, Pirard C, Smets M, Jadoul P, Squifflet Steril. 2003;79:1023–7.
J. Surgical management of endometriosis. Best Pract 24. Saccardi C, Cosmi E, Borghero A, Tregnaghi A,
Res Clin Obstet Gynaecol. 2004;18(2):329–48. Dessole S, Litta P. Comparison between transvagi-
11. Squifflet J, Feger C, Donnez J. Diagnosis and imaging nal sonography, saline contrast sonovaginography
of adenomyotic disease of the retroperitoneal space. and magnetic resonance imaging in the diagnosis of
Gynecol Obstet Investig. 2002;54:43–51. posterior deep infiltrating endometriosis. Ultrasound
12. Del Frate C, Rossano Girometti R, Pittino M, Del Obstet Gynecol. 2012;40:464–9.
Frate G, Bazzocchi M, Zuiani C. Deep retroperi- 25. Reid S, Winder S, Condous G. Sonovaginography:
toneal pelvic endometriosis: MR imaging appear- redefining the concept of a “normal pelvis” on trans-
ance with laparoscopic correlation. Radiographics. vaginal ultrasound pre-laparoscopic intervention for
2006;26:1705–18. suspected endometriosis. Aust J Ultrasound Med.
13. Fauconnier A, Chapron C, Dubuisson JB, Vieira M, 2011;14:21–4.
Dousset B, Bréart G. Relation between pain symp- 26. Reid S, Lu C, Hardy N, Casikar I, Reid G, Cario G,
toms and the anatomic location of deep infiltrating Chou D, Almashat D, Condous G. Office gel sono-
endometriosis. Fertil Steril. 2002;78(4):719–26. vaginography for the prediction of posterior deep
14. Chapron C, Fauconnier A, Dubuisson JB, Barakat infiltrating endometriosis: a multicenter prospective
H, Vieira M, Bréart G. Deep infiltrating endometrio- observational study. Ultrasound Obstet Gynecol.
sis: relation between severity of dysmenorrhoea and 2014;44:710–8.
extent of disease. Hum Reprod. 2003;18(4):760–6. 27. Leon M, Vaccaro H, Alcazar JL, Martinez J, Gutierrez
15. Vercellini P, Trespidi L, De Giorgi O, Cortesi I, J, Amor F, Iturra A, Sovino H. Extended transvaginal
Parazzini F, Crosignani PG. Endometriosis and pelvic sonography in deep infiltrating endometriosis: use of
pain: relation to disease stage and localization. Fertil bowel preparation and an acoustic window with intra-
Steril. 1996;65:299–304. vaginal gel: preliminary results. J Ultrasound Med.
16. Nisenblat V, Bossuyt PMM, Farquhar C, Johnson N, 2014;33:315–21.
Hull ML. Imaging modalities for the non-invasive 28. Pascual MA, Guerriero S, Hereter L, Barri-Soldevila
diagnosis of endometriosis. Cochrane Database Syst P, Ajossa S, Graupera B, Rodriguez I. Diagnosis
Rev 2016;(2). of endometriosis of the rectovaginal septum using
17. Noventa M, Saccardi C, Litta P, Vitagliano A, introital three-dimensional ultrasonography. Fertil
D’Antona D, Abdulrahim B, Duncan A, Alexander- Steril. 2010;94:2761–5.
Sefre F, Aldrich CJ, Quaranta M, Gizzo S. Ultrasound 29. Pascual MA, Guerriero S, Hereter L, Barri-Soldevila
techniques in the diagnosis of deep pelvic endome- P, Ajossa S, Graupera B, Rodriguez I. Three-
triosis: algorithm based on a systematic review and dimensional sonography for diagnosis of rectovagi-
meta-analysis. Fertil Steril. 2015;104(2):366–83. nal septum endometriosis: interobserver agreement. J
18. Chapron C, Barakat H, Fritel X, Dubuisson JB, Breart Ultrasound Med. 2013;32:931–5.
G, Fauconnier A. Presurgical diagnosis of posterior 30. Millischer AE, Salomon LJ, Santulli P, Borghese B,
deep infiltrating endometriosis based on a standard- Dousset B, Chapron C. Fusion imaging for evalu-
ized questionnaire. Hum Reprod. 2005;20:507–13. ation of deep infiltrating endometriosis: feasibility
19. Fedele L, Bianchi S, Carmignani L, Berlanda N, and preliminary results. Ultrasound Obstet Gynecol.
Fontana E, Frontino G. Evaluation of a new question- 2015;46(1):109–17.
naire for the presurgical diagnosis of bladder endome-
triosis. Hum Reprod. 2007;22:2698–701.
Rectovaginal Septum
Endometriosis
11
Gernot Hudelist and Kristine Aas-Eng
Pouch of
Douglas
Blad.
Vagina
Posterior Recto-
vaginal vaginal
wall septum
Fig. 11.2 Partly dissected rectovaginal septum extending from the pouch of Douglas to the perineal body (from The
Global Library of Women’s Medicine, free resource)
the cervix” [6]. The prevalence of endometriosis sensitivities of 18% compared with TVS (9%)
involving the RVS has been found to range and MRI (55%).
between 6 and 52% [7, 8] in patients with sus- Additional methods have been proposed to
pected deep endometriosis (DE). The varying improve sensitivity rates of TVS detecting rec-
prevalence rates may be attributable to differ- tovaginal DE. For example, the use of 3-D TVS
ences in sonographic definition of DE affecting for RVS DE appears to reach a sensitivity of
the RVS but also patient populations and the 76% and a specificity of 100% [14]. Ros et al.
sonographer’s experience in TVS. RVS endome- [15] looked at improving sensitivity of TVS in
triosis does not occur solely in this anatomical detection of rectal disease with bowel prepara-
compartment, i.e. the RVS, and is usually associ- tion from 73% without bowel preparation.
ated with endometriotic infiltration of the vagina Saccardi et al. [16] found saline contrast
and anterior rectal wall [9, 10], based on the pre- sonography, i.e. TVS with introduction of
sumption that it originates from these neighbour- saline solution in the vagina, had better sensi-
ing structures [9]. tivity comparable to MRI for diagnosing endo-
TVS is regarded as the first-line tool in diag- metriosis of the RVS of 81% and 83%,
nosing DE affecting the rectum and associated respectively, whereas TVS without contrast
structures [11, 12]. However, diagnosis of RVS had a sensitivity of 58%.
nodules may be difficult which is reflected by High sensitivity rates of 78% have been
sensitivity rates of TVS ranging between 9 and reported for detection of RVS endometriosis
78% [5, 6, 10]. Bazot et al. [13] compared TVS using simple vaginal examination and TVS when
with rectal endoscopic sonography (RES) and the two methods were used isolated or in a com-
found an improved sensitivity from 11 to 22% bined setting [6, 17]. However, the sensitivity for
using RES, although the patient number was the detection of rectosigmoid lesions that often
small (n = 9). These findings have been supported occur with RVS was higher with TVS of 90%
by a study comparing physical examination, compared to 39% vaginal examination alone.
TVS, RES and MRI in detecting DE [10]. Within Furthermore, a modified TVS method with trans-
this, physical examination and RES had similar vaginal “tenderness-guided” ultrasonography,
11 Rectovaginal Septum Endometriosis 99
a b
c d
Fig. 11.3 (a) Schematic drawing of the RVS (double- (from Guerriero et al. [18] with permission). (b–d)
headed green arrow) below (anatomically) the blue line Schematic drawing demonstrating DE of the RVS with
passing along the lower border of the posterior lip of the predominantly vaginal involvement (b), rectal involve-
cervix with the posterior vaginal fornix between the blue ment (c) or both structures (d) (from Guerriero et al. [18]
line and the red line according to the IDEA consensus with permission)
100 G. Hudelist and K. Aas-Eng
On TVS, RVS endometriotic lesions can be the anterior rectal wall, which is followed by the
described to appear isolated which is very uncom- RVS, is visualized as an anechogenic line due to
mon and extremely rare. Usually, DE of the RVS its three layers of muscle fibres and the covering
involve the vaginal wall, the rectal wall or both mucosa which appears hyperechogenic
(Fig. 11.3b, c, d). The IDEA group emphasizes (Fig. 11.4). In patients with DE of the posterior
the importance of locating the number, size and compartment, the endometriotic tissue infiltrating
anatomical distribution of DE nodules in the rec- the RVS and adjacent structures such as the vagina
tovaginal septum, vaginal wall, rectovaginal nod- and/or rectum usually appears as hypoechoic
ules, rectum, rectosigmoid junction, sigmoid and thickening of the posterior part of the vagina and/
uterosacral ligaments. We believe this is funda- or anterior wall of the bowel (Fig. 11.5a–c).
mental in planning medical and/or surgical treat- Rarely, cystic components of vaginal DE can be
ment and in the follow-up of patients with visualized as hypo- or a nechogenic cystic struc-
DE. The RVS DE nodules should be measured in tures which may vary in size and have smooth or
three orthogonal planes, i.e. midsagittal, antero- irregular contours [6, 20]. Full visualization of the
posterior and transverse [18]. Additionally, the RVS can only be achieved by lifting the probe at
estimated distance between the lower margin of the level of the vaginal introitus. The visualization
the lesion and the anal verge should also be mea- of the RVS should include concomitant visualiza-
sured in the opinion of the authors due to its rel- tion of the rectum and vagina since these struc-
evance for possible surgery. tures will most likely be affected at the same time
In the author’s practice, TVS and possible which therefore allows better orientation and
detection of RVS nodules in patients with DE are localization of disease infiltrating the RVS. DE of
done without bowel preparation or other enhance- the RVS predominantly starts from the level of the
ment techniques. This is predominantly explained upper third of the RVS and will extend down-
by the fact that most patients will not undergo wards into the middle third of the vagina. As a
cleansing of the bowel for personal and infra- consequence, special attention should be given to
structural reasons of our referral setting. Using this area. In cases where bowel contents may cre-
the IDEA algorithm, the transvaginal probe is ate acoustic artefacts or may appear as possible
held in the midsagittal plane of the pelvis visual- thickening of the rectal wall suggesting rectal DE,
izing the uterus and cervix. Then the handle of we suggest to repeat the examination following a
the probe is gradually moved upwards, and at the brief pause of 10–15 min and to possibly use
same time, the tip of the probe is moved down- bowel preparation in selected cases to increase the
wards to visualize the rectovaginal septum
including neighbouring structures such as the
posterior cervix and vaginal wall beginning from
the introitus. Concurrently the rectal wall is thor-
oughly assessed for endometriotic lesions involv-
ing or separated from the RVS.
a b
Fig. 11.5 (a) TVS image (midsagittal section) depicting wall (+) with focal infiltration of the upper vaginal fornix
DE of the RVS predominantly infiltrating the vagina and (*) next to the cervix (**). (c) TVS image (midsagittal
RVS (+) and focally the anterior rectal wall (++) which is section) depicting DE of the RVS predominantly infiltrat-
involved above the RVS. Normal RVS (*); cervix (**). (b) ing the vagina (+), RVS and the anterior rectal wall (++)
TVS image (midsagittal section) depicting DE of the RVS which is involved below the level of the posterior cervical
predominantly infiltrating the RVS and anterior rectal lip (*)
sonographic contrast of the vagina, RVS and rec- RVS. Lateral spread will often involve the auton-
tal wall combined with a gel tip in a glove or con- omous nerve fibres and thereby increase morbid-
dom covering the vaginal probe. ity in cases where DE is fully resected, especially
in cases of bilateral inferior hypogastric nerve
involvement.
11.4 Future Perspectives DE extending deep into the RVS usually
involves both the rectum and vagina. In women
Over the past decade, TVS has become a stan- where surgery is considered, TVS may allow to
dard for pre-surgical evaluation of patients with assess the risk of rectovaginal surgery as low
DE. In how far results of TVS influence surgical anterior resections with lesions with a distance
planning and practice is dependent on the grade less than 5–8 cm from the anal verge carry higher
of collaboration between the sonographer and the risks of anastomotic leaks and rectovaginal fistu-
surgeon. In the author’s practice, the ideal sce- las [3, 21]. The decision whether to perform pro-
nario is to perform both TVS and possible conse- tective ileostomies usually depends on the
quent surgery. TVS allows the surgeon to gain a distance between the anastomosis and the anal
non-invasive, in vivo image of the extent of DE verge, concomitant vaginal involvement and
prior to surgery. From the surgical point of view, resection of vaginal DE as well as possible
it is pivotal to estimate the extent of disease later- comorbidities of the patient. The accurate pre-
ally to pelvic sidewalls and caudally into the surgical use of TVS to measure the distance from
102 G. Hudelist and K. Aas-Eng
the anal verge to the lowermost part of the endo- 10. Bazot M, Lafont C, Rouzier R, Roseau G, Thomassin-
Naggara I, Darai E. Diagnostic accuracy of physical
metriotic nodule may provide this information examination, transvaginal sonography, rectal endo-
prior to surgery and will thereby influence the scopic sonography, and magnetic resonance imag-
surgical strategy. In addition, counselling of ing to diagnose deep infiltrating endometriosis. Fertil
women with DE considering surgery may gain Steril. 2009;92(6):1825–33.
11. Hudelist G, English J, Thomas AE, Tinelli A, Singer
increasing accuracy and quality by adequate CF, Keckstein J. Diagnostic accuracy of transvagi-
information of the extent of disease, possible sur- nal ultrasound for non-invasive diagnosis of bowel
gical complications such as fistula formation and endometriosis: systematic review and meta-analysis.
anastomotic leakage in cases of involvement of Ultrasound Obstet Gynecol. 2011;37(3):257–63.
12. Guerriero S, Ajossa S, Orozco R, Perniciano M,
the RVS. Future studies on the accuracy of TVS Jurado M, Melis GB, et al. Accuracy of transvaginal
regarding the extent of RVS DE and prediction of ultrasound for diagnosis of deep endometriosis in the
the level of bowel anastomosis in cases where rectosigmoid: systematic review and meta-analysis.
rectal surgery and/or vaginal resections are per- Ultrasound Obstet Gynecol. 2016;47(3):281–9.
13. Bazot M, Malzy P, Cortez A, Roseau G, Amouyal P,
formed are under way. Darai E. Accuracy of transvaginal sonography and
rectal endoscopic sonography in the diagnosis of
deep infiltrating endometriosis. Ultrasound Obstet
References Gynecol. 2007;30(7):994–1001.
14. Grasso RF, Di Giacomo V, Sedati P, Sizzi O, Florio G,
Faiella E, et al. Diagnosis of deep infiltrating endome-
1. Chapron C, Fauconnier A, Vieira M, Barakat H,
triosis: accuracy of magnetic resonance imaging and
Dousset B, Pansini V, et al. Anatomical distribution
transvaginal 3D ultrasonography. Abdom Imaging.
of deeply infiltrating endometriosis: surgical impli-
2010;35(6):716–25.
cations and proposition for a classification. Hum
15. Ros C, Martinez-Serrano MJ, Rius M, Abrao MS,
Reprod. 2003;18(1):157–61.
Munros J, Martinez-Zamora MA, et al. Bowel prep-
2. Stecco C, Macchi V, Porzionato A, Tiengo C,
aration improves the accuracy of the transvaginal
Parenti A, Gardi M, et al. Histotopographic study
ultrasound in the diagnosis of Rectosigmoid deep
of the rectovaginal septum. Ital J Anat Embryol.
infiltrating endometriosis: a prospective study. J
2005;110(4):247–54.
Minim Invasive Gynecol. 2017;24:1145.
3. Martin DC, Batt RE. Retrocervical, retrovaginal
16. Saccardi C, Cosmi E, Borghero A, Tregnaghi A,
pouch, and rectovaginal septum endometriosis. J Am
Dessole S, Litta P. Comparison between transvagi-
Assoc Gynecol Laparosc. 2001;8(1):12–7.
nal sonography, saline contrast sonovaginography
4. Kavallaris A, Kohler C, Kuhne-Heid R, Schneider
and magnetic resonance imaging in the diagnosis of
A. Histopathological extent of rectal invasion
posterior deep infiltrating endometriosis. Ultrasound
by rectovaginal endometriosis. Hum Reprod.
Obstet Gynecol. 2012;40(4):464–9.
2003;18(6):1323–7.
17. Hudelist G, Oberwinkler KH, Singer CF, Tuttlies F,
5. Bazot M, Thomassin I, Hourani R, Cortez A, Darai
Rauter G, Ritter O, et al. Combination of transvaginal
E. Diagnostic accuracy of transvaginal sonography
sonography and clinical examination for preopera-
for deep pelvic endometriosis. Ultrasound Obstet
tive diagnosis of pelvic endometriosis. Hum Reprod.
Gynecol. 2004;24(2):180–5.
2009;24(5):1018–24.
6. Hudelist G, Ballard K, English J, Wright J, Banerjee
18. Guerriero S, Condous G, van den Bosch T, Valentin
S, Mastoroudes H, et al. Transvaginal sonography vs.
L, Leone FP, Van Schoubroeck D, et al. Systematic
clinical examination in the preoperative diagnosis of
approach to sonographic evaluation of the pelvis in
deep infiltrating endometriosis. Ultrasound Obstet
women with suspected endometriosis, including terms,
Gynecol. 2011;37(4):480–7.
definitions and measurements: a consensus opinion from
7. Guerriero S, Ajossa S, Gerada M, Virgilio B, Angioni
the International Deep Endometriosis Analysis (IDEA)
S, Melis GB. Diagnostic value of transvaginal ‘ten-
group. Ultrasound Obstet Gynecol. 2016;48(3):318–32.
derness-guided’ ultrasonography for the prediction
19. Kuhn RJ, Hollyock VE. Observations on the anat-
of location of deep endometriosis. Hum Reprod.
omy of the rectovaginal pouch and septum. Obstet
2008;23(11):2452–7.
Gynecol. 1982;59(4):445–7.
8. Exacoustos C, Malzoni M, Di Giovanni A, Lazzeri L,
20. Dessole S, Farina M, Rubattu G, Cosmi E, Ambrosini
Tosti C, Petraglia F, et al. Ultrasound mapping system
G, Nardelli GB. Sonovaginography is a new tech-
for the surgical management of deep infiltrating endo-
nique for assessing rectovaginal endometriosis. Fertil
metriosis. Fertil Steril. 2014;102(1):143–50. e2
Steril. 2003;79(4):1023–7.
9. Hudelist G, Keckstein J, Wright JT. The migrat-
21. Bouaziz J, Soriano D. Complications of colorec-
ing adenomyoma: past views on the etiology of
tal resection for endometriosis. Minerva Ginecol.
adenomyosis and endometriosis. Fertil Steril.
2017;69(5):477–87.
2009;92(5):1536–43.
Rectum, Rectosigmoid,
and Sigmoid Endometriosis
12
Manoel Orlando Goncalves, Leandro Accardo de
Mattos, and Mauricio S. Abrao
adjacent endometriotic lesions (mainly retro- and that in special groups, its efficacy might even
and paracervical) with or without adherence be superior to that of the MRI in helping define
to the rectum or sigmoid. the therapeutic planning.
6-12 cm
Middle rectum
0-6 cm
Lower rectum
Iumen
mucosa
mucosa muscularis
submucosa
connective tissue
Fig. 12.3 TVUS-BP: longitudinal view of the intestine with the layers
a b
Fig. 12.5 TVUS-BP: paracervical endometriosis (a) adhered to and thickening the sigmoid serosa (arrows). With the
use of sepia (b), it is easier to see that the muscular propria layer is normal
a b
c d
Fig. 12.6 TVUS-BP: well-delimited polyp in the intesti- not curve the loop’s external form (arrow). Both protrude
nal lumen (a, b) completely surrounded by the wall into the lumen and are more vascularized (b, d) and well
(arrows). Gastrointestinal stromal tumor (c, d) that does delimited than endometriosis
Fig. 12.7 TVUS-BP: extensive DE infiltrating the submucosa (arrows). Longitudinal (white line) and anteroposterior
(yellow line) measurements
a b
Fig. 12.8 TVUS-BP: (a) DE infiltrating the circular circle (green line) measurements. In (a) we can see an
muscular layer, with normal hyperechogenic strip of the underestimated measurement of the transverse axis using
submucosa (arrow). (b) Calculation of the compromised a straight line in a curved lesion
circumference using the transverse (white line) and full
Fig. 12.9 TVUS-BP: two endometriosis lesions (arrows) in the same segment, separated by normal wall (curved arrow)
12 Rectum, Rectosigmoid, and Sigmoid Endometriosis 109
a b
Fig. 12.10 Types of lesions that can cause stenosis. (a) Large lesion involving more than 50% of the circumference.
(b) Endometriosis curving the intestine (>90°)
Abrão et al. demonstrated that when the sub- irregular thickening of this layer in the seg-
mucosa is compromised, more than 40% of the ment, irrespective of whether the hyperechoic
circumference is infiltrated at the histological strip that separates the external from the inter-
examination [26]. It is important to mention that nal muscularis propria was interrupted
this parameter is not a criterion for lumen stenosis. (Fig. 12.8a). The criteria used to evaluate the
Significant stenosis is suggested when (Fig. 12.10): infiltration of the submucosal layer are the
existence of hypoechoic tissue originating in
a) The lesions compromise more than 50% of the the serous layer and the muscularis propria
circumference and have an anteroposterior causing partial or total interruption of the
diameter of more than 1.0 cm. hyperechoic line corresponding to the submu-
b) The DE significantly curving the compro- cosal layer (Fig. 12.11).
mised segment—angle greater than 90°. When there is infiltration of several contigu-
To summarize, there are morphological and ous spots, the submucosal layer has a serrated
measurement criteria to diagnose stenosis via aspect (Fig. 12.7). In terms of diagnosis, the
TVUS; however, the subjective impression submucosal and mucosal layers can be con-
that there is little passageway for fecal content sidered a single layer, since this would not
(assessed by the transversal axis of the loop) is impact the decision on which therapy or surgi-
also important. If there is doubt, other tech- cal procedure to adopt [11, 21, 25]. Hudelist
niques may be used, such as colonoscopy, and Goncalves without and with intestinal
opaque enema, or CT with rectal contrast to preparation, respectively, evaluated the effi-
obtain more direct and accurate information ciency of TVUS to determine the depth of the
about the degree of the stenosis. intestinal lesion by endometriosis (Table 12.1).
–– Infiltrated intestinal layers –– Distance of the anal verge
There is DE when the lesion affects at least This is an important data and should be
the muscularis propria layer. The criterion evaluated preoperatively. The surgical treat-
used to predict whether the lesion has infil- ment of lower rectal lesions (defined as
trated up to at least the muscularis propria is beginning less than 8 cm from the anal
the existence of a nodule or hypoechoic, verge) is associated with a higher risk of
110 M. O. Goncalves et al.
a b
Fig. 12.11 TVUS-BP: (a) DE infiltrating the submucosa fornix (arrow) in the same patient, reinforcing the idea
(arrow), characterized by interruption of the white strip of that endometriosis is almost always a multifocal disease
the wall. (b) Deep endometriosis in the posterior vaginal
Table 12.1 TVUS in the evaluation of the layer infil- shaving, circular/linear stapler, or segmental
trated by intestinal endometriosis resection technique.
SM/M To determine the best therapeutic options for
At least MP (Sens/Spec) patients with DE that compromises the sig-
(Sens/Spec) (%) (%)
moid and/or rectum, it is important to under-
Goncalves 2010 with 100/100 83/94
bowel preparation stand the roles of clinical factors,
Hudelist 2009 without 98/99 62/96 preoperative morphologic characteristics
bowel preparation obtained from images, surgical consider-
MP muscularis propria, SM/M submucosa/mucosa, Sens ations, recurrence rate, and impact on qual-
sensibility, Spec specificity ity of life. The analysis of all these parameters
may contribute to restrain the current trend
postoperative anastomotic leaks [27] and tran- toward excessive use of laparoscopic
sient neurogenic bladder dysfunction [28]. colorectal resections [30].
It is difficult to objectively measure the dis-
tance of the anal verge via TVUS mostly
because of the axis of the segment between 3 12.3 Examination Technique
and 8 cm from the anal verge whose angle is
of approximately 90° in relation to the proxi- We always suggest the following bowel prepara-
mal and distal segments of the rectum. This tion prior to the ultrasound examination to detect
assessment is made using two parameters: the endometriosis:
first and the second rectal curves—which are
approximately 3.0 and 8.0 cm distant from the –– Day before: sodium picosulfate 10 mg—oral
anal verge, respectively. Thus, we can esti- simeticone 75 mg, oral—every 8 h
mate the distance of the lesions from the anal –– Day of the exam: rectal enema with 120 mL of
verge (Fig. 12.12). Obtaining this information sodium diphosphate 1 h before the exam
prior to surgery also allows the surgeon to take –– Two-hour fasting before the exam to reduce
a better strategic decision [29]. the possibility of intestinal peristalsis bringing
–– The suprapubic and transvaginal ultrasound feces or air from proximal intestinal segments
allows examination of at least 30–40 cm of the to the rectum or sigmoid
intestine above the anal verge.
The size, number of the lesions (if multiple - This preparation facilitates identification of
distance between them) and the compromised the different intestinal segments, the anal verge,
circumference are important information for and the degree of infiltration of the wall and the
the surgeon to determine whether to adopt the lesions, even when these are small or multiple.
12 Rectum, Rectosigmoid, and Sigmoid Endometriosis 111
Fig. 12.12 Drawing and TVUS showing the first (at 3 cm AV) and second curves (at 8 cm AV) of the rectum. The
peritoneal reflection (asterisk) is about 7 cm above the AV
Should there still be significant residue despite It is possible to obtain good results in identify-
this preparation, the patient receives another unit ing single lesions in the rectum or sigmoid with-
of phosphoenema and is reevaluated after 15 or out bowel preparation. However, to our
30 min. We have performed the exam with this knowledge, no study has been able to identify
preparation for over 15 years and have not had multiple foci without bowel preparation to date.
any problem regarding acceptance by the patient, In 2010, via TVUS with prior bowel preparation,
as long as she is previously informed about the our group assessed the multiplicity of lesions in
diagnostic advantages. the rectum and sigmoid [25] (Table 12.2).
112 M. O. Goncalves et al.
Table 12.2 TVUS-BP’s ability to detect rectosigmoid 12.4 he Intestinal Tract Exam:
T
endometriosis and estimate the existence of multifocality
Step by Step
Sensitivity Specificity Accuracy
(%) (%) (%)
Initiate evaluation with a suprapubic examination
Lesion 97 100 99
detection of the left iliac fossa [29, 33] using a high-resolu-
Presence of at 81 99 96 tion linear transducer (8–14 MHZ), the same
least 2 lesions used for breast ultrasound. We begin with trans-
versal and longitudinal cuts of the distal descend-
Table 12.3 Comparison between the TVUS with and ing colon and sigmoid, following them up to
without bowel preparation in the diagnosis of rectosig- where possible inside the pelvis. It is usually
moid endometriosis easier to locate the sigmoid by beginning the
Sensitivity Specificity search with transversal cuts on the lateral region
(%) (%) LR+ of the left paracolic gutter and further comple-
TVUS without prior 73 88 6.08 ment these cuts with sagittal images.
bowel preparation
TVUS with prior 100 99 25
With the same transducer, we always examine
bowel preparation the right iliac fossa to detect lesions in the appen-
LR+ likelihood ratio dix, ileum, and cecum. The screening of this area
begins with transversal cuts on the right paracolic
gutter to identify the cecum, which is the larger
Another point worth mentioning is that recent loop with residue observed in this region. After
studies employing transvaginal ultrasound with locating the end of the cecum, we try to find the
prior bowel preparation have also demonstrated exit of the appendix in this region. Its emergence
less learning curve time with this technique [31]. is often medial or central at the end of the cecum
In 2017 Cristina Ros et al. [32] improved sig- and follows inferiorly, at times “diving” into the
nificantly the ability to detect intestinal lesions pelvis beside the iliac vessels. When the tip or the
using prior bowel preparation (Table 12.3). entire appendix is in the pelvis, we must continue
Several authors have proposed different proto- the evaluation while performing the transvaginal
cols, such as water enema, tridimensional ultra- exam. The majority of the lesions are at the tip of
sound, exam guided by the patient’s pain, and the appendix, causing it to curve (shape of a
others. walking cane with a curved handle). Subsequently,
We believe that the main factors that lead to an with transversal cuts, we move 2 or 3 cm upward
accurate diagnosis of deep endometriosis, espe- to locate and follow the terminal ileum that
cially the intestinal one, are: emerges medially from the cecum (ileocecal
valve). We follow the ileum until it is inferiorly
–– Examiner’s specific experience in TVUS for possible with the linear transducer and later com-
identification of endometriosis plement this exam by analyzing the pelvic ileal
–– Facilitating protocols loops with the transvaginal transducer. The aspect
–– Examination of all sites in all patients, of the lesions is similar to that observed in the
whether or not there are specific symptoms rectosigmoid, and these may be single or multifo-
and even if the gynecological examination is cal/multicentric. When observing the lesions in
within normality the ileum and appendix, the differential diagnosis
for neoplasias (mainly neuroendocrine tumors)
Our team has always opted for the pelvic and must be borne in mind, for the aspect can be very
transvaginal ultrasound with prior intestinal prep- similar to that of DE (Fig. 12.13). A safe way to
aration in view of our belief that this is the most differentiate them has not yet been described;
effective and practical method to obtain a high however, when other foci of endometriosis are
level of accuracy. However, each group must test observed in the pelvis, there is very little possibil-
the protocols proposed and found in literature and ity of neoplasia. In case the lesions are located
determine which has the best outcomes for them. only on the right iliac fossa or if in doubt, the
12 Rectum, Rectosigmoid, and Sigmoid Endometriosis 113
a b
Fig. 12.13 Suprapubic ultrasound with high-resolution linear transducer: nodular thickening at the tip of the appendix
(arrows), being endometriosis in (a) and carcinoid tumor in (b)
patient must be submitted to surgery for excision lesions are located in the anterior wall, some are
and anatomic pathological analysis. more laterally located and can only be clearly
The suprapubic examination of the loops with seen with a transversal view. It is important to
a high-resolution transducer is more limited remember that endometriosis foci are seldom
when there is some content on the loops or in seen in the posterior wall of the rectum, for
obese patients. Nonetheless, employment of lesions that occupy the totality of the circumfer-
dosed compression with the transducer and the ence are rare, and there are no isolated lesions on
prior bowel preparation minimize these issues. the posterior wall. We recommend at least two
Subsequently, the transvaginal transducer is complete evaluations from the rectal sphincter to
introduced (transvaginal ultrasound with bowel the proximal sigmoid. In the first evaluation, the
preparation—TVUS-BP) and guided to the loop is examined mainly in its longitudinal axis
patient’s sagittal axis with the beam angled and, in the second, in its transversal axis. Three-
downward (30–60°) to locate the rectum dimensional transducers that allow the examiner
(Fig. 12.12). to manually angle the beam reduce the patient’s
We follow the intestine along the several seg- discomfort because it is thus not necessary to
ments: rectum, rectosigmoid transition, and sig- angle the transducer as much during transversal
moid, along the curves. Most patients have a evaluation of the lower and middle rectum.
curve to the right and another one immediately to A normal rectosigmoid wall is 1–2 mm thick.
the left after the rectum, leading to the left Diffuse circumferential thickenings are related to
adnexal region and passing beside the ipsilateral inflammatory processes (colitis) or diverticular
ovary (Fig. 12.14). However, there are many vari- disease. DE is characterized by focal thickenings
ations in the extension and topography of the sig- that begin in the most external layers (serosa and
moid. This also justifies the prior bowel muscularis propria) and may infiltrate even the
preparation, for it makes it easier to follow the mucosae. In most cases, if we make a transversal
loop. cut, the thickened areas will be located in the rec-
The examiner must evaluate the largest possi- tum between 9 and 3 o’clock. The sigmoid pres-
ble rectum and sigmoid segment (usually up to ents greater variability of foci location, but the
30–40 cm of the anal verge) in the longitudinal other characteristics (texture and morphology)
and axial axes of the bowel. Although most of the are similar to those of the rectum.
114 M. O. Goncalves et al.
Fig. 12.15 TVUS-BP: deep endometriosis of the rectum (curve arrow) adherence to the posterior vaginal fornix lesion
(arrow), causing complete Douglas cul-de-sac blockage
12.6 False Positives base or sessile with a wide base. Texture and vas-
cularization vary, but, in general, they are more
The main causes leading to false positives in vascularized than DE (Fig. 12.6a, b).
intestinal endometriosis are: Gastrointestinal stromal tumor (GIST): This is
the most difficult differential diagnosis, for its
–– Accentuated curves with fan-folded loops. nodules are hypoechogenic and quite homoge-
Solution: compression maneuver with the neous. However, unlike DE, they are usually
transducer, repairing the loop. round and have well-defined limits and do not
–– The sigmoid crosses the left round ligament curve the loop’s external form. Vascularization
(Fig. 12.16). Solution: rotate the transducer, varies but is generally more accentuated than in
and observe if the thickening extends out of DE (Fig. 12.6c, d).
the loop and heads toward the uterine horn. Adenocarcinomas: Primary neoplasias of the
Unless it is compromised by endometriosis, intestine, when observable at ultrasound, are
the ligament’s texture is similar to that of the more hyperechogenic than DE, with poorly
uterus, unlike the DE, which, in general, is defined limits, and they grow from the mucosae.
hypoechogenic. At color Doppler, they are hypervascular and are
–– The tube is adjacent or adhered to the intes- disorderly distributed.
tine. Solution: rotate the transducer, and Should there be doubts concerning differential
observe if the thickening extends outside the diagnosis, the colonoscopy is the standard exam.
loop. In addition, a Doppler allows detection
of the typical vascularization of the tube,
which is characterized by thin vessels that are 12.8 Exam Time
parallel to the greater axis and at time have a
spiral aspect. DE is quite hypovascular at Following the protocol we have developed, with
Doppler; when it is present, it has a disordered the suprapubic evaluation of the right iliac fossa
aspect or is perpendicular to the greater axis of and the proximal sigmoid (linear transducer) and
the loop. transvaginal, it takes us around 15–25 min to
examine the intestinal sites. Some factors impact
the exam time: inadequate preparation, number
12.7 Differential Diagnoses of detected lesions, and related adherence pro-
cess. Large uteri, retroverted uterus, or ovarian
Polyps: These are easily differentiated from DE cysts larger than 5 cm may also make the exami-
due to their location in the loop’s lumen and well- nation more difficult, mainly of the sigmoid, thus
defined limited. They may be long with a narrow increasing exam time.
a b
Fig. 12.16 TVUS-BP: (a) transversal view—apparent endometriosis (arrow) in the sigmoid (S) wall. (b) Turning the
transducer, it is possible to see that it is a false lesion caused by the normal left round the ligament (arrows)
12 Rectum, Rectosigmoid, and Sigmoid Endometriosis 117
mention increasing pregnancy possibility and 11. Bazot M, et al. Transvaginal sonography and rectal
endoscopic sonography for the assessment of pel-
reducing psychological and physical troubles vic endometriosis: a preliminary comparison. Hum
caused by endometriosis.Compliance with Reprod. 2003;18:1686–92.
Ethical Standards 12. Takeuchi H, et al. A novel technique using magnetic
resonance imaging jelly for evaluation of rectovaginal
endometriosis. Fertil Steril. 2005;83:442–7.
Funding This chapter did not receive external 13. Hottat N, et al. Endometriosis: contribution of 3.0-T
funds. pelvic MR imaging in preoperative assessment—ini-
tial results. Radiology. 2009;253:126–34.
Conflict of interest The authors certify that they 14. Abrao MS, et al. Comparison between clinical
examination, transvaginal sonography and magnetic
have no affiliations with or involvement in any resonance imaging for the diagnosis of deep endome-
organization or entity with any financial interest. triosis. Hum Reprod. 2007;22:3092–7.
15. Ribeiro HS, et al. [Double-contrast barium enema in
Ethical approval This chapter is a review which the diagnosis of intestinal deeply infiltrating endome-
triosis]. Rev Bras Ginecol Obstet. 2008;30:400–5.
does not contain any studies with human partici- 16. Biscaldi E, Ferrero S, Remorgida V, Rollandi
pants or animals performed by any of the authors GA. Bowel endometriosis: CT-enteroclysis. Abdom
Imaging. 2007;32:441–50.
17. Hudelist G, et al. Combination of transvaginal
sonography and clinical examination for preopera-
References tive diagnosis of pelvic endometriosis. Hum Reprod.
2009;24:1018–24.
1. Chapron C, et al. Surgery for bladder endometrio- 18. Guerriero S, et al. Diagnostic value of transvaginal
sis: long-term results and concomitant management ‘tenderness-guided’ ultrasonography for the predic-
of associated posterior deep lesions. Hum Reprod. tion of location of deep endometriosis. Hum Reprod.
2010;25:884–9. 2008;23:2452–7.
2. Chapron C, et al. Deeply infiltrating endometriosis: 19. Exacoustos C, et al. OC19.04: Sonographic evalua-
pathogenetic implications of the anatomical distribu- tion of posterior deep pelvic endometriosis: endovagi-
tion. Hum Reprod. 2006;21:1839–45. nal-, transrectal- and vaginosonography to assess the
3. Bazot M, et al. Accuracy of magnetic resonance imag- extension of the disease. Ultrasound Obstet Gynecol.
ing and rectal endoscopic sonography for the predic- 2005;26:340–1.
tion of location of deep pelvic endometriosis. Hum 20. Piketty M, et al. Preoperative work-up for patients
Reprod. 2007;22:1457–63. with deeply infiltrating endometriosis: transvaginal
4. Kavallaris A, Köhler C, Kühne-Heid R, Schneider ultrasonography must definitely be the first-line imag-
A. Histopathological extent of rectal invasion ing examination. Hum Reprod. 2009;24:602–7.
by rectovaginal endometriosis. Hum Reprod. 21. Hudelist G, Tuttlies F, Rauter G, Pucher S, Keckstein
2003;18:1323–7. J. Can transvaginal sonography predict infiltration
5. Remorgida V, et al. How complete is full thickness depth in patients with deep infiltrating endometriosis
disc resection of bowel endometriotic lesions? A pro- of the rectum? Hum Reprod. 2009;24:1012–7.
spective surgical and histological study. Hum Reprod. 22. Nisenblat V, et al. Combination of the non-invasive
2005;20:2317–20. tests for the diagnosis of endometriosis. Cochrane
6. Abrão MS, et al. Deep endometriosis infiltrating the Database Syst Rev. 2016;(7):CD012281.
recto-sigmoid: critical factors to consider before man- 23. Guerriero S, et al. Systematic approach to sono-
agement. Hum Reprod Update. 2015;21:329–39. graphic evaluation of the pelvis in women with sus-
7. Podgaec S, Gonçalves MO, Klajner S, Abrão pected endometriosis, including terms, definitions
MS. Epigastric pain relating to menses can be a and measurements: a consensus opinion from the
symptom of bowel endometriosis. Sao Paulo Med J. International Deep Endometriosis Analysis (IDEA)
2008;126:242–4. group. Ultrasound Obstet Gynecol. 2016;48:318–32.
8. Garry R, Clayton R, Hawe J. The effect of endome- 24. Chapron C, et al. Anatomical distribution of deeply
triosis and its radical laparoscopic excision on quality infiltrating endometriosis: surgical implications
of life indicators. BJOG. 2000;107:44–54. and proposition for a classification. Hum Reprod.
9. Simões Abrão M, et al. Rectal endoscopic ultrasound 2003;18:157–61.
with a radial probe in the assessment of rectovagi- 25. Goncalves MO, Podgaec S, Dias JA Jr, Gonzalez
nal endometriosis. J Am Assoc Gynecol Laparosc. M, Abrao MS. Transvaginal ultrasonography with
2004;11:50–4. bowel preparation is able to predict the number of
10. Chapron C, et al. Results and role of rectal endoscopic lesions and rectosigmoid layers affected in cases of
ultrasonography for patients with deep pelvic endo- deep endometriosis, defining surgical strategy. Hum
metriosis. Hum Reprod. 1998;13:2266–70. Reprod. 2010;25:665–71.
120 M. O. Goncalves et al.
26. Abrão MS, et al. Endometriosis lesions that com- 35. Duepree HJ, et al. Laparoscopic resection of deep
promise the rectum deeper than the inner muscularis pelvic endometriosis with rectosigmoid involvement.
layer have more than 40% of the circumference of J Am Coll Surg. 2002;195:754–8.
the rectum affected by the disease. J Minim Invasive 36. de Almeida A, Fernandes LF, Averbach M, Abrão
Gynecol. 2008;15:280–5. MS. Disc resection is the first option in the manage-
27. Ruffo G, et al. Laparoscopic colorectal resection for ment of rectal endometriosis for unifocal lesions with
deep infiltrating endometriosis: analysis of 436 cases. less than 3 centimeters of longitudinal diameter. Surg
Surg Endosc. 2010;24:63–7. Technol Int. 2014;24:243–8.
28. Dousset B, et al. Complete surgery for low rectal 37. Pereira RMA, et al. Use of circular stapler for lapa-
endometriosis: long-term results of a 100-case pro- roscopic excision of rectosigmoid anterior wall endo-
spective study. Ann Surg. 2010;251:887–95. metriosis. Surg Technol Int. 2008;17:181–6.
29. Goncalves MO, Dias JA Jr, Podgaec S, Averbach M, 38. Kondo W, et al. Surgical techniques for the treatment
Abrão MS. Transvaginal ultrasound for diagnosis of bowel endometriosis. J Minim Invasive Gynecol.
of deeply infiltrating endometriosis. Int J Gynaecol 2015;22:S131.
Obstet. 2009;104:156–60. 39. Revised American Society for Reproductive Medicine
30. Acien P, et al. Is a bowel resection necessary for deep classification of endometriosis: 1996. Fertil Steril.
endometriosis with rectovaginal or colorectal involve- 1997;67:817–21.
ment? Int J Womens Health. 2013;5:449–55. 40. Reid S, et al. Prediction of pouch of Douglas oblitera-
31. Young SW, et al. Initial accuracy of and learning curve tion in women with suspected endometriosis using a
for transvaginal ultrasound with bowel preparation for new real-time dynamic transvaginal ultrasound tech-
deep endometriosis in a US Tertiary Care Center. J nique: the sliding sign. Ultrasound Obstet Gynecol.
Minim Invasive Gynecol. 2017;24(7):1170–6. https:// 2013;41:685–91.
doi.org/10.1016/j.jmig.2017.07.002. 41. Hudelist G, et al. Uterine sliding sign: a simple
32. Ros C, et al. Bowel preparation improves the accuracy sonographic predictor for presence of deep infiltrat-
of transvaginal ultrasound in the diagnosis of recto- ing endometriosis of the rectum. Ultrasound Obstet
sigmoid deep infiltrating endometriosis: a prospective Gynecol. 2013;41:692–5.
study. J Minim Invasive Gynecol. 2017;24(7):1145– 42. Tammaa A, et al. Learning curve for the detection
51. https://doi.org/10.1016/j.jmig.2017.06.024. of pouch of Douglas obliteration and deep infil-
33. Young SW, et al. Sonographic evaluation of deep trating endometriosis of the rectum. Hum Reprod.
endometriosis: protocol for a US radiology practice. 2014;29:1199–204.
Abdom Radiol (NY). 2016;41:2364–79. 43. Millischer A-E, et al. Fusion imaging for evalua-
34. Panebianco V, et al. [Low anterior resection of the rec- tion of deep infiltrating endometriosis: feasibility
tum using mechanical anastomosis in intestinal endo- and preliminary results. Ultrasound Obstet Gynecol.
metriosis]. Minerva Chir. 1994;49:215–7. 2015;46:109–17.
Other Locations of Deep
Endometriosis
13
Stefano Guerriero, Silvia Ajossa,
Ornella Comparetto, Camilla Ronchetti,
Virginia Zanda, Bruno Piras, Alba Piras,
and Valerio Mais
a b
c d
Fig. 13.1 Some ultrasonographic images of scar endo- tures (c) and (d), using linear probe. The resolution is bet-
metriosis (straight arrows) in a 32-year-old woman with a ter in (c) and (d) due to higher frequencies with a more
cesarean section 6 years before. In the pictures (a) and (b), detailed and sensitive color Doppler evaluation (d)
the nodule visualized using convex probe and, in the pic-
Fig. 13.2 Ultrasonographic images of two nodules of scar endometriosis (straight arrows) in a 39-year-old woman
with a previous cesarean section 6 years before
124 S. Guerriero et al.
Fig. 13.5 The ultrasonographic appearance of Villar’s Fig. 13.6 A more detailed visualization (due to a better
nodule (straight arrows) in a 33-year-old woman without focalization) of Villar’s nodule (straight arrows) of
previous abdominal surgery Fig. 13.5. The solid appearance is more evident
a b
Fig. 13.7 The ultrasonographic appearance of Villar’s abdominal surgery. In this case, the ultrasonographic
nodule (straight arrows) using B-mode (a) and color appearance was more cystic than solid
Doppler (b) in a 20-year-old woman without previous
13 Other Locations of Deep Endometriosis 125
if there are no symptoms of pelvic endome- ultrasound (HIFU) ablation. This technique
triosis, and according to the IDEA consensus appears to be safe and effective for the treatment
that proposes four basic sonographic steps of abdominal wall endometriosis in 21 cases
when examining women with suspected or reported in the literature [22].
known endometriosis [17]. Three-dimensional (3D) sonography appears
to be a quick, easy, specific, and noninvasive tool
in the diagnosis and presurgical approach of
13.5 Future Perspectives extrapelvic endometriosis. The 3D reconstruc-
tion clearly showed the irregular shapes and bor-
Although hormonal therapy may be a useful ini- ders of the endometriotic nodule and gave a more
tial approach for reducing symptoms and for exact analysis of the surrounding tissue
decreasing the size of larger cutaneous lesions (Figs. 13.12, 13.13, 13.14, and 13.15). Moreover,
prior to planned surgical excision [20], surgery the depth of infiltration through the facial plane
for extragenital endometriosis clearly improves can easily be shown. Preoperative evaluation of
outcome through relief of symptoms, improved the dimension, volume, and infiltration of the
quality of life, increased fertility rates, and abdominal wall endometriotic mass could be
reduced recurrences [21]. Recently a new thera- very useful to estimate how large the excision
peutic method has been proposed for the treat- will be in order to use a mesh prosthesis [23].
ment of abdominal wall endometriosis: MRI may be an addition technique for the eval-
ultrasound (US)-guided high-intensity-focused uation of endometriosis before surgery especially
Fig. 13.12 Three-dimensional ultrasonographic appearance of a scar endometriosis (straight arrows) in a 39-year-old
woman with one previous cesarean section 6 years before
13 Other Locations of Deep Endometriosis 129
Fig. 13.13 Three-dimensional ultrasonographic appearance of a scar endometriosis (straight arrows) in a 32-year-old
woman with a cesarean section 6 years before
Fig. 13.14 Three-dimensional ultrasonographic appearance of Villar’s nodule (straight arrows) in a 20-year-old
woman without previous abdominal surgery
130 S. Guerriero et al.
Fig. 13.15 Three-dimensional ultrasonographic appearance of a rectus abdominis endometriosis (straight arrows) in
a 30-year-old woman with one previous cesarean section 4 years before
11. Yoon J, Lee YS, Chang HS, Park CS. Endometriosis of 18. Savelli L, Manuzzi L, Di Donato N, Salfi N, Trivella
the appendix. Ann Surg Treat Res. 2014;87(3):144–7. G, Ceccaroni M, Seracchioli R. Endometriosis of
12. De Riggi MA, Fusco F, Marino G, Izzo A. Giant the abdominal wall: ultrasonographic and Doppler
endometrial cyst of the liver: a case report and review characteristics. Ultrasound Obstet Gynecol.
of the literature. G Chir. 2016;37(2):79–83. 2012;39(3):336–40.
13. Basso MP, Christiano AB, Oliveira ALC, Cunrath GS, 19. Francica G. Reliable clinical and sonographic find-
Netinho JG. Appendicular endometriosis as a cause ings in the diagnosis of abdominal wall endome-
of chronic abdominal pain alone in the right iliac triosis near cesarean section scar. World J Radiol.
fossa: case report and literature review. J Coloproctol. 2012;4(4):135–40.
2012;32(1):80–3. 20. Ling CM, Lefrebre G. Extrapelvic endometriosis: a
14. Van Gorp T, Amant F, Neven P, Vergote I, Moerman case report and review of the literature. J Soc Obstet
P. Endometriosis and the development of malignant Gynaecol Can. 2000;22(2):97–100.
tumors of the pelvis. A review of the literature. Best 21. Veeraswamy A, Lewis M, Mann A, Kotikela S,
Pract Res Clin Obstet Gynaecol. 2004;18:349–71. Hajhosseini B, Nezhat C. Extragenital endometriosis.
15. Stevens EE, Pradhan TS, Chak Y, Lee YC. Malignant Clin Obstet Gynecol. 2010;53(2):449–66.
transformation of endometriosis in a cesarean section 22. Wang Y, Wang W, Wang L, Wang J, Tang
abdominal wall scar: a case report. J Reprod Med. J. Ultrasound-guided high-intensity focused ultra-
2013;58(5–6):264–6. sound treatment for abdominal wall endometriosis:
16. Ferrandina G, Palluzzi E, Fanfani F, Gentileschi S, preliminary results. Eur J Radiol. 2011;79(1):56–9.
Valentini AL, Mattoli MV, Pennacchia I, Scambia G, https://doi.org/10.1016/j.ejrad.2009.12.034. Epub
Zannoni G. Endometriosis-associated clear cell carci- 2010 Feb 8.
noma arising in caesarean section scar: a case report 23. Picard A, Varlet MN, Guillibert F, Srour M,
and review of the literature. World J Surg Oncol. Clemenson A, Khaddage A, Seffert P, Chene
2016;14:300. G. Three dimensional sonographic diagnosis of
17. Guerriero S, et al. Systematic approach to sono- abdominal wall endometriosis: a useful tool? Fertil
graphic evaluation of the pelvis in women with sus- Steril. 2011;95(1):289.e1–4.
pected endometriosis, including terms, definitions 24. Gougoutas CA, Siegelman ES, Hunt J, Outwater
and measurements: a consensus opinion from the EK. Pelvic endometriosis: various manifestations
International Deep Endometriosis Analysis (IDEA) and MR imaging findings. AJR Am J Roentgenol.
group. Ultrasound Obstet Gynecol. 2016;48:318–32. 2000;175(2):353–8.
Modified Ultrasonographic
Techniques
14
Simone Ferrero,
Umberto Leone Roberti Maggiore, Fabio Barra,
and Carolina Scala
14.2.1 Technique (95% CI, 64–80%), the specificity 88% (95% CI,
4–8%), the LR+ 6.2, and the LR− 0.3. For other
Twelve milliliter of ultrasound gel are introduced locations (uterosacral ligaments, rectosigmoid,
into the probe cover (usually a finger from a latex anterior pouch, and bladder), the sensitivity was
glove) instead of the usual 3–4 mL. The probe is lower (ranging from 67 to 33%) with a compara-
gently inserted in the vagina in order to minimize ble specificity. More recently, a prospective study
the risk of squeezing out the gel. The exam starts including 59 patients with clinical suspicion of
with the evaluation of the vaginal wall at the level DE (30 patients with surgical diagnosis of recto-
of the posterior vaginal fornix that can be exam- sigmoid endometriosis) compared the diagnostic
ined with a sliding up-and-down movement of the accuracy of magnetic resonance imaging (MRI)
probe. The patient is requested to inform the oper- and tg-TVS in diagnosing rectosigmoid endome-
ator about the onset and site of any tenderness triosis [4]. There was no significant difference in
experienced during the probe’s pressure in the the sensitivity and specificity of MRI and tg-TVS
posterior fornix. When tenderness is evoked, the in identifying rectosigmoid involvement. In par-
sliding movement is stopped, and particular atten- ticular, the specificity, sensitivity, and LR+ and
tion is paid to the painful site via gentle pressure LR− of tg-TVS were 86%, 73%, 5.317, and
with the probe’s tip for the detection of endome- 0.309, respectively.
triotic nodules [3]. Deep endometriotic nodules
appear as hypoechoic linear thickening or nod-
ules/masses with or without regular contours [4]. 14.3 Sonovaginography
The usual time required to perform tg-TVS in
patients with suspected DE is about 15–20 min; Sonovaginography (SVG) consists of TVS com-
however, less time is required when the exam is bined with the introduction of saline solution or
negative [3, 5]. gel into the posterior vaginal fornix to improve
the visualization of vaginal and rectovaginal sep-
tum DE. On regular TVS, these nodules may
14.2.2 Diagnostic Performance escape detection primarily because of the close
proximity of these structures to the transvaginal
A prospective study including 50 women with transducer [6]. The increased clarity on gel sono-
suspected rectovaginal endometriosis (31 with vaginography is achieved because the instilled
DE at surgery) investigated the accuracy of tg- gel causes standoff and partial distension of vagi-
TVS in the diagnosis of DE [3]. The study nal walls.
showed that this technique has a good to excel-
lent diagnostic performance with specificity of
95% (95% CI, 78–100%) and sensitivity of 90% 14.3.1 Technique
(95% CI, 80–93%); the positive predictive value
was 97% (95% CI, 85–100%), the negative pre- SVG was first described by Dessole et al. in 2003
dictive value was 86% (95% CI, 70–90%), the [7]. Immediately before the exam, the patients are
positive likelihood ratio (LR+) was 17.2, the neg- asked to partially empty the bladder in order to
ative likelihood ratio (LR−) was 0.1, and the leave a small amount of urine within to enhance
kappa value was 0.86 (95% CI, 0.56–0.91). This the examination of the anterior vaginal wall and of
diagnostic performance was subsequently con- the vesicovaginal septum [7]. After the patient seat
firmed in another prospective study including 88 in the gynecological position, the gynecological
women (72 with DE) [5]. With respect to the bed is slightly tilted in anti-Trendelenburg position
vaginal walls, the sensitivity was 91% (95% CI, to avoid saline solution reflux from the vagina dur-
79–97%), the specificity 89% (95% CI, 81–93%), ing the exam. A 24-mm Foley catheter is intro-
the LR+ 8.2, and an LR− 0.09. For endometriosis duced into the vagina, and its balloon is inflated
of rectovaginal septum, the sensitivity was 74% using 5–6 mL of saline solution. A limitation of
14 Modified Ultrasonographic Techniques 135
this technique is that an operator and an assistant anesthesia just prior to laparoscopy [9]; the blad-
are required to perform each exam [7]. The opera- der was emptied by using a urinary catheter, and
tor uses the right hand to handle the transvaginal the patient was slightly tilted in anti-Trendelen-
probe and the left hand to close the vaginal chan- burg position.
nel, narrowing the minor labia with the dorsal sur- A modified SVG technique consists in the
face of the forefinger and the middle finger. This simple introduction of 20 mL [6, 10, 11] or
maneuver is necessary to avoid the reflux of saline 50 mL [12] of ultrasound gel into the posterior
solution from the vagina during the exam. The vaginal fornix using a syringe prior to performing
assistant injects 200–400 mL of saline solution TVS in the office setting. The gel should be
through a Foley catheter [7]. loaded carefully into the syringe to decrease the
Other authors described the use of a purpose- presence of air bubbles/pockets within the gel.
designed hydraulic ring (Colpo-Pneumo Occluder, Recently, Sibal described in details a technique to
CooperSurgical, Berlin, Germany) that is placed minimize the presence of air bubbles within the
at the base of the transvaginal probe and is inflated filled syringe [6]. An assistant should hold the
with approximately 40 mL of saline solution in bottle of gel with its mouth facing downward.
order to prevent the escape of the 60–120 mL of The syringe is introduced into the lower part of
saline that is subsequently injected into the vagina the inverted bottle. Then, instead of pulling the
using a Foley catheter [8]. The saline solution in plunger out to fill the syringe, as is the usual prac-
the vagina creates an acoustic window between tice, the plunger is held steady in position, and
the transvaginal probe and the surrounding struc- the barrel (outer sleeve) is slowly pushed farther
tures; furthermore, it distends the vaginal walls [7, up into the inverted bottle of gel to fill the syringe
8]. This technique improves the visualization of with 20 mL of gel. The syringe must be filled
the vaginal walls, vaginal fornix, uterosacral liga- completely, so that the plunger comes in direct
ments, pouch of Douglas, rectovaginal septum, contact with the gel, thus further decreasing the
and vesicovaginal septum. During the exam, the possibility of air pockets when instilling the gel
transvaginal probe is not in contact with the uter- into the vagina. Some gel is usually sticking onto
ine cervix; the scan is performed by sliding the the external surface of the syringe, and it can be
probe back and forward, longitudinally and trans- used as a lubricant when the syringe is introduced
versally, with up, down, and angled movements into the vagina. Subsequently, the gel-lubricated
around the cervix, which was used as a reference tips of index and middle fingers of the gloved
point. The endometriotic lesions appear as right hand are introduced into the vagina. The
hypoechoic, irregular structures. syringe, held in the gloved left hand, is held such
SVG is well tolerated, and the intensity of that its tip lies in the groove above and between
pain perceived by the patients is similar to that the index and middle fingers. The syringe is
reported during TVS [7]. introduced into the vagina, directed by the fingers
Other techniques to perform SVG have been of the right hand in the vagina (Fig. 14.1). The
described. SVG can be performed by inserting fingers of the right hand are then removed, and
into the posterior vaginal fornix a condom the syringe is gently pushed farther inside along
attached to a saline giving set. The transvaginal the posterior vaginal wall such that there is
probe is then introduced into the vagina superior enough of it outside to grip and push the plunger
to the condom which is resting against the poste- to introduce the gel into the vagina. The syringe
rior vaginal wall. Once the transvaginal probe is must be inserted far enough into the vaginal canal
in situ, the condom is filled with 200–400 mL of such that the gel fills the posterior fornix com-
normal saline to enhance the visualization of the pletely [11]. The syringe is then withdrawn. A
retrocervical area, the posterior fornix, the poste- 20-mL volume of gel is thus placed in the upper
rior vaginal wall, and the rectovaginal septum vagina mainly in the posterior fornix. The
[9]. In the original study describing this tech- transvaginal transducer is gently introduced into
nique, the SVG was performed during general the vagina, carefully observing the vaginal side
136 S. Ferrero et al.
walls for any abnormalities as the probe is gradu- ducer is pushed up, the gel gets displaced, and
ally advanced upward. It is important to assess withdrawing and reinserting the transducer result
the lower vagina initially before assessing the in air bubbles getting into the vaginal gel, causing
upper vagina and cervix because once the trans- suboptimal imaging, in addition to loss of gel
volume in the upper vagina.
The ultrasound gel distends the vagina and
allows the anatomical contours of the inner
vagina to be clearly visualized (Figs. 14.2 and
14.3). The main advantage of using gel instead of
saline as a distention medium during SVG is that
gel SVG requires only one operator to insert the
gel and perform the examination [10, 11].
Some authors reported the use of bowel
preparation prior to SVG: an oral laxative
(sodium picosulfate, ten drops by mouth) the
night before the examination and a rectal enema
Fig. 14.3 Sonovaginography with gel. On the left, a vag- ule is enhanced by sonovaginography with gel. TV probe
inal nodule (asterisk) can be observed by transvaginal transvaginal probe
ultrasonography; on the right, the visualization of the nod-
14 Modified Ultrasonographic Techniques 137
(120 mL of sodium diphosphate) 1–2 h before ity of 93%, and LR+ of 14.0 for rectosigmoid
the examination [12]. involvement. The sensitivity, specificity, LR+,
and LR– for vaginal involvement were 60%,
98%, 30.0, and 0.41. The sensitivity, specificity,
14.3.2 Diagnostic Performance LR+, and LR– for retrocervical involvement
were 84%, 96%, 19.4, and 0.16 [12].
A preliminary prospective study including 46 A prospective study including 54 women
women scheduled for surgery because of recto- compared clinical evaluation, TVS, SVG (60–
vaginal endometriosis showed that SVG (200– 120 mL of saline solution), and MRI in the diag-
400 mL of saline solution in the vagina) diagnoses nosis of posterior DE [8]. SVG correctly
rectovaginal endometriosis more accurately than identified 43 (93.5%) cases of posterior DE, pre-
TVS. The diagnostic performance of SVG in senting higher accuracy than the other tech-
detecting rectovaginal endometriosis was sensi- niques. SVG had a sensitivity of 93.5%, a
tivity 90.6%, specificity 85.7%, PPV 93.5%, and specificity of 87.5%, a PPV of 97.7%, a NPV of
NPV 80.0% [7]. In a prospective pilot study 70.0%, a LR+ of 7.47, and a LR− of 0.07 in diag-
including 33 women with suspected endometrio- nosing posterior DE. There was no significant
sis, SVG (a condom attached to a saline giving difference in the pain perceived by the patients
set inserted in the posterior vaginal fornix) was during TVS and SVG.
performed immediately before laparoscopy
under general anesthesia [9]. The sensitivity,
specificity, positive predictive value, and negative 14.4 ectal Water Contrast
R
predictive value for SVG in the prediction of rec- Transvaginal Ultrasonography
tovaginal endometriotic nodules were 75%,
94.7%, 75%, and 94.7%. Another study per- Rectal water contrast transvaginal ultrasonogra-
formed by the same authors showed that SVG phy (RWC-TVS) is based on the concept of dis-
(10–20 mL of ultrasound gel into the vagina) has tending the rectosigmoid colon by using saline
sensitivity of 100%, specificity of 91.7%, NPV of solution while performing ultrasonography [13].
70%, and PPV of 100% in diagnosing DE of the The aim of this exam is to facilitate the identifica-
posterior compartment [10]. A multicenter pro- tion of rectosigmoid endometriotic nodules and
spective study including 189 women with clinical the assessment of their characteristics during TVS.
suspicion of endometriosis investigated the accu-
racy of SVG (20 mL of ultrasound gel into the
vagina) in diagnosing posterior DE [11]. For the 14.4.1 Technique
prediction of posterior compartment DE overall
(anterior rectum, rectosigmoid, uterosacral liga- A bowel preparation is advisable before the
ments, rectovaginal septum, and/or vagina), the exam. In some studies, patients were asked to
sensitivity was 86%, specificity was 93%, PPV drink four doses of a granular powder dissolved
was 83%, and NPV was 94%. For the prediction in 1000 mL of water per dose on the day before
of bowel endometriosis, the sensitivity was the exam [14]. However, in common clinical
88.4%, specificity was 93.2%, PPV was 79.2%, practice, bowel preparation consists of a rectal
and NPV was 96.5%. Specificity was high for all enema performed within few hours before the
locations, but sensitivity varied depending on ultrasonography to eliminate the feces present in
location (being as high as 88% for bowel nod- the rectosigmoid colon [15–17].
ules, but as low as 18% in the posterior vaginal A 6-mm (18 Ch) flexible catheter is inserted
wall and rectovaginal septum). A prospective through the anal os into the rectal lumen up to a
study including 51 patients with DE (50 mL of 15–20-cm distance from the anus (Fig. 14.4). A
ultrasound gel into the vagina after bowel prepa- gel infused with lidocaine may be used to mini-
ration) reported a sensitivity of 100%, a specific- mize the discomfort due to the passage of the
138 S. Ferrero et al.
catheter. After the connection of a 50-mL syringe there is no significant leakage of saline solution into
to the catheter, warm sterile saline solution is the space between the catheter and the anus. The
slowly injected inside the rectosigmoid under exam is performed both during and following saline
ultrasonographic control. Hundred milliliter of injection. The use of the water contrast allows to
saline solution are infused continuously at the dynamically evaluate the endometriotic lesions.
beginning of the procedure; subsequently, addi- After a sagittal scan of the uterine cervix is
tional saline solution (up to 350 mL) is injected obtained with the transvaginal probe, the sonog-
as requested by the ultrasonographer depending rapher focuses on the anterior and lateral sides of
on the distensibility of the intestinal wall the rectosigmoid, where deep endometriotic nod-
(Fig. 14.5). During the examination, a Klemmer ules are usually located. As in traditional TVS, at
forceps may be placed on the catheter to prevent RWC-TVS the normal layers of the rectosigmoid
backflow of the saline solution through the catheter can be evaluated. The serosa appears as thin
when the solution was not being injected. Usually, hyperechoic line, the muscularis propria is
hypoechoic with the longitudinal smooth muscle
(outer) and circular smooth muscle (inner) sepa-
rated by a faint thin hyperechoic line, the submu-
cosa is hyperechoic, and the mucosa is
hypoechoic. In RWC-TVS, the interface between
the lumen and the mucosal layer is hyperechoic
(Fig. 14.6) [16]. Rectosigmoid endometriotic
nodules appear as a thickening of the hypoechoic
muscularis propria or as rounded or triangular
Fig. 14.5 Progressive distention of the rectosigmoid colon during rectal water contrast transvaginal ultrasonography
14 Modified Ultrasonographic Techniques 139
Several studies investigated the diagnostic per- Fig. 14.9 Rectal water contrast transvaginal ultrasonog-
formance of RWC-TVS in diagnosing rectosig- raphy shows a retrocervical endometriotic nodule (largest
moid endometriosis and compared RWC-TVS diameter 15.5 mm) infiltrating the muscular layer of the
with other imaging techniques used for the diag- rectum. The rectum is dilated by saline solution (WC);
feces (F) can be observed in the rectum. U uterus
nosis of colorectal endometriosis.
The use of RWC-TVS for the diagnosis of
rectosigmoid endometriosis was originally reported more pain with this technique than
described in a prospective study including 35 TVS (Figs. 14.10 and 14.11, and Video 14.1).
patients with rectovaginal endometriosis [19]. A prospective study including 61 patients with
The exam showed good diagnostic performance suspected rectosigmoid endometriosis demon-
(Table 14.1), but it underestimated the depth of strated that RWC-TVS and transrectal sonogra-
infiltration in nodules reaching the submucosa. phy (TRS) have the same accuracy in the diagnosis
Subsequently, the same authors compared the of rectosigmoid endometriosis [17]. Furthermore,
performance of TVS and RWC-TVS in in the same study, the authors showed that RWC-
diagnosing intestinal infiltration in women with TVS and barium enema are equally effective in
suspicion of rectovaginal endometriosis [14]. the detection of a significant intestinal stenosis
RWC-TVS was more accurate than TVS in (≥50% of the lumen) due to endometriosis [17]
diagnosing intestinal infiltration, but patients (Videos 14.1 and 14.2, Fig. 14.12).
140
Fig. 14.10 Rectal hypoechoic endometriotic nodule with heads indicate the submucosa that is not infiltrated by the
blurred margins and hyperechoic foci on transvaginal endometriotic nodule. C uterine cervix, N nodule, WC
ultrasonography (on the left) and rectal water contrast water contrast. The same nodule is shown in Video 14.1
transvaginal ultrasonography (on the right). The arrow-
Fig. 14.13 Tomographic ultrasound images obtained during rectal water contrast transvaginal ultrasound. This series
of slices can provide information regarding the extent of infiltration of intestinal wall by endometriotic nodule
PPV 95%, NPV 97%, positive likelihood ratio techniques could be an option for those operators
30.3, and negative likelihood ratio 0.05. who do not achieve good results with TVS. The
selection of a particular modified ultrasono-
graphic technique depends on the skill and expe-
14.6 Future Perspective rience of the sonographer as well as the TVS
findings [24]. For example, SVG significantly
In patients with suspicion of DE, if the initial improves the visualization of the anterior and
scan reveals lesions in a determined area, it is posterior vaginal fornices. Similarly, RWC-TVS
unlikely that additional testing is required may improve the visualization of rectosigmoid
because of the high specificity of TVS [22]. In a nodules when the sonographers are learning to
meta-analysis, Guerriero et al. found that image the posterior compartment.
enhanced approaches are not more accurate than An advantage of modified ultrasonographic
plain TVS for this diagnosis of rectosigmoid techniques compared with other imaging
endometriosis [23]. Modified ultrasonographic modalities (such as MRI) is that they cause low
techniques should be used when the result of pain or discomfort for the patient and they can
TVS are inconclusive or if it is felt additional be performed directly by the gynecologists at
information on the features of DE should be low cost. Furthermore, these techniques can
obtained [24]. However, a limitation of TVS is also be performed as a dynamic test because
that it depends on the examiner’s ability and the operator can assess the changes in the posi-
experience; therefore, modified ultrasonographic tion of endometriotic nodules compared to the
144 S. Ferrero et al.
position of the pelvic organs (such as the bowel the rectovaginal septum in women with suspected
rectovaginal endometriosis: a pilot study. Australas J
and bladder) and assess their infiltration. Ultrasound Med. 2011;14(3):4–9.
Nowadays, the major challenge in the imaging 10. Reid S, Winder S, Condous G. Sonovaginography:
diagnosis of endometriosis remains the detec- redefining the concept of a “normal pelvis” on trans-
tion of superficial lesions. Future studies vaginal ultrasound pre-laparoscopic intervention for
suspected endometriosis. Australas J Ultrasound Med.
should assess whether modified ultrasono- 2011;14(2):21–4.
graphic techniques can allow the detection of 11. Reid S, Lu C, Hardy N, Casikar I, Reid G, Cario G,
superficial endometriotic lesions. et al. Office gel sonovaginography for the prediction
of posterior deep infiltrating endometriosis: a multi-
center prospective observational study. Ultrasound
Obstet Gynecol. 2014;44(6):710–8.
References 12. Leon M, Vaccaro H, Alcazar JL, Martinez J, Gutierrez
J, Amor F, et al. Extended transvaginal sonogra-
1. Piketty M, Chopin N, Dousset B, Millischer- phy in deep infiltrating endometriosis: use of bowel
Bellaische AE, Roseau G, Leconte M, et al. preparation and an acoustic window with intra-
Preoperative work-up for patients with deeply infil- vaginal gel: preliminary results. J Ultrasound Med.
trating endometriosis: transvaginal ultrasonography 2014;33(2):315–21.
must definitely be the first-line imaging examination. 13. Rubin C, Kurtz AB, Goldberg BB. Water enema: a
Hum Reprod. 2009;24(3):602–7. new ultrasound technique in defining pelvic anatomy.
2. Guerriero S, Condous G, Van den Bosch T, Valentin J Clin Ultrasound. 1978;6(1):28–33.
L, Leone FP, Van Schoubroeck D, et al. Systematic 14. Valenzano Menada M, Remorgida V, Abbamonte
approach to sonographic evaluation of the pelvis in LH, Nicoletti A, Ragni N, Ferrero S. Does transvagi-
women with suspected endometriosis, including nal ultrasonography combined with water-contrast
terms, definitions and measurements: a consensus in the rectum aid in the diagnosis of rectovaginal
opinion from the International Deep Endometriosis endometriosis infiltrating the bowel? Hum Reprod.
Analysis (IDEA) group. Ultrasound Obstet Gynecol. 2008;23(5):1069–75.
2016;48(3):318–32. 15. Ferrero S, Biscaldi E, Vellone VG, Venturini PL,
3. Guerriero S, Ajossa S, Gerada M, D’Aquila M, Piras Leone Roberti Maggiore U. Computed tomographic
B, Melis GB. “Tenderness-guided” transvaginal ultra- colonography vs rectal water-contrast transvaginal
sonography: a new method for the detection of deep sonography in diagnosis of rectosigmoid endome-
endometriosis in patients with chronic pelvic pain. triosis: a pilot study. Ultrasound Obstet Gynecol.
Fertil Steril. 2007;88(5):1293–7. 2017;49(4):515–23.
4. Saba L, Guerriero S, Sulcis R, Pilloni M, Ajossa S, 16. Leone Roberti Maggiore U, Biscaldi E, Vellone VG,
Melis G, et al. MRI and “tenderness guided” trans- Venturini PL, Ferrero S. Magnetic resonance enema
vaginal ultrasonography in the diagnosis of recto- vs rectal water-contrast transvaginal sonography in
sigmoid endometriosis. J Magn Reson Imaging. diagnosis of rectosigmoid endometriosis. Ultrasound
2012;35(2):352–60. Obstet Gynecol. 2017;49(4):524–32.
5. Guerriero S, Ajossa S, Gerada M, Virgilio B, Angioni 17. Bergamini V, Ghezzi F, Scarperi S, Raffaelli R, Cromi
S, Melis GB. Diagnostic value of transvaginal ‘ten- A, Franchi M. Preoperative assessment of intestinal
derness-guided’ ultrasonography for the prediction endometriosis: a comparison of transvaginal sonog-
of location of deep endometriosis. Hum Reprod. raphy with water-contrast in the rectum, transrectal
2008;23(11):2452–7. sonography, and barium enema. Abdom Imaging.
6. Sibal M. Gel sonovaginography: a new way of evalu- 2010;35(6):732–6.
ating a variety of local vaginal and cervical disorders. 18. Ferrero S, Biscaldi E, Morotti M, Venturini PL,
J Ultrasound Med. 2016;35(12):2699–715. Remorgida V, Rollandi GA, et al. Multidetector com-
7. Dessole S, Farina M, Rubattu G, Cosmi E, Ambrosini puterized tomography enteroclysis vs. rectal water
G, Nardelli GB. Sonovaginography is a new tech- contrast transvaginal ultrasonography in determining
nique for assessing rectovaginal endometriosis. Fertil the presence and extent of bowel endometriosis.
Steril. 2003;79(4):1023–7. Ultrasound Obstet Gynecol. 2011;37(5):603–13.
8. Saccardi C, Cosmi E, Borghero A, Tregnaghi A, 19. Menada MV, Remorgida V, Abbamonte LH, Fulcheri
Dessole S, Litta P. Comparison between transvagi- E, Ragni N, Ferrero S. Transvaginal ultrasonography
nal sonography, saline contrast sonovaginography combined with water-contrast in the rectum in the
and magnetic resonance imaging in the diagnosis of diagnosis of rectovaginal endometriosis infiltrating
posterior deep infiltrating endometriosis. Ultrasound the bowel. Fertil Steril. 2008;89(3):699–700.
Obstet Gynecol. 2012;40(4):464–9. 20. Philip CA, Bisch C, Coulon A, de Saint-Hilaire P,
9. Reid S, Bignardi T, Lu C, Lam A, Condous G. The use Rudigoz RC, Dubernard G. Correlation between
of intra-operative saline sonovaginography to define three-dimensional rectosonography and magnetic
14 Modified Ultrasonographic Techniques 145
resonance imaging in the diagnosis of rectosig- for diagnosis of deep endometriosis in uterosacral lig-
moid endometriosis: a preliminary study on the aments, rectovaginal septum, vagina and bladder: sys-
first fifty cases. Eur J Obstet Gynecol Reprod Biol. tematic review and meta-analysis. Ultrasound Obstet
2015;187:35–40. Gynecol. 2015;46(5):534–45.
21. Philip CA, Bisch C, Coulon A, Maissiat E, de Saint- 23. Guerriero S, Ajossa S, Orozco R, Perniciano M, Jurado
Hilaire P, Huissoud C, et al. Three-dimensional sono- M, Melis GB, Alcazar JL. Accuracy of transvaginal
rectography: a new transvaginal ultrasound technique ultrasound for diagnosis of deep endometriosis in the
with intrarectal contrast to assess colorectal endome- rectosigmoid: systematic review and meta-analysis.
triosis. Ultrasound Obstet Gynecol. 2015;45(2):233–5. Ultrasound Obstet Gynecol. 2016;47(3):281–9.
22. Guerriero S, Ajossa S, Minguez JA, Jurado M, Mais V, 24. Hoyos LR, Johnson S, Puscheck E. Endometriosis and
Melis GB, et al. Accuracy of transvaginal ultrasound imaging. Clin Obstet Gynecol. 2017;60(3):503–16.
Additional Radiological
Techniques (MRI)
15
Federica Schirru, Stefano Guerriero,
and Luca Saba
r esolution, a wide field of view and an excellent Pelvic Imaging working group of the European
tissue characterization. Moreover, it allows both Society of Urogenital Radiology (EPI-ESUR).
to detect endometrial implants hidden by adhe- Recommendations have been proposed in guide-
sions and to recognize lesions located in an extra- lines for indication for MRI, technical require-
pelvic site. In addition, MRI, also with the use of ments, patient preparation and MRI acquisition
contrast material, permits to distinguish deep pel- protocols [22].
vic endometriosis from other pelvic inflamma-
tory conditions or to solve differential diagnosis 15.2.2.1 Indications for MRI
problems, for instance, between benign and in Endometriosis
malignant ovarian masses or with other malig- In the literature, there is no common agreement
nancies of the pelvic organs [7, 8, 23–25]. In lit- on the use of US rather than MRI, and there are
erature, there is no general agreement on the use no publications for executing MRI in pelvic
of US rather than MRI. In general, papers pub- endometriosis. Common indications for pelvic
lished by gynaecologists support US diagnostic MRI are evaluation of pelvic pain and infertility
superiority, while those published by radiologists or assessment of adnexal mass; however, in
emphasize the value of MRI [22]. However, the many ESUR centres, the most frequent reason
most recent meta-analyses have shown that addi- that leads to MRI is the staging of deep pelvic
tional examinations, especially MRI, are recom- endometriosis (90% of cases). Therefore, con-
mended in symptomatic patients with negative sidering the most recent meta-analyses (as men-
US findings [22, 26]. Moreover, MRI is also sug- tioned in the previous paragraph), guidelines
gested as a second-line approach in preoperative suggest that [22]:
workup of deep pelvic endometriosis in patients
with unclear US [22]. The value of MRI can fur- –– MRI should be considered the second-line
ther grow and improve by means of an intense approach in evaluation of pelvic endometrio-
collaboration between radiologists and sis, especially in symptomatic patients with
gynaecologists. negative US findings.
The Computed Tomography (CT) has a mar- –– MRI is recommended before surgery for pre-
ginal role in the assessment of endometriosis operative workup of pelvic endometriosis.
because it lacks both sensitivity and specificity,
and often findings are nonspecific and non-diag- 15.2.2.2 Technical Requirements
nostic. However, CT might be useful in evaluat-
ing any complications of endometriosis, such as 1.5-T or 3.0-T System and Array Type
intestinal obstruction, hydronephrosis conse- Guidelines do not provide any recommendations
quent to ureteral compression, hemoperitoneum regarding the use of 1.5-T magnet rather than
and acute abdomen secondary to the rupture of an 3.0-T magnet; both are considered valid for
endometrioma [27]. studying endometriosis, but there are no suffi-
cient comparing studies in literature [22]. The
increased spatial resolution, due to the improved
15.2.2 M
agnetic Resonance Imaging signal-to-noise ratio of 3.0-T MRI versus 1.5-T,
Technique allows to identify smaller lesions of DPE and sur-
face implants by showing adhesions and perito-
Recently (in December 2016), the European neal irregularities [28–30]. However, due to the
Society of Urogenital Radiology (ESUR) has increased image heterogeneity at 3.0-T system,
published guidelines for optimal MRI protocols negative effects on fat-saturation techniques
and imaging interpretation in endometriosis. (which are very useful in the imaging study of the
These are based on a careful and detailed review disease) may occur [29, 31]. Therefore, more
of the most recent literature and on the consen- comparative studies are needed for a more accu-
sus opinion between experts from the Female rate evaluation of the two systems and for
15 Additional Radiological Techniques (MRI) 149
c hoosing what is the better one in the assessment Fasting before the onset of MRI is recom-
of endometriosis. mended by guidelines, but its length is variable
Both with 1.5-T magnet and with 3.0-T, pelvic (3, 4 or 6 h) [22]. It is useful in order to reduce
phased-array coils are recommended by guide- intestinal peristalsis.
lines for DPE evaluation [22]. These assure a Bowel preparation is advocated as “best prac-
high signal-to-noise ratio, high spatial resolution tice” for the detection of DPE. Several studies
with anatomical detail accuracy and improved suggest an intestinal preparation that involves the
tissue characterization. For such reasons, pelvic use of oral laxatives on the day before the exami-
phased-array coils should be used for the study of nation or a bowel enema with water. In addition,
pelvis. Although some authors have described a it is recommended that patients undergo a dietary
higher diagnostic accuracy of endoluminal coils preparation with a low-residue regimen on the
in evaluating the invasion and the infiltration day before and the day of examination [22, 33].
depth within the rectal wall or bladder, their use There is a common agreement on the impor-
seems limited by the small field of view and the tance of an adequate bladder distension in order
pain related to their positioning. Moreover, the to achieve a precise detection of endometrial
use of the endovaginal coil prevents endoluminal implants. A moderately filled or full bladder
filling with ultrasound gel, which is a useful tool allows to modify the angle of uterine antever-
for improving the visualization of the vagina and sion; in this manner, the visualization of pelvic
rectal wall [32]. anatomical structures is improved with a conse-
quent better detection of small endometrial
Timing of MRI Examination implants sited in the vesicouterine pouch or
The timing of MRI examination is controversial anterior to it. Another advantage of having a
and, in fact, there is not a common agreement. moderately full bladder is the reduction of
Some authors have argued that there is no greater motion artefacts (due to the intestinal peristalsis)
diagnostic accuracy of MRI performed during the because the sigma and the adjacent small intes-
menstrual cycle since the signal or the size of tine loops are displaced superiorly. For all these
endometriosis nodules do not significantly change reasons, a moderately full bladder is recom-
with menses [27]. In a recent paper, Menni et al. mended in the evaluation of DPE, and, in gen-
have suggested that MRI should be performed in eral, patients are instructed to not empty the
the first 12 days after the beginning of patient’s bladder 1 h before the examination [22]. In con-
last menstrual period. In fact, during this phase, trast, an empty or overfilled bladder might com-
endometrial haemorrhagic foci are best detected promise the evaluation of anatomic structures,
because of the maximum hyperintense signal of resulting in a worst detection of lesions. In addi-
blood products in the T1-weighted images [7]. In tion, the overfilled bladder may be the cause of
conclusion, guidelines do not recommend a spe- motion artefacts due to the activity of the detru-
cific timing, related to the menstrual cycle, of sor muscle [8, 24, 34].
MRI examination in the evaluation of DPE [22].
Patient Position
Patient Preparation: Fasting, Bowel MRI should be performed with the patient in the
Preparation, and Bladder Emptying supine position; however, the prone position may
Adequate patient preparation is necessary to be considered an option in claustrophobic patients
obtain high-quality images, and, despite this, no in order to reduce stress, anxiety and distress [22].
general consensus is found on patient preparation
before MRI examination. The MRI protocol Antiperistaltic Agent
should be chosen and tailored according to the Antispasmodic agents (e.g. hyoscine-N-butylbro-
principal indication, and it will be different mide, glucagon) are recommended in the evalua-
depending on whether endometriosis or an ante- tion of DPE, as they reduce motion artefacts
rior mass have to be evaluated. caused by bowel and uterine peristalsis [22, 32].
150 F. Schirru et al.
ence of mural nodules in an endometrioma is the images (“lightbulb-like” brightness), which is due
main indication because of the strong suspect of to the high concentrations of paramagnetic hae-
malignant transformation. It can also be useful to moglobin in blood degradation products. On
distinguish an endometrioma from a lutean ovar- T2-weighted images, the lesion is characterized
ian cyst or a tubo-ovarian abscess or to distin- by intermediate-to-low signal. A typical feature of
guish endometriosis from pelvic inflammatory endometrioma is the “T2-shading” sign, which
disease [23, 48]. consists of a low signal (T2 shortening) affecting
variable portions of the cyst (small portions or the
entire cyst). In particular, the phenomenon ranges
15.2.3 M
R Imaging Features from a homogeneous complete absence of signal
of Endometriosis to different gradations of decreased signal inten-
sity on T2-weighted sequences [53–55]. The
Endometriosis has three different clinical pat- dependence of signal intensity to the high concen-
terns of manifestation, which can occur alone or tration of protein and iron within the cyst, due to
coexist: recurrent haemorrhages, reflects the chronic
nature of endometrioma. It is important to high-
–– Ovarian endometrioma
light that any signal loss on T2-weighted images
–– Peritoneal endometriosis (with or without
is highly specific for endometrioma, regardless of
adhesions)
the degree of signal loss [21].
–– Deep endometriosis
Recently, Corwin et al. have describe an MRI
finding called “T2 dark spots”, found in some
15.2.4 Ovarian Endometrioma cases of haemorrhagic cystic ovarian lesions. “T2
dark spots” are defined as markedly hypointense
Endometrioma is described as an ovarian pecu- foci within the cyst on T2-weighted images with
liar pseudocyst lined by functioning endometrial- or without T2 shading. They may be located
like tissue composed of a highly vascularized within the cyst, often against the cyst wall, but
stroma and a surface epithelium. Its content is a not within the cyst wall itself [56].
dense dark fluid, consisting of high concentra- Another important feature is the presence of
tions of degenerated blood products accumulated multiple endometriotic cysts. This seems related
over successive menstrual cycles. Because of this to the fact that cysts undergo repeated rupture
aspect, endometrioma is also called “chocolate because of the hormonal stimulation resulting in
cysts”. In case of larger endometriomas, it could internal bleeding. The bilateralism and multiplic-
be possible to observe clots, thin septa, “haema- ity of hyperintense on T1-weighted adnexal cysts
tocrit effect”, fluid levels or peripheral nodules can be considered a valid diagnostic criterion to
(due to clots) [27, 33, 49]. distinguish the endometrioma from other haem-
Endometriomas can be either single or multi- orrhagic lesions, even greater specificity than the
ple, bilateral (in more than 50% of cases), uni- T1 signal hyperintensity alone [49, 57].
locular or multilocular. In case of inter-ovarian Chemical-selective T1-weighted fat-saturated
adhesions, a particular condition called “kissing sequences are very useful for the diagnosis of
ovaries” can be observed [50, 51]. endometriosis. In fact, the saturation of the fat
improves the contrast resolution among non-fat-
15.2.4.1 MRI Findings containing T1-hyperintense structures, making
Since endometrioma may contain variable possible to detect even very small endometriomas.
amounts of blood breakdown products, proteins Moreover, the loss of fat signal is advantageous in
and fluids, its appearance on MR imaging can be characterization of T1-hyperintense adnexal
variable [52]. lesions, allowing, for instance, the differentiation
Usually, it appears as a cystic mass with a between endometrioma and mature cystic teratoma
homogeneous hyperintense signal on T1-weighted [53, 55]. It should also be emphasized that chemi-
152 F. Schirru et al.
a b
c d
Fig. 15.1 Endometriomas in a 44-year-old woman with and without fat suppression, and T2-shading sign. Some
chronic pelvic pain and infertility. Axial T1-weighted (a), low signal spot (arrowheads) are visible inside the cysts
axial T2-weighted (b), axial T1-weighted with fat sup- that correspond to chronic retracted blood clots containing
pression (c) and sagittal T2-weighted MR images show in a high concentration of protein and/or hemosiderin (“dark
the right adnexa the presence endometriomas character- spot sign”)
ized by high signal in both T1-weighted sequences, with
15 Additional Radiological Techniques (MRI) 153
cystic teratomas, showed restricted diffusion size, could lead to a hemoperitoneum with acute
[56]. However, as already mentioned in the previ- abdomen [27, 61].
ous paragraphs, Balaban et al. has demonstrated Ovarian Torsion: uncommon. It represents a
that endometrioma has lower ADC values, at all b gynaecological emergency requiring urgent sur-
values, compared with those of haemorrhagic gical treatment to prevent ovarian necrosis. In
ovarian cysts. Therefore, further studies are general, findings include an endometrioma within
needed to clarify the role of DWI in evaluating an enlarged oedematous ovary with multiple fol-
these lesions. licles located peripherally [14]. Twisting of the
In conclusion, the MR imaging criteria for the ovarian pedicle is the most specific feature of
diagnosis of endometrioma are [20]: ovarian torsion, but it can be very difficult to
detect.
–– Multiple adnexal cysts with hyperintense sig- Malignant Transformation: it represents a very
nal on T1-weighted images rare complication, occurring in less than 1% of
–– One or more adnexal cysts with hyperintense patients with the disease [62, 63]. MRI findings
signal on T1-weighted images and “shading suspecting malignant degeneration include [49]:
sign” on T2-weighted images
–– Presence of enhanced mural nodules (well
Using these criteria, it has been demonstrated detected on contrast-enhanced subtracted
that MR imaging reaches a diagnostic accuracy images)
of 91–96%, a sensitivity of 90–92% and a speci- –– Loss of typical “T2-shading” sign on
ficity of 91–98% in the diagnosis of endometri- T2-weighted images
oma [53, 54, 57–59]. –– Presence of mural nodule of more than 30 mm
Routine follow-up is very important for endo- in size
metriomas because of risk for many complica- –– An interval increase in the size of the cyst
tions, in particular rupture.
Enhanced mural nodules are the most sensi-
15.2.4.2 Complications tive feature on MR imaging of malignancies; oth-
of Endometrioma ers, however, are useful in suspecting neoplastic
Usually, complications may occur in about 50% transformation but less reliable. It is important to
of patients with one or more endometriomas. The evaluate the enhanced mural nodules with con-
most frequent are: trast-enhanced dynamic subtraction images since
Reduced Fertility: this complication involves the haemorrhagic content of cysts (which is also
about 30–50% of women affected by endometri- hyperintense on T1-weighted images) may mask
osis. Many studies have reported a poorer preg- the enhancement of small nodules. Therefore, to
nancy outcome in affected women probably due better visualize areas of enhancement, it is man-
to the presence of adhesions involving the ovaries datory to use contrast-enhanced subtracted
and the fallopian tubes, as well as anomalies of images [20]. However, enhanced mural nodules
the endocrine and immune systems [27, 60]. represent a sensitive (97%) but not a specific
Adhesions: extremely frequent. Adhesions (56%) feature for the diagnosis of endometrioma-
appear as low signal stranding on both associated cancer. In fact, a whole range of
T1-weighted and T2-weighted images that mask benign conditions (such as polypoid endometrio-
organ interfaces; they could cause distortion of sis, intracystic blood clots or decidualized endo-
the normal pelvic anatomy. A characteristic diag- metriosis of pregnancy) should be considered in
nostic sign is the “kissing ovaries” characterized the differential diagnosis [27].
by the closing up of ovaries resulting in inter- The loss of “T2-shading” sign seems to be due
ovarian adhesions [20, 50, 51]. to tumour secretions that dilute blood degrada-
Acute Abdomen: this medical emergency is an tion products [63, 64]. Cystic components appear
uncommon complication of endometrioma. The hyperintense on both T1-weighted and
rupture of endometriotic cyst, even very small in T2-weighted images.
154 F. Schirru et al.
15.2.4.3 Differential Diagnosis these cases, each corpus luteum cyst appears
Typically, endometrioma appears as a cystic similar to endometrioma, but the patient’s medi-
adnexal mass with hyperintensity signal on cal history of a recent oocyte retrieval helps in the
T1-weighted images with and without fat sup- diagnosis [33].
pression, T2-shading sign, restricted diffusion Tubo-ovarian abscess: it represents one of the
(the most part of cases) and, on post-contrast late complications of pelvic inflammatory dis-
sequences, an intense enhanced wall. However, ease (PID). It consists of a pelvic inflammatory
some of these aspects may occur in other different mass within both the ovary and the fallopian tube
adnexal cystic masses, with a consequent overlap- are not separately distinguished. Typically, the
ping appearance. For instance, endometriomas pelvic mass shows a thin wall and a fluid content
are most commonly misdiagnosed as dermoid or that shows hypointense signal on T1-weighted
haemorrhagic cysts. Hence, a whole range of dif- images and heterogeneous or hyperintense signal
ferential diagnosis should be considered in order on T2-weighted images.
to make a correct evaluation. Mucinous lesions and ovarian carcinoma: the
General imaging differential considerations most important ovarian mucinous masses to be
include: considered in differential diagnosis are ovarian
Haemorrhagic cyst: it represents the most fre- mucinous cystadenoma, ovarian borderline muci-
quent and complex differential diagnosis of nous tumour and ovarian mucinous cystadeno-
endometrioma. MRI findings depend on the age carcinoma. In general, the degree of hyperintensity
of haemorrhage. The haemorrhagic cyst is usu- on T1-weighted images varies depending on the
ally a solitary unilocular adnexal mass, lined by a concentration of mucin; however, the signal
thin wall. Like endometrioma, it appears hyper- intensity is still lower than that of fat or blood. In
intense on T1-weighted sequences with and with- general, endometrioma has to be differentiated
out fat suppression or shows a peripheral halo of from almost all ovarian neoplasms.
signal hyperintensity on T1-weighted images. Decidualized endometriosis in pregnant
More frequently, it does not show the characteris- woman: it is a benign condition associated with
tic T2-shading sign, because there are not recur- ectopic endometrial tissue that undergone a decid-
rent bleedings so that the viscosity and ual reaction during pregnancy. It may mimic an
concentration of contents remain low; however ovarian cancer in pregnancy. These benign nod-
sometimes the T2-shading sign can be present. ules show the same signal intensity of the normal
The walls of the cyst do not show enhancement decidualized endometrium on T2-weighted
on post-contrast images. images. In addition, in the postpartum or at the
Dermoid cysts and mature cystic ovarian tera- termination of a pregnancy, decidualized endome-
tomas: together with the haemorrhagic cysts, triosis resolve or regress to uncomplicated endo-
these lesions are one of the most frequent differ- metriomas [56].
ential diagnoses of endometrioma. As fat-con-
taining lesions, they appear hyperintense on
T1-weighted images mimicking an endometri- 15.2.5 Peritoneal Endometriosis
oma. They can be differentiated by chemical- (with or Without Adhesions)
selective T1-weighted fat-saturated sequences in
which the loss of signal occurs only in these Peritoneal endometriosis is characterized by the
lesions and not in the endometrioma, because of presence of endometrial implants on the surface
the chemical shift artefact [49]. of the pelvic peritoneum.
Multiple corpora lutea: this differential diag- Small implants develop on the peritoneal sur-
nosis must be considered in women who have face and on the serosa of any abdominal and
been subjected to assisted conception treatments. pelvic organ. In general, on MR imaging they
After hormonal stimulation that induces ovula- appear as small solid masses or soft tissue thick-
tion, multiple corpora lutea frequently occur. In ening with irregular or stellate margins. Lesions
15 Additional Radiological Techniques (MRI) 155
of increased T2 signal within the solid masses, Deep endometriosis that involves the vesico-
which represent dilated endometrial glands [34, vaginal septum appears as a cystic lesion, with
56]. The appearance of lesions after administra- the same characteristics of an endometrioma
tion of the contrast material, on enhanced [34].
sequences, is very variable; enhancement depends MRI is considered the reference standard in
on how much inflammatory reaction and glandu- urinary tract endometriosis diagnosis. According
lar and fibrous tissue there is in the lesion. So, the to some papers, if examination is performed on
post-contrast appearance is neither specific nor 3-T MRI system, the sensitivity reaches 88%,
sensitive for the diagnosis of DE [34, 56]. and specificity is higher than 98% [29, 33, 69,
72]. Recently, authors have compared three-
15.2.6.2 Anatomical Locations dimensional colour Doppler US with MRI and
of Deep endometriosis cystoscopy in the diagnosis of bladder endome-
Many authors have subdivided the pelvis into triosis; they have showed that US seems to be
three different compartments depending on the superior to cystoscopy and is at least as effective
clinical and functional requirements: anterior, as MRI in diagnosing and planning the surgery
middle and posterior [68]. In the next paragraphs, for bladder endometriosis [73].
we will analyse the common anatomical locations The urinary bladder is involved in about
of solid nodules, considering the pelvic compart- 0.3–12% of women with pelvic endometriosis,
ments classification used by Coutinho et al. and the bladder is the most common affected
site of the urinary system (80%) [74]. Bladder
15.2.6.3 Anterior Compartment involvement may be extrinsic or intrinsic.
The anterior compartment contains the urinary Extrinsic involvement is more common and
bladder and urethra. Furthermore, the terminal often asymptomatic; lesions are sited on the
part of ureters is considered in this site. The serosal surface. Usually lesions involve the
bladder is separated from the vagina and the posterior wall [34]. On MR examination, nod-
uterus through fat planes known as vesicovagi- ules appear as localized or diffuse thickening
nal septum and prevesical space. The vesico- of the wall bladder, with low signal on
uterine pouch, or anterior cul-de-sac, is a T2-weighted sequences, which replace the nor-
peritoneum fold that lies between the bladder mal signal of detrusor muscle. Sometimes it is
(anterior) and the uterus (posterior). The vesico- possible to identify small foci with variable
uterine pouch is the most frequently affected signal on T1 and high signal on T2-weighted
site by endometriosis [68]. Implants into the sequences representing dilated endometrial
vesicovaginal septum, bladder and ureters are glands. On contrast-enhanced sequences, there
less common. is a greater enhancement of lesions than nor-
An involvement of other pelvic structures has mal detrusor muscle [75] (Fig. 15.2 c, d).
been reported in 50–75% of cases of urinary tract Endometriosis of the ureter is the second most
endometriosis involvement. Moreover, these common manifestation of urinary tract endome-
patients have also a more advanced stage of dis- triosis. In extrinsic form, endometrial tissue
ease than women without urinary tract involve- invades only the outer layer of the ureter (the
ment [69–71]. adventitia) and surrounding connective tissue,
Lesions of the anterior cul-de-sac appear as sometimes leading to obstruction of the ureter;
nodules that adhere to the anterior uterine sur- lesions originate from adjacent disease of the
face, with low signal intensity on T2-weighted ovary, broad ligaments or other uterosacral liga-
sequences. Because of the tight adherence to the ments. Both forms may manifest with obstructive
peritoneum of the bladder fold and the uterus, symptoms; cyclic haematuria is typical of the lat-
these lesions are associated to obliteration of the ter form [74]. On MRI examination, lesions
vesicouterine pouch and to anteflexion of the appear as irregular nodules with low signal on
uterus [34] (Fig. 15.2 a, b). T2-weighted sequences. Loss of the fat plane
15 Additional Radiological Techniques (MRI) 157
a b
c d
Fig. 15.2 Anterior compartment. (a, b) Endometriosis of Endometriosis of the bladder in a 30-year-old woman with
the vesicouterine pouch in a 34-year-old woman with pel- haematuria. Sagittal T2-weighted (c) and axial T2-weighted
vic pain. Sagittal T2-weighted (a) and coronal T2-weighted (d) MR images depict irregular focal thickening of the
(b) MR images show irregular hypointense nodular lesion bladder wall, which contains small intermingled hyperin-
that adheres to the anterior uterine surface and to the upper tense foci that correspond to the dilated endometrial
bladder wall surface. The lesion obliterates the vesicouter- glands. The deep infiltrating endometriotic lesion does not
ine recess. Anteflexion of the uterus is associated. (c, d) adhere to the anterior uterine surface
between the ureter and nodule is highly suspi- intravenous pyelogram, urography) have limited
cious of extrinsic involvement. Retractile adhe- value in providing accurate information about the
sions may be present and appear as periureteral extent of the disease and the degree of tissue infil-
hypointense lines arranged in confluent angles tration. Recently Sillou et al. demonstrated that
[76]. If the nodule is obstructive, dilatation of the MRI is more sensitive than surgery (91% vs.
ureteral portion cranial to the lesion can be stud- 82%) but less specific (59% vs. 67%) in diagnos-
ied with MRI urography. Unfortunately, both ing intrinsic involvement of ureteral endometrio-
MRI and other imaging techniques (US, Uro-CT, sis sites [74, 77].
158 F. Schirru et al.
a b
c d
Fig. 15.3 Adhesions. (a, b) Endometriosis in a 37-year- Axial T1-weighted (c) and sagittal T2-weighted (d) MR
old woman; axial T-weighted (a) and coronal T2-weighted images depict a tortuous distension of the left fallopian
(b) MR images show low signal stranding between the tube (white arrow) filled with haemorrhagic fluid, with
ovaries and between ovaries and uterus. The inter-ovarian high signal on T1-W sequences and low signal on
adhesions cause the closing up of right adnexa (white T2-W. An implant is visible on the serosal surface of the
arrow) and left adnexa (yellow arrow) with tethering to fallopian tube (yellow arrow)
the uterus. (c, d) Haematosalpinx in a 36 year-old woman.
account of fluid in the rectovaginal pouch may Implants often extent to the rectal wall posteri-
facilitate the detection of peritoneal reaction. MR orly or to vaginal cuff inferiorly, in particular to
examination has an important role in the evalua- vaginal fornices. The vaginal fornices are
tion of these lesions because they are not readily recesses into which the upper vagina is divided.
accessible at endoscopic viewing [33]. These vault-like recesses (anterior, posterior and
The retrocervical area is a virtual region lateral fornices) are formed by the protrusion of
behind the cervix, above the rectovaginal sep- the cervix into the vagina. The posterior fornix is
tum, and it is commonly affected by DE. the larger recess behind the cervix, close to the
160 F. Schirru et al.
a b
c d
Fig. 15.4 Posterior compartment endometriosis in T2-weighted images show low signal fibrotic thickening
45-year-old woman with a history of chronic pelvic pain from the torus uterinus and lower uterine segment to the
and dyspareunia. Sagittal T1-weighted (a), sagittal rectum (yellow arrow) associated to a solid nodular lesion
T2-weighted (b) and axial T2-weighted MR images show sited in the anterior sigmoid wall. Involvement of the
a large solid nodular implant in the rectovaginal septum torus uterinus and of the USL is visible on axial T2-w
and retrocervical area (white arrow) with intermingled images as a diffuse and irregular thickening within the
high signal foci due to bloody content. Sagittal ligaments (yellow arrowheads)
rectouterine pouch, more frequently involved by defined as a transverse thickening that binds the
endometriosis [8, 33]. insertion of USLs on the posterior wall of the cer-
The rectouterine folds contain a considerable vix; usually it is visible only if it is thickened.
amount of nonstriated muscular fibres and fibrous When the torus uterinus is involved by endometri-
tissue attached to the anterior surface of the otic implants, they appear as a mass or thickening
sacrum; they form the uterosacral ligaments. in the upper middle portion of the posterior cer-
Therefore, the uterosacral ligaments (USLs) are vix. Nodules may have regular or irregular mar-
fibrous fascial band on each side of the uterus that gins. In many cases, the involvement may be
passes along the lateral wall of the pelvis from the unilateral. Often, associated findings might be
uterine cervix and the vaginal vault to the sacrum uterine retroversion or angular rectal attraction,
[54, 73]. The torus uterinus is anatomically reflecting the fibrotic components [73].
15 Additional Radiological Techniques (MRI) 161
USLs are considered the sites most fre- Finally, the rectosigmoid is the most common
quently involved in deep endometriosis. Lesions segment of bowel involved in endometriosis. It
may affect one or both of USLs; their proximal occurs in 12–37% of patients and is associated
medial portion is the most commonly affected. with severe DE in other pelvic structures (such as
On MR imaging, normal USLs appear as thin USLs, ovaries, vagina, bladder and pelvic side-
regular semi-circular structures with low sig- wall) [81, 82]. Chapron et al. reported a high inci-
nal. On the contrary, if they are involved by dence of associated involvement of the ileocecal
endometriosis, morphologic abnormalities may region: 12% of the lesions involve the ileum, 8%
occur; they include diffuse or localized thicken- of the lesions involve the appendix and 6% of the
ing and nodules with regular or irregular mar- lesion involves the cecum. Considering that the
gin within the ligaments. Usually endometriotic success of surgical treatment is related to the com-
implants show low signal on T2-weighted plete excision of endometriotic implants, MRI
sequences; however, nodules can show cystic examination is fundamental to precisely assess the
cavities with high signal on T2- and low signal intestinal DE, in order to plan a proper surgical
on T1-weighted images or may have very small strategy [83]. DE intestinal implants have different
hyperintense foci on T1-weighted sequences, morphological characteristics. They appear as
with and without fat suppression, due to haem- nodular or plaque-like lesions. Plaque-like lesions
orrhagic content. Considering their position have ill-defined margins and rectrative or infiltra-
and proximity to the rectum and vaginal walls, tive behaviour. Nodules are generally attached to
USLs lesions may extend to infiltrate these the intestinal wall between the 10-o’clock and
structures [33, 34]. Even in this case, rectal or 2-o’clock position. They usually have a triangular
vaginal opacification with sterile gel should shape with the base attached to the intestinal wall
allow a better detection of implants occurring and the apex oriented towards the retrocervical
in these structures. region. Implants might be located on the serosal
The rectouterine pouch (called also posterior layer or infiltrate the deeper layers, causing thick-
cul-de-sac or pouch of Douglas) represents the ening of the rectosigmoid colon wall with fibrosis.
deepest point of the peritoneal cavity, sited Nodules may be rectractile or nonretractile and
between the bilateral rectouterine folds, behind may show regular or irregular margins with low
the uterus and in front of the rectum. It extends signal on T2-weighted images [33, 83]. A specific
till the middle third of the vagina in 93% of finding of solid invasive endometriosis of the
women [68]. The pouch of Douglas is another intestinal wall is the “mushroom cap” sign on
commonly involved site in DE. Sometimes solid T2-weighted images. The low- signal-intensity
infiltrative lesions of this region may be over- base of the mushroom represents the hypertrophy
looked because of their extent and invasion of the and fibrosis of the muscularis propria, while the
posterior myometrium, mimicking adenomyosis high-signal-intensity cap is attributed to the
[20]. Adenomyosis is a condition different, but mucosa and submucosa, displaced into the lumen
closely related, to endometriosis. It represents a [56] (Fig. 15.5). Further suspicious signs of DE
deep benign myometrial invasion of area of endo- intestinal involvement are the disappearance of the
metrial glands and stroma, with associated hyper- fat tissue plane between the uterus and the anterior
plasia and hypertrophy of surrounding rectosigmoid wall, the loss of the hypointense sig-
myometrium, that leads to uterine enlargement; it nal of the anterior intestinal wall on the
may form nodular lesions or be diffusely distrib- T2-weighted images and the presence of a tissue
uted [80]. DE implants appear as solid nodules of mass extending on the anterior rectosigmoid colon
different size, with irregular margins that lead to wall showing contrast enhancement on
a partial or complete obliteration of the rectouter- T1-weighted images. Contrast enhancement is
ine pouch, because of the strict adhesions. It is variable and depends on the degree of inflamma-
also possible to detect a lateralized fluid tion; moreover, inflammatory reaction causes dis-
collection. tortions of the pelvic anatomy and leads to
162 F. Schirru et al.
adhesion formation [33, 83]. Many authors report tification of the rectosigmoid endometriosis
that both MRI and TVUS are limited in their abil- (respectively, 73% and 90% for MRI and 73% and
ity to detect superficial endometriosis. According 86% for tenderness-guided TVUS) [84, 85]. In
to Abrao et al., TVUS had a sensitivity and speci- addition, MRI examination allows to evaluate the
ficity of 98% and 100% while MRI of 83% and distance between the lesion and the anal junction,
98%, respectively, for detecting rectosigmoid which is fundamental in presurgical planning, as
endometriosis. More recently, Saba et al. has dem- well as the size and number of lesions, and also the
onstrated that MRI and tenderness-guided TVUS depth of intestinal wall infiltration. All these infor-
have similar sensitivity and specificity in the iden- mation is essential for surgical planning.
a b
c d
Fig. 15.5 Rectosigmoid endometriosis in a 34-year-old cap” sign is well visible on sagittal T2-w image (the low
woman with pain during defecation and haematochezia signal-intensity base of the mushroom represents the mus-
synchronized with menses. Sagittal T1-weighted (a), cularis propria while the high-signal-intensity cap is
axial T1-weighted with fat suppression (b), sagittal (c), attributed to the mucosa and submucosa, displaced into
and coronal (d) T2-weighted MR images show hypoin- the lumen). Small intermingled hyperintense foci (arrow-
tense nodular thickening of the rectosigmoid wall that head), due to bloody content, are detected on T1-weighted
adheres to the posterior uterine surface. The “mushroom images with fat suppression
15 Additional Radiological Techniques (MRI) 163
nancies may spread by haematogenous and lym- –– Multiple adnexal cysts with hyperintense
phatic routes or perineural spread. Differential signal on T1-weighted images
diagnosis should consider primitive neoplasms –– One or more adnexal cysts with hyperin-
that originate in different organs (such as colon tense signal on T1-weighted images and
cancer or vaginal squamous cell cancer) or, if the “shading sign” on T2-weighted images
lesion occurs on a scar, with granuloma or der- • “T2 dark spots” finding seems to be highly
moid tumours [49]. specific for chronically haemorrhagic lesions;
it could be considered a useful tool to
differentiate ovarian endometriomas from
15.3 Technical Tips functional haemorrhagic cysts.
• MRI findings suspecting malignant degenera-
For the assessment and evaluation of tion of endometrioma:
endometriosis: –– Enhanced mural nodules (well detected on
contrast-enhanced subtracted images)
• Use MRI as second-line approach, especially –– Loss of “T2-shading” sign on T2-weighted
in symptomatic patients with negative US images
findings, and before surgery for preoperative –– Mural nodule of more than 30 mm in size
workup. –– Interval increase in the size of the cyst
• Fasting (3, 4 or 6 h), dietary preparation (low- • Deep endometriosis should be suspected in
residue regimen on the day before and the day case of:
of examination) and a moderately full urinary –– Haematosalpinx, as it may be the only find-
bladder are recommended; bowel preparation ing in some women
should be considered “best practice”. –– Partial or complete obliteration of the
• Use antispasmodic agents in order to reduce rectouterine pouch with a lateralized fluid
motion artefacts caused by bowel and uterine collection
peristalsis. –– Fixed pelvic organs (such as a fixed retro-
• Vaginal and rectal opacification may be used flexed uterus), posterior displacement of the
for a better visualization of anatomical struc- uterus and ovaries, angulation of bowel loops
tures that are close to each other; however, be and elevation of the posterior vaginal fornix
aware to avoid the presence of small air bub-
bles that could be mistaken for nodular wall
thickening. 15.4 Future Perspectives
• MRI protocol should be composed of:
–– 2D-T2-weighted sequences in the axial, In the future, MRI will have a more important
sagittal and oblique plane role in the assessment of endometriosis due to
–– T1-weighted sequences with and without technical advances and improvement of software.
fat suppression With its great capacity to detect and characterize
–– Half-Fourier single-shot turbo-spin-echo lesions, MRI has to be considered an important
acquisition tool in staging endometriosis and planning ade-
Diffusion-weighted imaging and susceptibility- quate presurgical counselling and treatment. We
weighted imaging may lead to additional postulate that it should reduce the need for diag-
information. nostic laparoscopy, even because the latter cannot
• The use of contrast material is reserved for detect lesions hidden by adhesions (and so not
specific cases (especially in the suspicious of easily accessible at endoscopic viewing) or can-
endometriosis-associated cancer) and there- not even assess the depth of infiltration of perito-
fore depends on the indication to MRI neal lesions. Diffusion weighted imaging (DWI)
examination. has greatly improved the diagnostic value of
• MRI criteria for endometrioma: MR imaging, giving information that allow to
15 Additional Radiological Techniques (MRI) 165
differentiate between benign or malignant lesions. 10. Bulun SE. Endometriosis. N Engl J Med.
Indeed, DWI with ADC measurements could be 2009;360(3):268–79. https://doi.org/10.1056/
NEJMra0804690. Review. PubMed PMID: 19144942.
useful tools in the differentiation between endo- 11. Koninckx PR, Martin DC. Deep endometriosis: a con-
metriosis and other pathologies, but more studies sequence of infiltration or retraction or possibly ade-
are needed in order to establish specific threshold nomyosis externa? Fertil Steril. 1992;58(5):924–8.
in ADC values that allow to differentiate between PubMed PMID: 1426377.
12. Woodward PJ, Sohaey MD, Mezzetti TP. From the
them. Therefore, it is still necessary to prove DWI archives of the AFIP. Endometriosis: radiologic-patho-
and ADC map usefulness in daily practice. logic correlation. Radiographics. 2001;21:193–216.
Diffusion tensor imaging (DTI) studies are 13. Olive DL, Schwartz LB. Endometriosis. N Engl J
increasingly popular among researchers because Med. 1993;328(24):1759–69.
14. Gougoutas CA, Siegelman ES, Hunt J, Outwater
of its ability to provide unique information about EK. Pelvic endometriosis: various manifestations
brain network; recently, even endometriosis and MR imaging findings. AJR Am J Roentgenol.
become an important field of application. Indeed, 2000;175(2):353–8.
DTI with tractography allow to detect changes 15. Agarwal N, Subramanian A. Endometriosis—mor-
phology, clinical presentations and molecular pathol-
and abnormalities in the structure of the sacral ogy. J Lab Physicians. 2010;2(1):1–9.
nerve roots, often site of endometriotic implants. 16. Schifrin BS, Erez S, Moore JG. Teen-age endometrio-
Despite DTI is currently a promising tool to study sis. Am J Obstet Gynecol. 1973;116:973–80.
nerves involvement, continuous studies are neces- 17. Gedgaudas-McClees RK. Gastrointestinal complica-
tions of gynecologic diseases. In: Textbook of gas-
sary to prove and validate its role. trointestinal radiology. Philadelphia: Saunders; 1994.
p. 2559–67.
18. Clement PB. Diseases of the peritoneum. In: Kurman
RJ, editor. Blaustein’s pathology of the female genital
References tract. 4th ed. New York: Springer; 1994. p. 660–80.
30.
1. Giudice LC, Kao LC. Endometriosis. Lancet. 19. Bianchi A, Pulido L, Espín F, Hidalgo LA, Heredia
2004;364(9447):1789–99. Review. A, Fantova MJ, Muns R, Suñol J. [Intestinal endome-
2. Shaw RW. Endometriosis. Current understanding and triosis. Current status]. Cir Esp. 2007;81(4):170–6.
management. Oxford: Blackwell; 1995. Review. Spanish.
3. Venturini PL, Semino A, De Cecco L, editors. 20. Brosens I, Puttemans P, Campo R, Gordts S, Kinkel
Endometriosi: Patofisiologia e Clinica. Carnforth: K. Diagnosis of endometriosis: pelvic endoscopy
Parthenon; 1995. and imaging techniques. Best Pract Res Clin Obstet
4. Olive DL. Endometriosis. Obstet Gynecol Clin North Gynaecol. 2004;18(2):285–303.
Am. 1997;24:219–445. 21. de Venecia C, Ascher SM. Pelvic endometriosis: spec-
5. Venturini PL, Prefumo F. Evers: Endometriosi: dalla trum of magnetic resonance imaging findings. Semin
Ricerca di Base alla Clinica. London: Parthenon; Ultrasound CT MR. 2015;36(4):385–93.
1998. 22. Bazot M, Bharwani N, Huchon C, Kinkel K, Cunha
6. Venturini P, Evers JLH. Endometriosis: basic research TM, Guerra A, Manganaro L, Buñesch L, Kido
and clinical practice. London: The Parthenon A, Togashi K, Thomassin-Naggara I, Rockall
Publishing Group; 1999. AG. European society of urogenital radiology (ESUR)
7. Menni K, Facchetti L, Cabassa P. Extragenital endo- guidelines: MR imaging of pelvic endometriosis. Eur
metriosis: assessment with MR imaging. A picto- Radiol. 2017;27(7):2765–75. https://doi.org/10.1007/
rial review. Br J Radiol. 2016;89(1060):20150672. s00330-016-4673-z.
https://doi.org/10.1259/bjr.20150672. Epub 2016 23. Suzuki S, Yasumoto M, Matsumoto R, Andoh
Feb 5. Review. PubMed PMID: 26846303; PubMed A. MR findings of ruptured endometrial cyst: com-
Central PMCID: PMC4846200. parison with tubo-ovarian abscess. Eur J Radiol.
8. Del Frate C, Girometti R, Pittino M, Del Frate G, 2012;81(11):3631–7. https://doi.org/10.1016/j.
Bazzocchi M, Zuiani C. Deep retroperitoneal pelvic ejrad.2011.06.013.
endometriosis: MR imaging appearance with laparo- 24. Zanardi R, Del Frate C, Zuiani C, Bazzocchi
scopic correlation. Radiographics. 2006;26(6):1705– M. Staging of pelvic endometriosis based on MRI
18. Review. PubMed PMID:17102045. findings versus laparoscopic classification according
9. Exacoustos C, Manganaro L, Zupi E. Imaging for the to the American Fertility Society. Abdom Imaging.
evaluation of endometriosis and adenomyosis. Best 2003;28(5):733–42.
Pract Res Clin Obstet Gynaecol. 2014;28(5):655–81. 25. Carbognin G, Guarise A, Minelli L, Vitale I, Malagó
https://doi.org/10.1016/j.bpobgyn.2014.04.010. Epub R, Zamboni G, Procacci C. Pelvic endometriosis: US
2014 May 2. Review. PubMed PMID: 24861247.
166 F. Schirru et al.
and MRI features. Abdom Imaging. 2004;29(5):609– 37. Bazot M, Gasner A, Ballester M, Daraï E. Value of
18. Epub 2004 May 27. Review. thin-section oblique axial T2-weighted magnetic res-
26. Guerriero S, Ajossa S, Orozco R, Perniciano M, Jurado onance images to assess uterosacral ligament endo-
M, Melis GB, Alcazar JL. Accuracy of transvaginal metriosis. Hum Reprod. 2011;26(2):346–53. https://
ultrasound for diagnosis of deep endometriosis in doi.org/10.1093/humrep/deq336.
the rectosigmoid: systematic review and meta-anal- 38. Bazot M, Jarboui L, Ballester M, Touboul C,
ysis. Ultrasound Obstet Gynecol. 2016;47(3):281–9. Thomassin-Naggara I, Daraï E. The value of MRI
https://doi.org/10.1002/uog.15662. Epub 2015 Nov 4. in assessing parametrial involvement in endome-
Review. PubMed PMID: 26213903. triosis. Hum Reprod. 2012;27(8):2352–8. https://doi.
27. Guerriero S, Spiga S, Ajossa S, Peddes C, Perniciano org/10.1093/humrep/des211.
M, Soggiu B, De Cecco CN, Laghi A, Melis GB, Saba 39. Kido A, Togashi K, Nishino M, Miyake K, Koyama
L. Role of imaging in the management of endometrio- T, Fujimoto R, Iwasaku K, Fujii S, Hayakawa K. Cine
sis. Minerva Ginecol. 2013;65(2):143–66. MR imaging of uterine peristalsis in patients with
28. Hottat N, Larrousse C, Anaf V, Noël JC, Matos C, endometriosis. Eur Radiol. 2007;17(7):1813–9. Epub
Absil J, Metens T. Endometriosis: contribution of 2006 Nov 22.
3.0-T pelvic MR imaging in preoperative assess- 40. Nakai A, Togashi K, Kosaka K, Kido A, Hiraga A,
ment—initial results. Radiology. 2009;253(1):126– Fujiwara T, Koyama T, Fujii S. Uterine peristalsis:
34. https://doi.org/10.1148/radiol.2531082113. comparison of transvaginal ultrasound and two dif-
29. Manganaro L, Fierro F, Tomei A, Irimia D, Lodise P, ferent sequences of cine MR imaging. J Magn Reson
Sergi ME, Vinci V, Sollazzo P, Porpora MG, Delfini Imaging. 2004;20(3):463–9.
R, Vittori G, Marini M. Feasibility of 3.0T pelvic MR 41. Leyendecker G, Kunz G, Wildt L, Beil D, Deininger
imaging in the evaluation of endometriosis. Eur J H. Uterine hyperperistalsis and dysperistalsis as dys-
Radiol. 2012;81(6):1381–7. https://doi.org/10.1016/j. functions of the mechanism of rapid sperm transport
ejrad.2011.03.049. in patients with endometriosis and infertility. Hum
30. Rousset P, Peyron N, Charlot M, Chateau F, Golfier Reprod. 1996;11(7):1542–51.
F, Raudrant D, Cotte E, Isaac S, Réty F, Valette 42. Katayama M, Masui T, Kobayashi S, Ito T, Sakahara
PJ. Bowel endometriosis: preoperative diagnos- H, Nozaki A, Kabasawa H. Evaluation of pelvic
tic accuracy of 3.0-T MR enterography—initial adhesions using multiphase and multislice MR imag-
results. Radiology. 2014;273(1):117–24. https://doi. ing with kinematic display. AJR Am J Roentgenol.
org/10.1148/radiol.14132803. 2001;177(1):107–10.
31. Cornfeld D, Weinreb J. Simple changes to 1.5-T MRI 43. Coutinho AC Jr, Krishnaraj A, Pires CE, Bittencourt
abdomen and pelvis protocols to optimize results at LK, Guimarães AR. Pelvic applications of dif-
3 T. AJR Am J Roentgenol. 2008;190(2):W140–50. fusion magnetic resonance images. Magn Reson
https://doi.org/10.2214/AJR.07.2903. Imaging Clin N Am. 2011;19(1):133–57. https://doi.
32. Schneider C, Oehmke F, Tinneberg HR, Krombach org/10.1016/j.mric.2010.10.003.
GA. MRI technique for the preoperative evaluation of 44. Balaban M, Idilman IS, Toprak H, Unal O, Ipek A,
deep infiltrating endometriosis: current status and pro- Kocakoc E. The utility of diffusion-weighted mag-
tocol recommendation. Clin Radiol. 2016;71(3):179– netic resonance imaging in differentiation of endo-
94. https://doi.org/10.1016/j.crad.2015.09.014. metriomas from hemorrhagic ovarian cysts. Clin
33. Chamié LP, Blasbalg R, Pereira RM, Warmbrand Imaging. 2015;39(5):830–3. https://doi.org/10.1016/j.
G, Serafini PC. Findings of pelvic endometriosis clinimag.2015.05.003.
at transvaginal US, MR imaging, and laparoscopy. 45. Manganaro L, Porpora MG, Vinci V, Bernardo S,
Radiographics. 2011;31(4):E77–100. https://doi. Lodise P, Sollazzo P, Sergi ME, Saldari M, Pace G,
org/10.1148/rg.314105193. Vittori G, Catalano C, Pantano P. Diffusion tensor
34. Coutinho A Jr, Bittencourt LK, Pires CE, Junqueira F, imaging and tractography to evaluate sacral nerve
Lima CM, Coutinho E, Domingues MA, Domingues root abnormalities in endometriosis-related pain: a
RC, Marchiori E. MR imaging in deep pelvic pilot study. Eur Radiol. 2014;24(1):95–101. https://
endometriosis: a pictorial essay. Radiographics. doi.org/10.1007/s00330-013-2981-0.
2011;31(2):549–67. https://doi.org/10.1148/ 46. Solak A, Sahin N, Genç B, Sever AR, Genç M,
rg.312105144. Sivrikoz ON. Diagnostic value of susceptibility-
35. Chamié LP, Blasbalg R, Gonçalves MO, Carvalho weighted imaging of abdominal wall endometriomas
FM, Abrão MS, de Oliveira IS. Accuracy of magnetic during the cyclic menstrual changes: a preliminary
resonance imaging for diagnosis and preoperative study. Eur J Radiol. 2013;82(9):e411–6. https://doi.
assessment of deeply infiltrating endometriosis. Int J org/10.1016/j.ejrad.2013.04.030.
Gynaecol Obstet. 2009;106(3):198–201. https://doi. 47. Takeuchi M, Matsuzaki K, Harada M. Susceptibility-
org/10.1016/j.ijgo.2009.04.013. weighted MRI of extra-ovarian endometriosis: prelim-
36. Bazot M, Darai E, Hourani R, Thomassin I, Cortez inary results. Abdom Imaging. 2015;40(7):2512–6.
A, Uzan S, Buy JN. Deep pelvic endometriosis: MR https://doi.org/10.1007/s00261-015-0378-z.
imaging for diagnosis and prediction of extension of 48. Grammatikakis I, Evangelinakis N, Salamalekis
disease. Radiology. 2004;232(2):379–89. G, Tziortzioti V, Samaras C, Chrelias C, Kassanos
15 Additional Radiological Techniques (MRI) 167
D. Prevalence of severe pelvic inflammatory disease extraovarian endometriosis: a review. Eur J Surg
and endometriotic ovarian cysts: a 7-year retrospective Oncol. 2006;32(1):6–11. Epub 2005 Nov 11.
study. Clin Exp Obstet Gynecol. 2009;36(4):235–6. 63. SCOTT RB. Malignant changes in endometriosis.
49. McDermott S, Oei TN, Iyer VR, Lee SI. MR imag- Obstet Gynecol. 1953;2(3):283–9. PubMed PMID:
ing of malignancies arising in endometriomas 13087921.
and extraovarian endometriosis. Radiographics. 64. Tanaka YO, Okada S, Yagi T, Satoh T, Oki A,
2012;32(3):845–63. https://doi.org/10.1148/ Tsunoda H, Yoshikawa H. MRI of endometriotic
rg.323115736. cysts in association with ovarian carcinoma. AJR
50. Kobayashi H, Sumimoto K, Moniwa N, Imai M, Am J Roentgenol. 2010;194(2):355–61. https://doi.
Takakura K, Kuromaki T, Morioka E, Arisawa K, org/10.2214/AJR.09.2985.
Terao T. Risk of developing ovarian cancer among 65. Darvishzadeh A, McEachern W, Lee TK, Bhosale
women with ovarian endometrioma: a cohort P, Shirkhoda A, Menias C, Lall C. Deep pelvic
study in Shizuoka, Japan. Int J Gynecol Cancer. endometriosis: a radiologist’s guide to key imaging
2007;17(1):37–43. features with clinical and histopathologic review.
51. Kobayashi H, Sumimoto K, Kitanaka T, Yamada Abdom Radiol (NY). 2016;41(12):2380–400.
Y, Sado T, Sakata M, Yoshida S, Kawaguchi R, 66. Turocy JM, Benacerraf BR. Transvaginal sonography
Kanayama S, Shigetomi H, Haruta S, Tsuji Y, Ueda in the diagnosis of deep infiltrating endometriosis: a
S, Terao T. Ovarian endometrioma—risks factors of review. J Clin Ultrasound. 2017;45(6):313–8. https://
ovarian cancer development. Eur J Obstet Gynecol doi.org/10.1002/jcu.22483.
Reprod Biol. 2008;138(2):187–93. Epub 2007 Dec 26. 67. Choudhary S, Fasih N, Papadatos D, Surabhi
52. Takeuchi M, Matsuzaki K, Nishitani H. Susceptibility- VR. Unusual imaging appearances of endometriosis.
weighted MRI of endometrioma: preliminary results. AJR Am J Roentgenol. 2009;192(6):1632–44. https://
AJR Am J Roentgenol. 2008;191(5):1366–70. https:// doi.org/10.2214/AJR.08.1560.
doi.org/10.2214/AJR.07.3974. 68. Fritsch H. Clinical anatomy of the female pelvis. In:
53. Togashi K, Nishimura K, Kimura I, Tsuda Y, Hamm B, Forstner R, editors. MRI and CT of the
Yamashita K, Shibata T, Nakano Y, Konishi J, Konishi female pelvis. New York: Springer; 2007. p. 1–24.
I, Mori T. Endometrial cysts: diagnosis with MR 69. Balleyguier C, Chapron C, Dubuisson JB, Kinkel
imaging. Radiology. 1991;180(1):73–8. K, Fauconnier A, Vieira M, Hélénon O, Menu
54. Siegelman ES, Outwater EK. Tissue characteriza- Y. Comparison of magnetic resonance imaging and
tion in the female pelvis by means of MR imaging. transvaginal ultrasonography in diagnosing blad-
Radiology. 1999;212(1):5–18. der endometriosis. J Am Assoc Gynecol Laparosc.
55. Nishimura K, Togashi K, Itoh K, Fujisawa I, Noma S, 2002;9(1):15–23.
Kawamura Y, Nakano Y, Itoh H, Torizuka K, Ozasa 70. Le Tohic A, Chis C, Yazbeck C, Koskas M, Madelenat
H. Endometrial cysts of the ovary: MR imaging. P, Panel P. [Bladder endometriosis: diagnosis and
Radiology. 1987;162(2):315–8. treatment. A series of 24 patients]. Gynecol Obstet
56. Corwin MT, Gerscovich EO, Lamba R, Wilson M, Fertil. 2009;37(3):216–21. https://doi.org/10.1016/j.
McGahan JP. Differentiation of ovarian endometrio- gyobfe.2009.01.018.
mas from hemorrhagic cysts at MR imaging: utility of 71. Fedele L, Bianchi S, Zanconato G, Bergamini V,
the T2 dark spot sign. Radiology. 2014;271(1):126– Berlanda N, Carmignani L. Long-term follow-up after
32. https://doi.org/10.1148/radiol.13131394. conservative surgery for bladder endometriosis. Fertil
57. Siegelman ES, Oliver ER. MR imaging of endo- Steril. 2005;83(6):1729–33.
metriosis: ten imaging pearls. Radiographics. 72. Saba L, Sulcis R, Melis GB, de Cecco CN,
2012;32(6):1675–91. https://doi.org/10.1148/ Laghi A, Piga M, Guerriero S. Endometriosis:
rg.326125518. the role of magnetic resonance imaging.
58. Outwater EK, Dunton CJ. Imaging of the ovary and Acta Radiol. 2015;56(3):355–67. https://doi.
adnexa: clinical issues and applications of MR imag- org/10.1177/0284185114526086.
ing. Radiology. 1995;194(1):1–18. 73. Thonnon C, Philip CA, Fassi-Fehri H, Bisch C, Coulon
59. Sugimura K, Okizuka H, Imaoka I, Kaji Y, Takahashi A, de Saint-Hilaire P, Dubernard G. Three-dimensional
K, Kitao M, Ishida T. Pelvic endometriosis: detec- ultrasound in the management of bladder endome-
tion and diagnosis with chemical shift MR imaging. triosis. J Minim Invasive Gynecol. 2015;22(3):403–9.
Radiology. 1993;188(2):435–8. https://doi.org/10.1016/j.jmig.2014.10.021.
60. Brosens I. Endometriosis and the outcome of in vitro 74. Kołodziej A, Krajewski W, Dołowy Ł, Hirnle
fertilization. Fertil Steril. 2004;81:1198–20. L. Urinary tract endometriosis. Urol J.
61. Ueda Y, Enomoto T, Miyatake T, Fujita M, Yamamoto 2015;12(4):2213–7.
R, Kanagawa T, Shimizu H, Kimura T. A retrospec- 75. Umaria N, Olliff JF. Imaging features of pelvic endo-
tive analysis of ovarian endometriosis during preg- metriosis. Br J Radiol. 2001;74(882):556–62. Review.
nancy. Fertil Steril. 2010;94(1):78–84. https://doi. 76. Balleyguier C, Roupret M, Nguyen T, Kinkel K,
org/10.1016/j.fertnstert.2009.02.092. Helenon O, Chapron C. Ureteral endometriosis: the
62. Benoit L, Arnould L, Cheynel N, Diane B, Causeret S, role of magnetic resonance imaging. J Am Assoc
Machado A, Collin F, Fraisse J, Cuisenier J. Malignant Gynecol Laparosc. 2004;11(4):530–6.
168 F. Schirru et al.
77. Sillou S, Poirée S, Millischer AE, Chapron C, Hélénon sis of recto-sigmoid endometriosis. J Magn Reson
O. Urinary endometriosis: MR imaging appearance Imaging. 2012;35(2):352–60. https://doi.org/10.1002/
with surgical and histological correlations. Diagn jmri.22832.
Interv Imaging. 2015;96(4):373–81. https://doi. 86. Yoon J, Lee YS, Chang HS, Park CS. Endometriosis of
org/10.1016/j.diii.2014.11.010. the appendix. Ann Surg Treat Res. 2014;87(3):144–7.
78. Foti PV, Ognibene N, Spadola S, Caltabiano R, Farina https://doi.org/10.4174/astr.2014.87.3.144.
R, Palmucci S, Milone P, Ettorre GC. Non-neoplastic 87. Soylu L, Aydın OU, Aydın S, Özçay N. Invagination of
diseases of the fallopian tube: MR imaging with the appendix due to endometriosis presenting as acute
emphasis on diffusion-weighted imaging. Insights appendicitis. Ulus Cerrahi Derg. 2013;30(2):106–8.
Imaging. 2016;7(3):311–27. https://doi.org/10.1007/ https://doi.org/10.5152/UCD.2013.19.
s13244-016-0484-7. 88. Hensen JH, Van Breda Vriesman AC, Puylaert
79. Gui B, Valentini AL, Ninivaggi V, Marino M, JB. Abdominal wall endometriosis: clinical presenta-
Iacobucci M, Bonomo L. Deep pelvic endometriosis: tion and imaging features with emphasis on sonogra-
don’t forget round ligaments. Review of anatomy, phy. AJR Am J Roentgenol. 2006;186(3):616–20.
clinical characteristics, and MR imaging features. 89. Barrow TA, Elsayed M, Liong SY, Sukumar
Abdom Imaging. 2014;39(3):622–32. https://doi. SA. Complex abdominopelvic endometriosis:
org/10.1007/s00261-014-0091-3. the radiologist’s perspective. Abdom Imaging.
80. Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clin- 2015;40(7):2541–56. https://doi.org/10.1007/
ical review of a challenging gynecologic condition. J s00261-015-0413-0.
Minim Invasive Gynecol. 2016;23(2):164–85. https:// 90. Badawy SZ, Shrestha P. Recurrent catamenial pneu-
doi.org/10.1016/j.jmig.2015.09.018. mothorax suggestive of pleural endometriosis. Case
81. Chamié LP, Pereira RM, Zanatta A, Serafini Rep Obstet Gynecol. 2014;2014:756040. https://doi.
PC. Transvaginal US after bowel preparation for org/10.1155/2014/756040.
deeply infiltrating endometriosis: protocol, imag- 91. Pramanik SR, Mondal S, Paul S, Joycerani
ing appearances, and laparoscopic correlation. D. Primary umbilical endometriosis: a rarity. J
Radiographics. 2010;30(5):1235–49. https://doi. Hum Reprod Sci. 2014;7(4):269–71. https://doi.
org/10.1148/rg.305095221. org/10.4103/0974-1208.147495.
82. Chapron C, Fauconnier A, Vieira M, Barakat H, 92. Ding Y, Gibbs J, Xiong G, Guo S, Raj S, Bui
Dousset B, Pansini V, Vacher-Lavenu MC, Dubuisson MM. Endometriosis mimicking soft-tissue neo-
JB. Anatomical distribution of deeply infiltrating plasms: a potential diagnostic pitfall. Cancer Control.
endometriosis: surgical implications and proposition 2017;24(1):83–8.
for a classification. Hum Reprod. 2003;18(1):157–61. 93. Heaps JM, Nieberg RK, Berek JS. Malignant neo-
83. Trippia CH, Zomer MT, Terazaki CR, Martin RL, plasms arising in endometriosis. Obstet Gynecol.
Ribeiro R, Kondo W. Relevance of imaging exami- 1990;75(6):1023–8.
nations in the surgical planning of patients with 94. Modesitt SC, Tortolero-Luna G, Robinson JB,
bowel endometriosis. Clin Med Insights Reprod Gershenson DM, Wolf JK. Ovarian and extraovar-
Health. 2016;10:1–8. https://doi.org/10.4137/CMRH. ian endometriosis-associated cancer. Obstet Gynecol.
S29472. 2002;100(4):788–95.
84. Abrao MS, Gonçalves MO, Dias JA Jr, Podgaec S, 95. Brooks JJ, Wheeler JE. Malignancy arising in extrago-
Chamie LP, Blasbalg R. Comparison between clinical nadal endometriosis: a case report and summary of
examination, transvaginal sonography and magnetic the world literature. Cancer. 1977;40(6):3065–73.
resonance imaging for the diagnosis of deep endome- 96. Sala E, Rockall A, Rangarajan D, Kubik-Huch
triosis. Hum Reprod. 2007;22(12):3092–7. RA. The role of dynamic contrast-enhanced and dif-
85. Saba L, Guerriero S, Sulcis R, Pilloni M, Ajossa fusion weighted magnetic resonance imaging in the
S, Melis G, Mallarini G. MRI and “tenderness female pelvis. Eur J Radiol. 2010;76(3):367–85.
guided” transvaginal ultrasonography in the diagno- https://doi.org/10.1016/j.ejrad.2010.01.026.
Biomarkers in Endometriosis
16
Vicki Nisenblat and M. Louise Hull
reliable low-invasive test for endometriosis is as either diseased or non-diseased 100% of the
expected to minimize surgical risks, reduce diag- time. In practice, false-positive and false-nega-
nostic delay, and provide an opportunity for ear- tive tests create a misclassification of some indi-
lier interventions with potential to improve viduals in the non-diseased and diseased groups.
patient outcomes and to decrease healthcare- The basic measures of how well a test discrimi-
related costs. Furthermore, the ability to assess nates between disease and non-disease states
the progression of endometriosis in a noninvasive include sensitivity, defined as the proportion of
way would advance clinical research in endome- all patients with the disease who indeed have a
triosis, including development of new effective positive test result, and specificity, defined as the
therapeutic and preventive strategies. proportion of all patients without the disease who
The literature on low-invasive peripheral have a negative test result. Sensitivity and speci-
and endometrial biomarkers and on imaging ficity are independent of the prevalence of the
diagnostic tests for endometriosis is growing, disease and are commonly used in the diagnostic
with a steady stream of new reports on accurate studies to evaluate and compare the performance
diagnostic tests. Although none of the pro- of different tests. A trade-off exists between the
posed tests have been considered sufficiently sensitivity and specificity of index test as their
accurate to legitimately replace laparoscopy in values vary inversely in relation to the cutoff
everyday practice, imaging tests are being point chosen to define a positive or negative
increasingly employed as a diagnostic adjunct result.
to surgery, and their use is being progressively The purpose of the test and the clinical conse-
explored. quences of under- and overdiagnosis of the con-
This chapter provides a synthesis of the up-to- dition determines the level of diagnostic
date research evidence on diagnostic accuracy of performance required for a clinically useful test.
low-invasive tests for endometriosis. It aims to In endometriosis, a noninvasive test could be
answer the question whether any low-invasive used as (1) a replacement test which replaces
diagnostic tests, either individually or in combi- diagnostic laparoscopy as it has similar or better
nation, may be considered sufficiently accurate to accuracy and (2) a triage test, used to identify the
either replace laparoscopy as a diagnostic test for individuals who likely to benefit from laparos-
endometriosis or be used as a triage test to copy, which may alter the number of those who
improve selection of women for a diagnostic sur- are offered a surgical intervention [10]. A replace-
gery. In addition, this chapter evaluates the appli- ment test is expected to have high sensitivity and
cability of the presented findings to clinical specificity, while triage tests could be highly sen-
practice and provides insight regarding future sitive but less specific or vice versa. A high sensi-
research in the field. tivity triage test rules out the condition if the test
is negative, but a positive result has little diagnos-
tic value (SnOUT test). Alternatively, a high
16.2 Quantifying Performance specificity triage test rules conditions “in” if the
of the Diagnostic Tests test is positive but is less informative if the result
for Endometriosis is negative (SpIN test). Both types of triage test
are clinically useful and can be implemented in
To discuss diagnostic test accuracy studies in a sequential manner to optimize a diagnostic algo-
meaningful way, the tests need to be interpreted rithm (Fig. 16.1).
in an appropriate clinical and methodological To assist with the interpretation of the diag-
framework. Diagnostic test accuracy refers to the nostic estimates and to put the results into clini-
degree of agreement between the diagnostic per- cal context, a series of Cochrane Library
formance of the test under study (index test) and diagnostic test reviews proposed the cutoff val-
that of a clinical gold standard (reference test). ues for the potentially clinically significant diag-
The ideal diagnostic test classifies all individuals nostic estimates. The diagnostic threshold for a
16 Biomarkers in Endometriosis 171
replacement test for endometriosis was deter- Highly diagnostic accuracy on its own is not
mined as a sensitivity ≥0.94 and a specificity sufficient to determine that a test is clinically use-
≥0.79, which is the same diagnostic accuracy ful, and the value of diagnostic tests ultimately
conferred by a diagnostic laparoscopy [6]. It was lies in their effect on patient outcomes. Evaluation
assumed that a 5% error in the correct diagnosis of the diagnostic test to advance the markers from
was statistically and clinically acceptable for a benchtop to clinically relevant products usually
triage test, whereas diagnostic uncertainty comprises a series of sequential steps to assess
should be limited to less than 50% of individu- clinical, financial, psychological, and societal
als. Therefore, the criteria for triage tests were consequences of the test [11]. Diagnostic perfor-
set as a sensitivity ≥0.95 and a specificity ≥0.50 mance of the test is an important initial step in the
for a SnOUT test and a sensitivity ≥0.50 and a pipeline of test evaluation and thus has to rely on
specificity ≥0.95 for a SpIN test [10]. high-quality reproducible evidence.
Furthermore, there is no consensus on optimal endometriosis and identified miRNA panels with
timing of the test in relation to phase of the men- high diagnostic estimates [30–33]. Each study,
strual cycle. Koninckx was the first to show that however, reported different set of miRNA bio-
plasma concentrations of CA-125 were higher markers, and the results could not be replicated
during menses than during follicular or mid- by others (personal communication). It becomes
luteal phase in both control and endometriosis increasingly evident that emerging advances in
groups and observed more pronounced differ- technology and bioinformatics provide a unique
ences in mild forms of the disease [22]. Since opportunity for elucidating biological pathways
then, the literature on inter-cycle differences of and discovering clinical biomarkers. Optimization
CA-125 remains inconsistent, and there is sub- and standardization of the laboratory and analyti-
stantial variation between the studies with regard cal methods with a focus on reproducible research
to timing of the test in menstrual cycle. Overall, are important to advance the preliminary discov-
biases in study design and limitations in report- eries into clinical applications.
ing in most studies contributed to low quality of A limited number of urinary tests have been
current evidence. The diagnostic role of CA- assessed for their potential to diagnose endome-
125 in endometriosis, either as a single test or triosis. A Cochrane Library diagnostic test accu-
when integrated in more complex diagnostic racy review of 8 studies with a total of 646
algorithms, remains elusive and needs to be participants evaluated 6 tests: enolase 1 (NNE),
established in patients with different clinical vitamin D binding protein (VDBP), cytokeratin
phenotypes. 19 (CK 19 or CYFRA 21-1), vascular endothelial
A number of biomarkers demonstrated high growth factor (VEGF), tumor necrosis factor-
diagnostic estimates for pelvic endometriosis or alpha (TNF-α), and urinary proteome [15]. Most
endometrioma in individual studies (Table 16.1). were evaluated in small individual studies and
Future research needs to confirm their diagnostic meta-analyses could not be performed. Of these,
value and in endometriosis using high-quality NNE, VDBP, and cytoskeleton molecule CK-19
diagnostic test accuracy methodologies in large showed low diagnostic estimates, whereas VEGF
cohorts of well-characterized patients. The list of and TNF-α did not distinguish women with and
blood-derived biomarkers continues to expand as without endometriosis and their diagnostic accu-
high-throughput profiling of the metabolome racy was not assessed.
[23–25], proteome [26–29], and miRNAs, the Matrix-enhanced laser desorption/ionization
posttranscriptional regulators of gene expression time-of-flight mass spectrometry (MALDI-
[30–33], becomes increasingly accessible. TOF-MS) was used to identify the urinary pro-
The high-throughput platforms carry great teome in two studies with some variation in
potential, since they enable comprehensive cov- methodology between studies and some inconsis-
erage of molecules of interest in small amount of tencies with regard to the identified peptide mark-
biological material. However, the identification ers. In one study, a test that included five urinary
and characterization of metabolic and proteomic peptides of 1433.9 Da, 1599.4 Da, 2085.6 Da,
fingerprint molecules is a challenging task, and 6798.0 Da, and 3217.2 Da had a sensitivity of
methodology is still under development. 0.91 [95%CI 0.59, 1.00] and a specificity of 0.93
Unstandardized approach to sample processing [95%CI 0.66, 1.00] [34]. Although clinically
and data handling and variation in analytical attractive, these findings require replication using
techniques across studies invariably limit transla- similar technical and analytical approaches
tional application of the “omics” science. High- before their value in clinical practice can be
throughput experiments have limited established. Recent reports indicated that nuclear
reproducibility and are rarely validated in large magnetic resonance (NMR) spectroscopy can be
independent cohorts. For example, several used to reveal the metabolome of women with
research groups have examined potential use of endometriosis in urine samples, but the diagnos-
circulating miRNA as diagnostic marker for tic validity of the test is yet to be established [35].
174 V. Nisenblat and M. L. Hull
Table 16.1 Peripheral and endometrial biomarkers of endometriosis that require further validation [14, 17, 44]
Blood Angiogenesis and growth • Vascular endothelial growth factor (VEGF) >680 pg/ml and
biomarkers markers >236 pg/ml
• Brain-derived neurotrophic factor (BDNF)
High-throughput markers • Metabolome signatures
• Proteome signatures
Immune system and • Interleukin-6 (IL-6) >12.2 pg/ml
inflammatory markers
Oxidative stress markers • Paraoxonase-1 (PON-1) <141.5 U/l
• Carbonyls <14.9 μM
Post-transcriptional • miR-9*
regulators of gene expression • miR-141*
(miRNAs) • miR-145*
• miR-20a
• miR-22
• miR-532-3p
Tumor markers • CA-125 (cut-off value > 43 U/ml)
Combination of several • Interleukin-6 (IL-6) >12.2 pg/ml + Tumor necrosis factor-α
blood tests (TNF-α) > 12.45 pg/ml
• IL-6 > 12.2 pg/ml + C-reactive protein (CRP) >438 μg/ml
• TNF-α > 12.45 pg/ml + CRP > 438 μg/ml
• CA-125 + Syntaxin-5 (STX-5) + Laminin-1 (LN-1)
• IL-6 > 12.2 pg/ml + TNF-α > 12.45 pg/ml + CRP > 438 μg/ml
• CA-125 > 17.6 IU/ml + VEGF > 236 pg/ml
• CA-125 + CA-19-9 + Survivin
• CA-125 > 50 IU/ml + C-C motif receptor-
1(CCR1) > 1.16 + Monocyte chemotactic protein-1 (MCP-
1) > 140 pg/ml
• CA-125 > 20 IU/ml + MCP-1 > 152.744 pg/ml + leptin > 3.14 ng/
ml
• CA-125 + IL-8 + TNF-α
• CA-125 + CA-19.9 + IL-6 + IL-8 + TNF-α + CRP
• miR-199a + miR-542-3p
• miR-199a + miR-122 + miR-145* + miR-542-3p
Tests that differentiate • Urocortin > 29 pg/ml
endometrioma from other • Urocortin > 33 pg/ml
benign ovarian cysts • Follistatin > 1433 pg/ml
• CA-125 > 30 U/ml and >36 U/ml
• CA-125 ≥ 25 U/ml + CA-19.9 ≥ 22 U/ml
Urinary High-throughput markers • Proteome signatures
biomarkers
Endometrial High-throughput markers • Proteome signatures
biomarkers Hormonal markers • 17-β hydroxysteroid dehydrogenase type 2 gene (17βHSD2)
Immune system and • Interleukin-1 receptor type II gene (IL-1R2)
inflammatory markers
Myogenic markers • Caldesmon
Neural and nerve sheath • Protein gene product 9.5 (PGP 9.5)
markers • Vasoactive intestinal polypeptide (VIP)
• Calcitonin gene-related protein (CGRP)
• Substance P (SP)
• Neuropeptide Y (NPY)
• Combined test (VIP + PGP 9.5 + SP)
cycle, which was associated with decreased other biomarkers were assessed in single studies
endometrial receptivity [36–38]. Dysregulated and could not be statistically evaluated in any
gene expression profiles and changes in hor- meaningful way. CYP19 (8 studies, 444 women)
mone-responsive, gene regulatory pathways were had a mean sensitivity of 0.77 (95% CI 0.70,
also identified in eutopic endometrium from 0.85) and a specificity of 0.74 (95% CI 0.65, 84).
endometriosis [39]. An analysis of the DNA PGP 9.5 (7 studies, 361 women) showed a mean
methylome in endometrium from women with sensitivity of 0.96 (95% CI 0.91, 1.00) and a
endometriosis and disease-free individuals specificity of 0.86 (95% CI 0.70, 1.00). While the
revealed different methylation patterns that fluc- pooled estimates for PGP 9.5 suggest it could
tuated across the phases of the menstrual cycle replace surgical diagnosis, there was significant
indicative of aberrant epigenetic regulation of the diversity in the diagnostic estimates between the
endometrium in endometriosis [40]. studies. It has been noted that PGP 9.5 expression
The inflammatory and hypoxic peritoneal is highly sensitive to variation in endometrial
environment identified in endometriosis was sampling and a narrow full-thickness biopsy with
linked to an aberrant expression of chemokines, an adequate amount of stroma is critical to its
cytokines, growth factors, and immune cells in detection. PGP 9.5 expression is also influenced
eutopic endometrium that are involved in immune by the microscopy method used and optimization
response, proliferation, cell migration, and neo- of the assay as studies that utilized conventional
vascularization [10]. Secretomic approaches light microscopy showed lower diagnostic esti-
have characterized protein composition of the mates [43] and some immunohistochemical
endometrial secretions and revealed the presence assays did not demonstrate a difference in PGP
of cytokines, growth factors, ions, carbohydrates, 9.5 staining between groups [44]. Thus, while the
and steroids, in human uterine fluid [41]. Taken data for PGP 9.5 are encouraging, this biomarker
together, these observations support the premise needs further validation in large independent
that eutopic endometrium and aspirated uterine high-quality studies using standardized endome-
fluid could contain diagnostic biomarkers rele- trial sampling and laboratory methods.
vant to endometriosis. Several additional biomarkers assessed in
A Cochrane Library diagnostic test accuracy individual studies displayed high diagnostic
review explored 95 endometriosis-associated bio- potential (Table 16.1). Additional work to com-
markers in eutopic endometrium and menstrual prehensively assess these biomarkers would be
fluid [42]. Included were angiogenesis factor pro- important to confirm their diagnostic role.
kineticin 1 (PROK-1), cell adhesion molecules Overall, most studies had major methodological
(integrins α3β1, α4β1, β1, and α6), DNA repair flaws, and the data should be interpreted with
molecule human telomerase reverse transcriptase caution.
(hTERT), endometrial and mitochondrial pro- Nonstandard methods of sample collection
teome, tumor marker (CA-125), inflammatory and processing, sampling at different phases of
marker interleukin-1 receptor type II (IL-1R2), the menstrual cycle, and inconsistency in pheno-
and myogenic marker caldesmon (CALD-1). typing the samples across studies lead to hetero-
Other hormonal markers (aromatase cytochrome geneity in papers that report the diagnostic
P450 (CYP19), 17β-hydroxysteroid dehydroge- accuracy of endometrial biomarkers. The method
nase type 2 (17βHSD2), and estrogen receptors of obtaining endometrial sample appeared to
(ER-α, ER-β)) and neural markers (protein gene influence the results of PGP 9.5, and this may be
product 9.5 (PGP 9.5), vasoactive intestinal poly- an issue for other biomarkers. Furthermore,
peptide (VIP), calcitonin gene-related protein different uterine or pelvic pathologies such as
(CGRP), substance P (SP), neuropeptide Y (NPY), such as leiomyoma or adenomyosis could engen-
and neurofilament (NF)) were also assessed. der overlapping endometrial aberrations.
The only markers with sufficient data for a Uterine fluid has been increasingly explored
meta-analysis were PGP 9.5 and CYP19 as the using proteomic and metabolomics methods to
176 V. Nisenblat and M. L. Hull
try and identify biomarkers of endometriosis. To decreased pelvic organ mobility indicate the
date there are no identified biomarkers in men- presence of endometriosis in specific clinical
strual fluid that distinguish women with and context.
without endometriosis with an acceptable sensi- In addition to their ability to identify endome-
tivity and specificity. triosis lesions in a noninvasive way, imaging tests
carry substantial advantages in preoperative
assessment of women with clinically suspected
16.3.3 Concluding Remarks deep endometriosis. In severe forms of the dis-
on Biomarkers ease, proper pelvic visualization at laparoscopy
for Endometriosis can be obscured by adhesions, while preoperative
lesion mapping can assist with completeness of
In summary, none of the peripheral or endome- surgical treatment. Furthermore, identifying deep
trial biomarkers can be used in clinical practice infiltrating lesions of the bowel, bladder, or ureter
outside a research setting. CA-125, the most can improve preoperative planning and patient
studied biomarker, could serve as a rule in triage counseling, which allows to establish appropriate
test (SpIN) , but the quality of CA-125 literature referral pathways and to utilize multidisciplinary
had not sufficiently improved in over several team approach in more effective way.
decades. The questions regarding its adequate Over the years, large number of studies
cutoff levels and optimal test timing and contri- attempted to define diagnostic performance of
bution to clinical decision-making remain unan- different imaging tests in endometriosis, integrat-
swered. While the majority of the investigated ing emerging technologies and modifications to
biomarkers were not diagnostically useful for more traditional methods. In ultrasound field,
endometriosis, for those markers that showed modified methods include transvaginal ultra-
adequate diagnostic estimates, the evidence sound with bowel preparation (TVUS-BP), instil-
remains either conflicting or insufficient for lation of contrast medium transrectally
meaningful recommendations. Low-quality het- (RWC-TVUS) or transvaginally (sonovaginogra-
erogeneous studies and unstandardized research phy), and “tenderness-guided” approach with
methods undermine the reliability of the pre- particular attention to the tender points evoked
sented results. There were no diagnostic studies during examination and 3-D technology. In MRI,
that focused on the downstream value of the test 3.0Tesla Magnetom system (3.0 T MRI); intro-
in terms of health or behavioral consequences. duction of ultrasonographic gel into the vagina,
Likewise, except for early low-quality reports on rectum, or rectosigmoid (MRI jelly method); or
CA-125, no studies specifically assessed the role utilization of three-dimensional coronal single-
of the biomarkers in monitoring disease progres- slab MRI (3D Cube) have been used in addition
sion or recurrence. to more traditional systems.
The Cochrane Library systematic review
assessed all the available imaging methods in one
16.4 Imaging Tests coherent document and demonstrated that trans-
as a Diagnostic Tool vaginal ultrasound (TVUS) and magnetic reso-
for Endometriosis nance imaging (MRI) were the most studied
modalities [45]. In studies that did not specify
While clinical presentations of endometriosis type of endometriosis and presumably looked at
vary, morphological characteristics of endometri- the overall pelvic endometriosis, no imaging
otic lesions appear to be consistent across differ- method met the diagnostic criteria for a replace-
ent patient phenotypes and, if visualized with ment test or a triage test (Table 16.2). TVUS was
imaging methods, serve as basis for radiological the best performing method and had sensitivity of
markers of the disease. In addition, distorted pel- 0.79 (95% CI 0.36, 1.00) and specificity of 0.91
vic anatomies such as retroverted uterus and (95% CI 0.74, 1.00), although there was
16 Biomarkers in Endometriosis 177
Table 16.2 Diagnostic performance of different imaging methods for the diagnosis of endometriosis: a meta-analysis
[47]
No. of studies; Pooled Pooled
No. of sensitivity specificity
Test participants (95% CI) (95% CI) Comments
Pelvic TVUS 5; 1222 0.79 (0.36, 0.91 (0.74, 1 outlier study was excludeda
endometriosis 1.00) 1.00)
MRI 7; 303 0.79 (0.70, 0.72 (0.51, 3.0T MRI (2 studies) showed the
0.88) 0.92) highest diagnostic accuracy
Ovarian TVUS 8; 765 0.93 (0.87, 0.96 (0.92, Studies published after 2006 (4
endometriosis 0.99) 0.99) studies) showed the highest
diagnostic accuracy
TRUS 1; 92 0.89 (0.74, 0.77 (0.64, Meta-analysis was not possible
0.97) 0.87)
MRI 3; 179 0.95 (0.90, 0.91 (0.86, 3.0T MRI (2 studies) showed the
1.00) 0.97 highest diagnostic accuracy
Deep endometriosis TVUS 9; 934 0.79 (0.69, 0.94 (0.88, TVUS-BP (1 study) showed the
(DE) 0.89) 1.00) highest diagnostic accuracy
MRI 6; 266 0.94 (0.90, 0.77 (0.44, 3.0T MRI (2 studies) and MRI
0.97) 1.00) jelly method (1 study) showed
the highest diagnostic accuracy
DCBE 1; 69 0.36 (0.24, 1.00 (0.16, Meta-analysis was not possible
0.48) 1.00)
DCBE double-contrast barium enema, MRI magnetic resonance imaging, TRUS transrectal ultrasound, TVUS transvagi-
nal ultrasound, TVUS-BP transvaginal ultrasound with bowel preparation
a
The excluded study utilized a sole single marker of endometriosis (kissing ovaries), in contrast to the other four studies
that surveyed pelvic anatomy
substantial diversity in diagnostic estimates TVUS, and transrectal ultrasound (TRUS) showed
between the studies. Integration of TVUS with that both MRI and TVUS provided comparable
history of dysmenorrhea or dyspareunia and vagi- estimates in diagnosing ovarian endometriosis,
nal examination for the presence of pelvic tender- while TRUS had lower diagnostic values [48].
ness, fixed retroverted uterus, or deeply infiltrating For DE, MRI approached the criteria for a
nodules resulted in improved sensitivity of 0.92 replacement test, and TVUS approached the cri-
(95% CI 0.78, 0.98) but lower specificity of 0.61 teria for a rule in (SpIN) triage test (Table 16.2).
(95% CI 0.48, 0.72) in a single study that included The direct comparison performed in one small
106 women and did not present direct compara- study demonstrated that MRI performed better
tive data with TVUS alone [46]. than 3D-TVUS in the diagnosis of DE, and there
For ovarian endometriosis, MRI met the crite- were no comparisons between MRI and other
ria for a replacement test and TVUS approached ultrasound methods [49]. Double-contrast b arium
these criteria and could qualify as a rule in (SpIN) enema (DCBE) was inferior to the other diagnos-
triage test (Table 16.2). Overall, the studies pub- tic methods for detecting DE.
lished after 2006 demonstrated higher sensitivity Notably, tenderness-guided TVUS and
for diagnosing endometrioma with ultrasound. TVUS-BP seemed to be the most accurate in
Combination with CA-125 and CA-19.9 at differ- detecting ovarian and deep endometriosis.
ent cutoff levels did not improve diagnostic per- Tenderness-guided TVUS (one study in 50
formance of TVUS for detecting endometrioma, women) showed sensitivity of 1.00 (95% CI 0.66,
as demonstrated in one study in a total of 118 1.00) and specificity of 1.00 (95% CI 0.91, 1.00)
women [47], and there were no studies on other in detecting ovarian endometrioma and sensitiv-
diagnostic combinations of imaging tests for ity of 0.90 (95% CI 0.74, 0.98) with specificity of
endometrioma. One small study that performed 0.95 (95% CI 0.74, 1.00) in detecting DE [50].
direct head-to-head comparison between MRI, TVUS-BP (one study in 57 women) demon-
178 V. Nisenblat and M. L. Hull
strated sensitivity of 0.97 (95% CI 0.83, 1.00) Cochrane review), both TVUS and MRI could
with specificity of 1.00 (95% CI 0.87, 1.00) for qualify as a SpIN triage test [54, 57]. Formal
endometrioma and sensitivity of 0.94 (95% CI comparative analyses between TVUS and MRI
0.81, 0.99) with specificity of 1.00 (95% CI 0.85, methods were not possible due to paucity of the
1.00) for DE [51], and the findings were repli- data.
cated by another group in 85 women with endo- Collectively, the meta-analysis revealed that
metrioma [52]. 3.0 T MRI showed higher although MRI was superior to TVUS in detecting
sensitivity and specificity for diagnosing pelvic, endometrioma and DE, both methods showed
ovarian, or deep endometriosis compared to other comparable high diagnostic estimates when mod-
conventional MRI methods. However, there were ified techniques were applied. Recently, MRI
no sufficient data for formal comparative analysis was promoted as the noninvasive imaging tech-
between different modified methods. nique of choice for the detection and classifica-
Substantial number of studies focused on tion of endometriosis [58], although major
mapping deep endometriotic lesions at specific advantages of MRI over TVUS were not consis-
anatomical sites, the approach which does not tently demonstrated. Both TVUS and MRI could
have primary diagnostic role but is important for accurately detect ovarian and deep endometrio-
planning surgical strategy (Table 16.3). For rec- sis, which is consistently reported by most sys-
tosigmoid endometriosis, which was evaluated in tematic reviews on the topic [53–57, 59]. TRUS
the largest number of studies, TVUS, TRUS, and does not appear to be superior to TVUS for any
MRI reached the criteria for a SpIN triage, indi- type or site of endometriosis, which questions
cating that positive findings could confirm recto- clinical application of this method considering
sigmoid involvement, whereas negative imaging the discomfort experienced by women during
result was nonconclusive. Multi-detector com- transrectal examination. That said, TRUS remains
puterized tomography enema (MDCT-e) a valid alternative for the subgroup of patients for
appeared to be the best performing modality for whom transvaginal examination is not possible or
rectosigmoid and other bowel endometriosis, not applicable.
showing sensitivity of 0.98 (95% CI 0.94, 1.00) Several factors limit translation of the above
with specificity of 0.99 (95% CI 0.97, 1.00) and findings into clinical practice. Firstly, diagnostic
sensitivity of 0.98 (95% CI 0.92, 1.00) with spec- efficacy was largely reported by small, uncon-
ificity of 1.00 (95% CI 1.00, 1.00), respectively. trolled studies lacking comparative data. Most
For other anatomical locations, TVUS met the tests showed considerable heterogeneity of the
criteria for a rule in SpIN triage test in mapping diagnostic estimates, which could be explained
DE to USL, rectovaginal septum (RVS), vaginal by variation in study design, populations studied,
wall, and POD, which is consistent with the pre- and surgical criteria applied. It is also possible
vious reports [53–55]. Combination of vaginal that advances in technology make it difficult to
examination with TVUS much improved diag- compare earlier studies with more recent ones.
nostic accuracy for detecting DE in RVS, vaginal Importantly, there is no consistency between the
wall, POD, and rectum, but this was demon- testing protocols and radiological diagnostic cri-
strated in only one well-designed study in 200 teria across the studies, particularly for the ultra-
women [56]. Modified ultrasound methods such sound methods. Finally, most studies were
as TVUS-BP and RWC-TVS showed the highest conducted at the specialized centers for endome-
diagnostic accuracy for the evaluated anatomical triosis with a high level of expertise in gyneco-
locations of endometriosis. MRI could qualify as logical imaging, which is likely to result in higher
a SpIN triage test only for POD and vaginal wall diagnostic accuracy, and the method may not per-
endometriosis with overall better performance of form that well in more general setting. It has been
3.0 T MRI and MRI jelly methods. TRUS could reported that competency in performing ultra-
not be adequately assessed for any of these sites sound for DE can be achieved within 40 proce-
due to paucity of the data. For the detection of dures [52, 60]. Thus, wide implementation of
bladder endometriosis (not evaluated in the training programs by the centers of excellence in
16 Biomarkers in Endometriosis 179
Table 16.3 Imaging methods for surgical mapping of endometriosis to specific anatomical sites: a meta-analysis [47]
No. of studies; Pooled Pooled
No. of sensitivity specificity
Test participants (95% CI) (95% CI) Comments
USL endometriosis TVUS 7; 751 0.64 (0.50, 0.97 (0.93, TVUS-BP (1 study) showed the
0.79) 1.00) highest diagnostic accuracy
TRUS 2; 232 0.52 (0.29, 0.94 (0.86,
0.74) 1.00)
MRI 4; 199 0.86 (0.80, 0.84 (0.68, 3.0T MRI (1 study) showed the
0.92) 1.00) highest diagnostic accuracy
RVS endometriosis TVUS 10; 983 0.88 (0.82, 1.00 (0.98, TVUS-BP (3 studies) and
0.94) 1.00) RWC-TVS (1 study) showed
the highest diagnostic accuracy
TRUS 2; 232 0.78 (0.51, 0.96 (0.89,
1.00) 1.00)
MRI 3; 288 0.81 (0.70, 0.86 (0.78,
0.93) 0.95)
Vaginal wall TVUS 6; 679 0.57 (0.21, 0.99 (0.96, tg-TVUS (1 study) showed the
endometriosis 0.94) 1.00) highest diagnostic accuracy
TRUS 2; 232 0.39 (0.08, 1.00 (1.00, 3.0T MRI (1 study) showed the
0.70) 1.00) highest diagnostic accuracy
MRI 4; 248 0.77 (0.67, 0.97 (0.92, 3.0T MRI (1 study) showed the
0.88) 1.00) highest diagnostic accuracy
POD obliteration TVUS 6; 755 0.83 (0.77, 0.97 (0.95, TVUS-BP (2 studies) showed
0.88) 0.99) the highest diagnostic accuracy
MRI 5; 154 0.90 (0.76, 0.98 (0.89, 3.0T MRI (3 studies) showed
1.00) 1.00) the highest diagnostic accuracy
Rectosigmoid TVUS 14; 1616 0.90 (0.82, 0.96 (0.94, TVUS-BP (2 studies) and
endometriosis 0.97) 0.99) RWC-TVS (2 studies) showed
the highest diagnostic accuracy
TRUS 4; 330 0.91 (0.85, 0.96 (0.91,
0.98) 1.00)
MRI 6; 612 0.92 (0.86, 0.96 (0.93, MRI jelly method (1 study) and
0.99) 0.98) 3.0T MRI (1 study) showed the
highest diagnostic accuracy
MDCT-e 3; 389 0.98 (0.94, 0.98 (0.94,
1.00) 1.00)
DCBE 2; 106 0.56 (0.32, 0.77 (0.41,
0.80) 1.00)
Bowel (ileum- TVUS 3; 314 0.89 (0.81, 0.96 (0.91,
rectum) 0.97) 1.00)
endometriosis TRUS 1; 134 0.96 (0.89, 1.00 (0.94, Meta-analysis was not possible
0.99) 1.00)
MDCT-e 2; 194 0.98 (0.92, 1.00 (1.00,
1.00) 1.00)
DCBE double-contrast barium enema, MDCT-e multi-detector computerized tomography enema, MRI magnetic reso-
nance imaging, RWC-TVS rectal water contrast transvaginal ultrasonography, TRUS transrectal ultrasound, TVUS trans-
vaginal ultrasound, TVUS-BP transvaginal ultrasound with bowel preparation, tg-TVUS tenderness-guided TVUS, USL
utero-sacral ligament, RVS recto-vaginal septum, POD pouch of Douglas
c onsidering only the ovarian and deep forms as capture complex underlying mechanisms of
“definite disease” [8]. To resolve the controversy, endometriosis and may improve diagnostic per-
noninvasive classification of different types of formance [68, 69].
endometriosis would enable large population Reproducible research involves replication of
studies on natural history and clinical outcomes of the results by independent groups to improve
surgical versus medical treatment in women with validation of promising discoveries and relies on
superficial peritoneal disease. As there are no refined radiological protocols and standardized
diagnostic studies that applied modified, presum- laboratory methods. Moreover, publishing nega-
ably more sensitive, techniques to detect superfi- tive findings, although less scientifically attrac-
cial peritoneal lesions, the role of imaging in tive, is important to guide clinically relevant
detecting this form of endometriosis remains experimental work [70].
unclear. Until new data emerge, the statement that The value of diagnostic test expands beyond
superficial endometriosis cannot be readily seen its diagnostic accuracy, and there is a growing
with imaging methods continues to hold true. awareness that test should show clear evidence
that it improves patient’s health. Patient outcome
studies that correlate test result with clinical out-
16.5 Future Perspectives comes [71] and test-treatment trials that inform
on patient outcomes following treatment based
The search for a noninvasive test for endome- on test results are essential within test evaluation
triosis has been an ongoing and challenging framework [11]. Meaningful economic evalua-
issue. Despite substantial research efforts, there tions require high-quality data to rely on and
is no rigorous scientific evidence to support the should be carried out once the clinical perfor-
use of any of the evaluated biomarkers in every- mance of the test is demonstrated [71].
day practice. Imaging tests are being increas- Finally, the authors of the original and review
ingly employed as a diagnostic adjunct to papers should shift from the standard “more stud-
surgery, but the evidence on their clinical effi- ies needed” to more constructive topic-specific
cacy and contribution to patient management suggestions for future work. This will contribute
remains elusive. There is an increasing demand to the collaborative effort to strengthen the clini-
on researches to reduce the effect of bias and to cally relevant diagnostic research in
demonstrate clinical value of the tests in future endometriosis.
evaluations.
It is important that future authors focus on
clinically relevant population comprising the
References
individuals who would benefit from the test in
clinical practice [61]. Adherence to the standards 1. Matsuzaki S, Canis M, Pouly JL, Rabischong B,
for reporting of the diagnostic studies [62, 63], Botchorishvili R, Mage G. Relationship between
bio-specimen handling [64, 65], and laparoscopy delay of surgical diagnosis and severity of disease in
[66] would result in more reliable assessment of patients with symptomatic deep infiltrating endome-
triosis. Fertil Steril. 2006;86:1314–6.
test performance. We still don’t have universally 2. Gao X, Yeh YC, Outley J, Simon J, Botteman M,
adopted criteria for any of the radiological meth- Spalding J. Health-related quality of life burden of
ods in endometriosis, and these are urgently women with endometriosis: a literature review. Curr
needed to standardize practice. Med Res Opin. 2006;22:1787–97.
3. Ballard KD, Seaman HE, de Vries CS, Wright JT. Can
Applying testing to different clinical pheno- symptomatology help in the diagnosis of endometrio-
types rather than to rASRM staging and sis? Findings from a national case-control study - Part
accounting for confounding effect of comor- 1. BJOG. 2008;115(11):1382–91.
bidities is expected to refine a personalized 4. Nnoaham KE, Hummelshoj L, Kennedy SH,
Jenkinson C, Zondervan KT, World Endometriosis
approach to diagnosis [67]. Combining several Research Foundation Women’s Health Symptom
tests in diagnostic algorithms is more likely to Survey Consortium. Developing symptom-based pre-
16 Biomarkers in Endometriosis 181
dictive models of endometriosis as a clinical screen- dysmenorrhea for monitoring therapy and for recur-
ing tool: results from a multicenter study. Fertil Steril. rence of endometriosis. Acta Obstet Gynecol Scand.
2012;98:692–701. 1998;77(6):665–70.
5. Eskenazi B, Warner M, Bonsignore L, Olive D, 20. Agic A, Djalali S, Wolfler MM, Halis G, Diedrich K,
Samuels S, Vercellini P. Validation study of non- Hornung D. Combination of CCR1 mRNA, MCP1,
surgical diagnosis of endometriosis. Fertil Steril. and CA125 measurements in peripheral blood as
2001;76(5):929–35. a diagnostic test for endometriosis. Reprod Sci.
6. Wykes CB, Clark TJ, Khan KS. Accuracy of laparos- 2008;15(9):906–11.
copy in the diagnosis of endometriosis: a systematic 21. Lanzone A, Marana R, Muscatello R, Fulghesu AM,
quantitative review. BJOG. 2004;111:1204–12. Dellacqua S, Caruso A, Mancuso S. Serum Ca-125
7. Johnson NP, Hummelshoj L, Consortium levels in the diagnosis and management of endome-
WESM. Consensus on current management of endo- triosis. J Reprod Med. 1991;36(8):603–7.
metriosis. Hum Reprod. 2013;28:1552–68. 22. Vouk K, Hevir N, Ribic-Pucelj M, Haarpaintner
8. Vercellini P, Giudice LC, Evers JL, Abrao M. Reducing G, Scherb H, Osredkar J, et al. Discovery of phos-
low-value care in endometriosis between limited phatidylcholines and sphingomyelins as bio-
evidence and unresolved issues: a proposal. Hum markers for ovarian endometriosis. Hum Reprod.
Reprod. 2015;30:1996–2004. 2012;27(10):2955–65.
9. Johnson NP, Hummelshoj L, Adamson GD, 23. Koninckx PR, Meuleman C, Oosterlynck D, Cornillie
Keckstein J, Taylor HS, Abrao MS, Bush D, Kiesel FJ. Diagnosis of deep endometriosis by clinical exam-
L, Tamimi R, Sharpe-Timms KL, Rombauts L. World ination during menstruation and plasma CA-125 con-
Endometriosis Society consensus on the classification centration. Fertil Steril. 1996;65(2):280–7.
of endometriosis. Hum Reprod. 2017;32:315–24. 24. Vicente-Muñoz S, Morcillo I, Puchades-
10. Nisenblat V, Bossuyt PMM, Shaikh R, Arora D, Carrasco L, Payá V, Pellicer A, Pineda-Lucena
Farquhar C, Jordan V, Scheffers CS, Mol BWJ, A. Pathophysiologic processes have an impact on
Johnson N, Hull ML. Blood biomarkers for the the plasma metabolomic signature of endometriosis
non invasive diagnosis of endometriosis. Cochrane patients. Fertil Steril. 2016;106(7):1733–41.
Database Syst Rev. 2016;(5):CD012179. doi:https:// 25. Letsiou S, Peterse DP, Fassbender A, Hendriks
doi.org/10.1002/14651858. MM, van den Broek NJ, Berger R, O DF, Vanhie
11. Bossuyt PMM, Reitsma JB, Linnet K, Moons A, Vodolazkaia A, Van Langendonckt A, Donnez
KGM. Beyond diagnostic accuracy: the clinical utility J, Harms AC, Vreeken RJ, Groothuis PG, Dolmans
of diagnostic tests. Clin Chem. 2012;58(12):1636–43. MM, Brenkman AB, D’Hooghe TM. Endometriosis
12. Giudice LC, Kao LC. Endometriosis. Lancet. is associated with aberrant metabolite profiles in
2004;364:1789–99. plasma. Fertil Steril. 2017;107(3):699–706.
13. Burney RO. The genetics and biochemistry of endome- 26. Liu HY, Zheng YH, Zhang JZ, Leng JH, Sun DW, Liu
triosis. Curr Opin Obstet Gynecol. 2013;25(4):280–6. ZF, et al. Establishment of endometriosis diagnostic
14. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, model using plasma protein profiling. Chung-Hua
Kennedy SH, Becker CM. Peripheral biomarkers Fu Chan Ko Tsa Chih [Chinese J Obstet Gynecol].
of endometriosis: a systematic review. Hum Reprod 2009;44(8):601–4.
Update. 2010;16:651–74. 27. Seeber B, Sammel MD, Fan X, Gerton GL, Shaunik
15. Liu E, Nisenblat V, Farquhar C, Fraser I, Bossuyt A, Chittams J, et al. Proteomic analysis of serum
PMM, Johnson N, Hull ML. Urinary biomarkers for yields six candidate proteins that are differentially
the non invasive diagnosis of endometriosis. Cochrane regulated in a subset of women with endometriosis.
Database Syst Rev. 2015;(12):CD012019. doi: https:// Fertil Steril. 2010;93(7):2137–44.
doi.org/10.1002/14651858. 28. Fassbender A, Waelkens E, Verbeeck N, Kyama CM,
16. Mol BW, Bayram N, Lijmer JG, Wiegerinck MA, Bokor A, Vodolazkaia A, et al. Proteomics analysis of
Bongers MY, van der Veen F, Bossuyt PM. The plasma for early diagnosis of endometriosis. Obstet
performance of CA-125 measurement in the detec- Gynecol. 2012;119(2 Pt 1):276–85.
tion of endometriosis: a meta-analysis. Fertil Steril. 29. Wolfler MM, Schwamborn K, Otten D, Hornung D,
1998;70(6):1101–8. Liu HY, Rath W. Mass spectrometry and serum pat-
17. Hirsch M, Duffy J, Davis CJ, Nieves Plana M, Khan tern profiling for analyzing the individual risk for
KS. Diagnostic accuracy of cancer antigen 125 for endometriosis: promising insights? Fertil Steril.
endometriosis: a systematic review and meta-analy- 2009;91(6):2331–7.
sis. BJOG. 2016;123(11):1761–8. 30. Jia SZ, Yang Y, Lang J, Sun P, Leng J. Plasma
18. Hirsch M, Duffy JMN, Deguara CS, Davis CJ, Khan miR-17-5p, miR-20a and miR-22 are down-regu-
KS. Diagnostic accuracy of Cancer Antigen 125 lated in women with endometriosis. Hum Reprod.
(CA125) for endometriosis in symptomatic women: a 2013;28(2):322–30.
multi-center study. Eur J Obstet Gynecol Reprod Biol. 31. Wang WT, Zhao YN, Han BW, Hong SJ, Chen YQ,
2017;210:102–7. Wang X, et al. Circulating microRNAs identified in
19. Chen FP, Soong YK, Lee N, Lo SK. The use of serum a genome-wide serum microRNA expression analy-
CA-125 as a marker for endometriosis in patients with sis as noninvasive biomarkers for endometriosis
182 V. Nisenblat and M. L. Hull
57. Medeiros LR, Rosa MI, Silva BR, Reis ME, Simon 65. Rahmioglu N, Fassbender A, Vitonis AF, Tworoger
CS, Dondossola ER, da Cunha Filho JS. Accuracy SS, Hummelshoj L, D’Hooghe TM, Adamson GD,
of magnetic resonance in deeply infiltrating endome- Giudice LC, Becker CM, Zondervan KR, Missmer
triosis: a systematic review and meta-analysis. Arch SA. World Endometriosis Research Foundation
Gynecol Obstet. 2015;291(3):611–21. Endometriosis Phenome and biobanking harmoniza-
58. Saba L, Sulcis R, Melis GB, de Cecco CN, Laghi tion project: III. Fluid biospecimen collection, pro-
A, Piga M, et al. Endometriosis: the role of mag- cessing, and storage in endometriosis research. Fertil
netic resonance imaging. Acta Radiol. 2014, Steril. 2014;102(5):1233–43.
56(3):355–67. 66. Becker CM, Laufer MR, Stratton P, Hummelshoj L,
59. Moore J, Copley S, Morris J, LIndsell D, Golding Missmer SA, Zondervan KT, Adamson GD. World
S, Kennedy S. A systematic review of the accuracy Endometriosis Research Foundation Endometriosis
of ultrasound in the diagnosis of endometriosis. Phenome and biobanking harmonization project:
Ultrasound Obstet Gynecol. 2002;20:630–4. I. Surgical phenotype data collection in endometriosis
60. Tammaa A, Fritzer N, Strunk G, Krell A, Salzer research. Fertil Steril. 2014;102(5):1213–22.
H, Hudelist G. Learning curve for the detection of 67. Vitonis AF, Vincent K, Rahmioglu N, Fassbender A,
pouch of Douglas obliteration and deep infiltrat- Buck Louis G, Hummelshoj L, Giudice L, Stratton P,
ing endometriosis of the rectum. Hum Reprod. Adamson GD, Becker CM, Zondervan KR, Missmer
2014;29(6):1199–204. SA. World Endometriosis Research Foundation
61. Rutjes AWS, Reitsma JB, Vandenbroucke JP, Glas Endometriosis Phenome and biobanking harmoniza-
AS, Bossuyt PMM. Case–control and two-gate tion project: II. Clinical and covariate phenotype data
designs in diagnostic accuracy studies. Clin Chem. collection in endometriosis research. Fertil Steril.
2005;51(8):1335–41. 2014;102(5):1223–32.
62. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, 68. Ahn SH, Singh V, Tayade C. Biomarkers in endo-
Glasziou PP, Irwig LM, et al. Towards complete and metriosis: challenges and opportunities. Fertil Steril.
accurate reporting of studies of diagnostic accuracy: 2017;107(3):523–32.
the STARD initiative. BMJ. 2003;326(7379):41–4. 69. Nisenblat V, Prentice L, Bossuyt PMM, Farquhar C,
63. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Hull ML, Johnson N. Combination of the non-inva-
Deeks JJ, Reitsma JB, et al., the QUADAS-2 Group. sive tests for the diagnosis of endometriosis. Cochrane
QUADAS-2: a revised tool for the quality assess- Database Syst Rev. 2016;7:CD012281.doi:https://doi.
ment of diagnostic accuracy studies. Ann Intern Med. org/10.1002/14651858.
2011;155(8):529–36. 70. Pusztai L, Hatzis C, Andre F. Nat Rev Clin Oncol.
64. Fassbender A, Rahmioglu N, Vitonis AF, Vigano 2013;10:720–4.
P, Giudice LC, D’Hooghe TM, Hummelshoj L, 71. Horvath AR, Lord SJ, StJohn A, Sandberg S, Cobbaert
Adamson GD, Becker CM, Missmer SA, Zondervan CM, Lorenz S, Monaghan PJ, Verhagen-Kamerbeek
KT. World Endometriosis Research Foundation WD, Ebert C, Bossuyt PM, Test Evaluation Working
Endometriosis Phenome and biobanking harmo- Group of the European Federation of Clinical
nization project: IV. Tissue collection, processing, Chemistry Laboratory Medicine. From biomarkers to
and storage in endometriosis research. Fertil Steril. medical tests: the changing landscape of test evalua-
2014;102(5):1244–53. tion. Clin Chim Acta. 2014;427:49–57.
Clinical Cases and Videos
17
Mauricio León, Hugo Sovino,
and Juan Luis Alcazar
History
17.6 Clinical Case Number 5
Multiparous of one vaginal birth, with anteced-
AGE: 35 years. ents of 1 year with left lumbar pain associated
Ethnic Origin: Latina. to dysmenorrhea and occasional dysuria,
Surgical Antecedents: LIE I surgery. without dyspareunia, dyschezia, hematuria, or
Family History of Endometriosis: no. hematochezia.
188 M. León et al.
History
17.8 Clinical Case Number 7
Nulligravida, referring with dysmenorrhea, dys-
AGE: 28 years. pareunia, dyschezia, and anal catamenial pain,
Ethnic Origin: Latina-Amerindian. without hematochezia, hematuria, or dysuria,
Surgical Antecedents: NO. for 2 years.
Family History of Endometriosis: no.
Vaginal Examination
History
Palpable nodule in the posterior vaginal fornix
Nulligravida, with antecedents of 2 years with and pouch of Douglas of 2.5 cm in diameter.
progressive dysmenorrhea accompanied by
dysuria, without dyspareunia, dyschezia, Video
hematuria, or hematochezia.
Explanation (video): A rectosigmoid anterior
Vaginal Examination rectal wall nodule of 43 × 13 × 14 mm with
involvement of vagina and uterosacral liga-
A painful nodule of 1.5 cm behind the cervix was ment. In addition, you can observe another
palpated. lesion of 16 × 16 × 11 mm.
Video Management
Explanation (video): Bladder base intramural Multidisciplinary equipment was used. In lapa-
nodule of 19 × 20 × 21 mm, without compro- roscopic surgery was found an anterior rectal
mise of intravesical ureters. Also can be nodule of 4 cm in diameter with uterosacral
observed a right uterosacral ligament nodule ligament and vaginal involvement. A discoi-
17 Clinical Cases and Videos 189
dal resection and termino-terminal resection necessary to remove the rectal lesion
were necessary to remove the rectal lesion completely.
completely.
A C
Abdominal wall endometriosis CA-125, 172, 173, 176
appendiceal endometriosis, 126 Cabergoline, 18
causes, 122 Canal of nuck endometriosis, see Inguinal endometriosis
definition, 121 Case studies, 185–189
evaluation of localization, 127 Chocolate cyst, 47
hepatic endometriosis, 126 Chocolate cysts, see Ovarian endometrioma
HIFU ablation, 128 Cochrane Library diagnostic test review, 170, 172, 173,
inguinal endometriosis, 122, 125 175, 176
intra-abdominal endometriosis, 125 Color score, 41, 42
MRI, 128 Combined technique, 18
oral contraceptives, 126 Computed tomography (CT), 148, 163
rectus abdominis endometriosis, 125, 126, 130 CYP19 biomarker, 175
scar endometriosis, 122–124, 128, 129 Cystic lesion, 47, 48
symptoms of, 122 Cystoscopy, 69
technical guidelines, 127, 128 Cytokeratin 19 (CK 19 or CYFRA 21-1), 173
3D sonography, 128
transabdominal sonography, 127
ultrasonographic findings, 127 D
Villar’s nodule, 122, 124, 129 Danazol, 16
Acoustic streaming, 51 Decidualized endometriosis, 51, 54, 153, 154
Add-back therapy, 16 Deep endometriosis, 28, 57, 67
Adenomyosis, 37–45, 161 anatomical locations, 156
Allodynia, 3, 4 anterior compartment, 156
Anterior compartment endometriosis, see Urinary tract anterior pelvic compartment (see Urinary badder
endometriosis (UTE) endometriosis)
Antiangiogenic agents, 17–18 bladder involvement, 156
Appendiceal endometriosis, 126 clinical and functional requirements, 156
Aromatase inhibitors, 17 contrast enhancement, 161
Asymptomatic ovarian endometrioma, 47 cyclic haematuria, 156
Atypical endometriomas, 50 endometrial tissue, 156
Avascular pelvic spaces, 7 endometriotic implants, 155, 161
fibrous tissue, 160
inflammatory reaction, 161
B intestinal wall infiltration, 162
Benign endometriomas, 51 middle compartment, 158
Biomarkers MRI, 155, 156
endometrial biomarkers, 174–176 nonstriated muscular fibres, 160
peripheral biomarkers, 172–174 posterior compartments, 158, 160
Bladder endometriosis, 19, 68–70 pouch of Douglas, 161
Bladder endometriotic nodule, 69–74 presurgical planning, 162
Bowel endometriosis, 9–10, 33 rectal opacification, 158
High-intensity-focused ultrasound (HIFU) ablation, 128 Mature cystic ovarian teratomas, 154
Hormone replacement treatment (HRT), 16 Mature cystic teratoma, 152
Hydronephrosis, 68, 74 Mean gray value (MGV), 53
Hydroureteronephrosis, 30 Medical management
Hyperalgesia, 3, 4 antiangiogenic agents, 17, 18
Hyperechogenic islands, 41 aromatase inhibitors, 17
Hypoestrogenizing drugs, 14 GnRH analogues, 16
NSAIDs, 16, 17
oral contraceptives, 14, 15
I progestins, 15–16
Ill-defined lesions, 37–40 risk and side effects, 13
Infiltrating endometriosis of the terminal ileum, 163 SERMs, 17
Inguinal endometriosis, 122, 125 vs. surgical treatment, 14
Inner lesion-free margin (IFM), 39 Medroxyprogesterone acetate (MPA), 15
Internal shadows, 40 miRNA biomarkers, 173
International Deep Endometriosis Analysis (IDEA), 28, Modified SVG technique, 135
30, 34, 57, 66, 89, 90, 94, 99 Morphological Uterus Sonographic Assessment (MUSA)
Intra-abdominal endometriosis, 125 consensus, 28
MRI jelly method, 176, 178
Mucinous lesions, 154
J Multi-detector computerized tomography enema
Junctional zone (JZ)/inner myometrium, 41 (MDCT-e), 178
Multiple corpora lutea, 154
Multiple endometriomas, 48
K Muscularis propria, 161
Kissing ovaries, 29, 51, 151, 153 Myometrial cysts, 39–41
Myometrial lesions, MUSA
adenomyosis cyst, 40, 41
L circumferential flow, 42, 43
Lambda sign, 50 color score, 41, 42
Lambda sing, 48 cyst, 41
Latzko’s space, 8 echogenicity, 37, 40
Letrozole, 17 future perspectives, 45
Levonorgestrel-releasing intrauterine device (LNG-IUD), IFM, 39
15, 16 ill-defined lesion, 39, 40
Low-invasive tests for endometriosis, 170 junctional zone/inner myometrium, 41, 44
location, 39
myometrial walls, 37
M OFM, 39
Magnetic resonance imaging radial vessels, 44
antispasmodic agents, 149 shadowing, 40
bladder distension, 149 sliding sign, 43
bowel preparation, 149 3D acquisition, 43
diffusion-weighted imaging, 150 uterine corpus, 43
endovaginal coil, 149 uterus total length, 43
half-Fourier single-shot turbo-spin-echo vessel morphology, 42
acquisition, 150 well-defined lesions, 39
indications, 148
intravenous contrast-enhanced MRI, 150–151
1.5-T magnet, 149 N
patient positioning, 149 Neoangiogenesis, 17
patient preparation, 149 Non-menstrual pelvic pain (NMPP), 2
pelvic phased-array coils, 149 Nonsteroidal anti-inflammatory drugs (NSAIDs), 16
susceptibility-weighted imaging, 150 Norethindrone acetate (NETA), 15
3.0-T magnet, 149 Norethisterone acetate, 17
timing of, 149
2D-T2-weighted sequences, 150
vaginal/rectal opacification, 150 O
Matrix-enhanced laser desorption/ionization time-of- Obliterated cul-de-sac fibroids, 5
flight mass spectrometry Okabayashi’s space, 8
(MALDI-TOF-MS), 173 Oral contraceptives, 14, 15
194 Index
S
P Saline contrast sonography, 98
Pain mapping, 73 Scar endometriosis, 122–124, 128, 129
Pararectal space, 8 Selective estrogen receptor modulators (SERMs), 17
Pelvic endometriosis, 7, 156 Septate endometrioma, 50
Pelvic floor hypertonicity, 3 Shadowing, 40
Pelvic sidewall anatomy, 8–9 Site-specific tenderness (SST), 28, 29, 58
Pelvic spaces, 7–8 Sliding sign technique, 29, 30, 43, 44, 63–66
Peripheral biomarkers, 172–174 SnOUT test, 170, 171
Peristalsis, 71–74 Soft marker, TVS, 28
Peritoneal endometriosis, 154, 155 ovarian mobility, 57–59
PGP 9.5 biomarker, 175 SST, 58, 59
Index 195