Author(s): Ivo Boškoski [*] 3 , Anche Volkanovska 2 , Andrea Tringali 1 , Vincenzo Bove 1 , Pietro Familiari 1 , Vincenzo Perri 1 , Guido Costamagna 1
ampullectomy; endoscopical mucosal dissection; endoscopic mucosal resection; gastrointestinal; neuroendocrine tumors
Neuroendocrine tumors (NETs), previously referred as 'carcinoids' (carcinoma-like), are a heterogeneous group of neoplasia that originates from the neuroendocrine cells. These cells are widely dispersed throughout the body with a regulatory function due to the secretion of biogenic amines. Most commonly NETs are localized in the GI tract. Other localizations include the bronchopulmonary tree and less often ovaries and testes  . More often NETs are sporadic and single, but they can also be multiple and be part of familial syndromes such as MEN1, von Hippel-Lindau or neurofibromatosis type 1.
Their clinical manifestation is diverse. 'Nonfunctioning' tumors are initially asymptomatic due to the small dimensions of the primary tumor (<20 mm). Uncommonly they can produce obstruction (bile duct or bowel), perforation or bleeding in the GI tract. They become symptomatic later in their course due to the mass effect of the primary tumor and/or when distant metastases occur [2,3] . When 'functioning', they can be discovered even when they are small due to the symptoms caused by the biogenic amines that they produce. The typical carcinoid syndrome (constellation of symptoms due to the secretion of bioactive products) is characterized by diarrhea, flushing and bronchospasm  . These biogenic amines can also cause carcinoid disease of the heart (right-sided cardiac valve disease) [4,5] . But this syndrome is relatively uncommon in localized disease, and when present the disease is usually advanced. These symptoms can also contribute to misdiagnosing the actual disease as they can be attributed to conditions that are more common (irritable bowel syndrome, food allergy etc.).
In the USA, the prevalence of gastroentero-pancreatic NETs has been calculated at 35 per 100,000 tumors  . Previously under-recognized, their prevalence has increased in the last years due to the increased use of computed tomography (CT) and endoscopy. Endoscopical diagnosis of NETs of the gut is more commonly incidental, or based on previous clinical suspicion. Different modalities of treatment are available (endoscopic, surgical and pharmacological) and treatment approach is dependent on the tumor site, size, type, histological grade, stage and symptoms.
The primary NET tumor is most often localized in the GI tract. Within the GI tract, the small intestine is the most frequent site (34%), then the rectum (23%), colon (19%), stomach (7.7%), pancreas (7.5%) and appendix (6.6%). Upper GI endoscopy detects NETs localized in the esophagus, stomach, duodenum and periampullary lesions. Lower GI endoscopy detects lesions in the colo-rectum and terminal ileum. Capsule endoscopy and push-enteroscopy are suitable for detection of lesions in the small intestine. While capsule endoscopy is more comfortable option for the patient, it lacks biopsy capabilities  .
Upon endoscopical examination of the GI tract, NETs appear as polypoid lesions of various dimensions, usually <20 mm, and can be solitary or multiple. Most commonly they are covered with normal mucosa. Rarely overlying mucosa is ulcerated or bleeding. Endoscopy...