Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 26, 2022; 10(27): 9573-9587
Published online Sep 26, 2022. doi: 10.12998/wjcc.v10.i27.9573
Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update
Efstathios Theodoros Pavlidis, Theodoros Efstathios Pavlidis
Efstathios Theodoros Pavlidis, Department of 2nd Surgical Propedeutic, Hippocration Hospital, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
Theodoros Efstathios Pavlidis, Department of 2nd Surgical Propedeutic, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
Author contributions: Pavlidis TE designed research, contributed new analytic tools, analyzed data and review; Pavlidis ET performed research, analyzed data review and wrote the paper.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
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:
Corresponding author: Theodoros Efstathios Pavlidis, Doctor, PhD, Chief Doctor, Director, Full Professor, Surgeon, Department of 2nd Surgical Propedeutic, Aristotle University of Thessaloniki, School of Medicine, Konstantinoupoleos 49, 54642 Thessaloniki, Greece.
Received: June 28, 2022
Peer-review started: June 28, 2022
First decision: July 13, 2022
Revised: July 16, 2022
Accepted: August 17, 2022
Article in press: August 17, 2022
Published online: September 26, 2022

The prevalence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing, and despite recent advances in their therapy, it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors. These tumors present many challenges concerning the molecular basis and genomic profile, pathophysiology, clinicopathological features, histopathologic classification, diagnosis and treatment. There has been an ongoing debate on diagnostic criteria and clinical behavior, and various changes have been made over the last few years. Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors (NETs). The diagnosis and management have changed over the past decade. Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools. Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents (64Cu-DOTATATE or 68Ga-DOTATATE) replacing enough octreoscan, has improved further the current diagnostic imaging. Promising results provide targeted therapies with biological agents, new drugs, chemotherapy and immunotherapy. However, the role of surgery is important, since it is the cornerstone of management. Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge. Endoscopy offers novel options not only for diagnosis but also for interventional management. The therapeutic option should be individualized based on current multidisciplinary information.

Keywords: Gastrointestinal neuroendocrine tumors, Neuroendocrine neoplasms, Mixed NEN, Neuroendocrine carcinoma, APUD cells, Carcinoids, Somatostatin analogs

Core Tip: Novel diagnostic modalities, including imaging, biomarkers and molecular factors such as liquid biopsy based on mRNA and NETest index, including 51 genes, have changed diagnosis and follow-up. Current available therapeutic options for gastrointestinal neuroendocrine tumors open new horizons promising better results. Surgery remains the cornerstone for resectable disease, but drug therapies, mainly somatostatin analogs, somatostatin receptor antagonists, molecular-targeted drugs and new chemotherapeutic agents are important in the palliative treatment of inoperable or recurrent cases. Advances in genomic profiling and endoscopic intervention could individualize management options.