Wan P, Zhou SQ, Ke QH. Very early recurrence after pancreatic cancer resection: Unmasking the "biological R2" enigma and rethinking prognostic paradigms. World J Gastrointest Surg 2025; 17(12): 114403 [DOI: 10.4240/wjgs.v17.i12.114403]
Corresponding Author of This Article
Qing-Hua Ke, MD, PhD, Chief Physician, Department of Chemoradiotherapy, Jingzhou No. 1 People's Hospital and First Affiliated Hospital of Yangtze University, No. 10 Tianhu Road, Shashi District, Jingzhou 434000, Hubei Province, China. 3803354759@qq.com
Research Domain of This Article
Oncology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 27, 2025 (publication date) through Dec 25, 2025
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Gastrointestinal Surgery
ISSN
1948-9366
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Wan P, Zhou SQ, Ke QH. Very early recurrence after pancreatic cancer resection: Unmasking the "biological R2" enigma and rethinking prognostic paradigms. World J Gastrointest Surg 2025; 17(12): 114403 [DOI: 10.4240/wjgs.v17.i12.114403]
World J Gastrointest Surg. Dec 27, 2025; 17(12): 114403 Published online Dec 27, 2025. doi: 10.4240/wjgs.v17.i12.114403
Very early recurrence after pancreatic cancer resection: Unmasking the "biological R2" enigma and rethinking prognostic paradigms
Peng Wan, Shi-Qiong Zhou, Qing-Hua Ke
Peng Wan, Shi-Qiong Zhou, Qing-Hua Ke, Department of Chemoradiotherapy, Jingzhou No. 1 People's Hospital and First Affiliated Hospital of Yangtze University, Jingzhou 434000, Hubei Province, China
Co-first authors: Peng Wan and Shi-Qiong Zhou.
Author contributions: Ke QH wrote the first draft, developed the main ideas, and led revisions; Wan P and Zhou SQ provided critical feedback, improved the structure, and added key examples. Wan P and Zhou SQ contributed equally to this manuscript as co-first authors.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qing-Hua Ke, MD, PhD, Chief Physician, Department of Chemoradiotherapy, Jingzhou No. 1 People's Hospital and First Affiliated Hospital of Yangtze University, No. 10 Tianhu Road, Shashi District, Jingzhou 434000, Hubei Province, China. 3803354759@qq.com
Received: September 18, 2025 Revised: October 4, 2025 Accepted: October 29, 2025 Published online: December 27, 2025 Processing time: 98 Days and 11.6 Hours
Abstract
Pancreatic ductal adenocarcinoma (PDAC), a "silent killer" with elusive early symptoms and poor prognosis, sees nearly half of patients experience recurrence within a year post-curative-intent surgery. Very early recurrence (VER), defined as recurrence within 12 weeks postoperatively and first termed "biological R2 resection" by Belfiori et al, remains a clinical puzzle. Martlı et al’s recent retrospective cohort study offers crucial insights into this understudied issue, identifies predictive factors that challenge long-held beliefs, and calls for a rethink of risk stratification and postoperative management for PDAC patients. Martlı et al studied 303 PDAC patients at a high-volume center from 2019 to 2024, with VER affecting 9.24% (28 patients) of the cohort. The study’s strength lies in combining traditional statistical analyses and machine learning (random forest modeling) to capture nonlinear relationships between clinicopathological factors and VER risk. Key findings include: (1) Poorly differentiated (G3) tumors are the strongest VER predictor (OR = 2.43, P < 0.001; random forest importance score = 0.35), with 92.85% of VER patients having G3 tumors (vs 45.81% of non-VER patients); (2) Contrary to prior studies, pancreatic head tumors (89.28% of VER patients vs 83.66% of non-VER patients, P = 0.031) were linked to VER; (3) Elevated red cell distribution width is a weaker predictor (random forest importance score = 0.20, P = 0.03 for group difference, P = 0.079 in multivariate analysis); and (4) VER correlates with significantly higher 6-month mortality (32.44% vs 14.77% in non-VER patients, P = 0.032).
Core Tip: Very early recurrence (VER) in pancreatic ductal adenocarcinoma (PDAC), a "biological R2 resection," occurs when macroscopically complete surgery fails to stop aggressive tumor progression. Martlı et al’s study of 303 PDAC patients identified G3 tumors (strongest predictor), pancreatic head location (contrary to prior assumptions), and elevated red cell distribution width as VER predictors, with VER doubling the 6-month mortality rate. These findings urge a shift to risk-stratified PDAC management, but the study’s retrospective, single-center design and lack of molecular data limit conclusions. Future research should validate predictors, test risk-stratified strategies, and explore VER’s molecular drivers.
