Transitional cell carcinoma of urinary bladeder

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Transitional cell carcinoma of urinary bladeder

  1. 1. Welcome
  2. 2. TRANSITIONAL CELL CARCINOMA OF URINARY BLADEDER Presented by DR. Md.Rezaul Karim FCPS (Surgery) MS Urology Thesis Part Student Urology Department, BSMMU, Dhaka.
  3. 3. Incidence : sex & race <ul><li>Second most common GU cancer </li></ul><ul><li>53,200 new case diagnosed annually in USA, (33%) in 2000. </li></ul><ul><li>M:F ratio is 2-3:1 </li></ul><ul><li>Black : white ratio 4:1 </li></ul><ul><li>Average age at diagnosis (65-69 yrs) </li></ul><ul><li>Mean age- Male 69yr, Female 74 yr, </li></ul><ul><li>Adolescent & young >30-40 yr (more indolent). </li></ul>
  4. 4. Etiology & Risk factors Schistosoma haematobium Artificial sweeteners Coffee & tea drinking Tryptophan metabolites Radiotherapy Metal works Chronic irritation Hair dresser, Painter Cyclophosphamide Rubber fire industry Analgesics (phenacetin) Textile industries Lather industries Cigarette smoking Risk factors are
  5. 5. Risk factors <ul><li>Others: Black foot disease </li></ul><ul><li>Arsenic ingestion </li></ul><ul><ul><ul><ul><ul><li>Chinese herb nephropathy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Heridity: </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>slightly elevated in relatives ( in smokers) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Genetic: </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Oncogenes- p21 ras mutation – high hist. grade </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Tumor suppressor gene- p53 high hist. grade, del 17p </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>pRb-aggressive TCC </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Loss of ch. 9 – both low & high grade </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>ch. 11 – cHa-ras in 40% bladder cancer. </li></ul></ul></ul></ul></ul>
  6. 6. Clinical carcinogens <ul><li>Exogenous carcinogens </li></ul><ul><li>α & β naphthylamine </li></ul><ul><li>Benzidine </li></ul><ul><li>4-aminobiphenyl </li></ul><ul><li>Cyclophosphamide </li></ul><ul><li>Phenacetin, artificial sweeteners </li></ul><ul><li>Endogenous carcinogens </li></ul><ul><li>Nitrosamine, tryptophane metabolites </li></ul>
  7. 7. Pathology <ul><li>Bladder papilloma </li></ul><ul><li>stage 0, benign condition, rare malig. transforamtion </li></ul><ul><li>but some associates with TCC </li></ul><ul><li>3% progress to frank carcinoma, recurrence -47% </li></ul><ul><li>Carcinoma in situ </li></ul><ul><li>velvety patch of erythematous mucosa </li></ul><ul><li>consists of poorly differentiated TCC confined to urothelium </li></ul><ul><li>focal or diffuse, concomitant </li></ul>
  8. 8. Carcinoma in situ cont.. <ul><li>High rate of recurrence >80% </li></ul><ul><li>may be asymptomatic or present with urinary frequency, urgency, dysuria </li></ul><ul><li>urine cytopathology positive – 80- 90%. </li></ul><ul><li>Rapidly shades in urine. </li></ul><ul><li>Cystoscopic appearance – cystitis. </li></ul><ul><li>Bears a very bad prognosis. </li></ul>
  9. 9. Pathology cont.. <ul><li>TCC </li></ul><ul><li>- >90% </li></ul><ul><li>papillary (70%), sessile (invasive), infiltrating, nodular(20%), mixed (20%), flat intraepithelial (CIS). </li></ul><ul><li>Papillary tumor are superficial. </li></ul><ul><li>Relative tumor frequency in urinary bladder </li></ul><ul><li>Posterior & lateral wall- 70% </li></ul><ul><li>Trigone & bladder neck- 20% </li></ul><ul><li>Vault of bladder – 10% </li></ul><ul><li>Diverticulum - <1% </li></ul>
  10. 10. Staging of TCC <ul><li>Jewett- Marshall staging system </li></ul><ul><li>Stage 0- CIS or superficial papillary tumor confined to the mucosa with no invasion </li></ul><ul><li>Stage A- Papillary tumor invading the lamina propria </li></ul><ul><li>Stage B1- Tumor with superficial muscle invasion </li></ul><ul><li>Stage B2- Tumor with deep muscle invasion </li></ul><ul><li>Stage C- Invasion of the perivesical fat </li></ul><ul><li>Stage D1- Involvement of adjacent viscera and/ or pelvic nodes </li></ul><ul><li>Stage D2 - Involvement of nodes above the aortic bifurcation or distant spread. </li></ul>
  11. 13. Staging cont.. <ul><li>TNM Classification </li></ul><ul><li>T = primary tumor </li></ul><ul><li>Tx- primary tumor can’t be assesed </li></ul><ul><li>Tis- Carcinoma in situ </li></ul><ul><li>Ta- Noninvasive papillary carcinoma </li></ul><ul><li>T1- Tumor invades submucosa/ lamina propria </li></ul><ul><li>T2a- Tumor invades superficial muscle </li></ul><ul><li>T2b- Tumor invades deep muscle </li></ul><ul><li>T3a- Tumor invades perivesical fat (microscopic) </li></ul><ul><li>T3b- Tumor invades perivesical fat (macroscopic) </li></ul><ul><li>T4a- Tumor invades adjacent organ </li></ul><ul><li>T4b- Tumor invades pelvic wall, abdominal wall. </li></ul>
  12. 14. Staging cont.. <ul><li>T1a superficial lamina propria above </li></ul><ul><li>muscularis mucosae </li></ul><ul><li>T1b deep lamina propria beyond </li></ul><ul><li>muscularis mucosae </li></ul><ul><li>( Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney and Richard D. Williams, BJU, 2004) </li></ul><ul><li>Seminal vesicle involvement should be included as pT4b. </li></ul><ul><li>( Prognosis of seminal vesicle involvement by TCC of the bladder, Siamak Daneshmand, Jhon P. Stein et al, J of Urol, Vol 172, 81-84, Jul’04) </li></ul>
  13. 15. TNM Classification cont.. <ul><li>N= Regional lymph nodes (below aortic bifurcation) </li></ul><ul><li>NX- Regional lymph nodes can’t be assessed </li></ul><ul><li>N0- No regional lymph nodes metastasis </li></ul><ul><li>N1- Metastasis in single node < 2 cm </li></ul><ul><li>N2- Metastasis in single node > 2 cm but <5 cm or multiple nodes < 5 cm </li></ul><ul><li>N3- Metastasis in nodes >5 cm. </li></ul><ul><li>M= Distant metastasis </li></ul><ul><li>MX- Presence of distant metastasis can’t be assessed </li></ul><ul><li>M0- No distant metastasis </li></ul><ul><li>M1- Distant metastasis </li></ul>
  14. 16. Staging cont.. <ul><li>Clinical staging </li></ul><ul><li>Imaging with US, CT, MRI </li></ul><ul><li>CXR, bone scan </li></ul><ul><li>Bimannual palpation after </li></ul><ul><li>TURBT </li></ul><ul><li>No thikening- superf. tumor </li></ul><ul><li>Tumor was palpable- </li></ul><ul><li>invasive tumor </li></ul><ul><li>Pathological staging </li></ul><ul><li>‘ p’ staging </li></ul><ul><li>hist. examination of the tissue from the base of </li></ul><ul><li>resected area </li></ul><ul><li>‘ P’ staging </li></ul><ul><li>hist. examination of </li></ul><ul><li>specimen after radical </li></ul><ul><li>cystectomy </li></ul>
  15. 18. Staging cont.. <ul><li>Bimannual palpation after TURBT </li></ul><ul><li>No palpable mass T1 </li></ul><ul><li>No mass but thickening T2 </li></ul><ul><li>Hard mass T3 </li></ul><ul><li>Hard fixed mass T4 </li></ul>
  16. 19. Grading of TCC <ul><li>Grade 0- papilloma </li></ul><ul><li>Grade 1- well differentiated, Papillary urothelial tumor of low malignant potential (10% will be invasive) </li></ul><ul><li>Grade 2- moderately differentiated, low grade urothelial tumor (50% will be invasive) </li></ul><ul><li>Grade 3- poorly differentiated, high grade urothelial tumor (>80% will be invasive) </li></ul>
  17. 22. Spread of tumor <ul><li>Origin: multicentic, field change disease </li></ul><ul><li>Direct extension </li></ul><ul><li>Lymphatic spread- pelvic LN, perivesical 16%, obturator 74%, exrternal iliac 65%, presacral 25%, common iliac 20% </li></ul><ul><li>Vascular spread- liver, lungs, bone, adrenal, intestine. </li></ul><ul><li>Implantation- abdominal wound, denuded urothelium, resected prostatic fossa, traumatized urethra- most commonly with high grade tumor. </li></ul>
  18. 23. Natural history <ul><li>55-60%- newly diagnosed bl. Cancer are well differentiated or moderately differentiated, majority develop recurrence after TURBT, 16-25% with high grade </li></ul><ul><li>40-45%- newly diagnosed bl. Cancer are high grade, more than half muscle invasive or more extensive at the time of diagnosis, more chance of recurrence & metastasis </li></ul><ul><li>Low grade tumor have recurrence with high grade </li></ul><ul><li>High & low grade simultaneously not uncommon </li></ul><ul><li>85-95% muscle invasive tumor already have invasion at the time of diagnosis, </li></ul><ul><li>about 50% muscle invasive tumor already have occult metastsis </li></ul>
  19. 24. Diagnosis <ul><li>History: </li></ul><ul><li>Painless hematuria (85%-90%), gross/ microscopic; intermittent rather constant. </li></ul><ul><li>Irritative voiding symptoms </li></ul><ul><li>Flank pain from ureteral obstruction </li></ul><ul><li>Lower leg odema & pelvic pain </li></ul><ul><li>Bone pain, loss of weight, abdomminal pain </li></ul>
  20. 25. Diagnosis <ul><li>Physical examination: </li></ul><ul><li>Superficial bl. Carcinoma- no sign </li></ul><ul><li>Palpable mass- at least muscle involved </li></ul><ul><li>Bimanual palpation at the time of cystoscopy- </li></ul><ul><li>movable tumor- stage ≥ T3a </li></ul><ul><li>fixed contiguous structure- stage IV </li></ul><ul><li>Hepatomegaly, supraclavicular lymphadenopa. </li></ul><ul><li>Lymphodema- from pelvic lymphadenopathy. </li></ul><ul><li>Anaemia </li></ul>
  21. 26. Diagnosis <ul><li>Investigations: </li></ul><ul><li>Urine analysis and C/S </li></ul><ul><li>Urine for cytolgy </li></ul><ul><li>Blood for TC,DC,Hb%,ESR </li></ul><ul><li>Blood urea & serum creatinine </li></ul><ul><li>Flow cytometry & image analysis </li></ul><ul><li>Tumor markers- BTA, BTA stat, BTA TRAK, NMP 22 </li></ul><ul><li>Cytokeatin 20, lewis x Ag, telomerase activity, HA, HA-ase, </li></ul>
  22. 27. Investigations cont.. <ul><li>UroVysin test- ‘FISH’ analysis </li></ul><ul><li>Sensitivity 81%, Specificity 96% </li></ul><ul><li>HA- more sensitive for low grade (92%, 93%) </li></ul><ul><li>Hyaluroniase- for high grade (100%, 89%) </li></ul><ul><li>Survivin- anti apoptosis protein (100%, 95%) </li></ul><ul><li>detect new or recurrent cases </li></ul><ul><li>Endothelial growth factor, p53, Her-2-neu- </li></ul><ul><li>more applicable to invasive disease </li></ul><ul><li>( Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney and Richard D. Williams, BJU, 2004, Vol 94: 18-21.) </li></ul>
  23. 28. Diagnosis <ul><li>Imaging </li></ul><ul><li>Ultrasound </li></ul><ul><li>IVU </li></ul><ul><li>CT scan </li></ul><ul><li>MRI </li></ul><ul><li>CXR </li></ul><ul><li>Radionuclide bone scan </li></ul><ul><li>Urethrocystoscopy </li></ul><ul><li>Biopsy </li></ul>
  24. 35. Management of superficial Bladder carcinoma <ul><li>Treatment options: </li></ul><ul><li>Tis Complete TUR followed by BCG </li></ul><ul><li>Ta ( single, low to moderate grade) Complete TUR </li></ul><ul><li>Ta ( large, multiple, high grade, recurrent)-Complete TUR followed by intravesical Chx or immunotherapy </li></ul><ul><li>T1 Complete TUR followed by intravesical Chx or immunotherapy but controversy- high grade-III, radical cystectomy if recurrence after a trial needs aggressive treatment </li></ul>
  25. 36. Mx of superf. TCC cont.. <ul><li>Transurethral resection (TUR) </li></ul><ul><li>Role of ReTURB </li></ul><ul><li>(Effect of routine repeat TUR for superficial bladder cancer: a long term observational study, Marc- oliver Grimm, C. Steinhoff et al, J of Urol.) </li></ul><ul><li>Complications- perforation, clot retention, ureteric orifice stricture </li></ul><ul><li>Laser therapy- Nd:YAG, Holmium, Potassium </li></ul><ul><li>titanyl phosphate (PTP) </li></ul><ul><li>Photodynamic therapy- </li></ul>
  26. 37. Mx of superf. TCC cont.. <ul><li>Intravesical chemotherapy- </li></ul><ul><li>Mitomycin-C- just after TUR, wkly </li></ul><ul><li>40 mg in 60 ml water </li></ul><ul><li>Complications: chemical cystitis, dec. bladder capacity </li></ul><ul><li>palmer desquamation. </li></ul><ul><li>Bacille Calmette Guerin: </li></ul><ul><li>M/A- activity through activation of CD8 cell </li></ul><ul><li>40 mg in 60 ml water for 6 wks, 3 wkly at 3 & 6 m </li></ul><ul><li>every 6 mo thereafter for 3 yrs. </li></ul><ul><li>(BCG therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progression, </li></ul><ul><li>P. Andius, S. Holmang, BJU,2004, Vol. 93: 980-984) </li></ul>
  27. 38. BCG cont.. <ul><li>Indications: </li></ul><ul><li>Cis, Residual tumor, Tumor prophylaxis </li></ul><ul><li>Contraindications: </li></ul><ul><li>immunosuppression, immunocompromised pt. </li></ul><ul><li>relative: poor overall performance, advance age, H/O TB </li></ul><ul><li>Side effects: </li></ul><ul><li>hematuria, granulomatous prostatitis, </li></ul><ul><li>fever- Isoniazid 300 mg for 3 mo </li></ul><ul><li>systemic BCGosis- INH+Rifam, Etham for 6 mo </li></ul><ul><li>BCG sepsis- standard life support, tripple therapy </li></ul>
  28. 39. Mx of superf. TCC cont.. <ul><li>Thiotepa </li></ul><ul><li>alkylating agent, 30 mg in 30 ml, wkly for 6 wks </li></ul><ul><li>Doxorubicin, epirubicin </li></ul><ul><li>Valrubicin- BCG refractory Cis who can’t tolerate </li></ul><ul><li>cystectomy </li></ul><ul><li>Ethoglucid- alkylating agent, podophylline derivative. </li></ul><ul><li>Combination- mitomycin(20mg) day 1 </li></ul><ul><li>doxorubicin(40mg) day 2 for 5wk </li></ul><ul><li>chemotherapy & BCG </li></ul>
  29. 40. Mx of superf. TCC cont.. <ul><li>Newer intravesical chemotherapy </li></ul><ul><li>Gemcitabine- twice wkly for 6 wks with a 1-wk break after first 3 wks. </li></ul><ul><li>salvage intravesical agent for BCG failure. </li></ul><ul><li>Mycobacterial cell wall extract- Myco. Phlei. </li></ul><ul><li>induction regimen for 6 wks followed by monthly maintenance dose </li></ul><ul><li>( Superficial TCC (Ta/T1/CIS) of the bladder, Badrinath R. Koney and Richard D. Williams, BJU, 2004) </li></ul>
  30. 41. Mx of superf. TCC cont.. <ul><li>Other forms of immunotherapy: </li></ul><ul><li>Interferon( α -2b)- combined with BCG(low dose) </li></ul><ul><li>Keyhole-Limpet Haemocyanin </li></ul><ul><li>Bropirimine- inducer of IF & NK cell </li></ul><ul><li>IL12, IL2, TNF </li></ul><ul><li>Gene therapy: </li></ul><ul><li>Cystectomy- persistent/ recurrent , high risk superf. who </li></ul><ul><li>failed to iv Chx., T1 high grade, multifocal. </li></ul>
  31. 42. Mx of superf. TCC cont.. <ul><li>Alternatives: </li></ul><ul><li>External beam radiation therapy- </li></ul><ul><li>refuse cystectomy, unsuitable for major surgery </li></ul><ul><li>Chemoprevention: </li></ul><ul><li>High water intake </li></ul><ul><li>Vitamins- megadoses(vit A,B6,C,E,Zinc) </li></ul><ul><li>Difluoromethylornithine- enzyme inhibition </li></ul><ul><li>Soy products- phytochemicals </li></ul><ul><li>Cyclooxigenase inhibitors- COX2 </li></ul>
  32. 43. Follow up <ul><li>Tumor categorized as low, medium & high risk and follow up according to risk </li></ul><ul><li>3 mo for 1 st yr </li></ul><ul><li>6 mo for 2 nd yr </li></ul><ul><li>Annually for thereafter. </li></ul><ul><li>High risk group needs frequent follow up- 1 st at 6wk </li></ul><ul><li>Urine cytology </li></ul><ul><li>Tumor marker in urine- NMP 22, Ha-HAase </li></ul><ul><li>sesitivity- 50-90%, specificity- 60-90% </li></ul><ul><li>IVU </li></ul>
  33. 44. Management of invasive and metastatic bladder cancer <ul><li>Treatment options: </li></ul><ul><li>T2-T3 Radical cystectomy(RC) </li></ul><ul><li>Neoadjuvant Chx followed by RC </li></ul><ul><li>Neoadjuvant Chx followed by irradiation </li></ul><ul><li>RC followed by adjuvant Chx </li></ul><ul><li>Any stage T,N+,M+ Systemic Chx followed by </li></ul><ul><li>selective surgery or irradiation </li></ul>
  34. 45. Rx of invasive bladder cancer cont.. <ul><li>Radical cystectomy </li></ul><ul><li>Indications: Muscle invasive bladder cancer in </li></ul><ul><li>absence of metastasis </li></ul><ul><li>Surgical technique: </li></ul><ul><li>Cystectomy, bil. Pelvic lymphadenectomy </li></ul><ul><li>Male- prostate bladder en block </li></ul><ul><li>Female- uterus, tubes, ovaries, ant wall of vagina </li></ul><ul><li>Nerve sparing modification in male </li></ul><ul><li>Preservation of urethra in male/ female </li></ul><ul><li>Role of pelvic lymphadenectomy </li></ul><ul><li>(Does extended lymphadenectomy increase the morbidity of radical cystectomy? C. Brossner, A. Pycha et al, </li></ul><ul><li>BJU, 2004:Vol 93: 64-66) </li></ul>
  35. 47. Radical cystectomy cont.. <ul><li>Complications: </li></ul><ul><li>Mortality 1-2% </li></ul><ul><li>Morbidity- cardiac arrest, postoperative pul </li></ul><ul><li>embolism, rectal injury, bowel obstr. </li></ul><ul><li>ureteral-enteric anastomotic stricture, meta. </li></ul><ul><li>disorder, vitamin def., chronic UTI, renal </li></ul><ul><li>calculous disease, depression </li></ul>
  36. 48. Radical cystectomy cont.. <ul><li>Follow up: </li></ul><ul><li>tumor recurrence, </li></ul><ul><li>complication related to interposition of bowel </li></ul><ul><li>Annual screening with </li></ul><ul><li>Physical examination, serum electrolytes </li></ul><ul><li>Chest X-ray (PT1) </li></ul><ul><li>semiannual- (PT2), quarterly- (PT3) with annual CT scan. </li></ul><ul><li>Upper tract imaging- to exclude ureteral stenosis, upper tract tumor. </li></ul>
  37. 49. Treatment cont.. <ul><li>Adjunct to standard surgical therapy </li></ul><ul><li>Preoperative radiation therapy </li></ul><ul><li>Neoadjuvant Chx </li></ul><ul><li>Perioperative Chx </li></ul><ul><li>Adjuvant Chx </li></ul><ul><li>Alternatives to standard therapy: </li></ul><ul><li>Radiation therapy- external beam radiation </li></ul><ul><li>hyperfractionation schedule </li></ul><ul><li>T2a- TUR & BCG immunoprophylaxis who were </li></ul><ul><li>unfit for or refused more aggressive surgery </li></ul><ul><li>(T2a TCC of the bladder: long-term experience with intravesical immunoprophylaxis with BCG, B. G. Volkmer, J.E. Gschwend et al, J of Urol, Vol 169, 931-935, March’2003) </li></ul>
  38. 50. Treatment cont.. <ul><li>Transurethral resection & partial cystectomy </li></ul><ul><li>TUR , partial cystectomy with Chx </li></ul><ul><li>Bladder preservation protocol: </li></ul><ul><li>TUR, neoadjuvant Chx (MCV), subsequent RTx </li></ul><ul><li>Contraindication- presence of HDN, Cis, a tumor that </li></ul><ul><li>can’t resect transurethrally. </li></ul><ul><li>Interstitial radiation therapy </li></ul><ul><li>preoperative external beam radiation, TUR or partial </li></ul><ul><li>cystectomy, susequent Iridium192 wire (low stage T1-T2) </li></ul><ul><li>Intraarterial Chx ( combined with RC, radiation ) </li></ul><ul><li>Hyperthermia and Chx </li></ul>
  39. 51. Treatment of metastatic bladder cancer <ul><li>Systemic chemotherapy </li></ul><ul><li>unresectable, diffusely metastatic </li></ul><ul><li>MVAC </li></ul><ul><li>Newer agent- Gemcitabine </li></ul><ul><li>Taxoids- Docetaxel, paclitaxel </li></ul><ul><li>Local salvage and palliative therapy </li></ul><ul><li>Selection of patient for urinary diversion following radical cystectomy </li></ul><ul><li>noncontinent divrsion, continent diversion </li></ul><ul><li>orthotopic neobladder </li></ul><ul><li>Counselling </li></ul>
  40. 52. Prognostic indicators <ul><li>Clinical & pathological parameters in superf. TCC </li></ul><ul><li>Laboratory parameters ( P53 nuclear accumulation ) </li></ul><ul><li>A,B,H and other blood group antigen </li></ul><ul><li>Lewisx Ag expressed </li></ul><ul><li>ABH – not present </li></ul><ul><li>Growth factor and their receptors </li></ul><ul><li>TGF β -1 </li></ul><ul><li>Amplification of c-erb-B2 oncogene </li></ul><ul><li>Chromosomal and genetic abnormalities </li></ul><ul><li>deletion Ch-9, deletion Ch 17p-P53, Ch13q- Rb gene. </li></ul>
  41. 53. Prognosis <ul><li>Tumor stage </li></ul><ul><li>Cis </li></ul><ul><li>PTa </li></ul><ul><li>PT1 </li></ul><ul><li>PT2 </li></ul><ul><li>PT3 </li></ul><ul><li>PT4 </li></ul><ul><li>5 year survival </li></ul><ul><li>90%-100% </li></ul><ul><li>90%-95% </li></ul><ul><li>40%-75% </li></ul><ul><li>55%-60% </li></ul><ul><li>30%-40% </li></ul><ul><li>5%-10% </li></ul>
  42. 54. What’s new <ul><li>Staging- T1a & T1b, T4b (sem. vesicle) </li></ul><ul><li>Tumor markers- UroVysin, HA,H-ase, Survivin </li></ul><ul><li>Role of ReTURB </li></ul><ul><li>New intravesical cheomtherapy- Gemcitabine </li></ul><ul><li>Role of lymphadenectomy in RC </li></ul><ul><li>Bladder preservation protocol in T2a with BCG </li></ul><ul><li>Prognostic significance in seminal vesical involvement. </li></ul>
  43. 55. References <ul><li>Emil A. Tanagho, Jack W. McAninch; Smith’s General Urology; 16 th edn.; McGraw Hill 2004. </li></ul><ul><li>Fagbemi S, Stadler W. New Chemotherapy regimens for advanced bladder cancer. Semin Uro Oncol 1998;16:23. </li></ul><ul><li>Gillenwater JY, Grayhack JT; Adult and Pediatric Urology; Mosby 1996. </li></ul><ul><li>Russel, Williams and Bulstrode; Baily & Love’s short practice of surgery; 24th edn; Arnold, 2000. </li></ul><ul><li>Walsh, Retik, Vaughan & Wein; Campbell’s urology; 8 th edn.; W.B. Saunders Company, 2002. </li></ul><ul><li>Salam MA; Principles & Practice of Uromlogy; 1 st edn; </li></ul><ul><li>MAS publication,2002. </li></ul>
  44. 56. Thank you

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