Proton pump inhibitor: The dual role in gastric cancer

Table 2 Summary of clinical studies associating of gastric pre-malignant conditions with long-term use of proton pump inhibitors

Author, year	Study design, country	Source of database	No. of PPI and control group	Information of PPI	Aims	Main outcomes
Kuipers et al[34], 1996	Prospective cohort, Netherland/ Sweden	Reflux esophagitis cohort (fundoplication/ omeprazole)	105 (PPI)/ 72 (fundoplication)	Type (omeprazole only), dose (20 and 40mg), duration (5 years)	Corpus gastritis, atrophic gastritis	Atrophic gastritis: 0/31 (fundoplication group) vs 18/59 (omeprazole group) with H. pylori infection at baseline (P < 0.001); 0/41 (fundoplication group) vs 2/46 (omeprazole group) without H. pylori infection at baseline (P = 0.62)
Lundell et al[35], 1999	RCT, Sweden	RCT comparing the efficacy of omeprazole and ARS	155 (PPI)/155 (ARS)	Type (omeprazole only), duration (3 years)	Gastric corpus glandular atrophy, intestinal metaplasia of corpus mucosa	No difference in glandular atrophy between H. pylori-infected omeprazole and ARS group (P = 0.57); No difference in intestinal metaplasia between H. pylori-infected omeprazole and ARS group.
Lundell et al[36], 2006	RCT, Sweden	RCT comparing the efficacy of omeprazole and ARS	117 (PPI)/98 (surgical arm)	Type (omeprazole only), duration (7 years)	Gastric corpus glandular atrophy	No significant change of gastric atrophy between H. pylori-negative omeprazole and ARS group; Two patients developed severe atrophy from none at baseline in H. pylori-infected omeprazole group, three patients developed mild atrophy from none at baseline in H. pylori-infected ARS group, no statistical difference.
Gental et al[37], 2003	Two RCTs, United States	Maintenance trial (n = 519), Safety trial (n = 807)	Maintenance trial: 519 (PPI)/169 (placebo); Safety trial: 807/PPI	Type (esomeprazole only), duration (6 months: maintenance trial; 12 months: safety trial)	Atrophy (antrum and corpus), intestinal metaplasia (antrum and corpus)	In the maintenance studies, the majority of omeprazole group had no change in the extent of atrophy and intestinal metaplasia. In the safety study, > 98% of omeprazole had either no change or improved atrophy scores in antrum and corpus, and intestinal metaplasia scores remained unchanged or improved compared with those that worsened.

PPI: Proton pump inhibitor; RCT: Randomized controlled trial; ARS: Anti-reflux surgery; H. pylori: Helicobacter pylori.