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Bladder tumors Bladder tumors 3 times more common in men 3 times more common in men 2 times more common in whites 2 times more common in whites Incidence.

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Presentation on theme: "Bladder tumors Bladder tumors 3 times more common in men 3 times more common in men 2 times more common in whites 2 times more common in whites Incidence."— Presentation transcript:

1 Bladder tumors Bladder tumors 3 times more common in men 3 times more common in men 2 times more common in whites 2 times more common in whites Incidence increase with age, median 70 yr Incidence increase with age, median 70 yr Never found incidentally Never found incidentally 5 yrs survival is higher in men 5 yrs survival is higher in men In young (<30-40 yrs) is well differentiated In young (<30-40 yrs) is well differentiated

2 Risk factors Risk factors Cyclophsphamide increase the risk 9 fold Cyclophsphamide increase the risk 9 fold Pelvic irradiation increase the risk 2 folds Pelvic irradiation increase the risk 2 folds Most bladder carcinogens are aromatic amines Most bladder carcinogens are aromatic amines Oncogens are activated mutant gene(RAS) Oncogens are activated mutant gene(RAS) Inactivation of tumor suppressor gene(P53) Inactivation of tumor suppressor gene(P53)

3 Bladder cancers (risk factors) Cigarette smoking increase risk by 2 folds Cigarette smoking increase risk by 2 folds Dose related, causative agent is Naphtylamine Dose related, causative agent is Naphtylamine Occupational exposure Occupational exposure Chemical,dye,rubber,leather,petrolium,printing Chemical,dye,rubber,leather,petrolium,printing Cyclophosphamide,artificial sweetener Cyclophosphamide,artificial sweetener Physical trauma to urotheliun like:infection,calculi,instrumentation Physical trauma to urotheliun like:infection,calculi,instrumentation Deletion of chromosome 9, 17p, 11p Deletion of chromosome 9, 17p, 11p

4 Bladder cancers (patholgy) 90% of bladder cancers are Transitional cell 90% of bladder cancers are Transitional cell Most commonly are papilary and exophytic Most commonly are papilary and exophytic Sessile or ulcerative lesions are rare but invasive Sessile or ulcerative lesions are rare but invasive Grading: cell size, nuclear size, number of mitosis, hyperchromatism, nucleoli Grading: cell size, nuclear size, number of mitosis, hyperchromatism, nucleoli Carcinoma in situ is a flat, anaplastic epithelium Carcinoma in situ is a flat, anaplastic epithelium May progress to invasive dis. May progress to invasive dis. Invasion, recurrence and progression is related with tumor grade Invasion, recurrence and progression is related with tumor grade

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8 Bladder tumor pathology Bladder tumor pathology

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10 Bladder tumors (pathology) Adenocarcinoma:<2% of all tumors Adenocarcinoma:<2% of all tumors Are mucus secreting,glandular or colloid Are mucus secreting,glandular or colloid Preceeded by cystitis and metaplasia Preceeded by cystitis and metaplasia Often arise along the floor of the bladder Often arise along the floor of the bladder Adenocarcinoma of urachus occur at dome Adenocarcinoma of urachus occur at dome Often localized at diagnosis but muscle invasion usually present Often localized at diagnosis but muscle invasion usually present Five years survival is <40% despite treatment Five years survival is <40% despite treatment

11 Bladder cancers (pathology) Squamous cell carcinoma: 5-10% Squamous cell carcinoma: 5-10% Chronic infection, chronic catheter use, vesical calculi Chronic infection, chronic catheter use, vesical calculi Bilharzial infection Bilharzial infection Nodular, invasive, poorly differentiated Nodular, invasive, poorly differentiated 60% of bladder cancers in Egypt, middle east and part of africa 60% of bladder cancers in Egypt, middle east and part of africa Mixed carcinoma:4-6%, most common type composed of transitional and squamous cell elements Mixed carcinoma:4-6%, most common type composed of transitional and squamous cell elements

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14 symptoms and signs symptoms and signs Hematuria: 85-90%, gross (70%) or microscopic,intermittent Hematuria: 85-90%, gross (70%) or microscopic,intermittent Symptoms of vesical irritability mostly with diffuse CIS Symptoms of vesical irritability mostly with diffuse CIS Bone pain, flank pain Bone pain, flank pain Mostly have no signs Mostly have no signs Bimanual examination under anesthesia Bimanual examination under anesthesia Lymphedema, hepatomegaly, supraclavicular lymphadenopathy Lymphedema, hepatomegaly, supraclavicular lymphadenopathy

15 Laboratoary findings Laboratoary findings Hematuria, pyuria, azotemia, anemia Hematuria, pyuria, azotemia, anemia Urine cytology : useful in screening of high risk population and assesing response to treatment Urine cytology : useful in screening of high risk population and assesing response to treatment Detection rate depend on volume and grade of tumor and adequacy of specimen Detection rate depend on volume and grade of tumor and adequacy of specimen Tumor markers : BTA test, NMP22, FDP, telomerase activity, Lewis X antigen Tumor markers : BTA test, NMP22, FDP, telomerase activity, Lewis X antigen May have role in initial evaluation, follow-up and prediction of natural history of tumor May have role in initial evaluation, follow-up and prediction of natural history of tumor

16 Tumor markers Tumor markers Suitable for survilance but not good tool for screening Suitable for survilance but not good tool for screening BTA and NMP22 have low sensitivity for small tumors BTA and NMP22 have low sensitivity for small tumors Immunocyst and FISH have higher sensitivity and specifity but are more expensive Immunocyst and FISH have higher sensitivity and specifity but are more expensive

17 Bladder tumor (imaging) Used to evaluate upper urinary tract, to asses the depth of muscle wall infilteration and the presence of regional or distant metastasis Used to evaluate upper urinary tract, to asses the depth of muscle wall infilteration and the presence of regional or distant metastasis IVP is the most common test for evaluation of hematuria IVP is the most common test for evaluation of hematuria CT & MRI can show the extent of bladder wall invasion and detect pelvic lymph node CT & MRI can show the extent of bladder wall invasion and detect pelvic lymph node Overall staging accuracy is 40-85% for CT and 50-90% for MRI Overall staging accuracy is 40-85% for CT and 50-90% for MRI Chest X ray, bone scan Chest X ray, bone scan

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20 Natural history Natural history I s defined by tumor recurrence and progression I s defined by tumor recurrence and progression Based on tumor stage,grade,size,multiplicity Based on tumor stage,grade,size,multiplicity 50-70% of bladder tumors are superficial 50-70% of bladder tumors are superficial 15% with regional and distant metastasis 15% with regional and distant metastasis 55% are low grade and 45% high grade 55% are low grade and 45% high grade 50% of high grade tumors are muscle invasive 50% of high grade tumors are muscle invasive High grade tumor are related with p53 abnormality High grade tumor are related with p53 abnormality Low grade tumors related with deletion of long arm of chromosome 9 Low grade tumors related with deletion of long arm of chromosome 9

21 Natural history Natural history There are strong correlations between tumor grade and stage with tumor recurrence, progression and survival There are strong correlations between tumor grade and stage with tumor recurrence, progression and survival Tumor recurrence is related to history of disease and grade, number and size of tumor Tumor recurrence is related to history of disease and grade, number and size of tumor Most important risk factor for progression is grade not stage Most important risk factor for progression is grade not stage It is more common in the first 12 months It is more common in the first 12 months

22 Bladder tummor (molecular markers) Microvessele density detect rate of angiogenesis Microvessele density detect rate of angiogenesis Mutation of P53 gene Mutation of P53 gene P53 gene is a tumor suppressor gene that plays a key role in the regulation of the cell cycle P53 gene is a tumor suppressor gene that plays a key role in the regulation of the cell cycle Retinoblastoma(Rb) gene is a tumor suppressor gene Retinoblastoma(Rb) gene is a tumor suppressor gene Alteration of Rb gene is associated with high grade, high stage bladder cancers. Alteration of Rb gene is associated with high grade, high stage bladder cancers.

23 Diagnosis Diagnosis Cystoscopy and deep biopsy Cystoscopy and deep biopsy Flourescent cystoscopy Flourescent cystoscopy TUR TUR

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26 Treatment modalities Intravesical chemotherapy,immunotherapy Intravesical chemotherapy,immunotherapy Transurethral resection of tumor Transurethral resection of tumor Partial cystectomy Partial cystectomy Radical cystectomy Radical cystectomy Radiotherapy Radiotherapy Chemotherapy Chemotherapy

27 Treatment selection Superficial bladder cancer: TUR followed by intravesical chemotherapy or immunotherapy Superficial bladder cancer: TUR followed by intravesical chemotherapy or immunotherapy More invasive but localized tumor(T2,T3): partial or radical cystectomy, radiation or surgery and systemic chemotherapy More invasive but localized tumor(T2,T3): partial or radical cystectomy, radiation or surgery and systemic chemotherapy Unresectable local tumors(T4b) : systemic chemotherapy followed by surgery or irradiation Unresectable local tumors(T4b) : systemic chemotherapy followed by surgery or irradiation Local or distant metastasis: systemic chemotherapy followed by irradiation or surgery Local or distant metastasis: systemic chemotherapy followed by irradiation or surgery

28 Intravesical chemotherapy Adjunctive: at TUR to prevent implantation Adjunctive: at TUR to prevent implantation Prophylactic: after complete TUR to prevent or delay recurrence or progression Prophylactic: after complete TUR to prevent or delay recurrence or progression Therapeutic: after incomplete TUR to cure residual disease Therapeutic: after incomplete TUR to cure residual disease Most agents are administered weekly for 6 weeks Most agents are administered weekly for 6 weeks Local toxicity is common but systemic toxicity is rare Local toxicity is common but systemic toxicity is rare Mitomycin C, Thiotepa, Doxorubicin, BCG Mitomycin C, Thiotepa, Doxorubicin, BCG

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31 Radiotherapy Alternatve to radical cystectomy in deeply infilterating bladder tumot Alternatve to radical cystectomy in deeply infilterating bladder tumot cGy over 5-8 week period cGy over 5-8 week period Local recurrence is common 33-68% Local recurrence is common 33-68% Only for patients who are poor candidate for surgery Only for patients who are poor candidate for surgery

32 Systemic chemotherapy Systemic chemotherapy The single most active agent is cisplatin The single most active agent is cisplatin MVAC is the most common regimen for patients with advanced bladder cancer MVAC is the most common regimen for patients with advanced bladder cancer 13-35% show complete response 13-35% show complete response Gemcitabin, Ifosfamide and cisplatin have lower toxicity than MVAC Gemcitabin, Ifosfamide and cisplatin have lower toxicity than MVAC


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