BLADDER TUMORS

It is the 7 th common cancer in Iraq. Male/ female ratio is 3/1. The

average age of presentation is 65 year.
Pathogenesis and predisposing factors: neoplastic transformation in the
urothelium is a multistep process, that an initiator factors which is carcinogenic
substance induce alteration in a normal cells DNA transforming it to a malignant
cells, than the promoter factors which is non carcinogenic substance induce
proliferation in the already transformed cells:
From predisposing factors:
1. Smoking. Smokers are 3 times more susceptible for bladder cancer than non
smoker. Bladder cancer in smokers has aggressive behavior, usually it of
high grade, more liable to be multifocal and recurrent. The causative factors
are alpha and beta nephthalamin which appear in the urine of those smoker.
2. Occupational exposure to some chemical in chemical factories as in rubber,
petroleum, leather, dye and printing industries. Specific
occupational carcinogens are benzedine, beta nephthalamin, 4 amino
biphenyl.
3. Drug as phenacitin and cyclophosphamide.
4. Chronic inflammatory conditions by stone, diverticulum, non specific
infection or due to bladder obstructive lesions.
5. Bilheraziasis. There is significant relation between bilherazia and bladder
cancer. Bilharzial ova excrete beta glucorondase which deconjugate
glucouronide from nitrosamine and tryptophan which are endogenous
carcinogen deactivated by conjugation with glucouronide, also bilharzial
ova act as promoter factor by chronic irritation.

Pathology

Normal urothelium composed of 3-7 layers of transitional cells. The most

common type of epithelial tumor is transitional cell cancer. The tumor either
pedunclated or less commonly sessile or ulcerative. Histologically it of 3 grades.
Carcinoma in situ are flat non papillary anaplastic epithelium of large cells and
have prominent nuclei, it has variable natural behavior. Sequamous cell cancer,
it is 10 % of bladder cancer. In Iraq it was the commonest type previously,its
incidence decrease with time to reach now that in the world while in Egypt it
was 60% of bladder cancer because of bilheraziasis but its percent decreas now,
squamous cell cancer may complicate chronic infection or vesical stone.

Adenocarcinoma is 3% of bladder cancer. It may originate at bladder vault

from urachal remnant or in the base due to chronic infection or from remnant of
prostate or urogenital sinus.
Bladder cancer progression either by direct extension to perivesical fat,
prostate, Pelvic wall, or by lymphatic extension to external and internal iliac
lymphs nodes than to common iliac and para arotic groups, hematogenous
spread is very late it is to the lung, liver, bones.
Bladder tumor staging according to TNM staging which is clinicopathological
staging:

Tis = carcinoma in situ

Ta = limited to epithelium
T1 = invade lamina properia
T2 = detrusor muscel invasion
T3 = invasion of perivesical tissue
T4 = extra vesicle involvement of near by organs.

Presentation
90% of patients have hematuria, macroscopic or microscopic, intermittent in
nature, total not initial or terminal, may associated with clot passage, usually
painless. Some patients have cystitis features (frequency, urgency and dysuria),
may have pus cells in urine without positive bacterial growth by culture
(malignant cystitis). Rarely the patient has symptoms of metastasis as
pathological fracture.
Usually the patient have no sign apart from anemia. Rarely patient with large
tumor has palpable bladder by clot retention or have palpable one kidney or both
by ureteric obstruction.

Investigation

1. G.U.E to evaluate hematuria.

2. Urine culture and sensitivity, super added infection should be controlled
prior to cystoscopy.
3. B. Urea, S. creatinin to have idea about base line renal function.
4. Urine cytology used for initial diagnosis or to fellow up patient
management, that cells from urine deposit dried on slide, stained by
Eusin and hematoxilen and checked for cytological changes.
5. U/S its sensitivity to detect bladder cancer is 75%. It gives idea about
vesicle growth, size, site, number and any dilatation of ureter.
6. I.V.U which evaluate renal function, may there is non visualized kidney
by prolonged ureteric obstruction, also to detect any associated filling
defect in renal pelvis or ureter. In cystogram phase to see any filling
defect by bladder tumor.
 7. CT scan, MRI, to evaluate bladder wall invasion and extra vesicle wall
extension and to evaluate pelvic lymph nodes involvement depending on
their size and any filling defects in ureter or renal pelvis .
8. Cystoscopy and examination under anesthesia to:
A. Inspect urethra, bladder.
B. Do biopsy.
C. Resection of exophytic part of the tumor and to do clinical staging
by bimanual exam under anesthesia by one hand in the vagina or rectum and
other hand on abdominal wall,
clinically the tumor of stage:
T1 = no mass palpable pre or post resection.
T2 = the just palpable mass disappear after resection.
T3 = hard mobile thickening or mass after resection.
T4 = hard fixed mass.

9.Photodynamic diagnosis (flurecence cystoscopy) indicated when there

is suspicion of CIS (hematuria +positive urine cytology with no vesicle
growth by U/S), it performed by using violet light (blue) cystoscopy after
intra vesicle instillation of 5- aminoleavulinic acid 2 hours prior to
cystoscopy . area of carcinoma in situ will appears red and normal mucosa
remain blue so it simplify diagnosis and fulguration of red area.

Treatment
A.Non invasive bladder tumor including Tis, Ta, T1, the ideal
treatment is trans urethral resection of that tumor but if the tumor is
multiple or of high grade or associated with carcinoma in situ in other
area of the bladder or recurrent after resection it needs additionally one
of the following measures:
1. Intravesical chemotherapy, usually given weekly for 6 weeks
intravesically using mitomycin C or adriamycin or thiotepa. It has
therapeutic effect for residual malignant lesion and has profelacative
effect by decrease the incidence of recurrence.
2. BCG it is a form of immunotherapy. BCG is an attenuated strain of
Mycobacterium bovies. Many strains available vary in organism
immunogenecity. BCG is very effective therapeutically and
prophylactically. It’s given weekly intravesically, from its side effect
irretentive bladder dysfunction.BCG induce inflammation which attract
lymphocyte to attack malignant cells.
3. Wide spread superficial tumor or highly recurrent tumor is indication for
cystectomy.

• Non invasive bladder tumor need periodic checking of the

bladder for early resection of recurrent tumor if detected.
B. Invasive bladder tumor stage T2, T3
 Surgery is first line of treatment. It either:
1. Partial cystectomy when there is single tumor without carcinoma in situ
in other area of bladder as in bladder dome adenocarcinoma or transitional
cell tumor in diverticulum. Pre operative irradiation 1000 rads or intravesical
chemotherapy minimize tumor cells implantation.
2. Radical cystectomy by removing the bladder with its covering
peritoneum, prostate, seminal vesicles in male and in female with the uterus,
and vaginal vault. All with draining iliac group of lymph nodes The ureters
diversion by:
A. Conduit of small bowel. It connects both ureters to the skin. Those patients
need external appliance.
B. Continent pouch made of detubularized small or large bowel or of both.
This pouch evacuated every 3-4 hours by clean intermittent catherization.
C. Orthotopic bladder substitute, intestinal detubularized pouch connected
to the urethra. It is continent by the natural sphincter.

Irradiation is second line of treatment because squamous and adenocarcinoma

are radioresistante tumor and initially transitional cell cancer only 50% of them
are radiosensitive. Irradiation either given as adjuvant measures after
cystectomy or indicated in surgically unfit patient by giving 7000 rads in 6
weeks in multiple sessions or given in combination with tumor debulking by
transurethral resection + irradiation + systemic chemotherapy.

Chemotherapy
Chemotherapy, only transitional cells cancer is chemosensative tumor.
Chemotherapy either given as single agent with other measures as surgery,
irradiation or given as regims M-VAC = methotrexate, vinblastin, adriamycin
and cispltenium or CMV = cesplatenium, Methotrexate and vinblastin.
Chemotherapy indicated as new adjuvant before cystectomy or adjuvant ( after
radical cystectomy) or in residual tumor after surgery.

Palliative treatment for advanced disease as nephrostomy for

obstructed ureters with renal impairment. In cases of profuse hematuria are
managed by palliative radiotherapy or endoscopic cauterization or bilateral
internal iliac arteries ligation or by salvaged cystectomy (removal as much
as possible of the bladder and tumor).

Uretral and or transitional cell cancer of renal pelvis it is only 5% of all

transitional cell cancer managed by nephroureteracatomy with removal of cuff
of bladder around ureteric orifice. Lower ureteric tumor can be managed by
excision and ureteric replantation.