• Stefano Crippa, Ilaria Pergolini, Ammar A Javed, Kim C Honselmann, Matthew J Weiss, Francesca Di Salvo, Richard Burkhart, Giuseppe Zamboni, Giulio Belfiori, Cristina R Ferrone, Corrado Rubini, Jun Yu, Giulia Gasparini, Motaz Qadan, Jin He, Keith D Lillemoe, CastilloCarlos Fernandez-DelCFDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Christopher L Wolfgang, and Massimo Falconi.
• School of Medicine, Vita-Salute San Raffaele University, Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
• Ann. Surg. 2022 Aug 1; 276 (2): 378-385.

ObjectiveTo describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC).Summary Of Background DataAlthough PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in ''early stage disease'' (PDAC ≤20 mm, R0/ N0 PDAC).MethodsThis multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models.ResultsPNI was found in 87% of 778 patients included in the study, with lower rates in PDAC ≤20 mm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis ( P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P < 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC ≤ 20 mm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 >37 and pain.ConclusionsPNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression.Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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