Quantitative Assessment of Gastric Corpus Atrophy in Subjects Using Omeprazole: A Randomized Follow-Up Study Nicole C. T. van Grieken, M.Sc., Gerrit A. Meijer, M.D., Ph.D., Marjan M. Weiss, M.Sc., Elisabeth Bloemena, M.D., Ph.D., Jan Lindeman, M.D., Ph.D., Jan P. A. Baak, M.D., Ph.D., Stefan G. M. Meuwissen, M.D., Ph.D., and Ernst J. Kuipers, M.D., Ph.D. Departments of Gastroenterology and Pathology, Free University Hospital; and Department of Pathology, Slotervaart Hospital, Amsterdam, The Netherlands OBJECTIVES: Atrophy of the gastric mucosa most frequently results from chronic Helicobacter pylori infection and is a risk factor for the development of gastric cancer. Profound acid suppression has been suggested to accelerate the onset of gastric mucosal atrophy. The aim of the present study was to evaluate the effects of H. pylori eradication and acid inhibition by omeprazole on gastric atrophy by means of quantitative analysis of tissue morphology. METHODS: Corpus biopsy specimens were obtained during endoscopy in 71 gastroesophageal reflux disease (GERD) patients at baseline and after 3 and 12 months. A total of 48 subjects were H. pylori positive and 23 were H. pylori negative. All subjects received omeprazole 40 mg once daily after the first endoscopy for 12 months. After random- ization, 27 of the 48 H. pylori–positive patients also re- ceived eradication therapy. In hematoxylin and eosin– stained slides the volume percentages of glands (VPGL), volume percentages of stroma (VPS), and volume percent- ages of infiltrate (VPI) were measured in the glandular zone of the mucosa. The results were evaluated by computerized morphometric analysis. RESULTS: In the eradication group, the mean VPGL in- creased from 63.0% to 67.7% and 71.5% after 3 and 12 months (p  0.001), respectively. The mean VPS and VPI decreased from 33.1% and 4.0% to 29.3% and 3.0% and to 26.4% and 2.1% (p  0.001 and p = 0.04), respectively. Patients with the lowest VPGL at baseline showed the largest increases of VPGL after eradication treatment as compared to patients with high a VPGL at baseline. In the H. pylori–persistent group the VPI showed a significant increase (p = 0.01), and in the H. pylori–negative group VPGL increased significantly from 71.9% to 75.2% (p = 0.03) after 12 months. CONCLUSIONS: Eradication of H. pylori leads to restitution of the volume percentage of glandular epithelium to normal levels, even during treatment with proton pump inhibitors. Whether this effect can also be seen in patients with marked atrophy needs further investigation. (Am J Gastroenterol 2001; 96:2882–2886. © 2001 by Am. Coll. of Gastroenterology) INTRODUCTION Helicobacter pylori–induced gastric mucosal atrophy is as- sociated with an increased risk for the development of distal gastric adenocarcinoma. It has been estimated that up to 9% of men and up to 30% of women with atrophy will develop gastric cancer within 15 yr (1–3). The development of atrophy is a slow process that may take decades, depending upon the severity of chronic mucosal inflammation and the level of acid production. The reversibility of mucosal atrophy after H. pylori erad- ication has been the subject of several studies with conflict- ing results (Table 1) (4 –11), which, to a certain extent, may be due to a poor interobserver reproducibility in the assess- ment of gastric atrophy. The updated Sydney System for the classification of gastritis therefore introduced a visual ana- log scale for the grading of mucosal atrophy (12); never- theless, the interobserver variability has remained signifi- cant (13–15). To overcome these inconsistencies in the assessment of gastric corpus atrophy, we previously developed a simple and rapid stereological method for quantitative assessment of mucosal atrophy, which yielded reproducible results that correlated very well with the updated Sydney classification (16). This point counting method allows for a reliable anal- ysis of data when studying the influence of H. pylori infec- tion and/or acid suppressive therapy on different tissue components. The aim of the present study was to quantitatively eval- uate histological changes in the gastric mucosa in gastro- seophageal reflux disease (GERD) patients treated with omeprazole, either with or without H. pylori eradication. MATERIALS AND METHODS After providing informed consent, patients referred for up- per GI endoscopy because of symptoms suggestive of THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 96, No. 10, 2001 © 2001 by Am. Coll. of Gastroenterology ISSN 0002-9270/01/$20.00 Published by Elsevier Science Inc. PII S0002-9270(01)02804-0