Urothelial carcinoma

Miettinen, M. (1995) Immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinoma. Mod. Pathol. 8, 384-388. 

Loehrer PJ, Einhom LH, Elson PJ, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma a cooperative group study. J Clin Oncol 1992 7 1066-1073. 

Loehrer PJ, Elson P, Dreicer R, et al. Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma an Eastern Cooperative Oncology Group trial. J Clin Oncol 1994 12 483-488. 

Redman BG, Smith DC, Flaherty L, Du W, Hussain M. Phase II trial of paclitaxel and carboplatin in the treatment of advanced urothelial carcinoma. J Clin Oncol 1998 5 1844-1848. 

D., Vereerstraeten, P., and Vanherweghem, J.L. (2000) Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). New Engl J Med 342 1686-1692. 

Santos, L., Amaro, T., Costa, C., Pereira, S., Bento, M.J., Lopes, P., Oliveira, J., Criado, B., and Lopes, C. 2003. Ki-67 index enhances the prognostic accuracy of the urothelial superficial bladder carcinoma risk group classification. Int. J. Cancer 105, 267-272. 

Ohlsson G, Moreira JM, Gromov P, Sauter G, Celis JE. Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas. Mol Cell Proteomics 2005 4(4) 570-581. 

Because of fear of malignancies the Belgian researchers who first described the condition have advocated prophylactic removal of the kidneys and ureters in patients with Chinese herb nephropathy. Of 39 patients who agreed to this, 18 (46%) had urothelial carcinoma, 19 of the others had mild to moderate urothelial dysplasia, and only two had normal urothelium (28). All tissue samples contained... 

One patient who had a urothehal malignancy 6 years after the onset of Chinese herb nephropathy later developed a breast carcinoma that metastasised to the liver (31). The urothelial mahgnancy contained aristolochic acid-DNA adducts and mutations in the p53 gene, and the same mis-sense mutation in codon 245 of exon 7 of p53 was found in DNA from the breast and liver tumors. However, DNA extracted from the urothelial tumor also showed a mutation in codon 139 of exon 5, which was not present in the breast and liver. 

Einhorn LH, Roth BJ, Ansari R, Dreicer R, Gonin R, Loehrer PJ. Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma. J Clin Oncol 1994 12(ll) 2271-6. 

Gemcitabine is an S-phase-specific pyrimidine nucleoside analogue of deoxycytidine (2, 2 -difluorodeoxycytidine) that is structurally similar to cytosine arabinoside. It has been used to treat metastatic urothelial carcinoma of the bladder, pancreatic cancer, and some other solid tumors. 

The evidence that methotrexate is carcinogenic is inconclusive and mostly based on case reports or analyses of cohort studies without control groups (100,109). For example, malignant neoplasms (urothelial carcinoma of the bladder, a malignant teratoma, and a dermal squamous cell carcinoma) have been described in three patients taking prolonged courses of methotrexate 7.5-15 mg/week (110). 

Studies on the tumor-inducing effects of heavy use of analgesics, especially those that contain phenacetin, have given contrasting results (SEDA-21, 100) (56,57). Two case-control studies have been published on the role of habitual intake of analgesics on the occurrence of urothelial cancer and renal cell carcinoma. 

Kliem V, Thon W, Krautzig S, Kolditz M, Behrend M, Pichimayr R, Koch KM, Frei U, Brunkhorst R. High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation.TranspI Int 1996 9 231-235. 

A further bladder follow-up of these kidney recipients (cystoscopy and biopsies per 6 months) resulted in the diagnosis of 8 urothelial carcinoma in situ, 4 non-invasive low-grade papillary urothehal carcinoma and 3 infiltrating urothelial cancer, 68 to 169 months after cessation of AA exposure (cumulative incidence of 39.5%). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies had to be performed [41]. 

Lemy A, Wissing KM, Rorive S, Zlotta A, Roumeguere T, Muniz Martinez MC, Decaestecker C, Salmon I, Abramowicz D, Vanherweghem JL, Nortier J. Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy a case series with 15-year follow-up. Am J Kidney Dis 2008 51 471 -477... 

Nortier JL, Schmeiser HH, Muniz Martinez MC, Arit VM, Vervaet C, Garbar CH, Daelemans P, Vanherweghem JL. Invasive urothelial carcinoma after exposure to Chinese herbal medicine containing aristolochic acid may occur without severe renal failure. Nephrol Dial Transplant 2003 18 426-428... 

End-stage renal disease is treated with dialysis and kidney transplantation. Hypertension and cardiovascular diseases affect the Balkan nephropathy patients less frequently, so they tolerate hemodialysis rather well compared to patients with other renal diseases. The Balkan nephropathy patients on long-term hemodialysis frequenfly develop upper urothelial or urinary bladder carcinoma. 

Bach PH, Gregg NJ, Delacruz L. Relevance of a rat model of papillary necrosis and upper urothelial carcinoma in understanding the role of ochratoxin A in Balkan endemic nephropathy and its associated carcinoma. Food Chem Toxicol. 1992 30(3) 205-11. 

A fluorescence in situ hybridization (FISH) technique, UroVysion, uses fluorescently labeled probes to detect aneu-ploidy of chromosomes 3,7, and 17, and deletion of the 9p21 locus that contains the tumor suppressor pi6, which is the most common alteration seen in urothelial carcinoma. Table 23-13 compares cytology with that of UroVysion for the detection of bladder cancer. 

Although the precise mechanism of aristolochic acid-induced nephropathy and urothelial carcinoma is yet to be characterized, recent data indicate direct DNA damage may be the cause. The major components of aristolochic acid are metabolized to mutagenic compounds called aristolactam I and aristolactam II, respectively, which have been demonstrated to form DNA adducts in humans. Direct cellular toxicity is an unlikely mechanism of injury since the onset is delayed and progression of renal failure continues after aristolochic acid exposure. ... 

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