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

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.

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

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.

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