Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Aug 27, 2023; 15(8): 1703-1711
Published online Aug 27, 2023. doi: 10.4240/wjgs.v15.i8.1703
Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma
Rui Wang, Ya Liu, Yan Liang, Li Zhou, Mao-Jia Chen, Xu-Bao Liu, Chun-Lu Tan, Yong-Hua Chen
Rui Wang, Xu-Bao Liu, Chun-Lu Tan, Yong-Hua Chen, Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Ya Liu, Department of General Surgery, Chengdu Second People's Hospital, Chengdu 610041, Sichuan Province, China
Yan Liang, Li Zhou, Core Facilities, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Mao-Jia Chen, Animal Experimental Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Chen YH and Tan CL contributed equally to this work; Chen YH, Tan CL and Liu XB conceived and designed the research; Wang R, Liu Y, Liang Y, Zhou L and Chen MJ collected the data and conducted the research; Wang R, Liu Y, Liang Y, Zhou L and Chen MJ analysed and interpreted the data; Wang R and Liu Y wrote the initial paper; Chen YH and Tan CL revised the paper; all authors contributed to the article and approved the submitted version.
Supported by the Key Research and Development Projects in Sichuan Province, No. 2019YFS0043; and 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University, No. ZY2017302-1.3.5.
Institutional review board statement: The study was approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (2014No.37).
Informed consent statement: All study participants or their legal guardians provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: All authors report no relevant conflict of interest for this article.
Data sharing statement: No additional data are available.
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: Yong-Hua Chen, MD, PhD, Associate Professor, Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China. chenyonghua2007@163.com
Received: April 5, 2023
Peer-review started: April 5, 2023
First decision: May 12, 2023
Revised: May 16, 2023
Accepted: June 6, 2023
Article in press: June 6, 2023
Published online: August 27, 2023
Processing time: 142 Days and 4 Hours
ARTICLE HIGHLIGHTS
Research background

Islet amyloid deposition and reduced β-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects.

Research motivation

To date, the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma (PDAC) have not been specifically addressed.

Research objectives

This study aimed to provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences (proximal vs distal residual pancreas) are associated with islet amyloid deposition.

Research methods

This retrospectively collected pancreatic tissue removed from tumors from 45 PDAC patients, including 14 patients with normal glucose tolerance (NGT), 16 patients with prediabetes and 15 new-onset diabetes (NOD) patients. Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans. Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained and analyzed.

Research results

Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition, fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions, especially in the prediabetes and NOD groups. Consistent with this finding, the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group (37.35 ± 12.16 cm3vs 69.79 ± 18.17 cm3, P < 0.001). As expected, islets that stained positive for amyloid (islet amyloid density) were found in the majority of PDAC cases. The proportion of amyloid/islet area (severity of amyloid deposition) was significantly higher in both prediabetes and NOD patients than in NGT patients (P = 0.002; P < 0.0001, respectively). We further examined the regional differences in islet amyloid deposits. Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups (3.98 ± 3.39% vs 0.50 ± 0.72%, P = 0.01; 12.03% vs 1.51%, P = 0.001, respectively).

Research conclusions

In conclusion, these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation.

Research perspectives

Future studies to evaluate the role of islet amyloid deposition in the pathogenesis of NOD secondary to PDAC may be justified.