Opinion Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2022; 28(39): 5658-5665
Published online Oct 21, 2022. doi: 10.3748/wjg.v28.i39.5658
Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine
Shunji Fujimori, Ryohei Hamakubo, Aitoshi Hoshimoto, Takayoshi Nishimoto, Jun Omori, Naohiko Akimoto, Shu Tanaka, Atsushi Tatsuguchi, Katsuhiko Iwakiri
Shunji Fujimori, Ryohei Hamakubo, Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, Chiba 270-1694, Japan
Aitoshi Hoshimoto, Takayoshi Nishimoto, Jun Omori, Naohiko Akimoto, Atsushi Tatsuguchi, Katsuhiko Iwakiri, Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 113-8603, Japan
Shu Tanaka, Department of Gastroenterology, Tama-Nagayama Hospital, Nippon Medical School, Tokyo 206-0025, Japan
Author contributions: Fujimori S contributed to the writing of this paper; Hamakubo R, Hoshimoto A, Nishimoto T, Omori J, and Tanaka S performed the small intestinal examinations; Akimoto N and Tatsuguchi A conducted the pathological examinations; Iwakiri K gave advice for the writing of the paper.
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: Shunji Fujimori, AGAF, MD, PhD, Director, Department of Gastroenterology, Chiba Hokusoh Hospital, Nippon Medical School, 1715 Kamagari, Inzai-City, Chiba 270-1694, Japan. s-fujimori@nms.ac.jp
Received: August 5, 2022
Peer-review started: August 5, 2022
First decision: September 8, 2022
Revised: September 18, 2022
Accepted: October 11, 2022
Article in press: October 11, 2022
Published online: October 21, 2022

The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

Keywords: Small intestine, Large intestine, Adenocarcinoma, Risk factor, Carcinogenesis

Core Tip: When investigating the risk factors for small intestinal adenocarcinoma, an important point to note is that small intestinal adenocarcinoma is often found in the proximal small intestine. Intestinal contents remain in the ileum longer than in the jejunum, so poorly absorbed food is unlikely to be a carcinogenic factor. Animal proteins and lipids, bile concentrations, and aerobic bacteria, which are thought to be concentrated in the proximal small intestine, may be carcinogens in the small intestine. Since small intestinal adenocarcinoma is much rarer than colorectal adenocarcinoma, it is unlikely that small intestinal villi are involved in carcinogenesis.