�UroToday.com - Despite continued downward trends of smoke incidence in the United States over the last 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 cadaver steady at 3:1 and, according to the SEER information in 2005, over 521,000 multitude have a history of bladder cancer in the US. Bladder cancer testament account for an estimated 14,one C deaths in 2008 and the c. H. Best chance for survival is to diagnose bladder cancer in former stages when it crapper be contained to trivial epithelial layers.
Detection of epithelial neoplasia of the urinary parcel 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 imbue 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 detection include optical inspection, fluorescent detection, molecular imaging, and the manipulation of tumor-associated markers. Fluorescent detection has improved predisposition for detection of tumors but with a decreased specificity so its topper use is in conjuction with standard visual inspection. Newer diagnostic light technologies such as optical coherent tomography (OCT) provide endoscopic means to improve rating of epithelial surfaces and the voltage for neoplasm invasion.
Bladder tumor markers which may assist in detection ar a valuable adjunct to diagnosis. The ideal neoplasm marker would have both high predisposition and high specificity and be inexpensive, performed in the function, and easy to render. Unfortunately the array of tests presently available deficiency one or more of these characteristics and this holy holy Grail of a test has not so far been discovered. Recent discoveries suggest that microarray engineering may allow a knock-down tool for tumor sleuthing.
Urinary cytology remains the standard by which other diagnostic tests are compared. Cytology has an mean sensitivity of 49% and specificity of 96% in one brushup of multiple studies. The use of nuclear mitotic apparatus protein (NMP-22) has an average sensitivity of 71% merely a specificity of 75% in a similar followup and is often put-upon in combination with cytology for selected higher jeopardy patients. Multicenter clinical trials with fluorescent in situ hybridization (FISH) have shown an overall 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 antecedently treated with Bacille-Calmette-Guerin (BCG) immunotherapy, an improvement over the former tests in this patient group. This fluorescent immunochemistry has a 95% NPV and is a strong predictor of upper urinary tract neoplasia.
Molecular biologic marker candidates are abundant and under evaluation for clinical use. Fibrin-fibrinogen debasement products (FDP) have a sensitivity and specificity of 68% and 86%, severally, but endure from false positive results when haematuria is present, a common symptom with urothelial malignity. Telomerase, which blocks programmed cell death, has high sensitivity simply poor specificity and has variable constancy. Hyaluronic acid/hyaluronidase has promise with improved sensitivity for lower grade lesions. Cytokeratins 18, 19, and 20 are highly expressed in transitional 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 simply not in normal tissue in one study. A host of other glycoproteins and atomic matrix proteins are under evaluation as well. Perhaps the to the highest degree promise has been found through evaluation of DNA microarrays where a recent 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 adhesion, and keratinisation while those for invasive disease related to different cell functions of extracellular matrix degradation, 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 important implication for future exercise 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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