• Chemotherapeutic agents.
  • The initial link between bladder cancer and exposure to aniline dyes was made in 1895.
  • Further connections have been established with the rubber manufacturing and textile printing industries.
  • Exposure to aromatic amines is the common event, and substances such as 2-naphtylamine, 4-aminobiphenyl, and 4-nitrobipbenyl are believed to be potent carcino­genic elements.
  • The latency period may be several decades.
• Tobacco exposure.
  • A two- to threefold relative risk for developing bladder cancer exists for cigarette smokers.
  • The relationship is less well-established for other to­bacco products.
• Chemotherapeutic agents.
  • As high as a nine fold relative risk may exist for patients exposed to cyclophos­phamide or ifosfamide chemotherapy.
  • The presence or absence of hemorrhagic cystitis does not correlate with the likelihood of developing carcinoma.
  • The major toxic metabolic agent is acrolein, and most lesions present as muscle-invasive tumors. Administration of Mesna at the time of therapy reduces the urothelial injury by acrolein.
• Schistosomiasis. Schistosoma haematobium
  • Endemic in Egypt, where 70 percent of bladder cancers have squamous cell pathology.
  • The disease characteristically results in bladder wall calcification, polyposis, ulcers, and urothelial hyperplasia leading to an end-stage con­tracted bladder.
  • The presence of high concentrations of N-nitroso compounds has been implicated as a possible etiologic factor for the development of bladder cancer, which usually presents with an early onset (fifth decade of life).
  • More than 40 percent of squamous cell carcino­mas associated with schistosomiasis are well-differenti­ated and typically carry a good prognosis, unlike squa­mous cell carcinomas of other etiologies.
• Pelvic irradiation.
  • A two- to fourfold increase in blad­der cancer incidence has been noted in women treated for cervical malignancy.
• Chronic irritation and infection.
  • Patients with in­dwelling urinary catheters for many years are subject to chronic bacterial infection, stone formation, and foreign body reactions.
  • A 15- to 20-fold increase in bladder can­cer (primarily squamous) has been noted in some series.
  • Malignant or pre-malignant changes have been noted in 2 to 8 percent of patients with Foley catheters in­dwelling for more than 10 years.
  • A yearly cystoscopic examination is recommended in these patients.
• Phenacetin.
  • The N-hydroxy metabolite of phenacetin is the probable active metabolite that causes urothelial tu­mors.
  • Upper tract lesions are most common. A long la­tency period and massive ingestion (5 to 10 kg) are char­acteristic of this condition.
• Bladder exstrophy.
  • This rare midline closure defect is associated with bladder adenocarcinoma.
  • Occurs in patients who underwent late closure and is thought to re­sult from chronic irritation.

• Coffee.
  • Coffee and tea have been implicated in a few studies.
  • The relationship is not strong and is further weakened by the confounding occurrence of associated smoking.
• Saccharin.
  • Artificial sweeteners have been shown to re­sult in bladder cancer in experimental animals.
  • No as­sociation has been proven in humans.

References

• Droller MJ: Bladder: Anatomical overview in surgical management of urologic disease: An anatomic approach, MJ Droller, St. Louis, Mosby Yearbook, p 575, 1992.
• Herr HW, Schwalb DM, Zhang ZF, et al: Intravesical bacillus Calmette-Guerin therapy prevents tumor progression and death from superficial bladder cancer: Ten-year follow-up of a prospective randomized trial. J Clin Oncol 13:1404, 1995.
• Lamm DL: Complications of bacillus Calmette-Guerin immunotherapy. Urol Clin North Am 19:565, 1992.
• Malkowicz SB: Superficial bladder cancer: The role of molecular markers in the treatment of high-risk superficial disease. Semin Urol Oncol 15:169-178, 1997.
• Messing EM, Catalona W: Urothelial tumors of the urinary tract. In: Campbell's Urology 7th ed. PC Walsh, AB ED Vaughan, AJ Wein, Vol 3, Chap 77, 2327, 1998.
• Spruck CH, Ohneseit PE, Gonzalez-Zulueta M, et al: Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 54:784-788, 1994.

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