Simple SummaryThis study investigates the potential impact of post-pancreatectomy acute pancreatitis (PPAP) on long-term outcomes after pancreaticoduodenectomy (PD). Patients who underwent PD from 2006 to 2021 were enrolled in the study. Thirty-two patients developed PPAP and were matched to 32 patients who did not present PPAP post-operatively. PPAP onset was related to a worse post-operative clinical course. No difference was evidenced in terms of overall survival between groups. However, although not statistically significant, patients with PPAP had worse disease-free survival as compared to the no-PPAP cohort.AbstractPost-pancreatectomy acute pancreatitis (PPAP) is a potentially life-threating complication. Although multiple authors demonstrated PPAP as a predisposing feature for a more detrimental clinical course, no evidence is currently present on its potential impact on long-term outcomes. The aim of this study is to evaluate how PPAP onset may influence overall (OS) and disease-free survival (DSF) after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). Patients who underwent PD for PDAC from 2006 to 2021 were enrolled. PPAP was defined according to the International Study Group of Pancreatic Surgery (ISGPS) definition. Propensity score matching (PSM) was performed in order to reduce potential selection biases. After PSM, 32 patients out of 231 PDs who developed PPAP (PPAP group) were matched to 32 patients who did not present PPAP (no-PPAP group). PPAP patients more frequently presented major post-operative complications (p= 0.02) and post-operative pancreatic fistula (POPF) (p= 0.003). Median follow-up was 26.2 months, with no difference between the two groups (p= 0.79). A comparable rate of local or distant metastases was noted in the two cohorts (p= 0.2). Five-year OS was comparable between the two populations (39.3% and 35.7% for the no-PPAP and PPAP populations, respectively;p= 0.53). Conversely, despite not being statistically significant, a worse 5-year DFS was evidenced in the case of PPAP (23.2%) as compared to the absence of PPAP (37.4%) (p= 0.51). With the limitations due to the small sample size, PPAP may potentially relate to worse long-term outcomes in terms of DFS. However, further studies with wider study populations are still needed in order to better clarify the prognostic role of PPAP.