initial management strategies for reflux-predominant uninvestigated dyspepsia (ud) in primary care...

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Due to this concern and the current debate, we designed a study to examine for any possible correlation between carditis and GERD in series of H. pylori infected subjects. Methods: Patients enrolled in a H. pylori eradication trial underwent urea breath testing (UBT) to confirm infection. Those with a positive UBT underwent 24-hr pH testing with a 4-channel probe. The leads were 5cm above the proximal LES border, at the proximal border, just below the LES (i.e. cardia), and intra-gastric. EGD was then performed with biopsies of the antrum, body, and cardia (5mm below SCJ). The samples were analyzed for inflammation, intestinal metaplasia, and atrophy using the Sydney Classification. Statistical comparisons were performed using non- parametric testing. Results: 17 H. pylori positive subjects have completed the study. 66.7% were male, 33% caucasian, 44% African American, mean age-55.4yo 15.7yrs. Intestinal metaplasia was found in 11.8% of subjects, and atrophy was also found in 11.8%. All patients had carditis present. Cardia inflam- mation severity did not significantly correlate with %total time pH 4, both in the location 5cm above the proximal LES border and in the cardia itself. Comparisons of %time pH 4 in the upright and supine position also did not show any statistical significance. There was a significant positive association between antral and cardia inflammation scores (r 0.59;p 0.034). Conclusions: Based on these preliminary findings, the degree of carditis severity does not correlate with the amount of gastro-esophageal reflux, or to the local exposure of the cardia to acid. There was a statistically significant association between the severity of antral and cardia inflamma- tion. This suggests a primary role of H. pylori in carditis, but no clear role for GERD. 8 Initial management strategies for reflux-predominant uninvestigated dyspepsia (UD) in primary care practice–the CADET-HR study David Armstrong MD 1 *, Alan Barkun FACG 2 , Naoki Chiba MD 1 , Sander Veldhuyzen Van Zanten MD 3 , Alan Thomson MD 4 , Sandra Smyth BSc 5 , Bijan Chakraborty MSc 5 , Paul Sinclair MSc 6 and CADET HR Investigators. 1 Gastroenterology, McMaster University, Hamilton, Ontario, Canada; 2 Gastroenterology, McGIll University, Montreal, Quebec, Canada; 3 Gastroenterology, Dalhousie University, Halifax, Nova Scotia, Canada; 4 Gastroenterology, University of Alberta, Edmonton, Alberta, Canada; 5 AstraZeneca, Mississauga, Ontario, Canada; 6 INSINCONSULTING, Guelph, Ontario, Canada; and 7 Canada. Purpose: Patients with reflux-predominant symptoms comprised 37.8% of a Canadian, primary-care UD study population (Thomson et al. Gastro 2001;120:A50); the optimal management strategy for reflux-predominant, UD patients is not known. The study’s aim was to determine the symptom response after 4 weeks treatment with an H 2 -receptor antagonist (ranitidine 150 mg bid (R)) or a proton pump inhibitor (PPI-omeprazole 20 mg daily (O)) as the initial phase of a “step-up”/maintenance strategy. Methods: A randomized, double-blind multicentre trial in 46 primary care Canadian practices. Major inclusion criterion: 3 months of heartburn (Carlsson-Dent definition) occurring 3 days during prior 7 days. Exclu- sion criteria: alarm features, predominant IBS, serious concomitant disease or relevant investigations on 1 occasion during the prior 6 months or 2 occasions during the prior 10 years. The primary outcome variable was “Heartburn relief”–the proportion of patients with no more than mild heartburn on 1 day of the previous 7 days, assessed at 4 weeks, from a daily diary, on a 7-point Likert scale. Results: In all, 390 patients were randomized (O–196, R–194). Mean age (O– 44 yrs, R– 44 yrs) and Helicobacter pylori infection rate (30.8%) were comparable to those in associated Canadian UD studies; compliance was good (O–94%, R–91%). Based on daily diary data, heartburn relief was reported by 55.1% (O) and 27.3% (R) of patients (p 0.001) whilst complete resolution of heartburn was reported by 36.2% (O) and 12.9% (R) of patients (p 0.001). Based on physicians’ assessments, complete heartburn relief (O– 46.3%, R–21.1%, p 0.001) was more common with O but complete relief of regurgitation, epiastric pain and nausea was comparable with O and R. Neither age nor H. pylor status affected symp- tom relief outcomes. Improvements in Gastrointestinal Symptom Rating Scales (GSRS) for indigestion, abdominal pain, and reflux (all p 0.05) and in all 5 GASTROQoL health-related quality of life scales (all p 0.003) were greater at 4 weeks with O than with R. Conclusions: Initial therapy with standard dose O produces symptom relief in twice as many patients as R at 4 weeks and this is associated with significantly greater health-related quality of life. The management of patients with reflux-predominant uninvestigated dyspepsia in primary care practice should be based on initial therapy with a once-daily PPI; re- assessment at 4 weeks will identify the remaining 45% of patients who require continued short-term therapy. 9 Esophageal carcinoma, alkaline reflux and male sex hormones Anil M. Bahadursingh, M.D., F.R.C.S. (Irl), Faisal H. Khan, M.D., Petra H. Nass, Ph.D., Firas F. Mussa, M.D., Mark D. Duncan, M.D., and John W. Harmon, M.D., F.A.C.S. 1 Johns Hopkins Medical Institutions, Department of Surgical Sciences, Johns Hopkins Bayview Medical Center, Baltimore, MD, United States. Purpose: Carcinoma of the esophagus is one of the fastest rising cancers in the USA. The male to female ratio is 6:1. This has coincided with the widespread use of Histamine antagonists and Proton Pump inhibitors, which decrease the gastric pH and predispose to alkaline reflux into the esophagus. A surgical rat model was created to cause alkaline reflux, we then blocked the release of gonadotropic hormones with Lupron (Gonado- trophin-releasing hormone analog) to prevent the production of male sex hormones. Methods: Alkaline reflux was surgically created in two groups of Sprague- Dawley rats (40 male and 40 female). Nitrosamine was given intraperito- neally once weekly for four weeks to induce carcinoma. The release of Gonadotrophic-Releasing hormone was blocked with a depot injection of Lupron in half of the rats in each group. In the others we gave the dilutent for the Lupron depot injection. We then quantified the number of cancers of the esophagus that developed in each group. Results: Male Lupron Dilutent Squamous Cell Cancer 1 2 Adenocarcinoma 12 2 Female Squamous Cell Carcinoma 5 3 Adenocarcinoma 2 1 Conclusions: Alkaline reflux is associated with esophageal carcinoma. The Gonadotropic-releasing hormone analog group had more carcinomas than the control. This may be due to the fact that Lupron is a weak agonist as opposed to a complete agonist and therefore had a more sustained action as a depot injection. 10 Incidence and prevalence of high grade dysplasia and carcinoma in Barrett’s esophagus with and without maintenance omeprazole therapy Simmy Bank*, Pankaj Singh, Anant Indaram and Ronald Greenberg. 1 Gastroenterology, Albert Einstein College of Medicine-Long Island Jewish Hospital, New Hyde Park, NY, United States. Purpose: To study the incidence and prevalence of high grade dysplasia and carcinoma in patients with Barrett’s. The effect of maintenance ome- prazole therapy was also assessed. Methods: This study consists of two parts: Part-A–A prospective, single center study of 52 Barrett’s (study group) and 68 esophagitis (control S3 AJG – September, Suppl., 2001 Abstracts

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Due to this concern and the current debate, we designed a study to examinefor any possible correlation between carditis and GERD in series of H.pylori infected subjects.Methods: Patients enrolled in a H. pylori eradication trial underwent ureabreath testing (UBT) to confirm infection. Those with a positive UBTunderwent 24-hr pH testing with a 4-channel probe. The leads were 5cmabove the proximal LES border, at the proximal border, just below the LES(i.e. cardia), and intra-gastric. EGD was then performed with biopsies ofthe antrum, body, and cardia (�5mm below SCJ). The samples wereanalyzed for inflammation, intestinal metaplasia, and atrophy using theSydney Classification. Statistical comparisons were performed using non-parametric testing.Results: 17 H. pylori positive subjects have completed the study. 66.7%were male, 33% caucasian, 44% African American, mean age-55.4yo �15.7yrs. Intestinal metaplasia was found in 11.8% of subjects, and atrophywas also found in 11.8%. All patients had carditis present. Cardia inflam-mation severity did not significantly correlate with %total time pH �4, bothin the location 5cm above the proximal LES border and in the cardia itself.Comparisons of %time pH �4 in the upright and supine position also didnot show any statistical significance. There was a significant positiveassociation between antral and cardia inflammation scores (r � 0.59;p �0.034).Conclusions: Based on these preliminary findings, the degree of carditisseverity does not correlate with the amount of gastro-esophageal reflux, orto the local exposure of the cardia to acid. There was a statisticallysignificant association between the severity of antral and cardia inflamma-tion. This suggests a primary role of H. pylori in carditis, but no clear rolefor GERD.

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Initial management strategies for reflux-predominant uninvestigateddyspepsia (UD) in primary care practice–the CADET-HR studyDavid Armstrong MD1*, Alan Barkun FACG2, Naoki Chiba MD1,Sander Veldhuyzen Van Zanten MD3, Alan Thomson MD4, SandraSmyth BSc5, Bijan Chakraborty MSc5, Paul Sinclair MSc6 and CADETHR Investigators. 1Gastroenterology, McMaster University, Hamilton,Ontario, Canada; 2Gastroenterology, McGIll University, Montreal,Quebec, Canada; 3Gastroenterology, Dalhousie University, Halifax,Nova Scotia, Canada; 4Gastroenterology, University of Alberta,Edmonton, Alberta, Canada; 5AstraZeneca, Mississauga, Ontario,Canada; 6INSINCONSULTING, Guelph, Ontario, Canada; and7Canada.

Purpose: Patients with reflux-predominant symptoms comprised 37.8% ofa Canadian, primary-care UD study population (Thomson et al. Gastro2001;120:A50); the optimal management strategy for reflux-predominant,UD patients is not known. The study’s aim was to determine the symptomresponse after 4 weeks treatment with an H2-receptor antagonist (ranitidine150 mg bid (R)) or a proton pump inhibitor (PPI-omeprazole 20 mg daily(O)) as the initial phase of a “step-up”/maintenance strategy.Methods: A randomized, double-blind multicentre trial in 46 primary careCanadian practices. Major inclusion criterion: �3 months of heartburn(Carlsson-Dent definition) occurring �3 days during prior 7 days. Exclu-sion criteria: alarm features, predominant IBS, serious concomitant diseaseor relevant investigations on 1 occasion during the prior 6 months or 2occasions during the prior 10 years. The primary outcome variable was“Heartburn relief”–the proportion of patients with no more than mildheartburn on �1 day of the previous 7 days, assessed at 4 weeks, from adaily diary, on a 7-point Likert scale.Results: In all, 390 patients were randomized (O–196, R–194). Mean age(O–44 yrs, R–44 yrs) and Helicobacter pylori infection rate (30.8%) werecomparable to those in associated Canadian UD studies; compliance wasgood (O–94%, R–91%). Based on daily diary data, heartburn relief wasreported by 55.1% (O) and 27.3% (R) of patients (p � 0.001) whilstcomplete resolution of heartburn was reported by 36.2% (O) and 12.9% (R)of patients (p � 0.001). Based on physicians’ assessments, complete

heartburn relief (O–46.3%, R–21.1%, p � 0.001) was more common withO but complete relief of regurgitation, epiastric pain and nausea wascomparable with O and R. Neither age nor H. pylor status affected symp-tom relief outcomes. Improvements in Gastrointestinal Symptom RatingScales (GSRS) for indigestion, abdominal pain, and reflux (all p � 0.05)and in all 5 GASTROQoL health-related quality of life scales (all p �0.003) were greater at 4 weeks with O than with R.Conclusions: Initial therapy with standard dose O produces symptom reliefin twice as many patients as R at 4 weeks and this is associated withsignificantly greater health-related quality of life. The management ofpatients with reflux-predominant uninvestigated dyspepsia in primary carepractice should be based on initial therapy with a once-daily PPI; re-assessment at 4 weeks will identify the remaining 45% of patients whorequire continued short-term therapy.

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Esophageal carcinoma, alkaline reflux and male sex hormonesAnil M. Bahadursingh, M.D., F.R.C.S. (Irl), Faisal H. Khan, M.D.,Petra H. Nass, Ph.D., Firas F. Mussa, M.D., Mark D. Duncan, M.D.,and John W. Harmon, M.D., F.A.C.S. 1Johns Hopkins MedicalInstitutions, Department of Surgical Sciences, Johns Hopkins BayviewMedical Center, Baltimore, MD, United States.

Purpose: Carcinoma of the esophagus is one of the fastest rising cancersin the USA. The male to female ratio is 6:1. This has coincided with thewidespread use of Histamine antagonists and Proton Pump inhibitors,which decrease the gastric pH and predispose to alkaline reflux into theesophagus. A surgical rat model was created to cause alkaline reflux, wethen blocked the release of gonadotropic hormones with Lupron (Gonado-trophin-releasing hormone analog) to prevent the production of male sexhormones.Methods: Alkaline reflux was surgically created in two groups of Sprague-Dawley rats (40 male and 40 female). Nitrosamine was given intraperito-neally once weekly for four weeks to induce carcinoma. The release ofGonadotrophic-Releasing hormone was blocked with a depot injection ofLupron in half of the rats in each group. In the others we gave the dilutentfor the Lupron depot injection. We then quantified the number of cancersof the esophagus that developed in each group.Results:

Male Lupron Dilutent

Squamous Cell Cancer 1 2Adenocarcinoma 12 2FemaleSquamous Cell Carcinoma 5 3Adenocarcinoma 2 1

Conclusions: Alkaline reflux is associated with esophageal carcinoma. TheGonadotropic-releasing hormone analog group had more carcinomas thanthe control. This may be due to the fact that Lupron is a weak agonist asopposed to a complete agonist and therefore had a more sustained action asa depot injection.

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Incidence and prevalence of high grade dysplasia and carcinoma inBarrett’s esophagus with and without maintenance omeprazoletherapySimmy Bank*, Pankaj Singh, Anant Indaram and Ronald Greenberg.1Gastroenterology, Albert Einstein College of Medicine-Long IslandJewish Hospital, New Hyde Park, NY, United States.

Purpose: To study the incidence and prevalence of high grade dysplasiaand carcinoma in patients with Barrett’s. The effect of maintenance ome-prazole therapy was also assessed.Methods: This study consists of two parts: Part-A–A prospective, singlecenter study of 52 Barrett’s (study group) and 68 esophagitis (control

S3AJG – September, Suppl., 2001 Abstracts