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29 Cards in this Set
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Bladder cancer stats About 360,000 new cases reported/year worldwide. Globally 7th most common in men & 17th in women 10,000 new cases per year UK (4th in Men & 7th Women) 5000 deaths per year What are the risk factors? |
Smoking- 50-65% cases in males and 20-30% in Females (Risk reduction=40% (1-4 years) 60% (25 years)-4 Amino-biphenyl / O-ToludineOccupational Exposure: (The 1st Industrial Disease) 20-25%– (Dyes, Rubbers, Textiles, Paints, Leather, Chemicals) 4 Amino-biphenyl /2 Naphthyl-amine / BenzidineChemotherapy• CyclophosphamideChronic Irritation: Long-term IDC (Paraplegics)-5% / ISC /Recurrent UTI Pelvic Radiation (x2-4)Schistosomiasis (600 million infected)
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What is the relationship between Haematuria and bladder cancer?
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• 80% (BC) have visible (VH) or non-visible (NVH) haematuria• 15% of patients with VH have BC• 15% in general population have NVH 3.4% NVH have BT, 0.8% NVH have UT TCCBromage et al BAUS 2010
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The usual work up of Haematuria clinic involves, Urinalysis, FBC, Renal Profile, Liver profileFlexi cystoscopy, Renal USS and KUB +/- CT-UWhat is the value of Cytology?
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Urine Cytology• Improved sensitivity-– 3 Separate Specimens on 3 Consecutive days– 41% 41% 60%– High grade lesions– Sensitivity 90%– Specificity 98-100%G1 9% G2 32% G3 70%Henney NM J Urol 1983;130;1083-1086
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In optical diagnosis of bladder cancer tell me about the use of NBI?
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Narrow Band ImagingRationale: Depth of light penetration increases with wavelengthTissue is illuminated with Blue ( 415 nm) and Green (540 nm) Preferentially absorbed by HbThe B/L= Superficial Capillary NetworkGreen light=Deeper Vessels.
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In optical diagnosis of bladder cancer tell me about the use of PDD?
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Photodynamic Diagnosis (PDD) Rationale: Abnormal heme metabolism in cancer cells Involves administration of exogenous 5-ALA/Hexvix which bypasses the rate limiting step in the biosynthesis of heme. Induces high levels of proto-porphyrin IX (PpIX) in neo-plastic or highly proliferating cells. Excitation of PpIX by blue light PDD-Best Utility Initial detection/localization of multifocal tumours. Complete resection of NMIBC tumours Unconfirmed +ve cytology (CIS) Rink et al Eur Urol 2013:624-638 O'Brien T BJU Int. 2013 Dec;112(8):1096-104.
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How do you perform a TURBT for bladder cancer?
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Bladder Tumour Resection•GA•Muscle relaxation•Bimanual examination before and after•Enbloc Resection if tumour <1cm•Fractionated resection: Large TumoursExophytic componentUnderlying bladder wall with detrusor muscle Edge of the resection area
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What are the indications for re-resection after primary TURBT?
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Re-Resection if: High grade T1tumours even if the first resection is considered complete. Multiple/large volume tumours. No muscle in the specimen. Intra-operative complication. Second opinion in absence of muscle in specimen the risk of understating is as high as 50% (some report 100% muscle in cystectomy for G3T1 when associated with CIS).Herr B.J.Urol 1997
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What is the Prognosis of superficial TCC ?
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EORTC Study 3 month recurrence rate in 18 institutions: SingleTCC 0–36%Multiple TCC 7 – 75 %“The Surgeon is one of the most important factors” Brausi et al 2002 Eur Urol
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What is the evidence for post resection intra vesicle chemotherapy?
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Post-Resection Inta-vesical Chemotherapy Overall advantage about 15% (52 vs 37%)-short term. Effect disappears over 5 years with no apparent benefit with maintenance therapy. • (Lamm DL Urol Clin North Am 1992;19:573-80) Sylvester meta analysis(2004) n= 1476 MMC 12% absulute reduction and 39% relative risk reduction recurrence, NNT 9 to prevent 1 recurrence. Timing crucial, Finnbladder group showed if overnight delay the recurrence 2 fold increase. C/I if perforations (oddens 2004)
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What are the histological variants of bladder cancer?
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Common Histological Variants• Transitional Cell • Squamous Cell• Adenocarcinoma Rare VariantsSmall CellSpindle CellTrophoblastic differentiation Micro-papillaryNested
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What is CIS?
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Carcinoma in Situ (CIS)Carcinoma in situ is a flat, high-grade, non-invasive urothelial carcinomaPrimary: Isolated CIS with no previous or concurrent exophytic tumoursConcurrent: Associated with exophytic tumoursSecondary: Detected during the follow-up of patients with a previous tumour
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In Bladder cancer what is the difference between recurrence and progression?
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Recurrence vs Progression• Recurrence: Tumours of same stage• Progression: Advanced tumours with muscleinvasion or metastases• G3 pTa (39% progression and 25% die of it-15 year FUP) » Herr HW JUrol 2000; 163;60-2
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When would you offer surgery for high risk NMIBC?
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Early Radical Cystectomy-High Risk NMIBC Large or multi-focal tumours Co-existent extensive CIS Lympho-vascular invasion Prostatic involvement Persistent G3pT1 on re-resection / Post BCG therapy
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What is BCG?
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BCG• Live, attenuated bovine tubercle bacillus. White powder for reconstitution in sterile preservative-free normal saline 1.8-15.9 x 108 colony forming units (CFU) throughout shelf-life Mode of Action 6 – Attachment of BCG to endothelial cells aided by fibronectin. – BCG stimulates cells to produce cytokines – CRW. and Gillatt D. J.R.Soc Med 2001; 7 94:119-123 Cells infiltrated by T-lymphocytes, neutrophils & macrophages T-lymphocytes & BCG-activated killer (BAK) cells induce cytotoxic effects. Lockyear CRW. and Gillatt D. J.R.Soc Med 2001; 94:119-123
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The optimal BCG regime is set out byLamm DL, Blumenstein BA, Crissman JD et al. J Urol 2000; 163: 1124-1129.6x BCG (induction) 6/52 pause, 3xBCG then 1-3 weekly instillations unto 27 doses over 36/12why is this thought to work?
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Rationale BCG Regimen During induction immune stimulation peaks at 6 weeks During maintenance at 3 weeks The dose response is bell shaped- suggests that excess BCG may actually reduce the anti-tumour activity – ZlottaARJUrol1997;157:492-498 – DeReijkeTMetal;JUrol1996;155:488-9
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what can you offer a patient with BCG resistant CIS?
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BCG Resistant CIS• RadicalCystectomy-Standard• Thermo-chemotherapy-50-80% • Intra-vesicalGemcitabine-50%• Photodynamic therapy (Photofrin 1.5mg/Kg)+ Red Laser (630nm) 15 J/cm2 -RR 75% (CIS)
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what is thermochemotherapy?
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Thermo-Chemotherapy• Uniform heating of the bladder by radiofrequency (microwave) radiationtemperature monitoring by thermocouplescirculation of the cooled MMC into and out of the bladder
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what is the likely hood of metastasis in MIBC?
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Micro-metastases in MIBCAlmost 50% patients have micro-metastatic disease at diagnosisMost become evident within a year after cystectomy Babaian et al 1980
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what is your preop imaging in Bladder cancer?
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CT pre TURBT or 2-3/52 later if suspected MIBCIf confirmed MIBCMust repeat if > 6-8 weeks oldCT Chest, Abdomen and PelvisMRI Scan (Standard or Diffusion Weighted) Bone Scan in Selected cases-Symptoms High ALP FDG-PET CT Vs CTHigher sensitivityEquivalent specificityCombination better but too expensive
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Do you offer Chemo to MIBC prior to surgery?
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Neo-adjuvant Chemotherapy347 Patients154 Surgery Alone Median Survival 46 months 153 Neoad+ Surgery Median Survival 77 months(Absolute survival benefit in 5%)Grossman HB NEJM 2003:349: 859-865 No- Neo-adjuvant ChemotherapyImpaired renal functionBilateral upper tract obstructionIntractable haematuria / severe urinary symptoms Poor performance statusPatient refuses neo-adjuvant chemotherapy
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what else is required with cystectomy for MIBC?
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Lymph-adenectomyLymph-adenectomy is a critical component of cystectomy 30-40% of node +ve patients can be cured by adequatelymphadenectomy !Survival after RC is closely related to no. of lymph nodes removed even amongst node negative patients(Herr HW J Clin Oncol 2004;22:2781-9, Leissner J,J Urol 2004;171:139-144, Abo-Elenein et al)
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In MIBC the nodes involved are usually Obturator =75%, External iliac= 65% Pre-sacral =25%. Common iliac=20% Para-vesical=15%,Lymph Node SpreadDo you perform a limited (level 1) or extended (level 2) PLND?
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Limited vs Extended-5 Yr RFS pT2N0- 5Y RFS67% limited77% extendedAll Stages pT2/pT3 – 5Y RFS 7% limited35% extendedDhar NB et al J Urol 2008:179;873-878
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are there any test in the prep workup to help identify poor cystectomy candidates?
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CPET: RationaleA patient’s ability to respond to the increased physiological demands of surgery is heavily reliant on their cardiac and pulmonary function.Patients are more likely to die when oxygen delivery is insufficient to meet the body’s oxygen requirements.Pre-operative CPET aims to quantify cardio-respiratory dysfunction.Anaerobic ThresholdWhen aerobic metabolism is unable to meet the ATP requirements for cell function, anaerobic metabolism will provide small amounts of ATP.The point of transition from aerobic to anaerobic is Anaerobic Threshold . Cut OffThe VO2 is the product of cardiac output and arterio- venous oxygen difference.Patients with a peak VO2 of < 14ml/kg/min have a worse overall prognosis
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what is an ideal urinary diversion?
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An Ideal Urinary Diversion!Low pressureFunctional capacity of 500mls Reliable complete continence Complete voluntary control of voiding No absorption of urinary solutes=“Normal Bladder”
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what are the early complications of an Ileal conduit?
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Early Complications-ICUDIschaemiaIleusBowel Anastomotic leak Urinary leak-1-3% Bowel obstruction Delayed Complications-ICUD – Parastomal hernia 4.5-31% – Stomal retraction 0-31% Upper Tract Deterioration 30% – UTI 0-23% – Stomal stenosis 0-15% – Bowel complications 5-10% – Stomal bleeding 0-8% Wood DN, Allen SE, Greenwell TJ, Shah PJR. Stomal Complications of Ileal Conduit are Significantly Higher when formed for Women with Intractable Urinary Incontinence. In press. J Urol 2004.Madersbacher S, Schmidt J, Eberle JM et al. Long-term outcome of ileal conduit diversion. J Urol. 2003 Mar;169(3):985-90.
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What are the contra indications for continent urinary diversion after cystectomy for MIBC
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Absolute Contraindications Impaired renal function GFR <40mls/min Impaired hepatic function Physical/Mental Impairment to do CISC Positive apical surgical margin Unmotivated patient Relative ContraindicationsAssociated co-morbiditiesAdvanced ageNeed for adjuvant chemotherapyPrior pelvic radiationBowel diseaseUrethral pathologyExtensive local disease with high risk of recurrence
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what is a mitrofanoff channel?
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Mitrofanoff Channel• 1st described in 1980• Continent supravesical catheterisable channel• Appendix on vascular pedicleMitrofanoff P. Chir Ped 1980; (21): 297-305 Contra-IndicationsInsufficient dexterityHarmon EP, Hurwitz G. South Med J 1994; 87 (10): 1005-1006 Early Complications Mortality0-4% Peri-stomal abscess Small bowel obstruction Ischaemic necrosis of channel (Higher ratesYang/Monti channel) 0-2.1% 4-20%0-12%
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What is a MAINZ II continent urinary diversion for MIBC?
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MAINZ II (Ureterosigmoidostomy) A rectosigmoid reservoir of increased capacity and lower pressure to protect the upper tracts. Good Continence 94-98% • Complications – Acidosis (NaHCO3) – Anastomoticstricture – Adenocarcinoma
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For MIBC there is a rationale of multimodal approach to bladder preservation, what are the key features?
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Bladder Preservation: Multi- Modality Approach• Rationale: Radical TURBT + DXT= local control Chemotherapy for micro-metastases Certain agents gem / cis/ 5FU – radio-sensitisation Bladder Preservation-Outcomes Overall CR=72% CR 78% if T2 Cystectomy rates=29% (17% immediate) Mean time to cystectomy in salvage group 13m Better preservation of Bladder & Sexual Function Low rates of significant late pelvic toxicity Radiation+ Chemotherapy 5FU 500mg/m2 during fraction 1-5 & 16-20 MMC 12mg/m on day 1 5 Year Overall Survival 48% vs 35% James ND et al NEJM 2012;366:1477-1488
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