Clinical and Translational Research
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2020; 26(20): 2618-2631
Published online May 28, 2020. doi: 10.3748/wjg.v26.i20.2618
Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients
Chiko Sato, Kingo Hirasawa, Yoko Tateishi, Yuichiro Ozeki, Atsushi Sawada, Ryosuke Ikeda, Takehide Fukuchi, Masafumi Nishio, Ryosuke Kobayashi, Makomo Makazu, Hiroaki Kaneko, Yoshiaki Inayama, Shin Maeda
Chiko Sato, Kingo Hirasawa, Yuichiro Ozeki, Atsushi Sawada, Ryosuke Ikeda, Takehide Fukuchi, Masafumi Nishio, Ryosuke Kobayashi, Makomo Makazu, Endoscopy Division, Yokohama City University Medical Center, Yokohama 232-0024, Japan
Yoko Tateishi, Department of Histopathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
Hiroaki Kaneko, Shin Maeda, Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
Yoshiaki Inayama, Division of Pathological Diagnosis, Yokohama City University Medical Center, Yokohama 232-0024, Japan
Author contributions: Sato C and Hirasawa K contributed to conception and design. Sato C, Hirasawa K, Ikeda R, Sawada A, Nishio M, Fukuchi T, Kobayashi R, Makazu M, and Kaneko H contributed to acquisition of data. Hirasawa K and Sato C contributed to the analysis and interpretation of data. Tateishi Y and Inayama Y contributed to histopathological evaluation. Hirasawa K contributed to the drafting of the article. Hirasawa K and Maeda S contributed to the critical revisions of the article. Hirasawa K and Maeda S approved the final version of the article. All authors contributed to experimental design, data collection, and data analysis. All authors read and approved the final manuscript.
Institutional review board statement: The study protocol was approved by the Ethics Committee of Yokohama City University Medical Center Hospital (Approval number: D1602024).
Informed consent statement: Patients were not required to provide informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts of interest related to the manuscript.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Kingo Hirasawa, MD, PhD, Associate Professor, Chief Doctor, Endoscopy Division, Yokohama Medical University Center Hospital, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024, Japan. kingo-h@urahp.yokohama-cu.ac.jp
Received: January 28, 2020
Peer-review started: January 28, 2020
First decision: February 27, 2020
Revised: March 25, 2020
Accepted: May 14, 2020
Article in press: May 14, 2020
Published online: May 28, 2020
Processing time: 111 Days and 3.2 Hours
ARTICLE HIGHLIGHTS
Research background

In recent years, awareness of eradication therapy has increased in Japan. As Helicobacter pylori(H. pylori) infections decrease, the proportion of gastric cancers arising from H. pylori uninfected gastric mucosa will increase. The emergence of gastric cancer arising in H. pylori uninfected patients though rarely reported, is a concern to be addressed and needs elucidation of its clinicopathological features.

Research motivation

Previously, H. pylori-uninfected gastric cancer including case report such as undifferentiated gastric cancer or fundic gland-type gastric cancer was reported. However, due to the rare frequency, there was very few reports. In the future, H.pylori-uninfected gastric cancer may increase relatively; therefore, importance of clarifying the clinicopathological features of those is desired. In this study, we experienced 30 cases of H. pylori-uninfected early gastric cancer and could classify histopathological features of these.

Research objectives

To clarify clinicopathological feature of H. pylori-uninfected gastric cancer (HpUNGC) treated by endoscopic submucosal dissection (ESD).

Research methods

This study is retrospective study. A total of 2462 patients with 3375 instances of early gastric cancers that were treated by ESD were enrolled in our study between May 2000 and September 2019. We defined a patient as H. pylori-uninfected using the following three criteria; i) the patient did not receive treatment for H. pylori, which was determined by investigating medical records and conducting patient interviews, ii) lack of endoscopic atrophy, and iii) the patient was negative for H. pylori after being tested at least twice using various diagnostic methods, including serum anti-H. pylori-IgG antibody, urease breath test, rapid urease test, and microscopic examination.

Research results

Of these, 30 lesions in 30 patients were diagnosed as HpUIGC. Histologically 30 HpUIGC lesions were classified into 4 types (fundic gland type adenocarcinoma, foveolar type well-differentiated adenocarcinoma, intestinal phenotype adenocarcinoma, and pure signet-ring cell carcinoma). Unlike previous reports, most of the lesions (22/30 lesions) were the differentiated type.

Research conclusions

In this study, we classified 30 HpUIGCs into 4 types histologically. Unlike previous reports, there were more differentiated cancers than undifferentiated cancers. Although the most of HpUIGC showed gastric phenotype, it is essential to recognize that there are not a few intestinal phenotype adenocarcinomas among HpUIGCs. HpUIGC is very rare, among which, histologically high incidence of undifferentiated adenocarcinoma. Besides undifferentiated adenocarcinoma and gastric fundic gland type adenocarcinoma, there is another HpUIGC having different histopathological features. HpUIGC may show various type of his-topathological features. Histologically, HpUIGC is classified into at least 4 types (fundic gland type adenocarcinoma, foveolar type well-differentiated adenocarcinoma, intestinal phenotype adenocarcinoma, and pure signet-ring cell carcinoma). To the best of our knowledge, the present study reports the largest number of HpUIGC cases that had been evaluated for both endoscopic and pathological findings. To recognize clinicopathological feature of HpUIGC will be helpful for early detection of HpUIGC in the future clinical practice.

Research perspectives

To recognize the various clinicopathological features of HpUIGC is useful for clinical diagnosis in the future. Because HpUIGC is rare frequency, we consider multicenter clinical trial for case collection to elucidate more detail of the clinicopathological characteristics of HpUIGC. Multicenter observational trial is the best method for the future research.