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Superficial Bladder Cancer

Done By Ehab Ahmed. Superficial Bladder Cancer. KAAU. Outlines. Epidemiology Risk factors Molecular pathway Pathology Presentation Diagnosis Chemoprevention Management Non-urothelial Bladder Cancer. Epidemiology. The most common malignancy affecting the Urinary System

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Superficial Bladder Cancer

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  1. Done By Ehab Ahmed Superficial Bladder Cancer KAAU

  2. Outlines • Epidemiology • Risk factors • Molecular pathway • Pathology • Presentation • Diagnosis • Chemoprevention • Management • Non-urothelial Bladder Cancer

  3. Epidemiology • The most common malignancy affecting the Urinary System • 80% in patients over 60 years of age • M:F is 3.4:1 • In some high incident regions, Bladder Cancer is associated with specific disease status or toxins exposures as in Balkan countries, Urinary Transitional Cell Carcinoma is associated with Balkan nephropathy

  4. RiskFactors • Chemical carcinogenesis: • Aromatic Amines or its derivatives as 2-Naphthylamine, Benzidine, Azodyes, and 4-Aminobiphenyl • Occupational : • Aluminum, Dye, Paint, Petroleum, Rubber • 20% Of cases

  5. Environmental : • Smoking : • Increase by 6-10 folds • Related to the extent of exposure, with long term • Analgesic abuse : • Chemical structure similar to Analine dye • Phenactin has been linked to CRD, Cancer of the Bladder, Renal Pelvis, and Ureters

  6. Artificial sweeteners : • Saccharin, and Cyclamates • Coffee consumption : • Week association • Reflect the confounding influence of Smoking • Upper tract cancer (TCC) • Pelvic radiation : • Cervical, Ovarian, and Prostate cancers

  7. Chronic infections : • Cystitis, Schistosomiasis • Mechanisms : • Repeated chronic irritations can lead to metaplastic changes, then dysplasia, and finally carcinoma • It predispose to obstructive uropathy, bacterial super infection, and production of Nitrosamines in the acidic urine environment • Inflammatory cells are rich sources of reactive oxygen species • Genetic variations in the genes involved in the inflammatory response alter their expression and function, potentially affecting the risk of developing cancer

  8. Chemotherapy : • Cyclophosphamide have up to 9 fold increase risk of Bladder Cancer • Others : • Black foot disease • Renal transplant recipient (prolong immunosuppressant)

  9. Molecular Pathways • Metabolic activation of carcinogens : • arylamines require in vivo activation to acquire carcinogenic potential • Through P45 enzymes • Detoxification of carcinogens : • Acetylation phenotype • Glutathione S transferase

  10. Pathology

  11. Pathologic tumor staging : • Lamina Propria Invasion • Muscularis Propria Invasion • Vascular Invasion

  12. Non-invasive Urothelial Neoplasm Flat lesions Papillary lesions CIS Dysplasia Urothelial Papilloma Inverted Papilloma PUNLMP LGPUC HGPUC

  13. Malignant Epithelial Tumors : • Transitional Cell Carcinoma : • 90% of Bladder Cancer • 75% Papillary and solid • Squamous Cell Carcinoma • Adenocarcinoma • Small Cell Carcinoma • Metastatic : • 15% of cases • Usually from Colon, Rectum, Prostate, and Cervix • Less commonly from Melanoma, Stomach, Breast, and Lung

  14. Presentation • Hematuria : • Intermittent, gross, painless, and total • Pain : • Usually due to locally advanced or metastatic disease • Flank, Suprapubic, Bone, and Perineal pain • Voiding symptoms : • Functional decrease in the bladder capacity, detrusoroveractivity, invasion of the trigone, and obstruction • Irritative (more common), and Obstructive • Constitutional symptoms : • Signs of advanced or metastatic diseases

  15. Staging • Histological grade : • Based upon the degree of resemblance to the normal tissue architecture, and degree of nuclear anaplasia • Bladder tumors are now classified as either low or high grade. This replaces the previous system of classification in which tumors were designated as low (G1), intermediate (G2), or high (G3) grade

  16. Clinical staging (TNM) : • Tx – Primary tumor cannot be assessed • T0 – No evidence of primary tumor • Ta – Non-invasive papillary carcinoma • Tis – Carcinoma in situ • T1 – Invade subepetheilial connective tissue • T2 – Invade the muscles • T2a – Superficial muscle (inner half) • T2b – Deep muscle (outer half) • T3 – Invade perivesical tissue • T3a – Microscopically • T3b – Macroscopically (extravesical mass) • T4 – Invade other organs • T4a – Invade Prostate, Uterus, and Vagina • T4b – Invade Pelvic and Abdominal wall

  17. Nx - Regional lymph node cannot be assessed • N0 - No lymph node metastasis • N1 - Single lymph node, 2 cm or less • N2 - Single lymph node 2-5 cm, or multiple lymph nodes less than 5 cm • N3 - Lymph nodes more than 5 cm • Mx - Distant metastasis cannot be assessed • M0 - No distant metastasis • M1 - Distant metastasis

  18. Stage grouping

  19. Diagnosis • Urinalysis : • Microscopic, gross examinations, and dipstick chemical test • Urine cytology : • 90% is sensitive for Cis • Limited sensitivity for upper tract TCC • Overall false negative rate is 65% • Specificity is 81-100% • Positive cytology considered poor prognostic factor • Urine flow cytometry : • Evaluation of abnormal DNA ploidy may be more accurate than cytology for detecting the presence of exfoliated malignant cells

  20. Urine immunocytochemistry and proteomocis assaays : • Immunocytochemistry : • More sensitive in detecting Low Grade Tumor than cytology • NMP22 Proteomics assays : • Analysis of protein expression in tissues, serum in order to identify tumors on the basis of unique protein expression pattern

  21. Radiographic evaluation : • IVP : • Cystogram phase detect 60-85% of large bladder cancer

  22. Ultrasound : • Can confirm Bladder mass but cannot determine depth of invasion, nodal involvement, and extravesical extension • Useful in evaluating upper tract

  23. CT Scan : • 80% accurate in differentiating locally advanced tumor form less invasive tumor

  24. Advantages : • Demonstrate extravesical extension, nodal involvement, visceral, pulmonary, or osseous metastasis • Disadvantages : • Cannot differentiate depth of Bladder wall invasion, although thickened wall suggest muscle invasive disease • Sensitivity for identification of nodal involvement is relatively low (false negative is 86%, and false positive is 16%)

  25. Cystoscopy : • Gold standard • It begins with bimanual examination under anesthesia • Abnormal areas should be sampled • RGP should be done if upper tract cannot be visualized by IVP • Cytology specimen should be taken if not previously done • Should document the following : • Tumor size, number, position, and growth pattern • Mucosa • Lower tract as urethra and prostate

  26. Fluorescence cystoscopy : • Intravesical installation of a porphryin such as 5-aminolevulinic acid • More effective than white light endoscope for the detection of multifocal tumors, thereby improving outcomes of TURBT • Sensitivity is 87-97%

  27. Purpose Comparison between hexaminolevulinate fluorescence cystoscopy with white light cystoscopy for detecting Ta and T1 papillary lesions in patients with bladder cancer

  28. Methods A total of 311 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM HAL for 1 hour. The bladder was inspected using white light cystoscopy, followed by blue light (fluorescence) cystoscopy. Papillary lesions were mapped and resected for histological examination

  29. Conclusion HAL fluorescence cystoscopy detected at least 1 more Ta and T1 papillary tumor than white light cystoscopy in approximately a third of the patients with such tumors. Whether this would translate to improved patient outcomes has yet to be determined. University of Texas M.Grossman HB et al, July 2007

  30. Metastatic work up : • Chest x-ray : • Non calcified densities • MRI • Sensitive to detect Lymph Node metastasis • Bone Scan • In patients with invasive or locally advanced tumors, and other skeletal symptoms or unexplained elevation in serum Alkaline Phosphatase (ALP)

  31. Chemoprevention • Use of various systemic agents to prevent or reverse changes in the urothelium • Two types : • Primary chemoprevention : • Block the formation of de novo Bladder Cancer in healthy individuals • Secondary chemoprevention : • Avoiding formation of additional tumors in patients who have been treated for bladder cancer

  32. Agents : • Retinoids (Vitamin A component) • Pyridoxine (Vitamin B6) • Vitamin C • Alpha tocopherol (Vitamin E) • Multivitamins • Difluoromethylomithine • Although some of the data supporting these agents is suggestive, NO role has been established for any of these agents in either primary or secondary chemoprevention

  33. Management • Prognostic factors : • Stage • Stage Ta, Tis, T1 • Grade • Multicentricity and frequency of recurrence : • Molecular markers

  34. Treatment options : • Endoscopic surgical management • Immunotherapy • Intravesical chemotherapy • Radical cystoectomy • Radiotherapy

  35. Risk stratification :

  36. Initial Treatment • Transurethral Resection (TURBT) : • Despite complete TURBT, up to 80% of patients with high risk tumors will recur within 12 month. So, adjuvant therapy is widely used

  37. Restaging TURBT : • Patients with high risk bladder cancer who are candidate for Intravesical therapy should undergo a repeat cystoscopy with biopsies of previous areas of involvement prior to therapy. This approach is important to detect previously under diagnosed disease and to reduce the tumor burden prior to therapy

  38. Random biopsies post-TURBT : • Any suspicious areas should be sampled • Not indicated in low-risk pt • 12.4% positive in high risk with normal cystoscopy • Prostatic urethral biopsy may be performed if neobladder creation is anticipated • ?tumor implantation

  39. Purpose evaluation of whether restaging transurethral resection (TUR) of superficial bladder cancer improves the early response to bacillus Calmette-Guerin (BCG) therapy

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