Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5344-5355
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5344
Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer
Yu-Ning Chu, Ya-Nan Yu, Xue Jing, Tao Mao, Yun-Qing Chen, Xiao-Bin Zhou, Wen Song, Xian-Zhi Zhao, Zi-Bin Tian
Yu-Ning Chu, Ya-Nan Yu, Xue Jing, Tao Mao, Xian-Zhi Zhao, Zi-Bin Tian, Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
Yun-Qing Chen, Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
Xiao-Bin Zhou, Department of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao 266021, Shandong Province, China
Wen Song, Endoscopy Center, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
Author contributions: Chu YN, Tian ZB, and Mao T contributed to study conception and design; Chu YN, Son W, Zhao XZ, and Chen YQ collected the data; Chu YN, Jing X, Zhou XB, and Yu YN analyzed and interpreted the data; Zhou XB reviewed the statistical methods and analysis; Chu YN wrote the manuscript; Tian ZB, Jing X, and Yu YN made the critical revision of the article.
Supported by the National Natural Science Foundation of China, No. 81502025; and the China Postdoctoral Science Foundation, No. 2018M632631.
Institutional review board statement: This study was approved by the Institutional Review Board of the Ethics Committee of the Affiliated Hospital of Qingdao University.
Informed consent statement: Patients were not required to give 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 this article.
Data sharing statement: No additional data are available.
Open-Access: 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:
Corresponding author: Zi-Bin Tian, MD, Director, Professor, Department of Gastroenterology, the Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao 266003, Shandong Province, China.
Telephone: +86-532-82911302 Fax: +86-532-82911302
Received: July 12, 2019
Peer-review started: July 15, 2019
First decision: August 18, 2019
Revised: August 28, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: September 21, 2019
Research background

The indications for endoscopic submucosal dissection (ESD) have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. However, the risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for early gastric cancer (EGC).

Research motivation

Evaluating the risk of LNM is critical for determining the best course of management for EGC patients. Unfortunately, the risk factors that have been identified in different studies are diverse, and whether patients who met the expanded indications for ESD can be managed safely remains controversial.

Research objectives

We aimed to determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. After working hard on this topic, we have re-evaluated and verified the current indications and guidelines for endoscopic treatment and analyzed the clinicopathological predictors of LNM, which provides strong evidence and reference to future research.

Research methods

We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. Specifically, we analyzed other clinical features, such as drinking and smoking history, obesity, family history of tumors, and the levels of the tumor marker carcinoembryonic antigen (CEA), which is an innovative aspect of this study.

Research results

LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasion (OR = 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. Also, the results of this research affirmed the feasibility of the absolute indications for ESD. However, whether it is reasonable to expand the indications remains to be further discussed.

Research conclusions

The absolute indications for ESD can be applied to Chinese patients, while the feasibility of expanding these indications requires further investigation. The predictive factors for LNM included submucosal invasion depth, LVI, mucinous adenocarcinoma, and large lesion size. This study provides clinicians with important reference when evaluating the risk of LNM and determining the best course of management for EGC patients.

Research perspectives

Besides invasion depth, LVI, and lesion size, taking the histology of tumors into consideration when deciding upon the ESD indications is vitally important. In addition, preoperative detection of tumor markers is of great necessity. The direction of the future research is to further optimize the ESD indications by analyzing the predictive factors for LNM in EGC. A well-designed multicentric prospective study is the best method for the future research.