Plasma apolipoprotein A2 isoforms predict the development of pancreatic fistula following distal pancreatectomy

doi:10.3748/wjg.v32.i16.116238

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World Journal of Gastroenterology

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Retrospective Cohort Study

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 Gastroenterol. Apr 28, 2026; 32(16): 116238
Published online Apr 28, 2026. doi: 10.3748/wjg.v32.i16.116238

Plasma apolipoprotein A2 isoforms predict the development of pancreatic fistula following distal pancreatectomy

Takashi Ono, Akira Matsushita, Daigo Yoshimori, Akira Hamaguchi, Takahiro Murokawa, Junji Ueda, Tetsuya Shimizu, Yoichi Kawano, Mampei Kawashima, Yoshiharu Nakamura, Kengo Nagashima, Ayumi Kashiro, Kazufumi Honda, Hiroshi Yoshida

Takashi Ono, Akira Matsushita, Daigo Yoshimori, Akira Hamaguchi, Takahiro Murokawa, Junji Ueda, Tetsuya Shimizu, Yoichi Kawano, Hiroshi Yoshida, Department of Gastroenterological Surgery, Nippon Medical School, Bunkyo-ku 113-8603, Tokyo, Japan

Mampei Kawashima, Yoshiharu Nakamura, Department of Gastroenterological Surgery, Nippon Medical School Chiba Hokusoh Hospital, Inzai 270-1694, Chiba, Japan

Kengo Nagashima, Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Shinjuku-ku 160-8582, Tokyo, Japan

Ayumi Kashiro, Kazufumi Honda, Department of Molecular Prevention, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku 113-8602, Tokyo, Japan

Ayumi Kashiro, Kazufumi Honda, Department of Molecular Prevention, Institute for Advanced Medical Sciences, Nippon Medical School, Bunkyo-ku 113-8602, Tokyo, Japan

Author contributions: Ono T, Matsushita A, Honda K, and Yoshida H conceptualized and designed the study; Matsushita A, Honda K, Nakamura Y, and Yoshida H provided administrative support; Ono T, Matsushita A, Kawano Y, Nakamura Y, and Yoshida H provided the study materials or patients; Ono T, Matsushita A, Hamaguchi A, Yoshimori D, Murokawa T, Ueda J, Shimizu T, Kawashima M, and Kashiro A collected and assembled the data; Ono T, Matsushita A, Nagashima K, and Honda K analyzed and interpreted the data; all authors contributed to the writing and revision of the manuscript, and approved the final version of the manuscript to be published.

Supported by Scientific Research from the Japan Society for the Promotion of Science, No. 23K08141; Japan Agency for Medical Research and Development, No. 25ama221431h0002; and Agency for Medical Research and Development Practical Research for Innovative Cancer Control, No. 25ck0106922h0002.

Institutional review board statement: The Institutional Review Board of Nippon Medical School provided approval for this study, No. A-2020-044.

Informed consent statement: Written informed consent was obtained from all participants.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Corresponding author: Akira Matsushita, MD, PhD, Department of Gastroenterological Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku 113-8603, Tokyo, Japan. akira-matsushita@nms.ac.jp

Received: November 6, 2025
Revised: December 18, 2025
Accepted: February 4, 2026
Published online: April 28, 2026
Processing time: 162 Days and 14.6 Hours

Abstract

BACKGROUND

Postoperative pancreatic fistula (POPF) is a major complication of distal pancreatectomy (DP). Although anatomical and surgical risk factors are known, the relationship between preoperative pancreatic exocrine function and POPF remains unclear. Plasma apolipoprotein A2 isoforms (apoA2-i) hold promise as potential biomarkers of pancreatic exocrine function.

AIM

To examine the association between incidence of POPF following DP and preoperative apoA2-i.

METHODS

This retrospective cohort study included 51 patients who underwent DP at Nippon Medical School Hospital between November 2021 and December 2024. Preoperative plasma apoA2-i (ATQ/ATQ and AT/AT) levels were measured using an enzyme-linked immunosorbent assay. The primary outcome was the occurrence of POPF, classified as grade BL or grade B/C according to the 2016 International Study Group of Pancreatic Surgery criteria.

RESULTS

Preoperative apoA2-AT/AT levels were significantly higher in patients who developed POPF (n = 30) than in those who did not (n = 21) (P < 0.001). Receiver operating characteristic curve analysis yielded an area under the curve of 0.802 [95% confidence interval (CI): 0.681-0.924] for predicting POPF. The optimal cutoff value calculated by Youden’s index was 58.17 μg/mL. Plasma apoA2-AT/AT levels ≥ 58.17 μg/mL were significantly associated with POPF (P < 0.001) and remained an independent risk factor for POPF following DP in both univariate (odds ratio = 55.7; 95%CI: 6.58-7319.4; P < 0.001) and multivariate (odds ratio = 163.9; 95%CI: 10.50-35710.29; P < 0.001) logistic regression analyses.

CONCLUSION

Preoperative measurement of apoA2-i may serve as a useful predictor of POPF following DP. These findings support its use for preoperative risk stratification and individualized perioperative management.

Keywords: Blood biomarker; Apolipoprotein A2-isoforms; Pancreatic fistula; Distal pancreatectomy; Pancreatic exocrine function

Core Tip: Postoperative pancreatic fistula (POPF) is a major complication after distal pancreatectomy. This retrospective cohort study of 51 patients investigated the association between POPF and preoperative plasma apolipoprotein A2 isoforms, as a marker of pancreatic exocrine function. Patients with POPF had significantly higher apoA2-AT/AT levels than those without. Receiver operating characteristic analysis yielded an area under the curve of 0.802, with optimal cutoff value of 58.17 μg/mL calculated by Youden’s index. Levels above this threshold were independently associated with POPF. Thus, preoperative apolipoprotein A2 isoforms levels may help predict POPF risk, enabling better perioperative planning and personalized care for patients undergoing distal pancreatectomy.