Pathologic response of the pancreas and duodenum to experimental intraoperative irradiation

The pancreas and duodenum of 24 beagle dogs were given intraoperative irradiation (IORT) with 6 MeV electrons. The dose range was 17.5 Gy to 40 Gy. Billroth II gastrojejunostomy was performed on all dogs prior to irradiation. Six control dogs received only Billroth II surgery. Starting 2 weeks after surgery, dogs in the irradiation groups were given 50 Gy 6 MV X rays external beam radiation therapy (EBRT) to the pancreas and duodenum. The total dose of 50 Gy was given in 2 Gy fractions over 5 weeks. Dogs were monitored for 135 days then necropsied. Gross and histopathologic changes in the pancreas and duodenum were evaluated and quantitative analysis of pancreatic lesions done. Duodenal ulcers were found following 32.5 Gy and 40 Gy IORT. The pancreases were atrophic in irradiated dogs and exocrine pancreatic insufficiency occurred in one dog given 25 Gy. Gross pancreatic atrophy correlated with IORT dose. Histopathologic evidence of radiation damage to the pancreas was observed in acinar cells. Islet cell lesions were not apparent. There was pancreatic fibrosis and damage to blood vessels and ducts. Dose-response relationships were observed for the index of damage to the pancreas as a whole, for pancreatic fibrosis and a decrease in normal acinar cells. Although 25 Gy IORT plus 50 Gy EBRT was tolerated by the duodenum to 135 days, these doses may cause later pancreatic injury as an expression of damage to blood vessels and ducts. Exocrine pancreatic insufficiency and diabetes mellitus may thus represent potential late complications of IORT following 25 Gy or higher doses.