Influence of pancreatic fistula on survival after upfront pancreatoduodenectomy for pancreatic ductal adenocarcinoma: multicentre retrospective study

Background: The effects of postoperative pancreatic fistula on survival rates remain controversial. The aim of the present study was to evaluate the influence of postoperative pancreatic fistula on overall survival and recurrence-free survival after upfront pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

Methods: Patients operated on between January 2007 and December 2017 at seven tertiary pancreatic centres for pancreatic ductal adenocarcinoma were included in the study. Postoperative pancreatic fistula was defined using the 2016 International Study Group on Pancreatic Surgery grading system. The impact of postoperative pancreatic fistula on overall survival, recurrence-free survival (excluding 90-day postoperative deaths) and corresponding risk factors were investigated by univariable and multivariable analyses. Comparisons between groups were made using the chi-squared or Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. Odds ratios were estimated with their 95% confidence intervals. Survival rates were calculated using the Kaplan-Meier method with their 95% confidence intervals.

Results: A total of 819 patients were included between 2007 and 2017. Postoperative pancreatic fistula occurred in 14.4% (n = 118) of patients; of those, 7.8% (n = 64) and 6.6% (n = 54) accounted for grade B and grade C postoperative pancreatic fistula respectively. The 5-year overall survival was 37.0% in the non-postoperative pancreatic fistula group and 45.3% in the postoperative pancreatic fistula cohort (P = 0.127). Grade C postoperative pancreatic fistula (excluding 90-day postoperative deaths) was not a prognostic factor for overall survival. The 5-year recurrence-free survival was 26.0% for patients without postoperative pancreatic fistula and 43.7% for patients with postoperative pancreatic fistula (P = 0.003). Eight independent prognostic factors for recurrence-free survival were identified: age over 70 years, diabetes, moderate or poor tumour differentiation, T3/T4 tumour stage, lymph node positive status, resection margins R1, vascular emboli and perineural invasion.

Conclusion: This high-volume cohort showed that grade C postoperative pancreatic fistula, based on the 2016 International Study Group on Pancreatic Surgery grading system, does not impact overall or recurrence-free survival (excluding 90-day postoperative deaths).