Background/Aims: Previous studies have reported a possible relevance between proton pump inhibitor (PPI) use and 3 new gastric mucosal changes: black spots (BSs), white flat elevated mucosa (WFEM), and cobblestone-like mucosa (CLM). The aim of this study was to investigate the association between these mucosal changes and multiple factors including PPI use. Methods: All subjects who underwent a routine esophagogastroduodenoscopy (EGD) were successively enrolled. Endoscopists carried out the EGD after being blinded about ­information on patient PPI usage and determined the presence of these mucosal changes. The ratio of each factor was ­compared in cases with and without each gastric finding. Results: Out of 1,214 patients, BSs were recognized in 75 (6.2%) cases, WFEM in 59 (4.9%), and CLM in 41 (3.4%). In logistic regression analysis, PPI use was significantly correlated with all of these findings (BSs: OR 2.94; 95% CI 1.66–5.21), (WFEM: OR 3.58; 95% CI 1.94–6.61), and (CLM: OR 4.57; 95% CI 2.34–9.96), and Helicobacter pylori eradication was related to BSs (OR 3.01; 95% CI 1.73–5.24) and WFEM (OR 2.11; 95% CI 1.08–4.11). Decision-tree analyses showed that H. pylori eradication was associated with all findings. Conclusions: All of the considered findings were correlated with PPI and H. pylori eradication.

1.
Holt S, Howden CW: Omeprazole. Overview and opinion. Dig Dis Sci 1991; 36: 385–393.
[PubMed]
2.
Poynard T, Lemaire M, Agostini H: Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. Eur J Gastroenterol Hepatol 1995; 7: 661–665.
[PubMed]
3.
Dekkers CP, Beker JA, Thjodleifsson B, Gabryelewicz A, Bell NE, Humphries TJ: Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study. Aliment Pharmacol Ther 1999; 13: 179–186.
[PubMed]
4.
Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van Rensburg CJ, et al: A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med 1998; 338: 719–726.
[PubMed]
5.
Chiba N, De Gara CJ, Wilkinson JM, Hunt RH: Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112: 1798–1810.
[PubMed]
6.
Kahrilas PJ, Howden CW, Hughes N: Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am J Gastroenterol 2011; 106: 1419–1425;quiz 26.
[PubMed]
7.
Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME: Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 2013:CD002095.
[PubMed]
8.
el-Zimaity HM, Jackson FW, Graham DY: Fundic gland polyps developing during omeprazole therapy. Am J Gastroenterol 1997; 92: 1858–1860.
[PubMed]
9.
Jalving M, Koornstra JJ, Wesseling J, Boezen HM, DE Jong S, Kleibeuker JH: Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy. Aliment Pharmacol Ther 2006; 24: 1341–1348.
[PubMed]
10.
Hongo M, Fujimoto K: Incidence and risk factor of fundic gland polyp and hyperplastic polyp in long-term proton pump inhibitor therapy: a prospective study in Japan. J Gastroenterol 2010; 45: 618–624.
[PubMed]
11.
Hatano Y, Haruma K, Ayaki M, Kamada T, Ohtani H, Murao T, et al: Black spot, a novel gastric finding potentially induced by proton pump inhibitors. Intern Med 2016; 55: 3079–3084.
[PubMed]
12.
Haruma K, Kato M, Inoue K, Murakami K, Kamada T: Ien no Kyoto Bunrui [Kyoto Classification of Gastritis]. Tokyo, Nihon Medical Center Press, 2014, pp 91–93 (in Japanese).
13.
Kiso M, Ito M, Boda T, Kotachi T, Masuda K, Hata K, et al: Endoscopic findings of the gastric mucosa during long-term use of proton pump inhibitor – a multicenter study. Scand J Gastroenterol 2017; 52: 828–832.
[PubMed]
14.
Miyamoto S, Kato M, Tsuda M, Matsuda K, Muranaka T, Abiko S, et al: Gastric mucosal cracked and cobblestone-like changes resulting from proton pump inhibitor use. Dig Endosc 2017; 29: 307–313.
[PubMed]
15.
Takahari K, Haruma K, Ohtani H, Kiyoto S, Watanabe A, Kamada T, et al: Proton pump inhibitor induction of gastric cobblestone-like lesions in the stomach. Intern Med 2017; 56: 2699–2703.
[PubMed]
16.
Nakagawa M, Abe M, Takada S, Yamabe T, Kinugasa H, Miyahara K, et al: Endoscopic features of gastric adenocarcinoma of fundic gland type. Stomach Intestine 2015; 50: 1521–1531.
17.
Cats A, Schenk BE, Bloemena E, Roosedaal R, Lindeman J, Biemond I, et al: Parietal cell protrusions and fundic gland cysts during omeprazole maintenance treatment. Hum Pathol 2000; 31: 684–690.
[PubMed]
18.
Stolte M, Bethke B, Ruhl G, Ritter M: Omeprazole-induced pseudohypertrophy of gastric parietal cells. Z Gastroenterol 1992; 30: 134–138.
[PubMed]
19.
Driman DK, Wright C, Tougas G, Riddell RH: Omeprazole produces parietal cell hypertrophy and hyperplasia in humans. Dig Dis Sci 1996; 41: 2039–2047.
[PubMed]
20.
Parfitt JR, Driman DK: Pathological effects of drugs on the gastrointestinal tract: a review. Hum Pathol 2007; 38: 527–536.
[PubMed]
21.
Kawaguchi M: Tahatsusei hakushoku henpei ryuki [multiple white and flat elevated lesions]. Stomach Intestine 2017; 52: 610 [in Japanese].
22.
Adachi K, Mishiro T, Okada M, Kinoshita Y: Prevalence of multiple white and flat elevated lesions in individuals undergoing a medical checkup. Intern Med 2017 (Advance Publication by J-STAGE: December 27, 2017).
23.
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53: 982–992.
[PubMed]
24.
Kimura K, Takemoto T: An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy 1969; 1: 87–97.
25.
Krishnamurthy S, Dayal Y: Parietal cell protrusions in gastric ulcer disease. Hum Pathol 1997; 28: 1126–1130.
[PubMed]
26.
Synnerstad I, Holm L: Omeprazole induces high intraglandular pressure in the rat gastric mucosa. Gastroenterology 1997; 112: 1221–1230.
[PubMed]
27.
Oberhuber G, Stolte M: Gastric polyps: an update of their pathology and biological significance. Virchows Arch 2000; 437: 581–590.
[PubMed]
28.
Ueyama H, Yao T, Nakashima Y, Hirakawa K, Oshiro Y, Hirahashi M, et al: Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma. Am J Surg Pathol 2010; 34: 609–619.
[PubMed]
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