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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2015; 21(32): 9512-9525
Published online Aug 28, 2015. doi: 10.3748/wjg.v21.i32.9512
Non-functional neuroendocrine tumors of the pancreas: Advances in diagnosis and management
Jordan M Cloyd, George A Poultsides
Jordan M Cloyd, George A Poultsides, Department of Surgery, Stanford University, Stanford, CA 94305, United States
Author contributions: Cloyd JM and Poultsides GA contributed solely to this manuscript.
Conflict-of-interest statement: The authors have no conflict of interest.
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: George A Poultsides, MD, Department of Surgery, Stanford University, 300 Pasteur Dr, H3680, Stanford, CA 94305, United States. gpoultsides@stanford.edu
Telephone: +1-650-7234646 Fax: +1-650-8523430
Received: May 7, 2015
Peer-review started: May 11, 2015
First decision: June 2, 2015
Revised: July 2, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: August 28, 2015
Processing time: 113 Days and 15.2 Hours
Abstract

Nonfunctional neuroendocrine tumors of the pancreas (NF-PNETs) are a heterogeneous group of neoplasms. Although rare, the incidence of NF-PNETs is increasing significantly. The classification of PNETs has evolved over the past decades and is now based on a proliferation grading system. While most NF-PNETs are slow growing, tumors with more aggressive biology may become incurable once they progress to unresectable metastatic disease. Tumors of higher grade can be suspected preoperatively based on the presence of calcifications, hypoenhancement on arterial phase computed tomography, positron emission technology avidity and lack of octreotide scan uptake. Surgery is the only curative treatment and is recommended for most patients for whom complete resection is possible. Liver-directed therapies (thermal ablation, transarterial embolization) can be useful in controlling unresectable hepatic metastatic disease. In the presence of unresectable progressive disease, somatostatin analogues, everolimus and sunitinib can prolong progression-free survival. This article provides a comprehensive review of NF-PNETs with special emphasis on recent advances in diagnosis and management.

Keywords: Pancreas; Neuroendocrine tumor; Neuroendocrine carcinoma; Islet cell; Octreotide

Core tip: Pancreatic neuroendocrine tumors (PNETs) are a fascinating and diverse group of neoplasms. While the clinical features of functional PNETs are frequently discussed, the majority of PNETs are actually non-functional. Although typically slow growing, tumors with more aggressive biology may progress to unresectable metastatic disease. Surgery should be considered for all patients for whom complete resection is possible, while liver directed therapies are useful for managing hepatic metastases. For patients with progressive metastatic disease, strong evidence supports the use of somatostatin analogues, everolimus and sunitinib in prolonging survival. The purpose of this article is to provide a comprehensive review of NF-PNETs.