Exocrine pancreatic function following intraoperative irradiation of the canine pancreas.

Abstract

Twenty-four beagles received intraoperative irradiation (IORT) with 6 meV electrons to the pancreas and the duodenum. Intraoperative irradiation doses of 17.5 to 40 Gy were given. Billroth II gastrojejunostomy was done to bypass the irradiated duodenum. Six control dogs received only the Billroth II surgery. Two weeks postoperatively, irradiated dogs were given 50 Gy of 6 MV X radiation (external-beam radiation [EBRT]) to the pancreas and duodenum in 2 Gy fractions over a 5-week period. Dogs were monitored clinically and exocrine pancreatic function was evaluated using an N-benzoyl-l-tyrosyl-para-aminobenzoic acid (BT-PABA) test between 3 and 135 days postoperatively. Necropsies were performed on the dogs at 135 days postoperatively. The degree of gross pancreatic atrophy in the irradiated group was dose related. The mean percentage of normal acinar cells correlated with IORT doses and para-aminobenzoic acid (PABA) values (P less than 0.1). Weight loss was significantly greater in the irradiated dogs compared to the control (P less than 0.05) and the mean percentage of body weight loss correlated with the mean PABA values (P less than 0.01). In this study, the use of the BT-PABA test to evaluate progressive exocrine pancreatic function following IORT and EBRT showed an expected trend. A progressive decrease in exocrine pancreatic function in the irradiated dogs as indicated by plasma PABA levels may have been partly due to late radiation damage to acinar cells, secondary to vascular and ductular damage. At 135 days postoperatively none of the dogs showed clinical signs of exocrine pancreatic insufficiency and the plasma PABA levels were within the normal presurgical range. The progressive decrease in plasma PABA levels indicated a potential for the late development of exocrine pancreatic insufficiency. The BT-PABA test could be useful for evaluating the progressive decrease in exocrine pancreatic function and residual radiation injury to the pancreas. Because the exocrine deficiency can be managed with replacement therapy, pancreatic injury may not be a serious complication after doses of less than 30 Gy IORT with 50 Gy EBRT. Data from this study are in agreement with previous clinical and experimental reports that the duodenum is dose-limiting for IORT. Doses of 20 Gy IORT or less plus 50 Gy EBRT for treatment of carcinoma of the pancreas may not result in serious long-term complications due to radiation injury of the duodenum.