Pancreatic Neuroendocrine Tumors: an Update

Pancreatic neuroendocrine tumors (pNETs) are rare and comprise only 1-2 % of all pancreatic neoplastic disease. Although the majority of these tumors are sporadic (90 %), pNETs can arise in the setting of several different hereditary genetic syndromes, most commonly multiple endocrine neoplasia type 1 (MEN1). The presentation of pNETs varies widely, with over 60 % having malignant distant disease at the time of initial diagnosis involving the liver or other distant sites. Functioning pNETs represent approximately 10 % of all pNETs, secrete a variety of peptide hormones, and are responsible for several clinical syndromes caused by profound hormonal derangement. Surgery remains the cornerstone of therapy and the only curative approach. It should be pursued for localized disease and for metastatic lesions amenable to resection. Multimodality therapies, including liver-directed therapies and medical therapy, are gaining increasing favor in the treatment of advanced pNETs. Their utility is multifold and spans from ameliorating symptoms of hormonal excess (functional pNETs) to controlling the local and systemic disease burden (non-functional pNETs). The recent introduction of target molecular therapy has promising results especially for the treatment of progressive well-differentiated G1/G2 tumor. In this review, we summarize the current knowledge and give an update on recent advancements made in the therapeutic strategies for pNETs.