ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms

Gastric neuroendocrine neoplasms (g-NENs) represent the most frequent digestive NENs and are increasingly recognized due to expanding indications of upper gastrointestinal endoscopy. Often silent and benign, g-NENs may however be aggressive when sporadic and may sometimes mimic the course of gastric adenocarcinoma. Duodenal neuroendocrine neoplasms (d-NENs) may be sporadic or associated with multiple endocrine neoplasia type 1 (MEN-1) and present with a functional syndrome (i.e. gastrinoma with Zollinger-Ellison syndrome). Since the last ENETS guidelines [1], new data have become available, especially focusing on g-NENs, while few changes have been reported concerning d-NENs over the last three years. Epidemiology New epidemiological data come from a study performed in Argentina [2], showing that g-NENs and d-NENs represent 6.9 and 2.0% of all digestive NENs, respectively. These data are similar to the SEER data, where g-NENs were found to represent 8.7% of all enteric NENs [3], and quite similar to a recent prospective Austrian study by Niederle et al. [4], where g-NENs represented 5.6% of all digestive NENs. The proportions of g-NENs with respect to the overall NEN rates do vary, however; g-NENs represented 23% of all NENs in the Austrian study compared to 6% in the SEER data, 5% in a Canadian study (Ontario) and 7.4% in a Taiwanese study [4,5,6,7]. These differences underline the need for multicenter prospective studies with long-term analysis to better describe the European epidemiology of these tumors. Clinical and Histological Features Well-differentiated g-NENs may be divided into three types (table 1): type 1 and 2 are ECLomas, due to chronic hypergastrinemia, associated with chronic atrophic gastritis (CAG) and Zollinger-Ellison syndrome, respectively. Type 3 g-NENs are rare and sporadic and are not a consequence of an underlying gastric mucosal abnormality; they are mostly single large lesions with a high metastatic potential and with a high grade (often G3 NEC) [8,9]. Some issues remain open with respect to the above definitions, as well-differentiated g-NENs with a range of grades (G1-G3) not associated with CAG have been described [10,11,12], and thus a further distinction among type 3 g-NENs may be appropriate. Mixed gastric neoplasms as endocrine/exocrine have also been described; 68 cases have been reported in the literature so far, but no data about the patients' survival rate are available [13].