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World J Gastrointest Pathophysiol. Feb 15, 2016; 7(1): 117-124
Published online Feb 15, 2016. doi: 10.4291/wjgp.v7.i1.117
Small bowel neuroendocrine tumors: From pathophysiology to clinical approach
Sofia Xavier, Bruno Rosa, José Cotter
Sofia Xavier, Bruno Rosa, José Cotter, Department of Gastroenterology, Centro Hospitalar do Alto Ave, 4835-044 Guimarães, Portugal
José Cotter, ICVS/3B’s Associate Laboratory, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
José Cotter, Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Author contributions: Xavier S performed the literature search, designed the text structure and wrote the text; Rosa B and Cotter J suggested the theme to be reviewed, and made the several critical corrections and revisions, including English editing, until the submitted version was achieved.
Conflict-of-interest statement: All the authors hereby declare that they do not have any conflict-of-interest (including but not limited to commercial, personal, political, intellectual, or religious interests) related to the work submitted herein.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Sofia Xavier, Department of Gastroenterology, Centro Hospitalar do Alto Ave, Rua dos Cutileiros, Creixomil, 4835-044 Guimarães, Portugal. smaxavier@gmail.com
Telephone: +351-253-540330 Fax: +351-253-513592
Received: June 28, 2015
Peer-review started: July 5, 2015
First decision: August 16, 2015
Revised: September 9, 2015
Accepted: December 16, 2015
Article in press: December 18, 2015
Published online: February 15, 2016
Processing time: 216 Days and 19.6 Hours
Abstract

Neuroendocrine tumors (NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging (NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.

Keywords: Neuroendocrine tumors; Gastrointestinal tumors; Small bowel neoplasms; Carcinoid; Diagnostic markers

Core tip: Annual incidence of neuroendocrine tumors (NETs) has risen in the last years to 40 to 50 cases per million probably due to better diagnostic tools. Recurrent loss of chromosomes 11 and 18 and gains of chromosomes 4, 5, 19 and 20 have been shown in NETs. Several cancer-related pathways were implied in NETs associated mutations, including PI3K/Akt/mTOR and TGF-β pathways. Genes involved in secretory activity were conserved in NETs, however alterations in transcription factors associated with neurodevelopmental process were reported. Studies suggest that miRNA may have a role in ileal NETs development and progression.