and the interaction with reflux acidity, in consecutive NERD patients with typical symptomsnot responding (<50% improvement) to full dose PPI, pH-impedance ambulatory monitoringwas performed on two occasions, off and on therapy, randomly, following stationary manome-try. Data obtained in 15 patients (F 11, mean age 47), showing a positive symptom-refluxassociation (SI and/or SAP), were compared to those of 27 NERD patients PPI-responders,with a positive SI and/or SAP (F 16, mean age 51). Reflux episodes were classified accordingto standardized protocols. Results: AET was pathological in 12/15 patients off PPI and in1/15 patients on PPI. Overall, 2639 refluxes were analyzed; off therapy, non-responderpatients, compared to responders, showed more frequent reflux episodes (mean 55±30 vs37±16/24h), higher proportion of acidic (83±15 vs 68±12%) and of proximal refluxes (59±14vs 34±9%), lower proportion of mixed (42±12 vs 55±14%) refluxes. During PPI therapy,in the non-responder patients, frequency of reflux episodes did not change, proportions ofacidic decreased to 21%, weakly acidic refluxes increased to 79%; proportions of mixed(36±10%) and proximal refluxes (60±18%) remained unchanged. Analysis of gastric pHconfirmed compliance and effectiveness of therapy in all patients. On therapy, in non-responder patients, acidic, compared to weakly acidic reflux, was significantly associatedwith liquid-gas composition (OR 1.6 [1.13-2.26]) and with proximal extent (OR 1.6 [0.7-3.8]). No interaction between acidity, proximal extent and physical properties was observedin non-responder patients off PPI (OR 0.9 [0.6-1.4] and 1 [0.8-1.4]) and in PPI-responderpatients (OR 1.2 [0.7-2.2] and 1 [0.7-1.6]). Conclusions: in PPI-resistant patients, duringtherapy, acidic content is associated with presence of gas and proximal spread of refluxate.It could be hypothesized that the interaction between chemical and physical properties areinvolved in the persistence of symptoms despite acid suppression in this subgroup ofNERD patients.

M1859

Incidence of GERD Symptoms Among Patients Under Acute NSAIDsTreatment: Genius Study Preliminary ResultsCarlos Martin de Argila, Maria Caballero-Correa, Pedro Martinez Jimenez

Introduction: GERD (Gastroesophageal Reflux Disease) prevalence is high and estimatedbetween 20% and 40% in the adult population. Both erosive GERD and non-erosive GERD(NERD) present typical symptoms like Reflux and regurgitation and these symptoms areproved to decrease quality of life. NSAIDs (Non-steroidal anti-inflammatory Drugs) are themost used drugs worldwide. NSAIDs use is related to oesophagic erosions and stenosis.However the incidence of GERD symptoms in NSAID users has not been studied yet.Objectives: To evaluate the incidence of GERD symptoms in patients under acute NSAIDstreatment (between 15 and 30 days). Methods: This is an observational, multisite, retrospect-ive study. A proportional number of investigators would be assessed for each of the 17spanish regions. The study lasted from March until July 2008. Preliminary Results: A totalof 2379 patients completed the study, of which 2259 were evaluable. In our study, weanalyzed separately patients undertaking ASA (acetyl-salycilic acid) from those with a differentNSAID treatment. 21% of the participants were taking ASA versus a 79% taking otherNSAIDs. Moreover, a 44,1% of patients receiving ASA were also taking another NSAID. Atotal of 944 patients (41,8%) reported having GERD symptoms after antiinflammatorytreatment was initiated, thus being 4.9 days afterwards (mean score; 95% CI = 4.67 ; 5.10).Preliminary results indicate GERD symptoms are more frequently among patients prescribedASA than those with other NSAIDs. Moreover, atypical GERD symptoms were present, asDysphagia (12,5% NSAIDs vs. 17,9% ASA group), Hoarseness (6.2% NSAIDs vs. 13.1%ASA), persistent hyccups (6,7% NSAIDs vs. 8.0% ASA), persistent Cough (12,7%NSAIDsand 24,5% AAS), Asthma (1,1% NSAIDs vs. 4.4% ASA) and Non-cardial chest pain (11,7%NSAIDs vs. 16,7% ASA). Heartburn was the most frequently symptom described, reportedin 66,6% of all NSAID/ASA users. Conclusion: No long NSAIDs/ASA treatment is neededto cause GERD symptoms among patients. However NSAIDs/ASA acute therapy appears tobe able to induce GERD symptoms. We are working on further analysis of our study formore analytic, and robust conclusions.

M1860

Cardia Type Gastritis Is GERD Associated in a West Los Angeles PopulationJeffrey B. Kaplan, Galen Cortina

Background: The clinicopathological nature of cardia-type gastritis is controversial. Priorinvestigations have implicated either H. pylori (HP) or reflux esophagitis as the major causeof cardia inflammation. The latter suggests that GERD include both esophagitis and cardia-type gastritis. The question remains, is cardia-type gastritis encountered more often in casesof reflux esophagitis or HP? In our practice HP seemed an unlikely association. Purpose:To study the association of cardia-type gastritis with gastroesophageal disease in the outpatientsetting. Design: Thirty-one consecutive biopsy cases meeting the inclusion criterion wereprospectively collected from outpatient clinics and a hospital based practice. To be includedin the study each case required a biopsy from the gastric antrum and/or body and a separatelysubmitted biopsy from the cardia. The clinicopathological associations (such as reflux, HP,etc.) was tabulated. The intensity of inflammation at each site was recorded according theModified Sydney Classification of gastritis. Results: Seven gastroenterologists practicing at5 medical facilities submitted the cases in the series. The sample consisted of 31 patientsaged from 21-78 years. Fifteen patients had clinicopathological reflux esophagitis, 2 hadclinical features equivocal for reflux, 1 had eosinophilic esophagitis, and 1 had HP gastritis.The remaining 12 cases did not have sufficient clinical or pathological findings to makean accurate association and were considered gastritis NOS. Overall, the degree of cardiainflammation was greater than the non-cardia gastric inflammation (65% of cardia inflamma-tion was scored as moderate to severe and only 10% of non-cardia inflammation was scoredas moderate to severe). Likewise, in the cases limited to known esophagitis, 67% had cardiainflammation scored as moderate to severe. Conclusions: In our practice cardia inflammationis associated with a variety of diseases including reflux esophagitis, HP, eosinophilic esophag-itis, and unknown etiologies. By far the greatest association was with reflux esophagitis(48%) and HP was not well represented (3%). In addition, the finding that the magnitudeof cardia inflammation typically exceeded that of the non-cardia suggests that the cardia isthe main site of gastritis in this set of cases. Finally, our study affirms the notion that reflux

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esophagitis is strongly associated with cardia-type gastritis. Cardia-type gastritis and refluxesophagitis should be grouped together in the clinopathological diagnosis of GERD in theappropriate setting. We propose that cardia predominant gastritis be evidence of GERD inthe appropriate setting.

M1861

Effect of AZD3355, a Novel GABAB Agonist, On Reflux and Lower EsophagealSphincter Function in Patients with GERD with Symptoms Despite ProtonPump Inhibitor TreatmentGuy E. Boeckxstaens, Hans Denison, Magnus Ruth, John Adler, Debra G. Silberg, DanielSifrim

Introduction. A proportion of patients (pts) with gastroesophageal reflux disease (GERD)continue to have reflux symptoms while taking a proton pump inhibitor (PPI). This studyassessed the effects of AZD3355, a novel GABAB receptor agonist, on reflux and loweresophageal sphincter (LES) function when used as add-on treatment in pts with GERDsymptoms despite PPI therapy. Methods. In this randomized, double-blind, placebo-con-trolled, cross-over study, pts received AZD3355 65 mg (capsule) or placebo twice on Day1 (morning and evening) and once on Day 2 (morning), in addition to existing PPI treatment(doses within the approved label for any GERD indication). After 5-28 days' washout, ptscrossed to the opposite treatment arm. Pts had a standardized meal 1 h after the morningdoses. On Day 1, ambulatory impedance-pH monitoring was conducted for 24 h after thefirst dose. On Day 2, stationary manometry and impedance-pH monitoring were analyseduntil 3 h after the meal. Results. In all, 27 pts were randomized and 25 completed thestudy. On Day 1, AZD3355 reduced the mean total number of reflux events by ~35%compared with placebo over 24 h, with the acid component being the most reduced (Table1). Esophageal acid exposure (mean % time during 24 h at pH < 4) was lower with AZD3355than placebo (upright: 1.2 [SD:2.0] vs 3.0 [SD:3.9]; supine: 0.3 [SD:0.8] vs 1.9 [SD:3.2]).There were fewer proximal reflux events over 24 h with AZD3355 than with placebo (mean8.7 [SD:8.2] vs 15.4 [SD:14.5]). On Day 2, AZD3355 reduced the geometric mean numberof transient LES relaxations (TLESRs) by 25% and increased the geometric mean LES pressureby 28% compared with placebo (Table 2). AZD3355 was well tolerated: the most commonadverse events were headache (11/27 pts on placebo and 8/25 on AZD3355) and paraesthesia(transient; 3/27 pts on placebo and 5/25 on AZD3355). Conclusions. AZD3355 had benefi-cial effects on TLESRs, LES pressure, total number of reflux events, esophageal acid exposureand proximal reflux events when used as add-on treatment in pts with GERD with symptomsdespite PPI therapy.Table 1. Arithmetic mean no. of reflux events over 24 h on Day 1 (n = 21).

Table 2. Stationary measurements over 3 h on Day 2 (n = 21).

M1862

A New Strategy for the Treatment of Refractory Gastroesophageal RefluxDisease Based On Experimental Results Using a Novel Rat Reflux ModelTomoki Higo, Ken-ichi Mukaisho, Keisuke Ohue, Kunitsugu Kubota, Kazuaki Tsuchiya,Tomohisa Hattori, Takanori Hattori

BACKGROUND: Antisecretory therapies, especially those using proton pump inhibitors(PPIs) are the preferred treatment for patients with gastroesophageal reflux disease (GERD).However, refractory GERD, which can result in an incomplete or lack of response to PPItherapy, can affect up to 40% of patients who use a once daily PPI therapy. Moreover, long-term use of PPIs can result in several adverse effects including the development of corpusatrophic gastritis in H. pylori-infected patients, increased fundic gland polyps, increased riskof community-acquired pneumonia, and increased risk of hip joint fracture. Using a newlyestablished rat model of GERD, present study analyzed the therapeutic effects of rikkunshito,which is a Kampo medicine that is widely prescribed for patients having chronic hypofunctionof the gastrointestinal tract. MATERIALS AND METHODS: Eight-week-old male Wistar ratswere used in this study. First, their forestomach was removed. Then, the esophagus wasconnected directly to the glandular stomach, and the flow of duodenal contents was artificiallyreversed back into the glandular stomach. As a result, gastric juice including the duodenalcontents flowed into the esophagus through the gastroesophageal stoma. The rats weredivided into two groups; those treated with rikkunshito and those that received no treatment.The rats were killed one and four weeks post-operatively. The histological features of thedissected esophagi were examined. The extent of esophagitis was measured from the neo-gastroesophageal junction onwards. Any remarkable histological finding such as hyperplasiaand regenerative atypia was also evaluated. RESULTS: The inflammation of the esophaguswas much less pronounced in the rikkunshito-treated group compared to the control, non-treated group, at both one and four post-operative weeks. The extent of esophagitis fromthe neo-gastroesophageal junction onward was significantly less in the group treated withrikkunshito (2.91 ± 0.36 cm; mean ± SE) than in the non-treated group (4.40 ± 0.45 cm)after one week (Student's t-test; p = 0.0251). The degree of hyperplasia and regenerativeatypia was also less in the rikkunshito-treated group after four weeks. DISCUSSION: It

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