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PATHOGENESIS

BLADDER CANCER
BLADDER CANCER

• Transitional cell epithelium lines the urinary tract from the renal
pelvis to the ureter, urinary bladder, and the proximal two-thirds of
the urethra.

• Cancers can occur at any point:

• 90% - bladder
• 8% - renal pelvis,
• 2% in the ureter or urethra.

• Bladder cancer is the fourth most common cancer in men and the
thirteenth in women,
• The incidence is roughly four times higher in men
• than in women and twofold higher in white men
than in black men, with a median age of 65 years.

• Once diagnosed, urothelial tumors exhibit


polychronotropism, which is the tendency to
recur over time in new locations in the urothelial
tract.
EPIDEMIOLOGY

• Cigarette smoking is believed to contribute to up to :

• 50% of urothelial cancers in men


• nearly 40% in women.

• . Other implicated agents include:


• aniline dyes, drugs phenacetin and chlornaphazine, external beam
radiation. Chronic cyclophosphamide exposure also increases risk

• . Exposure to Schistosoma haematobium, a parasite found in many


developing countries, Is associated with an increase in both
squamous and transitional cell carcinomas of the bladder
• More than 95% of urothelial tumors in the
United States are transitional cell in origin

PATHOGENESIS

• The multicentric nature of the disease and high


recurrence suggests a field effect in the urothelium
that results in a predisposition to develop cancer.
Molecular genetic analyses suggest that the superficial
and invasive lesions develop along distinct molecular
pathways.
• Low-grade noninvasive papillary tumors harbor
constitutive activation of the receptor tyrosine kinase-
Ras signal transduction pathway and high frequencies
of fibroblast growth factor receptor 3 and
phosphoinositide-3 kinase α subunit mutations
• In contrast, CIS and invasive tumors have a
higher frequency of TP53 and RB gene
alterations. Within all clinical stages, including
Tis, T1, and T2 or greater lesions, tumors with
alterations in p53, p21, and/or RB have a
higher probability of recurrence, metastasis,
and death from disease.
CLINICAL PRESENTATION
• Hematuria = 80–90% of patients and often
reflects exophytic tumors.

• bladder- (40%) most common source of gross


hematuria

• benign cystitis - 22%

• bladder cancer -15%


• Microscopic hematuria- is more commonly of
prostate origin (25%);
• 2% of bladder cancers produce microscopic
hematuria.

• .- After hematuria, irritative symptoms are the


next most common presentation.

• flank pain –may be due to Ureteral obstruction .