3 Bladder Carcinoma Second most common CA of genitourinary tract 7% men; 2% womenAve. age at dx is 65 years old75% localized in the bladder25% spread to regional lymph nodes and distant sites
4 Bladder CA: Risk Factors Cigarette smoking50% men, 31% womenα- and β-naphthylamineOccupational exposure15-35% men, 1-6% womenchemical, dye, rubber, petroleum,leather, and printing industriesbenzidine, betanaphthylamine and 4 -aminobiphenyl,Cyclophosphamide (Cytoxan)Ingestion of artificial sweetenersPhysical trauma to the urotheliuminduced by infection,instrumentation, and calculi
5 Bladder CA: Pathogenesis Activation of oncogenesInactivation or loss of tumor suppressor genes“Field Defect” - loss of genetic material on chromosome 9Chromosome 11pcontains the c-Ha-ras proto-oncogenedeleted in approximately 40% of bladder cancersIncreased p 21Expressed by the c-Ha-ras protein productdetected in dysplastic and high-grade tumors but not in low-grade bladder cancersDeletions of chromosome 17pdetected in over 60% of all invasive bladder cancers, but have not been described in superficial tumors
6 Bladder CA: Staging Tis - In-situ disease Ta - Epithelium only T1 - Lamina propria invasionT2 - Superficial muscle invasionT3a - Deep muscle invasionT3b - Perivesical fat invasionT4 - Prostate or contiguous muscleT4a - Invasion of prostate, uterus, vaginalT4b - Invasion of pelvic wall, abdominal wall
7 Bladder CA: Staging Nodal (N) stage Nx – cannot be assessed N0 – no nodal metastasesN1 – single node <2cm involvedN2 – single node involved 2–5cm in size or multiple nodes none >5 cmN3 – one or more nodes >5 cm in size involvedMetastases (M) stageMx – cannot be definedM0 – no distant metastasesM1 – distant metastses present
8 Bladder CA: Histopathology 98% of all bladder cancers are epithelial malignancies, with most being transitional cell carcinomas (TCCs)
9 Normal Urothelium3–7 layers of transitional cell epithelium resting on a basement membraneBasal cellsare actively proliferating cellsrests on the basement membraneLuminal cellsmost important feature of normal bladder epitheliumlarger umbrella-like cells thatbound together by tight junctions
10 Normal Urothelium Lamina propria Muscularis propria occasional smooth-muscle fibersMuscularis propriadeeper, more extensive muscle elementsMuscle wall of the bladderinner and outer longitudinally oriented layersmiddle circularly oriented layer
11 PapillomaPapillary tumor with a fine fibrovascular stalk supporting an epithelial layer of transitional cells with normal thickness and cytology (WHO)RareBenignAffects younger patients
12 Transitional Cell CA 90% of all bladder cancers are TCCs Most commonly appear as papillary, exophytic lesions (SUPERFICIAL)Less commonly - sessile or ulcerated (INVASIVE)Carcinoma in situ (CIS)flat, anaplastic epitheliumUrothelium lacks the normal cellular polarityCells contain large, irregular hyperchromatic nuclei with prominent nucleoli
14 Nontransitional Cell CA: Adenocarcinoma <2% of all bladder cancersPrimary adenocarcinomas of the bladderpreceded by cystitis and metaplasiaarise along the floor of the bladderMucus-secretingGlandular, colloid, or signet-ring patternsLocalizedMuscle invasion5 year – survival = 40%
15 Nontransitional Cell CA: Squamous cell carcinoma 60% of all bladder cancers in Egypt, parts of Africa, and the Middle East5% and 10% of all bladder cancers in USHistory of chronic infection, vesical calculi, or chronic catheter useBilharzial infection owing to Schistosoma haematobium
18 Nontransitional Cell CA: Mixed Carcinomas 4–6% of all bladder cancersComposed of a combination of transitional, glandular, squamous, or undifferentiated patternsMost common: transitional and squamous cellLarge and infiltrating at the time of diagnosis
21 Tumors Metastatic to the Bladder MelanomaLymphomaStomach, breast, kidney, lung and liver
22 Clinical Findings: Symptoms Hematuria (85–90%)Accompanied by symptoms of vesical irritabilityFrequencyUrgencyDysuriaIrritative voiding symptoms seem to be more common in patients with diffuse CISAdvanced disease:bone pain from bone metastasesflank pain from retroperitoneal metastases or ureteral obstruction.
23 Clinical Findings: Signs Bimanual examination under anesthesiabladder wall thickening or a palpable massBladder is not mobile = fixation of tumor to adjacent structures by direct invasionSigns of metastatic diseaseHepatomegalySupraclavicular lymphadenopathyOccasionally, lymphedema from occlusive pelvic lymphadenopathyRarely, unusual sites such as the skin presenting as painful nodules with ulceration
25 Laboratory Findings Urinary Cytology Exfoliated cells low sensitivity for low-grade superficial tumorsinter-observer variabilityExfoliated cellsDetecting cancer in symptomatic patientsAssess response to treatmentDetection rates are high for tumors of high grade and stage as well as CIS
26 Laboratory Findings BTA test (Bard Urological,Covington, GA) BTA stat test (Bard Diagnostic Sciences,Inc, Redmond, WA)BTA TRAK assay (Bard Diagnostic Sciences, Inc)Determination of urinary nuclear matrix protein (NMP22; Matritech Inc, Newton,MA)Immunocyt (Diagnocure, Montreal, Canada)UroVysion (Abbott Labs, Chicago, IL)
27 Laboratory FindingsDetect cancer specific proteins in urine (BTA/NMP22)Augment cytology by identifying cell surface or cytogenetic markers in the nucleus
28 Imaging Cystoscopy and biopsy Evaluation of the upper urinary tract (+) infiltrating bladder tumors → assess the depth of muscle wall infiltration and the presence of regional or distant metastases
29 IV Urography vs. CT Urography IV and CT urography - one of the most common imaging tests for the evaluation of hematuriaCT urographymore accurateevaluation of the entire abdominal cavity, renal parenchyma, and ureters in patients with hematuria
30 IV urogram - represents a papillary bladder cancer.
31 Bladder TumorsPedunculated, radiolucent filling defects projecting into the lumenNonpapillary, infiltrating tumors → fixation or flattening of the bladder wallUreteral obstruction →Hydronephrosisusually associated with deeply infiltrating lesions and poor outcome after treatment
33 Cystoscopy Superficial, low-grade tumors Higher grade lesions CIS single or multiple papillary lesionsHigher grade lesionslarger and sessileCISflat areas of erythema and mucosal irregularity
34 Fluorescent Cystoscopy Enhance the ability to detect lesions by as much as 20%Hematoporphyrin derivatives that accumulate preferentially in cancer cells are instilled into the bladderFluorescence incited using a blue lightCancer cells with accumulated porphyrin such as 5-aminolevulenic acid or hexaminolevulinate (HAL) are detected as glowing red under the fluorescent light
36 Transurethral Resection (TUR) Palpable mass and mobility of the bladder are noted and any degree of fixation to contiguous structuresCystoscopy is repeated with one or more lenses (30° and 70°)Resectoscope is then placed into the bladderVisible tumors are removed by electrocautery.
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