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BLADDER CARCINOMAS
Incidence
Bladder cancer is the second most common cancer of the genitourinary tract. It
accounts for 7% of new cancer cases in men and 2% of new cancer cases in women.
The incidence is higher in whites than in African Americans, and there is a positive
social class gradient for bladder cancer in both sexes. The average age at diagnosis
is 65 years. At that time, approximately 75% of bladder cancers are localized to the
bladder; 25% have spread to regional lymph nodes or distant sites.
Risk Factors and Pathogenesis
1. Cigarette smoking accounts for 65% of cases in men and 20–30% in women.
In general, smokers have approximately a two to threefold increased risk of
bladder cancer than nonsmokers. The causative agents are thought to be
alpha- and beta- naphthylamine, which are secreted into the urine of smokers.
2. Occupational exposure Workers in the chemical, dye, rubber, petroleum,
leather, and printing industries are at increased risk. Specific occupational
carcinogens include benzidine, beta-naphthylamine, and 4-aminobiphenyl,
and the latency period between exposure and tumor development may be
prolonged.
3. Gender men are 2.5 times more likely to develop the disease then women, the
cause are unclear but may be associated with greater urine residual in the
bladder.
4. Race black people have a lower incidence than white people but it carries a
poorer prognosis.
5. Chronic inflammation bladder inflammation, stones, long term catheter, ova
of shistosoma haematobium (bilharziasis) are implicated in the development
of SCC of the bladder
6. Drugs phenacetin and cyclophosphamide.
7. Pelvic radiotherapy.
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The exact genetic events leading to the development of bladder cancer are
unknown, but they are likely to be multiple and may involve the activation of
oncogenes and inactivation or loss of tumor suppressor genes Loss of genetic
material on chromosome 9 appears to be a consistent finding in patients with
both low-grade, low-stage and high-grade, high-stage disease, which suggests
that this may be an early event in bladder cancer development. Loss of
chromosome 9 in multiple tumors from an individual patient supports the
concept that genetic changes in bladder cancer represent a “field defect” that
may occur throughout the urothelium.
Staging
- Tis – carcinoma in situ
- Ta – intraepithelial tumour
- T1 – tumour involving the lamina properia
- T2a – tumour reach the superficial layer of detrusal muscle
- T2b – tumour reach deep layer of detrusal muscle
- T3a – microscopic invasion of perivesical tissue
- T3b – macroscopic invasion of perivesical tissue
- T4a – invasion any of prostate, uterus, vagina and bowel
- T4b – invasion of pelvic or abdominal wall
Histopathology
Ninety-eight percent of all bladder cancers are epithelial malignancies, with the
predominant majority being transitional cell carcinomas (TCCs). About 5% are
adenocarcinomas or squamous cell carcinomas.
Transitional Cell Carcinoma
Approximately 90% of all bladder cancers are TCCs. These tumors most commonly
appear as papillary, exophytic lesions; less commonly, they may be sessile or
ulcerated. CIS is recognizable as flat, anaplastic epithelium.
Nontransitional Cell Carcinomas
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1. Adenocarcinoma—Adenocarcinomas account for <2% of all bladder cancers.
Primary adenocarcinomas of the bladder may be preceded by cystitis and
metaplasia. adenocarcinomas arising from the urachus occur at the dome. Five-year
survival is usually <40%, despite aggressive surgical management.
2. Squamous cell carcinoma—Squamous cell carcinoma accounts for between 5%
and 10% of all bladder cancers . it is associated here with a history of chronic
infection, vesical calculi, or chronic catheter use. It may also be associated with
bilharzial infection owing to Schistosoma haematobium, these tumors are often
nodular and invasive at the time of diagnosis.
3. Undifferentiated carcinomas—Undifferentiated bladder carcinomas, which are
rare (accounting for <2%),
4. Mixed carcinoma—Mixed carcinomas constitute 4–6% of all bladder cancers and
are composed of a combination of transitional, glandular, squamous, or
undifferentiated patterns. Most mixed carcinomas are large and infiltrating at the
time of diagnosis.
Clinical Findings
A. Symptoms
- Hematuria is the presenting symptom in 85–90% of patients with bladder
cancer. It may be gross or microscopic, intermittent rather than constant
- Irritative voiding symptoms seem to be more common in patients with diffuse
CIS. Pain is unusual (E.G. obstructive uropathy).
- Recurrent UTI and pneumonia due to malignant colovesical fistula, more
advanced cases may presented with lower limb swelling due to lymphatic or
venous obstruction, bone pain, weight loss, anorexia, confusion and anuria.
Urachal adenocarcinoma may presented with umbilical discharge mucous or
bloody or presented with deep umbilical mass.
B. Signs
General examination may revel pallor, indicating anemia due to blood loss or
chronic renal impairment.
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Palpable mass due to large volume or invasive bladder tumour, hepatomegaly
and supra clavicular lymphadenopathy are sign of metastatic disease.
Lymphoma from occlusive pelvic lymphadenopathy may be seen occasionally.
C. Laboratory Findings
1. Routine testing—The most common laboratory abnormality is hematuria.
It may be accompanied by pyuria, which on occasion may result from
concomitant urinary tract infection. Azotemia may be noted in patients
with ureteral occlusion. Anemia may be a presenting symptom owing to
chronic blood loss, or replacement of the bone marrow with metastatic
disease.
2. Urinary cytology—Exfoliated cells from both normal and neoplastic
urothelium can be readily identified in voided urine. Cytologic examination
of exfoliated cells may be especially useful in detecting cancer in
symptomatic patients and assessing response to treatment. Detection rates
are high for tumors of high grade and stage as well as CIS but not as
impressive for low-grade superficial tumors.
3. Tumour markers
o bladder tumor antigen (BTA)
o Lewis X antigen
o Hyaluronidase
o NMP22 (nuclear matrix protein)
o Telomerase
These test have been demonstrated to enhance detection of bladder cancer
when used either individually or in combination with cytology
D. Imaging
Although bladder cancers may be detected by various imaging techniques,
their presence is confirmed by cystoscopy and biopsy.
1. Intravenous urography remains one of the most common imaging test for
the evaluation of hematuria.
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2. Computed tomography (CT) urography which is more accurate for
evaluation of the entire abdominal cavity, renal parenchyma and ureters in
patient with hematuria.
3. CT and MRI have been used to characterize the extent of bladder wall
invasion and detect enlarged pelvic lymph node. With overall staging
ranging from 40% to 85% for CT and from 50% to 90% for MRI.
Treatment: at initial presentation approximately 50 – 70% of bladder tumour are
superficial, stage Tis or Ta. Regional or distant metastases are found in
approximately 25%. unfortunate, 80% of patient with invasive or metastatic disease
have no previous history of bladder cancer.
- Initial treatment option for bladder cancer
Tis – complete TUR followed by intravesical BCG.
Ta (single, low to moderate grade, not recurrent) – complete TUR