Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2019; 25(34): 5197-5209
Published online Sep 14, 2019. doi: 10.3748/wjg.v25.i34.5197
Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals
Zhi-Jie Wang, Ke An, Rui Li, Wei Shen, Man-Dula Bao, Jin-Hua Tao, Jia-Nan Chen, Shi-Wen Mei, Hai-Yu Shen, Yun-Bin Ma, Fu-Qiang Zhao, Fang-Ze Wei, Qian Liu
Zhi-Jie Wang, Man-Dula Bao, Jia-Nan Chen, Shi-Wen Mei, Hai-Yu Shen, Yun-Bin Ma, Fu-Qiang Zhao, Fang-Ze Wei, Qian Liu, Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Ke An, Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
Rui Li, Department of General Surgery, Beijing Hospital, Beijing 100730, China
Wei Shen, Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China
Jin-Hua Tao, Department of Colorectal Surgery, University of Chinese Academy of Sciences Zhejiang Cancer Hospital, Hangzhou 310022, China
Author contributions: Wang ZJ and Tao JH designed the research; An K, Li R, Shen W, Bao MDL, Ma YB, and Wei FZ collected the data; Chen JN, Mei SW, Shen HY, and Zhao FQ analyzed the data; Wang ZJ drafted the article; Liu Q revised the paper.
Supported by the Medicine and Health Technology Innovation Project of Chinese Academy of Medical Sciences, No. 2017-12M-1-006.
Institutional review board statement: Our investigation received approval from the ethics committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Informed consent statement: All patients signed an informed consent form before the study.
Conflict-of-interest statement: The authors declare that there is no conflict of interest in regard to this research.
Data sharing statement: No additional data are available.
STROBE statement: The authors have carefully read the STROBE statement checklist of items and prepared the manuscript based on the requirements of the STROBE statement checklist of items.
Open-Access: This 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 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Qian Liu, MD, Chief Doctor, Professor, Surgeon, Teacher, Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. fcwpumch@163.com
Telephone: +86-10-87787110 Fax: +86-10-87787110
Received: July 1, 2019
Peer-review started: July 1, 2019
First decision: August 2, 2019
Revised: August 12, 2019
Accepted: August 19, 2019
Article in press: August 19, 2019
Published online: September 14, 2019
Research background

Colorectal high-grade neuroendocrine neoplasms (HGNENs) are aggressive malignancies with a dismal prognosis. Due to the rarity of this disease, there are still no related large multicenter prospective randomized studies. Therefore, no standard management recommendations have been established.

Research motivation

Most previous reports are case reports and retrospective studies with small samples from single center of Western countries, and few data from multicenter studies or China can be found. Moreover, there is a trend that colorectal HGNENs will be classified as neuroendocrine carcinomas (NECs) and neuroendocrine tumors G3 (NETs G3) based on their morphological differentiation. In prior studies, all colorectal HGNENs were considered NECs.

Research objectives

Based on the latest classification and grading recommendations, we aimed to improve our understanding of this rare disease through multicenter data from China.

Research methods

We performed an observational study and enrolled patients with colorectal HGNENs from three Chinese hospitals. Information regarding the clinicopathologic features and clinical outcomes was collected and delineated. The prognostic factors were analyzed using the Kaplan-Meier method and the Cox proportional hazards regression model.

Research results

Colorectal HGNENs are highly aggressive, and more than half of the patients have developed distant metastasis at the date of diagnosis. It is difficult to distinguish HGNENs from adenocarcinoma through clinical presentations, and immunohistochemical evaluation is necessary. Survival analysis demonstrated that colorectal NETs G3 had a significantly better prognosis than NECs. Therefore, colorectal HGNENs were not a homogenous group of malignancies, and colorectal NETs G3 should be treated with different strategies from NECs. Moreover, increasing age and distant metastasis were statistically confirmed to be independent risk factors for poor clinical outcomes.

Research conclusions

Colorectal HGNENs are aggressive and heterogeneous groups of malignancies. Patients with younger age, good morphological differentiation, and without metastatic disease can have a relatively favorable prognosis.

Research perspectives

More large prospective multicenter clinical studies need to be performed so that standard management recommendations can be established. Moreover, colorectal NETs G3 is an emerging term for colorectal HGNENs with good differentiation and that present significantly different biological behavior from NECs. Distinguishing colorectal NETs G3 from NECs is not always easy. It is imperative to further explore their respective molecular mechanisms and genetic changes so that better diagnostic and treatment strategies can be achieved in the future.