Enhanced colonic carcinogenesis with azoxymethane in rats after pancreaticobiliary diversion to mid small bowel

Since biliary excretion of metabolites might determine the pattern of intestinal neoplasms induced by azoxymethane, the number and distribution of tumors were studied in rats after pancreaticobiliary diversion to the mid small bowel. Pancreaticobiliary diversion was performed either immediately before the first of 16 weekly injections of azoxymethane or 10 days after the last. Seven months after pancreaticobiliary diversion, persistent ileal hyperplasia was manifested by higher levels of mucosal RNA and DNA compared with controls (34--102%: P less than 0.001), while there was little residual adaptation in the colon. Qualitative and quantitative analysis of fecal bile acids 6--26 wk after pancreaticobiliary diversion showed few differences. Pancreaticobiliary diversion doubled the incidence of colonic tumors, whether operation preceded (P less than 0.005) or followed (P less than 0.02) the course of azoxymethane. Suture-line tumors were common in the small bowel, particularly in the transposed duodenal stump. Despite intense ileal hyperplasia as a consequence of pancreaticobiliary diversion, the ileum remained resistant to chemical carcinogenesis. The potentiation of colonic neoplasms by pancreaticobiliary diversion probably depends on the stimulation of colonic mucosal proliferation.