Dickie Robinson Victoria Hopkinson M W Lau. Outline / Objectives Dickie Epidemiology Diagnosis Pathology Staging Victoria Haematospermia Cytology and

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Dickie Robinson Victoria Hopkinson M W Lau Slide 2 Outline / Objectives Dickie Epidemiology Diagnosis Pathology Staging Victoria Haematospermia Cytology and alternatives to cytology Haematuria and key papers Slide 3 Case 1 79 female retired teacher WHO performance status 2 Presented via A&E with haematuria Irrigation for 2-3 days, no intervention required Flexible cystoscopy as an outpatient 1 week later Slide 4 Case 1 cont.. Solitary tmuour in the trigone. Nurse endoscopic, new in the job, asks should I arrange any scans? Slide 5 Upper tract imaging in bladder cancer FactorRR95% CIp Value Grade1.7(0.2-14.8)ns CIS1.16(0.3-3.7)ns T stage2.29(0.7-7.4)ns Trigone tumor5.8(2.18-15.9)0.0005 Bladder tumor size0.5(0.1-1.7)ns Multiplicity0.48(0.1-1.3)ns In this case also a judgment call as 79 years old and WHO 2. Palou J Urol 2005 174(3):859-861 Retrospective study of 1,529 primary NMIBC patients - examination of the upper urinary tract with excretory urography. 28 patients (1.8%) had synchronous UUTT, 17.9% were multiple and 46% were invasive. 7.5% of trigone tumours were associated with UUTT, but this only corresponded to 41% of the UUTTs first diagnosed (ie. if only scan trigonal tumours will miss 59% of UUTT) EAU guidelines 2013 on NMIBC simply references the above paper. Slide 6 Case 1 cont. Wednesday morning, patient in surgical admission lounge having been listed for a TURBT. 1.Explain the consent process for TURBT 2.Key steps of a TURBT Slide 7 Consent for TURBT Should commence in clinic / prior to day of surgery and be backed up with written information / website etc.. Common (greater than 1 in 10) Mild burning or bleeding on passing urine for short period after operation Temporary insertion of a catheter for bladder irrigation Need for additional treatments to bladder in attempt to prevent recurrence of tumours including drugs instilled into the bladder Occasional (between 1 in 10 and 1 in 50) Infection of bladder requiring antibiotics No guarantee of cancer cure by this operation alone Recurrence of bladder tumour and/or incomplete removal Rare (less than 1 in 50) Delayed bleeding requiring removal of clots or further surgery Damage to drainage tubes from kidney (ureters) requiring additional therapy Injury to the urethra causing delayed scar formation Perforation of the bladder requiring a temporary urinary catheter or open surgical repair Hospital-acquired infection Colonisation with MRSA (0.9% - 1 in 110) Clostridium difficile bowel infection (0.01% - 1 in 10,000) MRSA bloodstream infection (0.02% - 1 in 5000) BAUS Bladder Tumour Resection Procedure Specific Information for Patients http://www.baus.org.uk/Resources/BAUS/Documents/PDF%20Documents/Patient%20information/TURBT.pdf Slide 8 Steps in TURBT (modified from EAU guidelines on NMIBC 2013) The goal of the TURBT is to make the correct diagnosis and in Ta-T1 tumours to remove all visible lesions. It is crucial in the diagnosis and treatment of BC. Theatre team briefing, WHO checks, VTE prophylaxis, warming & antibiotics. EUA Visualisation of the of the urethra, entire bladder and U.O.s. Bladder capacity. Small tumours (< 1 cm) can be resected en bloc. Larger tumours should be resected separately in fractions, including the exophytic part of the tumour, the underlying bladder wall with the detrusor muscle, and the edges of the resection area. Abnormal areas of urothelium (?CIS) - cold-cup biopsies or biopsies with a resection loop. Random (mapping) biopsies, should be performed in patients with positive urinary cytology and absence of visible bladder tumour. (Recommended biopsies: trigone, bladder dome, and from the right, left, anterior and posterior bladder walls). Biopsy prostatic urerthra in cases of suspected CIS or bladder neck tumours. In patients with palpable mass before TURB, EUA should be repeated after resection. Requirement for catheter +/- irrigation dependent upon findings. Document findings (EUA, capacity, size, multiplicity and location of tumours, residual tumour at end of procedure). Mitomycin-C for Ta-T1 tumours. Slide 9 Case 1 cont.. 2 weeks later, asleep in MDT, rumbled and asked what the histology represents: Low grade papillay TCC. What is the difference between the WHO 1973 and 2004 classification of urothelial bladder cancer? Slide 10 WHO 1973 vs. 2004 Current U.K. guidelines recommend pathologists report using both systems to allow prospective audit of outcomes. It was hoped that 2004 system would be more reproducible. PUNLMPs are not cancers (Harnden BJUI 2006 99:723-30) Conflicting evidence regarding comparisons of the prognostic power of each system.(MacLennan E Urol 2007 51(4):889-897 and Chen PLosOne 2012 7(10):e471499) Slide 11 TNM classification 75-80% NMIBC at presentation T - Primary tumour TX Primary tumour cannot be assessed T0 No evidence of primary tumour Ta Non-invasive papillary carcinoma Tis Carcinoma in situ: flat tumour T1 Tumour invades subepithelial connective tissue T2 Tumour invades muscle T2a Tumour invades superficial muscle (inner half) T2b Tumour invades deep muscle (outer half) T3 Tumour invades perivesical tissue: T3a Microscopically T3b Macroscopically (extravesical mass) T4 Tumour invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall T4a Tumour invades prostate, uterus or vagina T4b Tumour invades pelvic wall or abdominal wall N - Lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single lymph node in the true pelvis (hypogastric, obturator, external iliac, or presacral) N2 Metastasis in multiple lymph nodes in the true pelvis (hypogastric, obturator, external iliac, or presacral) N3 Metastasis in common iliac lymph node(s) M - Distant metastasis MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Slide 12 Molecular biological grading Placing tumours into categories according to their molecular phenotype will become the standard in the future, H&E grading is likely to become obsolete in prognostication. Occurring in breast cancer. Unlikely to be based upon old fashioned ideas regarding biomarkers such as expression of p53 and cell cycle regulators etc.. It will almost certainly take the form of multiplexed sequencing. Robinson 2013 Slide 13 Urothelial carcinoma tumour groupings based upon hierarchical clustering of gene expression. Sjdahl G et al. Clin Cancer Res 2012;18:3377-3386 2012 by American Association for Cancer Research Slide 14 Molecular pathways of development M Knowles 2006. Slide 15 Case 2 69 male retired army sergeant. Storage LUTS, pelvic pain and visible haematuria. Smoker, IHD, type 2 diabetes, walks with 2 sticks. What next? Had flexi cystoscopy shown solid tumour. EUA mobile bladder mass. TURBT residual tumour. Slide 16 Case 2 H&E sections of tumour. Slide 17 Pearls of keratin in classical description of SCC Entire tumour filled with whorls of keratin. IHC staining of SCC bladder cancer tissue for cytokeratin. Slide 18 Histological types of bladder cancer Urothelial / TCC 90% SCC 5% Higher incidence in areas endemic for schistosomiasis. Adenocarcinoma 2% Other sub-types 3% Slide 19 WHO 2004 Histological types of tumours of the urinary bladder 44 different sub-types listed! Benign Urothelial papilloma Inverted papilloma Papillary urothelial neoplasia of low malignant potential Malignant papillary Papillary carcinoma low grade high grade with squamous with glandular differentiation Malignant non-papillary Flat carcinoma in situ Invasive carcinoma Variants of invasive carcinoma Nested pattern Small tubular pattern Microcystic pattern Inverted pattern Squamous differentiation Glandular differentiation Micropapillary Sarcomatoid carcinoma Clear cell urothelial carcinoma Plasmocytoid With syncitiotrophoblasts With unusual stromal reactions Pseudosarcomatous stroma Stromal osseous or cartilaginous metaplasia Osteoclast-type giant cells With prominent lymphoid infiltrate Squamous cell carcinoma Usual type Variant Verrucous Basaloid With sarcomatoid features Adenocarcinoma (from bladder mucosa, urachal, with extrophy) Usual intestinal type Mucinous (including colloid) Signet-ring cell Clear cell Hepatoid Mixture of above patterns Adenocarcinoma NOS Tumours of mixed cell types Undifferentiated carcinomasa Small cell carcinoma Large cell neuroendocrine carcinoma Lymphoepithelioma-like carcinoma Giant cell carcinoma Undifferentiated carcinoma NOS Metastatic carcinoma Slide 20 Variants TCC variants (80% all TCC have mixed differentiation) Nested Can be confused with Vonn Brunn nests M:F = 6:1 Neo-adjuvant chemo ineffective V poor prognosis (30% 3 year survival) Micropapillary 0.7-2.2% M:F = 10:1 BCG ineffective Neo-adjuvant chemo ineffective Adverse phenotype Other non-TCC variants Small cell Men >70 yrs Consider metastatic Chemo-radiothepy treatment of choice V poor prognosis (20% 5 year survival) Sarcoma M:F = 2:1 Previous chemo or XRT other tumours Normal overlying urothelium Not related to smoking Treatment with cystectomy Slide 21 SCC Risk Factors Chronic urinary tract infection Schistosomiasis Increased urothelial proliferation N-butyl-N-(4- hydroxybutyl)nitrosamine is generated in very high levels in the urine. Chronic infection with S hematobium converts nitrates to nitrites and subsequently to nitrosamines. Myths SCC in Egypt only 27% of MIBC was 80% in 1980 improved eradication increased smoking similar pattern elsewhere Incidence in SCI is only