�UroToday.com - Despite continued downward trends of smoking incidence in the United States over the lowest decade, the incidence of bladder cancer continues to rise with an estimated 68,800 new cases expected to be diagnosed in 2008. The proportion of male to female incidence remains steady at 3:1 and, according to the SEER data in 2005, over 521,000 people have a history of bladder cancer in the US. Bladder cancer will account for an estimated 14,C deaths in 2008 and the c. H. Best chance for survival is to diagnose bladder cancer in early stages when it privy be contained to superficial epithelial layers.
Detection of epithelial neoplasia of the urinary tract remains ambitious due to the anatomic contour of the bladder. Papillary growths may be readily visible but other flat lesions and carcinoma in situ, a propagate high grade intraepithelial neoplasia, can be difficult to detect. The same is true of the spectrum of abnormalities that include atypia and dysplasia which are associated with or have malignant potential. Methods of signal detection include visual inspection, fluorescent detection, molecular imaging, and the exercise of tumor-associated markers. Fluorescent detection has improved sensitivity for detection of tumors but with a reduced specificity so its c. H. Best use is in conjuction with standard visual review. Newer diagnostic light technologies such as optical coherent tomography (OCT) provide endoscopic means to improve valuation of epithelial surfaces and the potential for neoplasm invasion.
Bladder tumor markers which may assist in detection are a valuable adjunct to diagnosis. The ideal tumor marker would have both high sensitiveness and high specificity and be inexpensive, performed in the office, and easy to render. Unfortunately the array of tests currently available deficiency one or more of these characteristics and this holy grail of a test has not so far been discovered. Recent discoveries suggest that microarray applied science may provide a powerful tool for tumor detection.
Urinary cytology remains the standard by which early diagnostic tests are compared. Cytology has an average sensitivity of 49% and specificity of 96% in one revue of multiple studies. The use of nuclear mitotic apparatus protein (NMP-22) has an ordinary sensitivity of 71% simply a specificity of 75% in a similar reexamination and is often exploited in combination with cytology for selected higher danger patients. Multicenter clinical trials with fluorescent in situ hybridization (FISH) have shown an boilersuit sensitivity of 69%, specificity of 78%, and negative predictive value (NPV) of 95%. Fluorescent immunochemistry assaying 3 antibodies to mucin glycoprotein and carcinoembryonic antigen (CEA) has provided 85% sensitivity in patients previously treated with Bacille-Calmette-Guerin (BCG) immunotherapy, an improvement over the other tests in this patient group. This fluorescent immunochemistry has a 95% NPV and is a strong predictor of upper urinary tract neoplasia.
Molecular biological marker candidates are abundant and under evaluation for clinical use. Fibrin-fibrinogen degradation products (FDP) have a sensitivity and specificity of 68% and 86%, respectively, but suffer from mistaken positive results when haematuria is present, a coarse symptom with urothelial malignance. Telomerase, which blocks programmed cell death, has high sensitivity merely poor specificity and has variable stability. Hyaluronic acid/hyaluronidase has promise with improved sensitivity for lower level lesions. Cytokeratins 18, 19, and 20 are extremely expressed in transitional electric cell carcinoma (TCC) but likewise with infections. The anti-apoptotic protein survivin has been detected in 64% of cystectomy specimen tumors and 94% of metastatic lymph nodes just not in normal tissue in 1 study. A host of other glycoproteins and nuclear matrix proteins are under evaluation as well. Perhaps the nigh promise has been set up through evaluation of DNA microarrays where a late study of 14, 551 different genes identified 40 genes that were upregulated in superficial TCC and 34 different genes upregulated with invasive TCC. The fact that the upregulated genes for superficial TCC were related to epithelial cell dedifferentiation, apoptosis, transcription, cell adherence, and keratinisation while those for invasive disease related to dissimilar cell functions of extracellular matrix abjection, angiogenesis, and immune reply strongly suggests that we may be able to have an array of markers to differentiate superficial from invasive disease. This is an extremely interesting and significant implication for future use of goods and services of bladder tumor markers.
Presented by: Michael J. Manyak, MD, FACS, at the Masters in Urology Meeting - July 31, 2008 - August 2, 2008, Elbow Beach Resort, Bermuda
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Wednesday 13 August 2008
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