Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastrointest Oncol. Nov 15, 2026; 18(11): 124427
Published online Nov 15, 2026. doi: 10.4251/wjgo.124427
Published online Nov 15, 2026. doi: 10.4251/wjgo.124427
Perineural invasion in pancreatic ductal adenocarcinoma: Molecular mechanisms and clinical significance
Rong Hu, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
Rong Hu, Hong-Chen Zhang, Xiao-Feng Zhang, Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University; Hangzhou Institute of Digestive Diseases; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Hangzhou 310006, Zhejiang Province, China
Co-first authors: Rong Hu and Hong-Chen Zhang.
Author contributions: Hu R and Zhang HC contributed equally to this article, they are the co-first authors of this manuscript; Hu R drafted most of the manuscript and prepared the initial tables; Zhang HC drafted the original manuscript, substantially rewrote and revised the manuscript after peer review, redesigned and revised the tables, prepared the figures, and drafted the responses to reviewers; Zhang XF designed the manuscript outline and coordinated its preparation; and all authors thoroughly reviewed and endorsed the final manuscript.
AI contribution statement: Some graphic elements in the Figure 1 come from the BioRender standard materials/icons library and were used in accordance with BioRender’s license.
Supported by the Construction Fund of Key Medical Disciplines of Hangzhou, No. 2025HZGF05; Zhejiang Provincial Key Research and Development Program, No. 2024C03048; and Zhejiang Provincial Key Discipline of Integrated Traditional Chinese and Western Medicine (Digestive Diseases), No. 2024-XK-61.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Xiao-Feng Zhang, MD, Chief Physician, Professor, Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University; Hangzhou Institute of Digestive Diseases; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, No. 261, Huansha Road, Hangzhou 310006, Zhejiang Province, China. zhangxiaofeng@hospital.westlake.edu.cn
Received: June 15, 2026
Revised: August 12, 2026
Accepted: September 21, 2026
Published online: November 15, 2026
Processing time: 133 Days and 23.2 Hours
Revised: August 12, 2026
Accepted: September 21, 2026
Published online: November 15, 2026
Processing time: 133 Days and 23.2 Hours
Core Tip
Core Tip: This article organizes perineural invasion in pancreatic ductal adenocarcinoma around a spatially organized neural-invasion niche, integrating neural-immune-stromal-metabolic crosstalk while preserving differences in evidence strength. Its key contribution is to connect this niche framework with a dual pain model that distinguishes mechanical injury and com