Therapy for Locoregional Disease. Stomach/Duodenum, Colon/Rectum

Neuroendocrine neoplasms (NENs) of the gastrointestinal (GI) tract are a heterogeneous group of tumors originating from neuroendocrine cells distributed throughout the gut and frequently presenting with correlated hypersecretory syndromes, especially in metastatic diseases. Gut-derived NENs have been classified according to their embryological origin into tumors of the foregut (bronchi, stomach, pancreas, gallbladder, duodenum), midgut (duodenum, ileum, appendix, right colon), and hindgut (left colon, rectum). The incidence of NENs diagnosed has increased in the last years, with GI primary tumors representing the majority of diagnosis. NENs may occur as part of complex familial endocrine cancer syndromes such as multiple endocrine neoplasia type 1 (MEN 1), multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1, Von Hippel–Lindau syndrome, and Carney’s complex, although the majority occurs as sporadic isolated tumors. The management of NENs of the GI tract in the setting of locoregional disease consists of different therapeutic approaches, in particular medical treatment and endoscopic procedures, and it varies greatly depending on the site of origin. In patients with gastric NENs (gNENs), the approach depends on the clinical presentation of the tumor, classified in three types. Type 1 gNENs are associated with hypergastrinemia and chronic atrophic gastritis; the frequency of metastasis is low. Type 2 gNENs occur in patients with hypergastrinemia due to Zollinger-Ellison syndrome in combination with MEN 1. Type 3 gNENs are sporadic and have a more malignant course, frequently presenting with metastasis at the time of diagnosis. Duodenal NENs are rare (less than 2% of all GI-NENs), and gastrinomas are the most frequent type of tumors originating in this site. Rectal NENs are commonly small and generally low to intermediate grade (G1–2), whereas colonic NENs are often aggressive, poorly differentiated, and higher grade (G3).