Neoadjuvant Radiation Is Associated with Fistula Formation Following Pancreaticoduodenectomy

Post-operative pancreatic fistulas remain a significant source of morbidity following pancreatic surgery. Few studies have evaluated the effect of neoadjuvant chemotherapy and radiation on this adverse outcome. This study aims to evaluate the effects of neoadjuvant therapy on 30-day morbidity and mortality following pancreaticoduodenectomy. A retrospective analysis was performed utilizing the targeted pancreas module of the National Surgical Quality Improvement Project (NSQIP) from 2014 to 2015 for patients undergoing pancreaticoduodenectomy with pancreaticojejunal reconstruction. A fistula was defined according to the NSQIP definition. Patient demographics, operative variables, and 30-day outcomes were compared between those who received no neoadjuvant therapy, chemoradiation, chemotherapy alone, and radiation alone. Univariate analysis was completed using chi-square, Fisher exact test, Student's t test, and Mann-Whitney U test where appropriate. Independent predictors of fistula formation were established using multivariable regression. A P value < 0.05 was considered significant. Three thousand one hundred fourteen patients were included of which 559 patients (18%) developed a pancreatic fistula. Two thousand six hundred thirty-five (85%) patients did not undergo neoadjuvant therapy, 207 (6.6%) had chemoradiation, 256 (8.2%) had chemotherapy alone, and 16 (0.5%) had radiation alone. Patients who developed a fistula had increased 30-day mortality (4.9 vs. 1.7%, P < .001) and major morbidities. Following multivariable analysis, neoadjuvant radiation (OR 2.1, 95% CI 1.0-4.5) was associated with increased fistula formation while neoadjuvant chemotherapy (OR 0.5, 95% CI 0.3-0.9) was protective. Neoadjuvant chemotherapy provides protection against the development of pancreatic fistulas while neoadjuvant radiation potentiates formation likely due to their effects on the texture of the pancreatic gland. Given the morbidity of pancreatic fistula formation, these factors should be considered in neoadjuvant regimens.