title: Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?
abstract: OBJECTIVE
  Reporting on three cases of gastric neuroendocrine tumors (g-NETs) in patients taking long-term proton pump inhibitors (PPIs). These tumors are not classifiable considering current criteria. g-NETs are currently grouped as: types 1 and 2, related to hypergastrinemia due to chronic atrophic gastritis and Zollinger-Ellison syndrome respectively, and type 3, normogastrinemic and more aggressive. Although the g-NETs onset in patients taking PPIs is biologically plausible, only a few cases have been reported so far.
  
  
  METHODS
  From January 2005 to July 2014, 31 g-NETs were referred to our Unit: 24 (77%), one (3%) and three (10%) resulted types 1, 2 and 3, respectively. Three cases (10%) did not meet the current classification criteria.
  
  
  RESULTS
  The three patients were administered long-term PPIs for gastro-esophageal reflux disease. Patient 1: a 78-year-old man, with a 4-mm well-differentiated g-NET (Ki-67<1%) and marked hypergastrinemia. Patient 2: a 58-year-old man affected by a 6-mm well-differentiated (Ki-67 = 4%) g-NET, with normal gastrin levels. Patients 3: a 67-year-old woman with an 18-mm well-differentiated g-NET (Ki-67 <2%), with mild hypergastrinemia. In the three patients, histology and pertinent blood tests excluded chronic atrophic gastritis, Helicobacter pylori infection or Zollinger-Ellison syndrome. The first two patients underwent endoscopic polypectomy; in the third case total gastrectomy was performed. Further clinical, endoscopic and imaging follow-up did not show any g-NET recurrence.
  
  
  CONCLUSIONS
  The present data point to the existence and epidemiological relevance of g-NETs associated with PPIs intake. These neoplasms are not included in the current classification, thus their treatment and follow-up have not been established.
authors.affiliation: Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Gastroenterology and Endoscopic Unit , Milan , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavalcoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zilli
authors.forename: Dario
authors.initials: D
authors.lastname: Conte
authors.forename: Clorinda
authors.initials: C
authors.lastname: Ciafardini
authors.forename: Sara
authors.initials: S
authors.lastname: Massironi
mesh_terms: D000368:Aged; D004724:Endoscopy; D005260:Female; D005743:Gastrectomy; D005755:Gastrins / Q000097:blood; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000473:pathology; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D005755:Gastrins; D054328:Proton Pump Inhibitors
keywords: Chronic atrophic gastritis; Zollinger-Ellison syndrome; classification system; gastric neuroendocrine tumors; gastrin; proton pump inhibitor