Neuroendocrine Tumor Disease- An Evolving Landscape.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogeneous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEP-NENs has markedly increased over the last three decades. Symptoms are often absent with early disease, or vague and non-specific even with advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used bio marker but has substantial limitations. Identification of circulating tumor-derived mRNA transcripts presents a novel approach to predict development of metastases. The proliferative marker Ki-67\% is utilized for tumor grading and determination of therapy; it, however, has limitations. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy. Identification of NENs that express somatostatin receptors allow for somatostatin receptor scintigraphy and PET imaging utilizing novel radiolabelled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure, however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity. With exception of streptozotozin in management pancreatic NENs there is little place for standard chemotherapy although new agents targeting either mTOR or angiogenic pathways pathways have shown efficacy in these lesions.