Neuroendocrine enteropancreatic tumors (NEEPTs) include tumors developing from the pancreatic islets and the duodenal loop, and those developing from gut serotonin-secreting cells (mid-gut carcinoids). When functioning, they are rare tumors with frequently inconsistant clinical and biological characteristics. Provocative dynamic tests are very useful. Their natural history, with the exception of insulinomas and mid-gut carcinoids, is still incompletely known due to their rarity, relatively recent description, slow evolution and the absence of definitive reliable markers for prognosis. The following factors affect the natural history of NEEPTs. (1) Inclusion or not within the spectrum of multiple endocrine neoplasia type-1 (MEN1), such an integration often dramatically modifies the management strategy. In patients with MEN1, NEEPTs are often multiple, diffusely spread in the duodenopancreatic area and of small size. Definite cure by surgery is then very scarce. Mid-gut carcinoid tumors are the most protean NEEPTs. In contrast to appendiceal carcinoids, usually with a benign course, mid-gut carcinoids have a more malignant course and are very common indeed: local transmural invasion, early metastasis to lymph nodes and/or liver, and symptoms from hormone oversecretion. Carcinoid syndrome is usually well controlled by long-acting somatostatin analogs. (2) Disease spreading, i.e. liver and bone metastases, are the major causes of death in patients with NEEPTs. Liver metastases (LMs) are synchronous in about 75% of the patients with LMs but may develop during follow-up (about 25% of the patients with LMs were without LMs at the initial evaluation). Development of bone metastases has a very poor prognosis accompanying LM progression.
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