Informing Decision-making for Transected Margin Reresection in Intraductal Papillary Mucinous Neoplasm-derived PDAC: An International Multicenter Study

Joseph R Habib; Ingmar F Rompen; Benedict Kinny-Köster; Brady A Campbell; Paul C M Andel; Greg D Sacks; Adrian T Billeter; Hjalmar C van Santvoort; Lois A Daamen; Ammar A Javed; Beat P Müller-Stich; Marc G Besselink; Markus W Büchler; Jin He; Christopher L Wolfgang; I Quintus Molenaar; Martin Loos

doi:10.1097/SLA.0000000000006532

Informing Decision-making for Transected Margin Reresection in Intraductal Papillary Mucinous Neoplasm-derived PDAC: An International Multicenter Study

Ann Surg. 2024 Sep 12. doi: 10.1097/SLA.0000000000006532. Online ahead of print.

Authors

Joseph R Habib^{1

2}, Ingmar F Rompen^{1

3

4

5}, Benedict Kinny-Köster³, Brady A Campbell⁶, Paul C M Andel^{1

2}, Greg D Sacks¹, Adrian T Billeter⁷, Hjalmar C van Santvoort², Lois A Daamen^{2

8}, Ammar A Javed¹, Beat P Müller-Stich⁷, Marc G Besselink^{4

5}, Markus W Büchler⁹, Jin He⁶, Christopher L Wolfgang¹, I Quintus Molenaar², Martin Loos³

Affiliations

¹ New York University Langone Health, Department of Surgery, New York, USA.
² Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Department of Surgery, Utrecht, the Netherlands.
³ Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
⁵ Cancer Center Amsterdam, the Netherlands.
⁶ Johns Hopkins Hospital, Department of Surgery, Baltimore, USA.
⁷ Clarunis University Digestive Health Care Center Basel, Basel, Switzerland.
⁸ University Medical Center Utrecht, Division of Imaging and Oncology, Utrecht, the Netherlands.
⁹ Department of Pancreatic Surgery, Champalimaud Foundation, Lisbon, Portugal.

PMID: 39263741
DOI: 10.1097/SLA.0000000000006532

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.

Summary background data: 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 six 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 (RFS).

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 to those with an R1 status (65.8 vs. 26.3 mo P<0.001). Patients without dysplasia at the pancreatic neck margin had similar OS compared to those with low-grade dysplasia (mOS: 78.8 vs. 66.8 months, P=0.344). However, high-grade dysplasia (mOS: 26.1 mo, P=0.001) and invasive cancer (mOS: 25.0 mo, P<0.001) were associated with significantly worse OS compared to no or low-grade dysplasia. Patients who underwent conversion of high-risk margins (high-grade or invasive cancer) to a low-risk margin (low-grade or no dysplasia) after intraoperative frozen section had significantly superior OS compared to those with a high-risk neck margin on final pathology (mOS: 76.9 vs. 26.1 mo 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.