Modification of pancreatic carcinogenesis in the hamster model. 5. Effect of partial pancreatico-colostomy.

Studies were conducted to evaluate the possibility of a bile reflux mechanism in the etiology of induced pancreatic cancer. N-Nitrosobis(2-oxopropyl)amine (BOP) was administered to Syrian hamsters after partial pancreatico-colostomy. Either the gastric or the splenic lobe of the pancreas was anastomosed to the transverse colon in groups 1 and 2, respectively. Group 3 were sham-operated controls and group 4 were controls without surgery. Shortly after surgery all 4 groups received a single subcutaneous BOP injection (20 mg/kg body weight) and survivors were sacrificed 46 weeks after BOP treatment. BOP-induced pancreatic tumor patterns were not altered by pancreatico-colostomy when compared with those in sham-operated controls. In all BOP-treated hamsters the number and distribution of benign and malignant lesions were similar in each individual pancreatic segment, including the anastomosed lobe (A-lobe); some hamsters developed tumors only in the A-lobe. As in other pancreatic regions, the initial hyperplasia in the A-lobe primarily affected peri- and intra-insular ductules and less frequently involved the ducts. These findings support the theory that the carcinogen is bloodborne and indicate that BOP-responsive pancreatic cells are distributed on a volume basis in distinct proportions within the pancreatic segments. As in previous experiments a higher incidence of pancreatic neoplasms was found in BOP-treated controls (those not operated upon) than in partially pancreatico-colostomized hamsters, including those with sham operations. Hyperplastic and dyplastic development of colonic mucosa around the anastomosis could be related to a local effect of carcinogen or of its metabolites, which are known to be excreted via pancreatic secretions.