Aspirin Resistance 2003 08 13

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1 : Bladder Cancer Dr Anne Kiltie Senior Lecturer/Honorary Consultant Clinical Oncologist St. James’s Hospital UK
2 : Epidemiology 4th male, 7th female cancer 23/100 000 incidence; 8.9/100 000 mortality Pathology usually TCC (95%) also SqCC, adeno, small cell, lymphoma, sarcoma, carcinosarcoma
3 : UK Cancer Incidences, 2000
4 : UK Cancer Mortalities, 2002
5 : Lifetime Risks
6 : Incidence and mortality
7 : Aetiology Smoking (causes more than 50%) Other risk factors Age, male sex Chronic bladder inflammation, schistosomiasis External beam radiation, cyclophosphamide At risk occupations (carcinogens, aniline dyes, diesel) Hairdressers, machinists, printers, painters Truck drivers Rubber, chemical, textile, metal, leather industries
8 : Staging
9 : Symptoms Haematuria (80%) ‘Cystitis’ and sterile pyuria Bladder irritability Anaemia Urinary tract infection Pain (advanced disease) Ureteric orifice obstruction hydronephrosis, kidney failure
10 : Investigations Cystoscopy KUB Ultrasound kidneys/abdomen CT scan/MRI scan Bone scan if symptomatic or raised alk phos
11 : Superficial Bladder Cancer 70%, Ta, T1, CIS Recurs at primary site or elsewhere in UT 22% cause death May be lifelong disease Diagnose by cystoscopy TUR then mitomycin C single shot (30-50% decrease recurrence rate) Further management depending on pathology and risk factors (see next slide):
12 : Superficial Bladder Cancer
13 : T1G3 Disease 30-40% progress (60% if associated CIS) 20% mortality rate at 5 years Management options include Cystectomy, radiotherapy, chemotherapy, BCG with close follow-up, or follow-up with cystectomy at recurrence
14 : Muscle invasive disease T2-T3 disease (40-60% 5 year survival) Options are cystectomy (+/- reconstruction) or radiotherapy +/- chemotherapy Radical cystectomy (2-3% mortality rate) Side effects include loss of native bladder and impotence. Involves lymph node dissection and removal of bladder and prostate and seminal vesicles or anterior vaginal wall, uterus, fallopian tubes and ovaries
15 : Muscle Invasive Bladder Cancer - Radiotherapy
16 : Radiotherapy Linear accelerator 55 Gy in 20 fractions over 4 weeks 3 or 4 fields CT planned treatment Verification on set
17 : Muscle Invasive Side effects include Acutely - tiredness, cystitis, diarrhoea, loss of local hair, skin reddening Later - bladder telangiectasia (5%), fibrosis and shrinkage, altered bowel habit (<50%), proctitis (5%), vaginal adhesions/stenosis, impotence (20-30%) incontinence (1%)
18 : Muscle Invasive Recent Leeds results:
19 : Muscle Invasive Chemotherapy may be added to surgery or radiotherapy 5% survival benefit at 5 years for neoadjuvant chemotherapy Give high dose MVAC with G-CSF support
20 : Muscle invasive SPARE trial in UK: Neoadjuvant chemo - high dose MVAC or GC If complete response at check cystoscopy then randomise to radiotherapy or cystectomy If not CR then for surgery
21 : Muscle Invasive EORTC trial ongoing of adjuvant chemo 30994 (advantage that not all patients need it, but sicker post-op usually) Can give chemotherapy concurrently with radiotherapy e.g. weekly gemcitabine 100mg/m2 in phase II trial - just closed. Can give other modalities with radiotherapy, e.g. BCON study of carbogen and nicotinamide to overcome hypoxia - results awaited.
22 : Stage T4 Disease T4a -prostate, uterus, vagina involved T4b - pelvic side wall or abdominal wall 10 % 5 year survival for T4a - give chemotherapy if fit and then radiotherapy to pelvis palliative treatment for T4b
23 : Metastatic Disease Chemotherapy is the main treatment option Gold standard was MVAC (methotrexate, vinblastine, adriamycin, cisplatin) but very toxic - need good PS and renal function, best for nodal disease only Newer drugs - taxol, gemcitabine Gemcitabine/cisplatin is as good as MVAC with less neutropenia and mucositis
24 : Metastatic Trials EORTC 30987: gem/cisplat +/- taxol (now closed) EORTC 30986: carbo/gem vs carboMV if not fit for cisplatin (now in phase III) Vinflunine as 2nd line vs placebo - results awaited
25 : Metastatic Disease Radiotherapy has role in metastatic disease to treat bone metastases, brain metastases, cutaneous metastases, etc.
26 : Case Study 72 year old previously fit man Smoker, hypertension 2 month history of haematuria Investigations flexible cystoscopy - bladder tumour USS - kidneys normal, mass indenting bladder
27 : Surgery - TURBT to muscle 4 cm tumour posterior wall of bladder EUA - no mass palpable T2 tumour
28 : Staging: CXR normal MRI abdo/pelvis - 4 cm posterior wall bladder tumour confined to bladder; no nodes; no bone mets; liver, kidneys, spleen - normal Biochemistry normal except Alk Phos 350 (?) FBC - Hb 12.1 WCC 4.8 Plt 351
29 : Further staging of raised alkaline phosphatase Bone scan - Paget’s disease right femur, no mets
30 : Treatment: Options: cystectomy or radiotherapy +/- neoadjuvant chemotherapy Surgery and radiotherapy equivalent outcomes Neoadjuvant chemo 5% benefit in 5 year survival
31 : Patient wishes bladder preservation so referred for radiotherapy
32 : XRT alone 55 Gy in 20 fractions (4 week wait)
33 : Tolerates well Tiredness, diarrhoea/proctitis (fybogel), dysuria (2 litres fluids per day, cranberry juice)
34 : 6 weeks - reaction settling Check cystoscopy 3 months – clear CT scan 6 months - nodes in pelvis, no other disease, bladder clear Referred to Medical Oncology for chemo - ? 15% chance of cure with nodes only
35 : Poor renal function, so entered into EORTC 30986 trial of gem/carbo vs CMV Shrinkage of nodes No scope for further radiothearpy


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