Systematic Reviews
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World J Gastroenterol. Jul 14, 2022; 28(26): 3258-3273
Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3258
Endoscopic techniques for diagnosis and treatment of gastro-entero-pancreatic neuroendocrine neoplasms: Where we are
Roberta Elisa Rossi, Alessandra Elvevi, Camilla Gallo, Andrea Palermo, Pietro Invernizzi, Sara Massironi
Roberta Elisa Rossi, HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
Alessandra Elvevi, Camilla Gallo, Andrea Palermo, Pietro Invernizzi, Sara Massironi, Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
Author contributions: Rossi RE designed the research; Rossi RE, Elvevi A, Gallo C, Palermo A, and Massironi S performed the literature search and wrote the first draft of the paper; Rossi RE, Invernizzi P and Massironi S reviewed for important intellectual content; Rossi RE and Massironi S wrote the final version of the paper; all the authors approved it.
Conflict-of-interest statement: None.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Roberta Elisa Rossi, MD, PhD, Doctor, HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Via G. Venezian 1, Milan 20133, Italy. robertaelisa.rossi@gmail.com
Received: October 27, 2021
Peer-review started: October 27, 2021
First decision: December 27, 2021
Revised: January 4, 2022
Accepted: April 15, 2022
Article in press: April 15, 2022
Published online: July 14, 2022
Processing time: 258 Days and 15.3 Hours
ARTICLE HIGHLIGHTS
Research background

The prognosis of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) is widely variable depending on several factors including the site of the primary tumor, the grading, and the stage. The correct localization of the primary tumor site, as well as a complete histologic diagnosis, represent the milestones for the proper management and the prognosis of these tumors. Standard axial endoscopy and endoscopic ultrasonography (EUS) still play a pivotal role in several GEP-NENs.

Research motivation

The incidence of GEP-NENs has hugely increased over the last decades; given the well-known heterogeneity of these tumors and the lack of large prospective studies, there is an urgent need to standardize their management.

Research objectives

To analyze current evidence on the role of endoscopy in the management of GEP-NENs (both diagnosis and potential treatment). A specific focus will be reserved to capsule endoscopy, double-balloon enteroscopy and ultrasound endoscopy.

Research methods

An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published in the last 15 years, using both medical subject heading (MeSH) terms and free-language keywords: gastro-entero-pancreatic neuroendocrine neoplasms; endoscopy; ultrasound endoscopy; capsule endoscopy; double-balloon enteroscopy; diagnosis; therapy; staging.

Research results

EUS represents the diagnostic gold standard for pancreatic NENs (panNENs) and the technique of choice for the locoregional staging of gastric, duodenal and rectal NENs. EUS proved to be the most accurate diagnostic technique in panNEN detection. EUS–fine needle aspiration is a diagnostic advanced EUS technique, which represents the gold standard least invasive option to obtain the histological identification of a suspected pancreatic neoplasm or peripancreatic lymph node. The diagnosis of small bowel NENs (sbNENs) has been improved with the advent of capsule endoscopy (CE) and double-balloon enteroscopy (DBE), even if data regarding the efficacy and safety of these techniques in the detection of sbNENs are scanty and mainly based on small retrospective series, given the rarity of the disease and the still-limited use of these techniques in routine clinical practice. In selected localized gastrointestinal NENs with the absence of features associated with lymph node metastases, endoscopic therapy is generally an appropriate treatment with radical intent. In highly selected G1 or low G2 small neoplasms without radiological signs suspicious for malignancy EUS-guided pancreatic locoregional ablative treatments, using either ethanol injection or radiofrequency ablation, have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden.

Research conclusions

Endoscopy plays a key role in GEP-NENs for both the diagnosis and the treatment. In selected localized GEP-NENs, endoscopic therapy is appropriate with radical intent. The multidisciplinary management and the referral to high-volume tertiary centers remain fundamental.

Research perspectives

Further studies are needed: (1) To better define the actual role of CE and DBE in the diagnosis of sbNENs; and (2) To better analyze the possible role of endoscopic confocal laser endomicroscopy in the diagnosis of panNENs and radiofrequency ablation as a potential treatment. Possible future intriguing perspectives can be represented by the application, also in panNENs, of the novel techniques of locoregional delivery of drugs.