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29 Cards in this Set

  • Front
  • Back

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-Toludine
Occupational Exposure: (The 1st Industrial Disease) 20-25%


– (Dyes, Rubbers, Textiles, Paints, Leather, Chemicals) 4 Amino-biphenyl /2 Naphthyl-amine / Benzidine


Chemotherapy
• Cyclophosphamide


Chronic Irritation: Long-term IDC (Paraplegics)-5% / ISC /Recurrent UTI Pelvic Radiation (x2-4)
Schistosomiasis (600 million infected)

What is the relationship between Haematuria and bladder cancer?

• 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 TCC


Bromage et al BAUS 2010

The usual work up of Haematuria clinic involves, Urinalysis, FBC, Renal Profile, Liver profile


Flexi cystoscopy, Renal USS and KUB +/- CT-U


What is the value of Cytology?

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

In optical diagnosis of bladder cancer tell me about the use of NBI?

Narrow Band Imaging


Rationale: Depth of light penetration increases with wavelength


Tissue is illuminated with Blue ( 415 nm) and Green (540 nm) Preferentially absorbed by Hb
The B/L= Superficial Capillary Network


Green light=Deeper Vessels.

In optical diagnosis of bladder cancer tell me about the use of PDD?

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.

How do you perform a TURBT for bladder cancer?

Bladder Tumour Resection


•GA
•Muscle relaxation
•Bimanual examination before and after


•Enbloc Resection if tumour <1cm


•Fractionated resection: Large Tumours


Exophytic component
Underlying bladder wall with detrusor muscle Edge of the resection area

What are the indications for re-resection after primary TURBT?

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

What is the Prognosis of superficial TCC ?

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

What is the evidence for post resection intra vesicle chemotherapy?

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)

What are the histological variants of bladder cancer?

Common Histological Variants


• Transitional Cell • Squamous Cell
• Adenocarcinoma


Rare Variants


Small Cell
Spindle Cell
Trophoblastic differentiation Micro-papillary
Nested

What is CIS?

Carcinoma in Situ (CIS)


Carcinoma in situ is a flat, high-grade, non-invasive urothelial carcinoma


Primary: Isolated CIS with no previous or concurrent exophytic tumours


Concurrent: Associated with exophytic tumours


Secondary: Detected during the follow-up of patients with a previous tumour

In Bladder cancer what is the difference between recurrence and progression?

Recurrence vs Progression


• Recurrence: Tumours of same stage
• Progression: Advanced tumours with muscle


invasion or metastases


• G3 pTa (39% progression and 25% die of it-15 year FUP) » Herr HW JUrol 2000; 163;60-2

When would you offer surgery for high risk NMIBC?

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

What is BCG?

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

The optimal BCG regime is set out by


Lamm 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 36/12


why is this thought to work?

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

what can you offer a patient with BCG resistant CIS?

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)

what is thermochemotherapy?


Thermo-Chemotherapy


• Uniform heating of the bladder by radiofrequency (microwave) radiation


temperature monitoring by thermocouples


circulation of the cooled MMC into and out of the bladder


what is the likely hood of metastasis in MIBC?

Micro-metastases in MIBC


Almost 50% patients have micro-metastatic disease at diagnosis


Most become evident within a year after cystectomy Babaian et al 1980

what is your preop imaging in Bladder cancer?

CT pre TURBT or 2-3/52 later if suspected MIBC


If confirmed MIBC


Must repeat if > 6-8 weeks old


CT Chest, Abdomen and Pelvis
MRI Scan (Standard or Diffusion Weighted) Bone Scan in Selected cases-


Symptoms High ALP


FDG-PET CT Vs CT


Higher sensitivity
Equivalent specificity
Combination better but too expensive

Do you offer Chemo to MIBC prior to surgery?

Neo-adjuvant Chemotherapy


347 Patients
154 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 Chemotherapy


Impaired renal function
Bilateral upper tract obstruction
Intractable haematuria / severe urinary symptoms Poor performance status
Patient refuses neo-adjuvant chemotherapy

what else is required with cystectomy for MIBC?

Lymph-adenectomy


Lymph-adenectomy is a critical component of cystectomy 30-40% of node +ve patients can be cured by adequate


lymphadenectomy !


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)

In MIBC the nodes involved are usually Obturator =75%, External iliac= 65% Pre-sacral =25%. Common iliac=20% Para-vesical=15%,


Lymph Node Spread


Do you perform a limited (level 1) or extended (level 2) PLND?

Limited vs Extended-5 Yr RFS



pT2N0- 5Y RFS


67% limited


77% extended


All Stages pT2/pT3 – 5Y RFS


7% limited


35% extended


Dhar NB et al J Urol 2008:179;873-878

are there any test in the prep workup to help identify poor cystectomy candidates?

CPET: Rationale


A 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 Threshold


When 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 Off


The 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

what is an ideal urinary diversion?

An Ideal Urinary Diversion!


Low pressure
Functional capacity of 500mls Reliable complete continence Complete voluntary control of voiding No absorption of urinary solutes


=“Normal Bladder”

what are the early complications of an Ileal conduit?

Early Complications-ICUD


Ischaemia
Ileus
Bowel 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.

What are the contra indications for continent urinary diversion after cystectomy for MIBC

Absolute Contraindications


Impaired renal function GFR <40mls/min Impaired hepatic function Physical/Mental Impairment to do CISC Positive apical surgical margin Unmotivated patient


Relative Contraindications


Associated co-morbidities
Advanced age
Need for adjuvant chemotherapy
Prior pelvic radiation
Bowel disease
Urethral pathology
Extensive local disease with high risk of recurrence

what is a mitrofanoff channel?

Mitrofanoff Channel


• 1st described in 1980


• Continent supravesical catheterisable channel


• Appendix on vascular pedicle


Mitrofanoff P. Chir Ped 1980; (21): 297-305


Contra-Indications


Insufficient dexterity


Harmon 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%

What is a MAINZ II continent urinary diversion for MIBC?

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

For MIBC there is a rationale of multimodal approach to bladder preservation, what are the key features?

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