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Carcinoma urinary bladder

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lecture by Dr. Ahmed Rehman

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Carcinoma urinary bladder

  1. 1. HEMATURIA and Carcinoma Urinary Bladder
  2. 3. Learning Objectives <ul><li>to enumerate causes of hematuria </li></ul><ul><li>To enlist positive features on elaborate history and relevant clinical examination in a case of hematuria and of a bladder tumour </li></ul><ul><li>able to suggest and interpret relevant investigations in a case of hematuria and of a bladder tumour </li></ul><ul><li>to give justification for and against a diagnosis </li></ul><ul><li>Classify bladder tumours </li></ul><ul><li>Enlist steps in management of hematuria & TCC </li></ul><ul><li>Enlist differents roles an internist has to play in TCC </li></ul>
  3. 4. Bladder tumours <ul><li>Primary </li></ul><ul><ul><li>Urothelial, 95 % </li></ul></ul><ul><ul><li>Con tissue </li></ul></ul><ul><ul><ul><li>Angioma, fibroma, myoma, sarcoma </li></ul></ul></ul><ul><ul><li>Extra adrenal pheochromocytoma </li></ul></ul><ul><li>Secondary </li></ul><ul><ul><li>Sigmoid, rectum, prost, uterus, ovary, bronchus </li></ul></ul>
  4. 5. Types <ul><li>Benign papillary tomours </li></ul><ul><ul><li>Simple frond with villi on vascular core </li></ul></ul><ul><ul><li>Sea anemone </li></ul></ul><ul><li>Inverted papiloma </li></ul><ul><ul><li>Proliferation under normal mucosa ( covered) </li></ul></ul><ul><li>Carcinomas </li></ul><ul><ul><li>TCC , (mix, metaplasia in TCC) 90 % </li></ul></ul><ul><ul><li>Squmous cell (bilharzia, stone irritation) 5% </li></ul></ul><ul><ul><li>Adenocarcinoma , ( urachal remnents, fundus) 2% </li></ul></ul>
  5. 6. Urothelial tumours <ul><li>TCC </li></ul><ul><ul><li>Risk factors </li></ul></ul><ul><ul><ul><li>Smoking 40% </li></ul></ul></ul><ul><ul><ul><li>Occupation /exposure to chemicals </li></ul></ul></ul><ul><ul><ul><li>Oncogenes ras, c-erb B 1 & 2, E2F3 </li></ul></ul></ul><ul><ul><ul><li>Suppersor p53, p21, p16, retinoblastoma genes </li></ul></ul></ul><ul><ul><ul><ul><ul><li>mettaloproteinases </li></ul></ul></ul></ul></ul>
  6. 7. Clinical features <ul><li>Hematuria , may not be reported </li></ul><ul><li>Clot retention </li></ul><ul><li>LUTS </li></ul><ul><li>Dysurea ( malignant cystitis) </li></ul><ul><li>Pain </li></ul><ul><ul><li>Pelvic, suprapubic, genital, thigh </li></ul></ul><ul><ul><li>Advance malignancy, nerve involvement </li></ul></ul><ul><ul><li>Loin– pyelonephritis, ureteric obs/hydronephrosis </li></ul></ul>
  7. 8. Hematuria <ul><li>Gross blood in urine </li></ul><ul><li>Microscopic 3 to 5 RBCs per HPF </li></ul><ul><li>Always abnormal = </li></ul><ul><ul><li>whether macro, </li></ul></ul><ul><ul><li>micro, </li></ul></ul><ul><ul><li>single episode </li></ul></ul><ul><ul><li>or patient on anticoagulants </li></ul></ul>
  8. 9. 3 glass test <ul><li>Terminal : proximal urethra, baldder neck/trigone, </li></ul><ul><li>Initial: distal to ext sphincter, </li></ul><ul><li>total : baldder / upper tract </li></ul><ul><li>Bleed per urethra </li></ul>
  9. 10. <ul><li>History & exam not sufficent to make diagnosis, so always needs investigations. </li></ul><ul><li>Degree bears no relation with severity of disease. </li></ul><ul><li>Always take it serious until proved otherwise </li></ul>
  10. 11. Cause may be any where in urinary tract <ul><li>Kidneys ----- Surgical Causes </li></ul><ul><ul><li>Congenital – polycystic, PUJ, medullary sponge kidney </li></ul></ul><ul><ul><li>Trauma – stone, rupture, runner’s hematuria </li></ul></ul><ul><ul><li>Inflammation – Nonspecific, TB, </li></ul></ul><ul><ul><li>Neoplastic – RCC, TCC pelvis, Wilm’s </li></ul></ul><ul><ul><li>papillary necrosis </li></ul></ul><ul><ul><li>Vascular / Congestion – AV malformations, RHF,renal vein thrombosis, </li></ul></ul><ul><ul><li>Infarction – arterial thrombosis / embolism </li></ul></ul><ul><ul><li>Medical causes </li></ul></ul><ul><ul><li>Glomerular disorders – glomerulonephritis, IgA nephropathy, Benign idiopathic hematuria </li></ul></ul><ul><ul><li>Lymphoma, multiple myeloma, amiloidosiss </li></ul></ul>
  11. 12. Surgical Causes <ul><ul><li>Ureters </li></ul></ul><ul><ul><ul><li>Stones, TCC ureter, VUR, stricture, </li></ul></ul></ul><ul><li>Bladder </li></ul><ul><ul><li>Trauma, stone, catheter trauma </li></ul></ul><ul><ul><li>Inflammation – cystitis, TB, Bilharzia, post-radiation cystitis, cyclophosphamide chemo. </li></ul></ul><ul><ul><li>Neoplastic – TCC, adeno squaamous </li></ul></ul><ul><li>Prostate </li></ul><ul><ul><li>BPH, CaP, prostititis, </li></ul></ul>
  12. 13. Surgical Causes <ul><li>Urethra </li></ul><ul><ul><li>Trauma, rupture, stone, catheter trauma </li></ul></ul><ul><ul><li>Inflmmation – urethritis </li></ul></ul><ul><ul><li>Neoplaastic – TCC urethra, penile Ca </li></ul></ul><ul><ul><li>Atrophic urethritis </li></ul></ul>
  13. 14. Surgical Causes <ul><li>Miscellaneous </li></ul><ul><ul><li>Endometriosis </li></ul></ul><ul><ul><li>Diverticulitis </li></ul></ul><ul><ul><li>Appendicitis </li></ul></ul><ul><ul><li>Abdominal aortic aneurysm </li></ul></ul><ul><ul><li>Foreign body </li></ul></ul>
  14. 15. Surgical Causes <ul><li>False hematuria food colors / drugs staining red (beet roots, Dindevan, pyridium,furadantin, rifampicin,= differentiation made with microscopy (RBCs) </li></ul><ul><li>False +ve dipstick test. hemoblobin, erthrocytes, myoblobin, pigmenturia. DD= microscopy </li></ul><ul><li>Factitious = source outside urinary system </li></ul><ul><ul><li>Vaginal bleeding, malingering </li></ul></ul>
  15. 16. Medical Causes, cause of hematuria may not be in urinary tract but outside it <ul><li>Systemic disorders </li></ul><ul><ul><li>Haematological </li></ul></ul><ul><ul><ul><li>Bleeding disorders </li></ul></ul></ul><ul><ul><ul><ul><li>purpura, sickle cell disease, hemophilia, scurvy </li></ul></ul></ul></ul><ul><ul><ul><li>therapeutic anticoagulants, </li></ul></ul></ul><ul><li>Miscellaneous </li></ul><ul><ul><li>Malaria, SLE, Henoch Schonlein purpura, hypersensitivity angiitis, bacterial endocarditis, Wegener’s granulomatosis, Good pastures Syndrome </li></ul></ul>
  16. 17. Points in history <ul><li>Pain – renal, ureteric stone, clot, cysts, hydronephrosis, adv. Tumors, trauma </li></ul><ul><li>Trauma, wt. loss, LUTS, dysuria, fever, riger, constitutional symptoms </li></ul><ul><li>Pattern of hematuria- gross, micro, partial, total, persistant/continuous, intermittent, </li></ul><ul><li>Clots long threadlike, amorphous, fresh, old </li></ul><ul><li>Smoking, occupaton, travel to schist areas, </li></ul><ul><li>Rash, joint pain (SLE) </li></ul><ul><li>URTI-PSGN </li></ul><ul><li>Purpura, rash, echymosis, easy bruiseability, bleed from multiple sites </li></ul><ul><li>Medication – color, anticoagulants </li></ul><ul><li>Exercise, sepsis, systemic diseases = liver, renal failue </li></ul><ul><li>Mass, TB </li></ul>
  17. 18. Management Steps <ul><li>History </li></ul><ul><ul><li>Presenting complaints with details </li></ul></ul><ul><ul><li>Direct questions regarding other urinary symptoms </li></ul></ul><ul><ul><ul><ul><li>Differential Diagnosis </li></ul></ul></ul></ul><ul><ul><li>Direct questions regarding stage of disease </li></ul></ul><ul><ul><li>Direct questions regarding systemic illnesses. </li></ul></ul><ul><ul><li>Direct questions regarding risk factors </li></ul></ul>
  18. 19. Management Steps <ul><li>Examination </li></ul><ul><ul><li>Appearance </li></ul></ul><ul><ul><li>Vitals </li></ul></ul><ul><ul><li>GPE </li></ul></ul><ul><ul><li>Systemic exam </li></ul></ul><ul><ul><ul><li>Abdomen ----- DRE </li></ul></ul></ul><ul><ul><ul><li>Chest </li></ul></ul></ul>
  19. 20. Clinical examination <ul><li>No physical sign / Anything could be found </li></ul><ul><li>Disoriented – liver / renal failue </li></ul><ul><li>Catheter / irrigation / drip / canulla </li></ul><ul><li>Pain agony – stone, HN, retention </li></ul><ul><li>Cechhexia, </li></ul><ul><li>Pulse shock, sepsis </li></ul><ul><li>BP , normal, shock, high ( HTN, renal failure) </li></ul><ul><li>Temp infection </li></ul><ul><li>Resp renal failure, acidosis </li></ul><ul><li>Purpura, rash, echymosis </li></ul><ul><li>Pallor / degree, anemia hematuria, renal failure </li></ul><ul><li>Jaundice, edema, L.nodes </li></ul><ul><li>Palpable visreras, L,S,K,K,UB,LN, masses, </li></ul><ul><li>prostate, urethra, testes, epid- vas (TB), meatus,stricure, retention </li></ul>
  20. 21. Workup <ul><li>Esteblish hematuria - dipstick </li></ul><ul><li>Urine RE/microsscopy-RBCs </li></ul><ul><li>Urine CS – infection, doesn’t rule out other causes </li></ul>
  21. 22. flow cytometery <ul><li>Urinary cytology </li></ul><ul><li>May be helpful, being noninvasive, but not established to a point to replace routine workup. </li></ul><ul><li>tumour markers- NMP22, BTA </li></ul><ul><li>Yield varies from study to study & grade and type lesion </li></ul>
  22. 23. Management Steps <ul><li>Investigations </li></ul><ul><ul><li>Base line </li></ul></ul><ul><ul><ul><li>urea creatinine </li></ul></ul></ul><ul><ul><ul><li>Hb </li></ul></ul></ul><ul><ul><li>Specific </li></ul></ul><ul><ul><ul><li>IVU </li></ul></ul></ul><ul><ul><ul><li>? Contrast CT Scan/ MRI, local & nodal staging </li></ul></ul></ul><ul><ul><ul><li>Ultrasound </li></ul></ul></ul><ul><ul><ul><li>Sophisticated tests timour markers </li></ul></ul></ul><ul><ul><ul><li>cystoscopy </li></ul></ul></ul>
  23. 24. Advantages of US <ul><li>cheap, </li></ul><ul><li>easy, </li></ul><ul><li>easily available, </li></ul><ul><li>noninvasive, </li></ul><ul><ul><li>no countraindication, </li></ul></ul><ul><ul><li>nontoxic, </li></ul></ul><ul><ul><li>no side eff/reaction </li></ul></ul>
  24. 25. Disadvantages US <ul><li>good for renal parenchyma but not for pelvicaliceal system and ureter </li></ul><ul><li>not very good for bladder, small lesions-miss </li></ul><ul><li>Observer dependant, inter and intraobserver variability </li></ul>
  25. 26. Imaging: US findings <ul><li>Kidney : size, echogenicity, cortical thickness, cysts, mass, hydronephrosis, stone, C/m ratio </li></ul><ul><li>Ureter : dilated, stonne, mass, ureterocele </li></ul><ul><li>Bladder : stone, wall thickness / smooth, mass, clot, diverticula, capacity, pre- and postvoid volume </li></ul><ul><li>Prostste size, echogenicity </li></ul>
  26. 27. IVU <ul><li>Conventional, NOW CONTROVERTIAL </li></ul><ul><li>Invasive </li></ul><ul><li>IV contrast, </li></ul><ul><li>side eff/ adverse eff – anaphylaxis, toxicity,- </li></ul><ul><li>drug, </li></ul><ul><li>radiation) </li></ul><ul><li>Very good for pelvicaliceal system and ureter </li></ul><ul><li>May not be diagnostic </li></ul><ul><li>Many would proceed to cystoscopy after USG leaving IVU </li></ul>
  27. 28. IVU <ul><li>Demonstrates </li></ul><ul><li>anatomy –normal / cong abormalities </li></ul><ul><li>function </li></ul><ul><li>secretion thru kidney, </li></ul><ul><li>transport thru collecting system, </li></ul><ul><li>storage in bladder and evacuation. </li></ul>
  28. 29. IVU <ul><li>Principle </li></ul><ul><li>Indications </li></ul><ul><ul><li>Stone, hematuria, trauma, congenital abnormalities, mass, assessment of function, obstruction </li></ul></ul><ul><li>Preparation </li></ul><ul><ul><li>Purgation, hydration </li></ul></ul><ul><li>Precautions </li></ul><ul><ul><li>Not during pain, renal status, hydration, clear KUB, allergy </li></ul></ul><ul><li>Procedure </li></ul><ul><ul><li>Test dose, procedure – timings </li></ul></ul><ul><li>Side / adverse reactions – management of </li></ul><ul><li>Contra-indications </li></ul><ul><li>Interpretation </li></ul><ul><li>Disadvantages </li></ul><ul><li>Constrast and other things required </li></ul><ul><ul><li>radiation </li></ul></ul>
  29. 30. IVU Findings <ul><li>Faint mass shadow on plain film, </li></ul><ul><li>ROS, </li></ul><ul><li>Hydronephrosis </li></ul><ul><li>Wall smoothness </li></ul><ul><li>filling defect, </li></ul><ul><ul><li>mass shadow, </li></ul></ul><ul><ul><li>Radiolucent stone </li></ul></ul><ul><ul><li>clot, fungus, FB </li></ul></ul>
  30. 31. Management Steps <ul><li>Prepare for surgery / aneasthesia </li></ul><ul><ul><li>Fitness </li></ul></ul><ul><ul><ul><li>Co-morbidities ( smoking = IHD, COPD) </li></ul></ul></ul><ul><ul><li>Hb. Transfusions </li></ul></ul><ul><ul><li>Cloting profile </li></ul></ul>
  31. 33. Cysto-urethro-scopy <ul><li>Visualizes lower tract starting at ext meatus, leading to bladder.( U, P, BN, ) </li></ul><ul><li>bladder </li></ul><ul><ul><li>capacity, bleeding site, edema/ congestion,ulcer, mass, granuloma, orifices, diverticula, trabeculations, stone, </li></ul></ul><ul><li>Biopsy , brushings cytology, </li></ul><ul><li>Retrograde uro/pyelography / uretero-renoscopy </li></ul><ul><li>USG+cystoscopy +/_ RPG may obviate need for IVU in most but not all cases, in which case a formal IVU or a constrast CT scan is required </li></ul>
  32. 34. Management Steps <ul><li>EUA, Bimanual examination </li></ul><ul><li>Cystoscopy , Flexible / Rigid </li></ul><ul><ul><li>Inspection </li></ul></ul><ul><ul><li>Resection, as complete as possible </li></ul></ul><ul><ul><ul><li>Superficial biopsy A </li></ul></ul></ul><ul><ul><ul><li>Deep / base biopsy B </li></ul></ul></ul><ul><ul><ul><li>Random mucosal biopsies C </li></ul></ul></ul><ul><ul><ul><li>irrigation </li></ul></ul></ul><ul><ul><li>Bimanual examination </li></ul></ul>
  33. 35. Management Steps <ul><li>Histopathology report should include </li></ul><ul><ul><li>Type of lesion </li></ul></ul><ul><ul><li>Type of tumour </li></ul></ul><ul><ul><li>Grade of tumour (degree of differentiation) </li></ul></ul><ul><ul><li>Muscle included / involved </li></ul></ul><ul><ul><ul><li>Superficial disease ========= 85% </li></ul></ul></ul><ul><ul><ul><li>Invasive disease ========= 15% </li></ul></ul></ul><ul><ul><li>Random mucosal biopsies ? CIS </li></ul></ul>
  34. 36. Open excision or biopsy <ul><li>Avoided </li></ul><ul><li>Up-staging </li></ul><ul><li>Radiation </li></ul><ul><li>cauterize </li></ul>
  35. 37. Management Steps <ul><ul><li>? Further staging </li></ul></ul><ul><ul><ul><li>Superficial disease not required </li></ul></ul></ul><ul><ul><ul><li>Invasive disease / CIS </li></ul></ul></ul><ul><ul><ul><ul><li>Bone scan </li></ul></ul></ul></ul><ul><ul><ul><ul><li>CXR </li></ul></ul></ul></ul><ul><ul><ul><ul><li>LFTs / ultrasound </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Ct scan abdomen pelvis with double contrast / MRI </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Local invasion, liver, lymph nodes </li></ul></ul></ul></ul></ul>
  36. 38. 3 biological behaviral pattrens Non-muscle invasive (superficial) disease Muscle invasive disease Flat noninvasive CIS (primary CIS) pTa, pT1 pT2+ CIS 70% new cases 25% 5% Good prognosis Bad, 5 yr survival 50% Poor unless treated early Recur 70%, invade 15% Invade, metastasize Invade, metastasize Exophytic, papillary Single, multiple Solid, large,1 or more Irregular, ulcerated Flat, velvety mucosa, angry looking vessels Pedunculated (stalk) Broad base Field change +/_ (con CIS) Lamina propria muscularis Intra epithelial Comptete resection Persist on Bim Exam Met death 30-50% 50% deaths mets Down stage/salvage cyst Endoscopic + intravesical Primary surgical treatme Endo+intrrav+/-surgry
  37. 39. Stage wise treatment Stage Description Traetment Tis Ca insitu Complete TURBT Intravesical BCG-> repeat-> RC* Ta Single, low to moderate grade, not recurent Complete TUR alone Ta Large, multiple, high grade, recurrent Complete TUR intravesical chemo- or immunotherapy T1 Complete TUR-> intravesical chemo- or immunotherapy T1G3 Complete TUR ->Intavesical BCG -> repeat ->radical cystectomy T2 <ul><ul><li>Radical Cystectomy (RC) * </li></ul></ul>T2-4 <ul><ul><li>RC, Radiation , </li></ul></ul><ul><li>Neoadj Radiation -> RC ( salvage) </li></ul><ul><li>Neoadj chemo -> RC </li></ul><ul><li>RC -> adj chemo </li></ul><ul><li>Combined chemo-radio </li></ul>Any T, N+, M+ <ul><li>Systemic chemo followed by selective surgery or irrediation </li></ul>
  38. 40. Metastatic disease <ul><li>Systemic Chemotherapy </li></ul><ul><li>Radiotherapy </li></ul><ul><li>Combined chemo-radio </li></ul>
  39. 41. Intravesical Chemo- or Immunotherapy <ul><li>Mytomycin C </li></ul><ul><li>Thiotepa </li></ul><ul><li>Doxyrubicin </li></ul><ul><li>BCG </li></ul><ul><li>Newer agents </li></ul><ul><ul><li>Alpha interferon </li></ul></ul><ul><ul><li>bropiramine </li></ul></ul>
  40. 42. Systemic Chemotherapy <ul><li>MVAC </li></ul><ul><ul><li>(methotraxate, vinblastine, doxyrubicin, Cisplatin) </li></ul></ul><ul><li>CMV </li></ul><ul><ul><li>(Cisplatin, methotraxate, vinblastine) </li></ul></ul><ul><li>CISCA </li></ul><ul><ul><li>(Cisplatin, doxyrubicin, cyclophosphamide) </li></ul></ul>
  41. 43. New Systemic Chemotherapy <ul><li>Gemcitabine </li></ul><ul><li>Paclitaxel </li></ul><ul><li>ifosfamide </li></ul>
  42. 44. Radical Cystectomy <ul><li>pT2-3, M0N0, CIS </li></ul><ul><li>Incision </li></ul><ul><li>Pelvic Lymphadenectomy </li></ul><ul><li>Frozen sections </li></ul><ul><li>Organs </li></ul><ul><li>Urethractomy </li></ul><ul><li>diversion </li></ul>
  43. 45. diversions <ul><li>Incontenant reservoirs </li></ul><ul><ul><li>Ileal condouit </li></ul></ul><ul><li>Contenant reservoirs </li></ul><ul><ul><li>Ureterosigmoidostomy </li></ul></ul><ul><ul><li>Orthotopic neobladder </li></ul></ul><ul><ul><li>Catheterizable stoma pouches </li></ul></ul><ul><ul><ul><li>Metrofenof ‘s </li></ul></ul></ul><ul><ul><ul><li>Indiana </li></ul></ul></ul><ul><ul><ul><li>struder </li></ul></ul></ul>
  44. 46. Open Procdures / Biopsy <ul><li>Should never be performed </li></ul><ul><li>Cauterize </li></ul><ul><li>Radiotherapy </li></ul>
  45. 47. Radiation <ul><li>External beam Radiation </li></ul><ul><ul><li>5000 –7000 cGy </li></ul></ul><ul><ul><li>5 –8 weeks </li></ul></ul><ul><li>Local </li></ul><ul><li>Beads / wires </li></ul>
  46. 48. Management of associated problems <ul><li>Pain </li></ul><ul><li>Bleed </li></ul><ul><li>renal failure </li></ul><ul><li>others </li></ul>
  47. 49. Follow Up <ul><li>Cystoscopy </li></ul><ul><ul><li>3 monthly for 2 years </li></ul></ul><ul><ul><li>6 monthly for 3years </li></ul></ul><ul><ul><li>Yearly upto 10 years </li></ul></ul><ul><ul><li>Recurrence ===== new cycle </li></ul></ul><ul><li>IVU yearly for upper tract </li></ul>
  48. 50. Prognosis <ul><li>Treatment option wise prognosis </li></ul>
  49. 51. Resident’s Role <ul><li>History & Exam & Investigations </li></ul><ul><li>Identify active problems n treat </li></ul><ul><ul><li>Retention ------ catheter </li></ul></ul><ul><ul><li>Clots ------- bladder wash , 3 ways foley and irregation </li></ul></ul><ul><ul><li>Persistant hematutia ------- ‘alam‘ washes </li></ul></ul><ul><ul><li>Systemic illnesses medical conslt </li></ul></ul><ul><ul><li>Metastatic disease problems oncologist conslt </li></ul></ul><ul><ul><li>Transfusions donor orgs </li></ul></ul><ul><ul><li>Fitness for aneasthesia </li></ul></ul><ul><ul><li>Surgical items donor orgs </li></ul></ul><ul><ul><li>Pre- and postop care </li></ul></ul><ul><ul><li>Bowl preparation </li></ul></ul><ul><ul><li>Stoma counsilling and care </li></ul></ul><ul><ul><li>Counselling and moral build up </li></ul></ul><ul><ul><li>Coordination with different consultants </li></ul></ul>
  50. 52. remember <ul><li>Hematuria, many causes, always abnormal </li></ul><ul><li>Antibiotic, not sole treatment of </li></ul><ul><li>Ultrasound, not good in </li></ul><ul><li>IVU / cystoscopy, essential in </li></ul><ul><li>Histopath, details are imp </li></ul><ul><li>Followup, key to avoid recurence </li></ul>
  51. 53. Hematuria of obscure origin <ul><li>20% </li></ul><ul><li>Just explain that investigations that are usually carried oout have not demonstrated any cause - </li></ul><ul><li>Do reassure but Never explain that all is OK, a future investigation may show some cause in evolution or appearing then </li></ul><ul><li>Follow up is required </li></ul><ul><li>Emmergency cystoscope in cases of active rebleed </li></ul>

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