Netazepide

A review.Holmberg et al. described reduction of gastric and oesophageal adenocarcinomas following discontinuation of proton-pump inhibitor therapy .While PPIs have for long been suspected to cause gastric adenocarcinomas originating from the enterochromaffin-like (ECL) cell via hypergastrinemia , a role by PPIs in oesophageal adeno-carcinogenesis has not been accepted. Gastrin, a peptide hormone, affects cell function only via the CCK- 2 (gastrin) receptor, which is localized on the ECL cell, and possibly on some cells in Barrett's mucosa .The CCK-2 receptor in Barrett's mucosa was postulated to mediate the oesophageal adeno-carcinogenic effect .However, previous studies have indicated that PPI treatment reduces the risk of oesophageal carcinomas, and the gastrin antagonist netazepide failed to affect Barrett's oesophagus .Furthermore, in just published AGA guidelines on Barrett's oesophagus PPI treatment was still advocated.Therefore, the role of PPIs in oesophageal adeno-carcinogenesis is not clear, and future studies are required.

Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.