Neuroendocrine Pancreatic Tumors: Guidelines for Management and Update

Pancreatic neuroendocrine tumors (PanNETs) are a diverse group of rare neoplasms. Commonly referred to as islet cell tumors, PanNETs are classified as functional or nonfunctional depending on their production of specific pancreatic endocrine hormones (e.g. insulin, gastrin, glucagon, and others) and association with the resultant clinical syndromes. While most PanNETs are sporadic, syndromic patients, in particular those with multiple endocrine neoplasia type 1 (MEN-1) and von Hippel Lindau (VHL), are at increased risk of developing these tumors. Recent investigations of patients with sporadic and syndromic PanNETs have elucidated critical pathways in tumor development, such as mammalian target of rapamycin (mTOR) signaling and its downstream growth factors such as vascular endothelial growth factor (VEGF). Prognosis ranges from favorable for localized, low-grade neoplasms to poor for advanced, high-grade tumors. Regardless of the stage at presentation, surgery is the first-line therapy for patients with disease amenable to surgical resection. We favor formal pancreatectomy with conventional lymph node sampling for the vast majority of patients, either through open or laparoscopic techniques. Those with insulinomas, however, may be candidates for enucleation. Cytoreductive surgery is also recommended for patients with locoregional recurrences or hepatic metastases. Regional adjuvants such as radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and others are often employed in an attempt to palliate symptoms and prolong survival. Unfortunately, cytotoxic chemotherapy has been largely ineffective in treating patients with PanNETs. The somatostatin analogue octreotide, however, has been effective in palliating symptoms and slowing the progression of disease. Other promising systemic agents, including sunitinib and everolimus, have targeted critical PanNET signaling pathways. In summary, surgery remains the principal therapeutic strategy for patients with PanNETs, but continued research may identify more robust systemic therapies for those with advanced disease.