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. Materials and 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.

Key Words:

• Chronic atrophic gastritis
• classification system
• gastric neuroendocrine tumors
• gastrin
• proton pump inhibitor
• Zollinger-Ellison syndrome

Acknowledgments

Authorship statement: Sara Massironi designed the study. Federica Cavalcoli wrote the first version of the paper. Alessandra Zilli and Federica Cavalcoli collected the data, entered the data into the database and performed literature research. Clorinda Ciafardini performed literature research and all the assays on plasma chromogranin A and gastrin. Dario Conte and Sara Massironi critically revised the paper. All the authors approved the final version of the article, including the authorship list.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.