Malignancies of the urinary tract and their relation to analgesic abuse.

A relationship between analgesic abuse and urothelial renal pelvic tumors was first observed in 1965. Since then more than 100 cases of such tumors have been reported in abusers of phenacetin-containing drugs; most of these cases have been from Sweden. Many patients had a preexisting nephropathy with renal papillary necrosis. The total consumption of the drugs could be estimated to several kilograms, and the average period of consumption was 17 yr in the Göteborg study. The manifest development of the tumor often came a few years after the cessation of the drug abuse. The clinical picture and the pathologic findings are described and the five-year survival rate is given. Multiple tumors in the urinary tract were common. Carcinogenic factors are discussed. Phenacetin is an aromatic amide with N-hydroxylated metabolites, closely related to known carcinogenic amines like the naphthylamines which earlier caused occupational bladder cancer. Furthermore, the data on exposition (consumption) time and tumor induction time were very similar in occupational bladder cancer and in renal pelvic cancer related to analgesic abuse. Animal experiments of long-term phenacetin feeding have produced a high degree of papillary epithelial hyperplasia. Further investigations are under way.