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Bladder Carcinomas. Bladder Carcinomas. Incidence Risk factors Staging Histopathology Papilloma Transitional Cell Carcinoma Nontransitional Cell Carcinoma Adenocarcinoma Squamous cell carcinoma Undifferentiated carcinomas Mixed carcinoma Rare epithelial and nonepithelial cancers
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Bladder Carcinomas • Incidence • Risk factors • Staging • Histopathology • Papilloma • Transitional Cell Carcinoma • Nontransitional Cell Carcinoma • Adenocarcinoma • Squamous cell carcinoma • Undifferentiated carcinomas • Mixed carcinoma • Rare epithelial and nonepithelial cancers • Clinical Findings • Treatment
B L A D D E R C A R C I N O M A Incidence • The second most common cancer of the genitourinary tract • Accounts for 7% of new cancer cases in men • Accounts for 2% of new cancer cases in women • Average age at diagnosis is 65 years • 75% of bladder cancers localized to the bladder • 25% have spread to regional lymph nodes or distant sites
B L A D D E R C A R C I N O M A Risk Factors • Cigarette smoking • Occupational exposure • Management with cyclophosphamide(Cytoxan) • Physical trauma to the urothelium
B L A D D E R C A R C I N O M A Risk Factors • Cigarette smoking • 50% of cases in men • 31% of cases in women • Confers a twofold increased risk of bladder cancer than nonsmokers; dose-related • Causative agents: alpha- and beta-naphthylamine secreted into the urine of smokers • Occupational exposure • Management with cyclophosphamide(Cytoxan) • Physical trauma to the urothelium
B L A D D E R C A R C I N O M A Risk Factors • Cigarette smoking • Occupational exposure • 15–35% of cases in men • 1–6% of cases in women • Increased risk: workers in the chemical, dye, rubber, petroleum, leather, and printing industries • Specific occupational carcinogens include benzidine, betanaphthylamine, and 4-aminobiphenyl • Latency period may be prolonged • Management with cyclophosphamide(Cytoxan) • Physical trauma to the urothelium • Infection, instrumentation, calculi
B L A D D E R C A R C I N O M A Risk Factors • Cigarette smoking • Occupational exposure • Management with cyclophosphamide(Cytoxan) • Physical trauma to the urothelium • Infection, instrumentation, calculi
B L A D D E R C A R C I N O M A Staging Nodal (N) stage • Nx– cannot be assessed • N0 – no nodal metastases • N1 – single node <2 cm involved • N2 – single node involved 2–5cm in size or multiple nodes none >5 cm • N3 – one or more nodes >5cm in size involved Metastases (M) stage • Mx – cannot be defined • M0 – no distant metastases • M1 – distant metastases present
B L A D D E R C A R C I N O M A Histopathology • Papilloma • Transitional Cell Carcinoma • Nontransitional Cell Carcinoma • Adenocarcinoma • Squamous cell carcinoma • Undifferentiated carcinomas • Mixed carcinoma • Rare epithelial and nonepithelial cancers • Villous adenomas, carcinoid tumors, carcinosarcomas, melanomas • Pheochromocytomas, lymphomas, choriocarcinomas, and various mesenchymal tumors
B L A D D E R C A R C I N O M A Papilloma • Papillary tumor with a fine fibrovascular stalk supporting an epithelial layer of transitional cells with normal thickness and cytology • Rare benign condition • Usually occurs in younger patients
B L A D D E R C A R C I N O M A Transitional Cell Carcinoma • 90% of all bladder cancers • Most commonly appear as papillary, exophytic lesions • Superficial • Less commonly, may be sessile or ulcerated • Often invasive • Carcinoma in situ (CIS) • flat, anaplastic epithelium • Urotheliumlacks the normal cellular polarity, and cells contain large, irregular hyperchromatic nuclei with prominent nucleoli
B L A D D E R C A R C I N O M A Nontransitional Cell Carcinoma: Adenocarcinoma • <2% of all bladder cancers • 2 types: • Primary adenocarcinomas of the bladder • Preceded by cystitis and metaplasia • Often arise along the floor of the bladder • Adenocarcinomas arising from the urachus • Occur at the dome • Both tumor types are often localized at the time of diagnosis, but muscle invasion is usually present • Histology: mucus-secreting and may have glandular, colloid, or signet-ring patterns • Five-year survival: <40%, despite aggressive surgical management
B L A D D E R C A R C I N O M A Nontransitional Cell Carcinoma: Squamous cell carcinoma • 5% -10% of all bladder cancers in the US • History of: • Chronic infection • Vesical calculi • Chronic catheter use • Bilharzial infection owing to Schistosomahaematobium(60%)
B L A D D E R C A R C I N O M A Nontransitional Cell Carcinoma: Undifferentiated carcinomas • Rare (<2%) • No mature epithelial elements • Very undifferentiated tumors with neuroendocrine features and small cell carcinomas tend to be aggressive and present with metastases
B L A D D E R C A R C I N O M A Nontransitional Cell Carcinoma: Mixed carcinomas • 4–6% of all bladder cancers • Composed of a combination of transitional, glandular, squamous, or undifferentiated patterns • Most common type comprises transitional and squamous cell elements • Most are large and infiltrating at the time of diagnosis
B L A D D E R C A R C I N O M A Rare Epithelial and NonepithelialCancers • Rare epithelial cancers: villous adenomas, carcinoid tumors, carcinosarcomas, melanomas • Rare nonepithelial cancers: pheochromocytomas, lymphomas, choriocarcinomas, and various mesenchymal tumors • Cancers of the prostate, cervix, and rectum may involve the bladder by direct extension • Most common tumors metastatic to the bladder include (in order of incidence) • Melanoma, lymphoma, stomach, breast, kidney, lung and liver
B L A D D E R C A R C I N O M A Signs and symptoms • Hematuria(85–90%) • Gross or microscopic, intermittent rather than constant • Vesical irritability • Frequency, urgency, and dysuria • Irritativevoiding symptoms • More common in patients with diffuse CIS • Symptoms of advanced disease: • Bone pain from bone metastases or • Flank pain from retroperitoneal metastases or ureteral obstruction
B L A D D E R C A R C I N O M A Laboratory Findings • Urinalysis • Hematuria; may be accompanied by pyuria • Azotemia in patients with ureteral occlusion (primary bladder tumor or lymphadenopathy) • CBC • Anemia (chronic blood loss, or replacement of the bone marrow with metastatic disease) • Urinary cytology • Voided urine: exfoliated cells from both normal and neoplasticurothelium • Barbotage: larger quantities of cells can be obtained by gently irrigating the bladder with isotonic saline solution through a catheter or cystoscope
B L A D D E R C A R C I N O M A Laboratory Findings
B L A D D E R C A R C I N O M A Imaging • Uses: • To evaluate the upper urinary tract • To assess the depth of muscle wall infiltration in infiltrating bladder tumors • To detect the presence of regional or distant metastases • Intravenous urography • One of the most common imaging tests for the evaluation of hematuria • Computed tomography (CT) urography • More accurate for evaluation of the entire abdominal cavity, renal parenchyma, and ureters in patients with hematuria • Largely replaces intravenous pyelography • Bladder tumors: pedunculated, radiolucent filling defects projecting into the lumen; nonpapillary, infiltrating tumors may result in fixation or flattening of the bladder wall
B L A D D E R C A R C I N O M A Imaging • CT and magnetic resonance imaging (MRI) • Characterize the extent of bladder wall invasion • Detect enlarged pelvic lymph nodes • Overall staging accuracy ranging from 40% to 85% for CT and from 50% to 90% for MRI ( • Rely on size criteria for the detection of lymphadenopathy: • LN >1 cm = metastases • Chest X-Ray • Metastasis to the lungs • Radionuclide bone scan • Metastasis to the bones • Can be avoided if the serum alkaline phosphataseis normal
Image of the urinary bladder obtained on an intravenous urogram. The filling defect represents a papillary bladder cancer.
MRI scan of invasive bladder carcinoma: A: T1-weighted image; B: T2-weighted image. Bladder wall invasion is best assessed on T2-weighted images because of heightened contrast between tumor (asterisks) and detrusormuscle along with ability to detect interruption of the thin high-intensity line representing normal bladder wall. The heterogeneous appearance of the prostate (arrow) on the T2-weighted image owes to benign prostatic hypertrophy, confirmed at cystectomy.
B L A D D E R C A R C I N O M A Cystouretheroscopy and Tumor Resection • The diagnosis and initial staging of bladder cancer is made by cystoscopy and transurethral resection (TUR).
B L A D D E R C A R C I N O M A Cystouretheroscopy and Tumor Resection • Once a tumor is visualized or suspected, the patient is scheduled for examination under anesthesia and transurethral resection (TUR) or biopsy of the suspicious lesion. • The objectives are tumor diagnosis, assessment of the degree of bladder wall invasion (staging), and complete excision of the low-stage lesions amenable to such treatment.
B L A D D E R C A R C I N O M A Treatment Principles • Initial low-grade small tumors low risk of progression • TUR alone followed by surveillance or intravesicalchemotherapy • T1, high-grade, multiple, large, recurrent tumors or those associated with CIS on bladder biopsies higher risk of progression and recurrence • Intravesical chemotherapy or immunotherapy after complete and careful TUR
B L A D D E R C A R C I N O M A Treatment Principles • T2, T3, more invasive, but still localized, tumors • More aggressive local treatment, including partial or radical cystectomy • Combination of radiation and systemic chemotherapy • Unresectable local tumors (T4B) are candidates for • Systemic chemotherapy, followed by surgery (or possibly irradiation)
B L A D D E R C A R C I N O M A Treatment: Intravesical Chemotherapy • Immunotherapeutic or chemotherapeutic agents instilled into the bladder directly via catheter • Avoids the morbidity of systemic administration • Most common agents in the US are mitomycin C, thiotepa, and Bacillus Calmette-Guérin(BCG) • Unable to reach cancer cells: • that have grown deeply into the bladder wall • in the kidneys, ureters, and urethra, or in other organs • Used only for noninvasive (stage 0) or minimally invasive (stage I) bladder cancers.
B L A D D E R C A R C I N O M A Treatment: Surgery • Transurethral resection • Initial form of treatment for all bladder cancers • Allows a reasonably accurate estimate of tumor stage and grade and the need for additional treatment • Patients with single, low-grade, noninvasive tumors may be treated with TUR alone
B L A D D E R C A R C I N O M A Treatment: Surgery • Partial Cystectomy • Removal of a part of the bladder • For patients with solitary, infiltrating tumors (T1–T3) localized along the posterior lateral wall or dome of the bladder • For patients with cancers in a diverticulum
B L A D D E R C A R C I N O M A Treatment: Surgery • Radical Cystectomy • Removal of the entire bladder, nearby lymph nodes (lymphadenectomy), part of the urethra, and nearby organs that may contain cancer cells. • Inmen: prostate, seminal vesicles, and part of the vas deferens • Inwomen: cervix, uterus, ovaries, fallopian tubes, and part of the vagina • The “gold standard” of treatment for patients with muscle invasive bladder cancer http://www.healthline.com/images/staywell/36680.jpg http://www.webmd.com/cancer/bladder-cancer/cystectomy-for-bladder-cancer
B L A D D E R C A R C I N O M A Treatment: Radiotherapy • External beam irradiation (5000–7000 cGy), delivered in fractions over a 5- to 8-week period, is an alternative to radical cystectomy in well-selected patients with deeply infiltrating bladder cancers
B L A D D E R C A R C I N O M A Treatment: Chemotherapy • Early results with single chemotherapeutic agents and, more recently, combinations of drugs have shown that a significant number of patients with metastatic bladder cancer respond partially or completely • Regional or distant metastases: 15% • With invasive disease: 30–40% develop distant metastases despite radical cystectomyor definitive radiotherapy