Morphological changes of the human gastric mucosa under long-term proton pump inhibitor therapy and their clinical relevance

Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience

“…The increases in gastrin levels observed were not unexpected. Increases in serum gastrin are an expected physiological response to the increase in intragastric pH resulting from PPI treatment; 33 gastrin is therefore a marker of acid suppression. 34 In the dexlansoprazole MR studies, increased gastrin levels were reversed shortly after patients switched to placebo.…”

Long‐term, open‐label trial: safety and efficacy of continuous maintenance treatment with pantoprazole for up to 15 years in severe acid‐peptic disease

“…Initial concerns resulted from animal studies showing that hypergastrinaemia at high PPI doses resulted in ECL cell hyperplasia in the oxyntic mucosa and the development of gastric carcinoids in up to 30% of female rats. 3,14 However, in humans, the progression of ECL cell hyperplasia to dysplasia and possible neoplasia has only been observed in rare cases of pronounced hypergastrinaemia and chronic atrophic gastritis (e.g. in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I), and PPI treatment was not identified as a factor in this transition.…”

“…in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I), and PPI treatment was not identified as a factor in this transition. 15 Indeed, no dysplastic or neoplastic ECL cell changes have been observed during long-term treatment with PPIs in humans, 14 studies of up to 10 years PPI treatment have provided reassurance that observed increases in serum gastrin levels are of limited clinical concern, 1, 2, 8,16,17 and the development of a frank carcinoid tumour is exceptional even in cases of prolonged acid suppression. 16,18,19 Fasting gastrin levels observed in the current study are consistent with data from long-term treatment with omeprazole, 16, 17 rabeprazole 8 and lansoprazole, 18 along with previous long-term assessment of pantoprazole, 1,2 which shows that long-term therapy with PPIs generally results in serum gastrin levels <250 ng/L and only rarely produces levels >500 ng/L.…”

“…These results correspond with those reported in other long-term studies of PPI therapy. 14,18,20 Current clinical guidelines recommend treatment for H. pylori eradication in H. pylori-positive patients prior to initiation of long-term PPI treatment. 21,24 In the current study, initially, there were no plans to perform H. pylori eradication, although treatment for H. pylori could be initiated if indicated.…”

Introduction to histological studies of gastric secretion

“…The "finely tuned" homeostasis of the gastric epithelium can be disturbed by such exogeneous factors as, e.g., the proton pump inhibitors that result in nearly complete inhibition of gastric acid secretion. The contribution by Lamberts (2000) on the long-term administration of these drugs summarizes changes found in the exocrine and endocrine epithelium and analyzes their impact on treatment of patients with acid-related diseases of the upper gastrointestinal tract. INTRODUCTION…”