ANTIEPILEPTIC TREATMENT AND RISK FOR HEPATOBILIARY CANCER AND MALIGNANT-LYMPHOMA

The possible influence of phenobarbital and phenytoin treatment on can cer risk was investigated in a case-control study nested in a cohort o f 8004 epileptic patients in Denmark. Information on anticonvulsive tr eatments was abstracted for 95% of 60 patients with cancers of the liv er and biliary tract or malignant lymphoma and for 94% of 171 cancer-f ree control patients. Use of anticonvulsive drugs was correlated with angiographic procedures that used Thorotrast, a well-known human liver carcinogen. After exclusion of study subjects exposed to Thorotrast, no association was seen between treatment with phenobarbital and cance r of the liver (odds ratio, 1.0; 95% confidence interval, 0.1-8.0) or biliary tract (odds ratio, 0.8; 95% confidence interval, 0.1-4.2). Fur thermore, a histopathological evaluation of slides from 7 of 9 liver c ancer patients not treated with Thorotrast revealed that 3 of the 4 ca ses of hepatocellular carcinoma involved cirrhosis of the liver, which suggested an etiological role for alcohol or viral hepatitis. A possi ble link was observed between use of phenytoin and risk for non-Hodgki n's lymphoma (1.8; 0.5-6.6), with a rising trend in risk with increasi ng dose. Our results suggest that the increased risk for cancers of th e liver and biliary tract among Danish epileptic patients is likely to be due to Thorotrast administration and factors associated with cirrh osis of the liver rather than to anticonvulsive treatment.