Gastric carcinoids after long-term use of a proton pump inhibitor

Aliment Pharmacol Ther. 2012 Oct;36(7):644-9. doi: 10.1111/apt.12012. Epub 2012 Aug 5.


Background: Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and give hypergastrinemia secondary to gastric hypoacidity. PPI treatment therefore induces enterochromaffin-like (ECL) cell hyperplasia. Long-term hypergastrinemia in rodents and man also leads to ECL cell neoplasia. Whether long-term PPI treatment will induce ECL cell neoplasia in man has been disputed.

Aim: To describe gastric carcinoids in two patients with a history of long-term PPI use.

Results: Two patients had been taking PPI for 12-13 years due to gastro-oesophageal reflux disease. At routine upper gastrointestinal endoscopy a solitary tumour was found in the oxyntic mucosa of both patients. Histology from the tumours showed in both cases a well-differentiated neuroendocrine tumour. Biopsies from flat oxyntic mucosa showed no signs of atrophic gastritis and a normal presence of parietal cells in both cases, but hyperplasia of ECL cells. The tumour in patient 1 was resected endoscopically. After cessation of PPI treatment the tumour regressed in patient 2 and the ECL cell hyperplasia regressed in both patients. In patient 2 serum gastrin and chromogranin A were elevated during PPI treatment, and normalised after cessation of treatment. In patient 1, unfortunately, we had serum only after treatment, and at that time both parameters were normal.

Conclusion: These cases show that hypergastrinemia secondary to proton pump inhibitors treatment, like other causes of hypergastrinemia, may induce enterochromaffin-like cell carcinoids in man.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biopsy
  • Carcinoid Tumor / chemically induced*
  • Carcinoid Tumor / pathology
  • Enterochromaffin-like Cells / drug effects*
  • Female
  • Gastric Mucosa / drug effects
  • Gastroesophageal Reflux / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / adverse effects*
  • Stomach Neoplasms / chemically induced*
  • Stomach Neoplasms / pathology
  • Time Factors


  • Proton Pump Inhibitors