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ssubjects and on the same day (n=5). Second, we evaluated the reproducibility under adifferent set of conditions using the same examiner, the same subjects, but on different days(n=5). Finally, we evaluated pH profile in the upper GI tract and the differences betweenpatients taking proton pump inhibitor (PPI) and those taking H2 blocker. Results: Satisfactorydata could be obtained from all patients without any complications. First, the reproducibilitycoefficient of each pH value by this method was 0.91 [95%CI (CI): 0.89-0.99, P < 0.01](different examiner, same subjects and same day, n=5) and 0.83 (95%CI: 0.59-0.98, P <0.01) (same examiner, same subjects and different days, n=5). Based on the above studyresults, we concluded that this method has high reproducibility. As to the intra-luminal pHprofile, pH in duodenum was strictly controlled more compared to other sites. The pHprofile in the stomach of patients taking PPI was significantly higher than those taking H2blocker in patients with no endoscopic gastric mucosal atrophy (Fig.1), while there wereno significantly differences in moderate to severe endoscopic gastric mucosal atrophy (Fig.2). Conclusions: We have established a new method for assessing intra-luminal pH at 8sites from esophagus to duodenum at one time in daily practice.

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Dynamics of Aquaporin-4 in Gastric Parietal Cells in the Hyperplastic GastricFundic Mucosa of Histamine Type 2 Receptor Knockout MiceSeiichiro Fukuhara, Hidekazu Suzuki, Juntaro Matsuzaki, Hitoshi Tsugawa, Kenro Hirata,Sawako Okada, Yoichiro Abe, Masato Yasui, Toshifumi Hibi

Background. The basolateral water channel protein—aquaporin-4 (AQP4)—is known tobe specifically expressed in the basal parietal cells of the stomach. Although the actual roleof AQP4 in the gastric mucosa is not known, AQP4 expression is considerably decreasedin gastric cancer (Gastroenterol Clin Biol. 33:72-6, 2009). Gastric mucosal hyperplasiatogether with deregulation of the sonic hedgehog gradient in the gastric fundic gland isobserved in histamine type 2 receptor knockout (H2RKO) mice and is considered to berelated to preneoplastic lesion formation (J. Pathol. 213:161-9, 2007). The present studyinvestigated the expression dynamics of AQP4 by using acid suppression and Helicobacterpylori (H. pylori) infection. Methods. Male H2RKO mice (age, 23-65 weeks) and controls(C57BL/6) were used for the study. The H2RKO mice were inoculated with H. pylori at 5weeks and were sacrificed at 25 weeks. AQP4 and H+/K+-ATPase expression levels wereinvestigated by quantitative RT-PCR. The gastric mucosal distributions of AQP4 and H+/K+-ATPase were examined using immunohistochemistry. Results. Gastric mucosal hyperpla-sia with multiple cystic dilatations was observed in H2RKO mice. The number of AQP4-positive parietal cells was higher, and the distribution of AQP4-positive parietal cells wasextended to a greater degree towards the surface of the fundic glands in H2RKO mice thanin the controls. Although AQP4 mRNA and H+/K+-ATPase mRNA expression levels weresignificantly enhanced in H2RKO mice (p < 0.01), they were significantly recovered by agingand H. pylori infection. The ratio between AQP4 and H+/K+-ATPase significantly increased

S-464AGA Abstracts

in the H2RKO mice—even in older mice—but was not preserved by H. pylori infection (p< 0.01). Conclusion. Acid suppression increased the expression and distribution of AQP4in the gastric mucosa. Because AQP4 expression and distribution were not preserved by H.pylori infection, increased AQP4 levels might play a protective role against gastric preneo-plastic transformation.

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Peptic Ulcers After the Great East Japan Earthquake and Fukushima DaiichiNuclear DisasterTakuto Hikichi, Masaki Sato, Yutaka Ejiri, Ryoichi Ishihata, Atsushi Irisawa, YutaTakahashi, Yukiko Kanno, Jun Nakamura, Kou Watanabe, Tsunehiko Ikeda, TadayukiTakagi, Hiromasa Ohira, Katsutoshi Obara

[Background] Peptic ulcers (including gastric ulcers and duodenal ulcers) are known toincrease in number under stressful conditions, as they did when the Kobe earthquakeoccurred in 1995. The Great East Japan Earthquake, which struck March 11, 2011, notonly caused tsunami damage that far exceeded seismic damage; it also caused concern aboutradioactive exposure because of the Fukushima Daiichi nuclear plant's hydrogen explosions.We examined the characteristics of peptic ulcer cases in Fukushima Prefecture after theearthquake. [Methods] Comparing the number of cases of upper gastrointestinal endoscopyand the percentage of peptic ulcer cases among them at six facilities in Fukushima Prefecturefor two months after the Great East Japan Earthquake with those around the same time oneyear prior, we examined the characteristics of peptic ulcers after the earthquake disaster.The study facilities were in three areas: two facilities in Area 1 were located on the Pacificcoast (45 km from Fukushima Daiichi Nuclear Plant); three facilities in Area 2 were located40 km away from the Pacific coast (60 km from Fukushima Daiichi Nuclear Plant): onefacility in Area 3 was 100 km away from the Pacific coast (about 100 km from FukushimaDaiichi Nuclear Plant). [Results] Upper gastrointestinal endoscopy cases showed a numericalyear-on-year decrease of 58.7% (1636/2647: 48.0%, 69.0% and 62.7%, respectively, forArea 1, Area 2, and Area 3). However, the percentage of peptic ulcer cases among themwas 5.0% (81/1636), which showed no significant difference compared to the percentageof 6.1% (125/2647) in the prior year (p=0.31: Area 1 was 7.7%—8.2%; Area 2, 4.8%—3.8%; and Area 3, 5.2%—4.4%). The percentage of gastric ulcers among peptic ulcers was70.4%, which showed no significant difference from 71.7% in the prior year. Among patientswith peptic ulcer two months after the Great East Japan Earthquake (mean age, 65.1: 33—95), male patients accounted for 67.9%, those with a history of ulcer, 38.3%, and bleedingcases, 51.9%. As the causes of ulcers, H. pylori-positive were 62.2%, internal use of NSAIDs,22.2%, and internal use of antithrombogenic drug, 18.5%. Moreover, comparing theiroccurrence time, the cases of bleeding of the group in which ulcer occurred within onemonth after the earthquake (n=39) were more than those of the group in which ulceroccurred one month and later (n=42) (64.1% vs. 40.5%; p=0.03). [Conclusion] After theGreat East Japan Earthquake, the percentage of peptic ulcers among upper gastrointestinalendoscopy cases did not increase. However, the bleeding cases which occurred withinone month after the earthquake were more numerous than expected, demonstrating thatemergency responses immediately after the earthquake were important.

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Risk of Serious (UGI) Complications With Concomitant use of Non-SelectiveNSAIDs and Low-Dose Aspirin: A Series of Systematic Reviews ofRandomized Controlled Trials (RCT), Cohort Studies and Case ControlStudiesGrigorios I. Leontiadis, Yuhong Yuan, Frances Tse, Richard H. Hunt, Paul Moayyedi

Background: Non-selective (ns) NSAID use is associated with increased risk of serious UGIcomplications, mainly peptic ulcer bleeding and perforation. Concomitant use of low-doseaspirin further increases risk. However, the magnitude of this risk and uncertainty aroundthis estimate are confounded by the clinical and methodological heterogeneity of availablestudies. Aim: To estimate the risk of serious UGIC with concomitant use of nsNSAIDs andlow-dose of aspirin compared to nsNSAIDs alone using systematic review and meta-analyses.Methods: Comprehensive literature search in MEDLINE, EMBASE, CENTRAL, TOXILINEand LILACS up to April 2010 without language restrictions for fully-published studies(RCTs, cohort or case control studies) assessing the relative risk of confirmed serious UGIcomplications in adults on nsNSAIDs concomitantly with low-dose aspirin for ≥ 4 weeks,compared to nsNSAIDs alone. Study selection and data extraction were conducted independ-ently by two authors. We calculated pooled odds ratios (OR) with the Mantel-Haenszel andinverse variance method (random effects model) and assessed heterogeneity with theCochrane Q test. Results: No RCTs randomized patients to nsNSAID plus aspirin vs.nsNSAID alone. In 15 RCTs comparing nsNSAIDs with placebo, 5 allowed concomitant useof aspirin, but the risk of UGIC with nsNSAIDs plus aspirin compared to nsNSAIDs alonewas not calculable. Four RCTs that randomized participants to coxibs vs. nsNSAIDs provideddata on UGIC separately for users and non-users of aspirin, thus allowing calculation of theOR for UGIC for nsNSAIDs plus aspirin compared to nsNSAIDs alone (these were cohort-type analyses; not randomized arms): pooled OR 1.85; 95% confidence interval (CI) 0.81-4.22, with significant heterogeneity (p=0.002). The hazard ratio in 1 eligible cohort studywas 1.32; 95% CI 0.85-1.78. When the cohort study and the cohort analyses from RCTswere pooled together, the pooled ratio was 1.68, 95% CI 0.94-3.01, with significant hetero-geneity, p=0.004. Three case control studies evaluated UGI complications in patients takingnsNSAIDs plus aspirin compared to nsNSAIDs alone (OR 2.09; 95% CI 1.08-4.06, with nosignificant heterogeneity). Two case control studies compared nsNSAIDs plus aspirin vs.aspirin alone (OR 1.36, 95% CI 0.69-2.68). Four case control studies evaluated nsNSAIDsplus aspirin vs. neither medication (OR 5.41, 95% CI 2.13-13.72, with significant heterogen-eity, p<0.001). Conclusions: There are no data from direct randomized comparisons; how-ever, evidence from cohort studies (including post hoc analyses of cohorts from RCTs) andcase control studies suggests that among users of nsNSAIDs concomitant use of low-doseaspirin is associated with an additional 1.5- to 2-fold risk of serious UGI complicationscompared to those who are on nsNSAIDs alone.