Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

The gut is similar to an endocrine organ, and produces several hormones and substances with endocrine, paracrine, autocrine and neurocrine effects. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are tumors derived from neuroendocrine cells, and they can occur anywhere along the gut. In the GEP-NETs, normal physiological regulations of hormones are lost, and hormones are released autonomously. Although the majority of GEP-NETs are sporadic, they can also be part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1) syndrome, von-Hippel-Lindau disease, tuberous sclerosis and neurofibromatosis type 1. GEP-NETs are rare, with an incidence of 2.5-5 cases per 100,000. Due to increased availability of advanced endoscopic and radiological imaging, the diagnosis of benign and incidentally identified lesions has also increased over the past decades. Except for nonfunctioning GEP-NETs, the extensive release of hormones by the tumor into the circulation leads to diverse clinical manifestations. Hormones and peptides [chromogranin, neurotensin, pancreatic polypeptide (PP), or neuron-specific enolase] are frequently ectopically released by nonfunctional GEP-NETs but these peptides do not cause distinct clinical syndromes. In recent years, there have been significant advances in the treatment of these tumors. In this review, the clinical features of the different types of GEP-NETs, as well as different aspects of their diagnosis and medical management will be discussed.