Informing Decision-making for Transected Margin Reresection in Intraductal Papillary Mucinous Neoplasm-derived Pancreatic Cancer

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Abstract
Objective: To assess the prognostic impact of margin status in patients with resected intraductal papillary mucinous neoplasms (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and to inform future intraoperative decision-making on handling differing degrees of dysplasia on frozen section. Background: The ideal oncologic surgical outcome is a negative transection margin with normal pancreatic epithelium left behind. However, the prognostic significance of reresecting certain degrees of dysplasia or invasive cancer at the pancreatic neck margin during pancreatectomy for IPMN-derived PDAC is debatable. Methods: Consecutive patients with resected and histologically confirmed IPMN-derived PDAC (2002–2022) from 6 international high-volume centers were included. The prognostic relevance of a positive resection margin (R1) and degrees of dysplasia at the pancreatic neck margin were assessed by log-rank test and multivariable Cox-regression for overall survival (OS) and recurrence-free survival. Results: Overall, 832 patients with IPMN-derived PDAC were included, with 322 patients (39%) having an R1-resection on final pathology. Median OS (mOS) was significantly longer in patients with an R0 status compared with those with an R1 status (65.8 vs 26.3 mo P P =0.344). However, high-grade dysplasia (mOS: 26.1 mo, P =0.001) and invasive cancer (mOS: 25.0 mo, P P <0.001). Conclusions: In IPMN-derived PDAC, normal epithelium or low-grade dysplasia at the neck have similar outcomes, while pancreatic neck margins with high-grade dysplasia or invasive cancer are associated with poorer outcomes. Conversion of a high-risk to low-risk margin after intraoperative frozen section is associated with survival benefit and should be performed when feasible.

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