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World J Gastrointest Surg. May 27, 2022; 14(5): 397-408
Published online May 27, 2022. doi: 10.4240/wjgs.v14.i5.397
Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms
Qing-Yang Que, Lin-Cheng Zhang, Jia-Qi Bao, Sun-Bin Ling, Xiao Xu
Qing-Yang Que, Lin-Cheng Zhang, Jia-Qi Bao, Sun-Bin Ling, Xiao Xu, Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
Qing-Yang Que, Lin-Cheng Zhang, Jia-Qi Bao, Sun-Bin Ling, Xiao Xu, Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
Qing-Yang Que, Lin-Cheng Zhang, Jia-Qi Bao, Sun-Bin Ling, Xiao Xu, NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
Qing-Yang Que, Lin-Cheng Zhang, Jia-Qi Bao, Sun-Bin Ling, Xiao Xu, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
Xiao Xu, Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Que QY, Ling SB, and Xu X formulated the research goals and aims; Que QY, Bao JQ, Zhang LC, Ling SB, and Xu X performed the research; Que QY, Bao JQ, and Zhang LC wrote the manuscript; All authors have read and approve the final manuscript.
Supported by State Key Program of National Natural Science Foundation of China, No. 81930016; Zhejiang Provincial Natural Science Foundation of China, No. LY21H160026.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of 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: Xiao Xu, FACS, MD, PhD, Academic Fellow, Chief Doctor, Professor, Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, No. 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China. zjxu@zju.edu.cn
Received: October 25, 2021
Peer-review started: October 25, 2021
First decision: December 27, 2021
Revised: January 19, 2022
Accepted: April 9, 2022
Article in press: April 9, 2022
Published online: May 27, 2022
Processing time: 211 Days and 17.3 Hours
Abstract

Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.

Keywords: Gastroenteropancreatic neuroendocrine neoplasms; Neuroendocrine carcinomas; Surgery; Hepatic debulking; Liver transplant; Transplant oncology

Core Tip: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) encompass a heterogeneous group of tumors with unique indolent biological behavior. The role of surgery in high-grade or advanced GEP-NENs is still controversial. There are several highlights of this review. First, we address the surgical benefits of selected high-grade GEP-NENs and summarize the tumor biological markers correlated with a prognosis. Second, we review various surgical strategies, including curative resection, debulking, resection after neoadjuvant therapy for metastatic GEP-NENs, and the latest clinical evidence. Finally, liver transplantation presents a curative therapeutic option for GEP-NEN patients with liver metastasis. We summarize the new findings and propose directions for future development.