Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and pain

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of death in 2030 and it is characterized by poor prognosis, recurrence and resistance to therapies. Several factors contribute to the complexity of this disease, among those the invasion of nerves by PDAC cells....

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Main Authors: Federico Selvaggi, Elisa Bannone, Eugenia Melchiorre, Michele Diana, Roberto Cotellese, Gitana Maria Aceto
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Surgery Open Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589845025000168
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author Federico Selvaggi
Elisa Bannone
Eugenia Melchiorre
Michele Diana
Roberto Cotellese
Gitana Maria Aceto
author_facet Federico Selvaggi
Elisa Bannone
Eugenia Melchiorre
Michele Diana
Roberto Cotellese
Gitana Maria Aceto
author_sort Federico Selvaggi
collection DOAJ
description Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of death in 2030 and it is characterized by poor prognosis, recurrence and resistance to therapies. Several factors contribute to the complexity of this disease, among those the invasion of nerves by PDAC cells. This condition, defined as perineural invasion (PNI), is responsible of PDAC progression and pain generation. To date, PNI emerges as a hallmark feature of PDAC, showing the same oncological weight of lymph node metastasis in terms of prognosis. Targeting PNI could help improve prognosis and pain relief in PDAC patients. Only recently, a severity scoring system has been proposed to quantify PNI in histological samples although prospective validation and standardization are strongly advocated. More information about peripancreatic soft tissue infiltration and a “true” curative surgery could be found in understanding the molecular mechanisms of PNI. The incorporation of PNI markers for grading mesopancreas and retroperitoneal invasion is required to overcome current limitations of the histological workup. We discuss the modern understanding of PNI in PDAC, and the state of the art in clinical setting. Although there are still a lot to learn about PDAC, PNI represents one of the biological detonators and an important focus of future research.
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spelling doaj-art-2e5666a933d44f878e43c4cf63ecfe312025-08-20T03:15:28ZengElsevierSurgery Open Science2589-84502025-03-0124586010.1016/j.sopen.2025.02.007Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and painFederico Selvaggi0Elisa Bannone1Eugenia Melchiorre2Michele Diana3Roberto Cotellese4Gitana Maria Aceto5Villa Serena Foundation for Research, 65013 Città Sant'Angelo, Italy; Corresponding author.Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, ItalySchool of Medicine, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Surgery, University Hospital of Geneva, Geneva, SwitzerlandVilla Serena Foundation for Research, 65013 Città Sant'Angelo, ItalyVilla Serena Foundation for Research, 65013 Città Sant'Angelo, Italy; Department of Sciences, University “G. d'Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; Correspondence to: G.M. Aceto, Department of Sciences, University “G. d'Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of death in 2030 and it is characterized by poor prognosis, recurrence and resistance to therapies. Several factors contribute to the complexity of this disease, among those the invasion of nerves by PDAC cells. This condition, defined as perineural invasion (PNI), is responsible of PDAC progression and pain generation. To date, PNI emerges as a hallmark feature of PDAC, showing the same oncological weight of lymph node metastasis in terms of prognosis. Targeting PNI could help improve prognosis and pain relief in PDAC patients. Only recently, a severity scoring system has been proposed to quantify PNI in histological samples although prospective validation and standardization are strongly advocated. More information about peripancreatic soft tissue infiltration and a “true” curative surgery could be found in understanding the molecular mechanisms of PNI. The incorporation of PNI markers for grading mesopancreas and retroperitoneal invasion is required to overcome current limitations of the histological workup. We discuss the modern understanding of PNI in PDAC, and the state of the art in clinical setting. Although there are still a lot to learn about PDAC, PNI represents one of the biological detonators and an important focus of future research.http://www.sciencedirect.com/science/article/pii/S2589845025000168PancreasPancreatic cancerCurative resectionPerineural infiltration
spellingShingle Federico Selvaggi
Elisa Bannone
Eugenia Melchiorre
Michele Diana
Roberto Cotellese
Gitana Maria Aceto
Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and pain
Surgery Open Science
Pancreas
Pancreatic cancer
Curative resection
Perineural infiltration
title Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and pain
title_full Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and pain
title_fullStr Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and pain
title_full_unstemmed Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and pain
title_short Perineural invasion in pancreatic cancer: Current biological function in R status, prognosis, and pain
title_sort perineural invasion in pancreatic cancer current biological function in r status prognosis and pain
topic Pancreas
Pancreatic cancer
Curative resection
Perineural infiltration
url http://www.sciencedirect.com/science/article/pii/S2589845025000168
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