Esophagopharyngeal acid regurgitation before and during treatment with omeprazole in patients with posterior laryngitis

test. A subgroup of patients (n=11) underwent treated with rabeprazole20 mg bid for 7 days to determinethe response in reducing heartburn symptoms to acid suppression. GERD was defined as the presenceof any of the following: total % time pH<4.0 > 4.3%, DeMeester score >14.3, or Grade >2 esophagitis (Savary-Miller). Results: 41 patients were recruited. 27 patients (mean age 53+7 years, 20 M: 7 F) had evidenceof GERD; 14 patients did not have evidenceof GERD (GERD Neg) (mean age 46+8 years, 9 M: 5 F). Basedon symptom questionnaires,the frequency, severityand duration of heartburnwere similar betweengroups. The GERDgroup had a higher symptom index (SI) on 24 hour pH monitoring in comparison to the GERDNeg group (67 + 9% vs. 36 + 7%; p
is very low. In patients with advancedliver cirrhosis and portal hypertension regular control endoscopies should be performed, as hyperplastic antral polyps can develop. 2237 Absence of Symptoms in Erosive Esophagitis (EE) Patients Treated with Esomeprazole is a Highly Reliable Indicator of Healing David A. Johnson, Eastern Virginia Sch of Medicine, Norfolk, VA; Nimish B. Yakil, Univ of Wisconsin Medical Sch, Milwaukee, Wl; Clara Hwang, Jeffrey G. Levine, AstraZeneca LP, Wayne, PA Purpose: Esomeprazolehas beendemonstratedto be highly effectivefor healingGERDpatients with EE in large, well-controlled, US trials. In these trials, healing was objectively assessed by endoscopy at predetermined endpoints. In clinical practice, it is neither practical nor desirableto endoscopicallyverify healing in all patients. Methods: A total of 4877 EE patients were treated with esomeprazole40 mg (E40, n = 2446) or omeprazole20 mg (020, n = 2431) once daily for up to 8 weeks in US multicenter, randomized, double-blind parallelgroup trials. In this analysis, we examinedthe healing rate among asymptomatic patients at week 4 and determinedthe percentagesof patients who were asymptomatic on each therapy who were also healed.Symptoms were evaluatedby investigatorson the same day endoscopy was performed. A chi-square test was performed to detect the difference in EE healing rate between E4O vs 020 in patients who were asymptomatic at week 4, Results: Heartburn was resolved in 2935 patients and acid regurgitation was resolved in 3572 patients. In those patients who were asymptomatic at week 4, the healing rate was significantly higher in those receiving esomeprazoleversus omeprazole(see table). Conclusions: The practicing clinician can be more confident that EE patients who are asymptomatic after 4 weeks treatment are also healedfollowing therapy with.esomeprazole.Supported by a grant from AstraZenecaLP, Wayne, PA.

2240 Direst Comparison of the Efficacy and Tolerebility of Pantoprazole 20rag (00) with Omeprezole lOmg (OD) as Relapse Prophylaxisfor Patients with Healed Reflux Oesophagitis I Barrison, Hemel Hempstead Hosp, Hemel Hempstead United Kingdom; N Y. Haboubi, Nevill Hall Hosp, AbergavennyUnited Kingdom; A M. Edwards, 8ASF Pharma, Nottingham United Kingdom Introduction: Long-term therapy is warranted in the majority of patients with healed reflux oesophagitissince relapseoccurs in approximately36 to 100% of patients within six months, irrespective of the healing treatment. Aims: To compare the Iong-tarm use (12 month) of pantoprazole20rag once daily with omeprazoielOmg daily as relapseprophylaxis for patients with healed reflux oesophagitis. Methods: Patients with acute reflux oesophaoitis grade II or ill (Savary-Miller Classification) were entered into an eight week run-in period, receiving pantoprazole 4Grog daily. Those with endoscopy-confirmed healing were entered into the double-blind period. During this 12 month period patients were assessedevery three months for symptoms of reflux oesophagitis. Endoscopieswere performed at 26 and 52 weeks into the study and also if patient's symptoms had relapsedfor at least three consecutive days. If the endoscopy confirmed relapse of reflux oesophagitis the patient was withdrawn. Results: 232 patients entered the double-blind period, 197 of which were included in the intend to treat population, 163 in the per protocol population (78 in pantoprazole20mg group and 88 in the omeprazole lOmg group). Of the patients who discontinued the study, 36.2% and 43.6% were withdrawn for endoscopic evidenceof relapse in the pantoprazole20rag treated and omeprazolelOmg treated groups respectively.For the per protocol populationthe KaplanMeier estimation of remission probability was significantly greaterfor the pantoprazole20mg group (0.817) than for the omeprazolelOmg group (0.706) (P
EE Statusin AsymptomaticGERDPatientsalter 4 Weeksof Treatment Symptoms

E40 Healed

E40 Not Healed

020 Healed

020 Not Healed

Heart.bum Acid Regurg.

1294(83.4) 1474(81.0")

257 (16.6) 346 (19.0)

1044(75.4) 1255 (71.6)

340 (24.6) 497 (28.4)

Dataare presentedas numberand percentageof patients "p < 0.001vs. 020 2238 Nocturnal Gastric Acid Secretion is Not Synonymouswith Nocturnal Esophageal Acid Exposure Except in the Presence of Hiatal Hernia Amar Bansal, Colin W. Howden, Michael P. dunes, Northwestern Univ Medical Sch, Chicago, IL Introduction: While PPIs are clearly the most effective agents in controlling gastric acid secretion, suboptimal control of gastric acid secretion, particularly at night, is increasingly recognized.The present study was a retrospectiveanalysis of pts with a clinical diagnosis of GERD undergoing esophagealpH monitoring (priM). The specific aim was to determine the prevalence of esophagealacid exposure, particularly at night, in pts on PPIs. Methods: 250 consecutive pH studies done for GERD-relatedsymptomatolooy were reviewed. Pts having undergone fundoplication or myetomy were excluded. Primary variables of interest were %time pH<4 for the entire study as well as for the nocturnal period (0001-0600hrs). Pathologic esophagealacid exposure (PAE) was defined as pH<4 >5% of the study period. Additional variablesof interest included symptom index and presenceof hiatal hernia (HH)asdetermined from endoscopic reports. Results: PAE was noted in 35% of pts studied on no muds. 107/ 250 pts were studied on PPIs and 100 pts taking PPI qD or bid were evaluatedfurther. Study indications in these pts included GERD(61),chest pain(17), cough(8), asthma(2) and other(9). PAE was noted in 18/60 (30%)of qD PPI users and 14/40(35%) of bid PPI users. 16132 PPI pts with PAE had some nocturnal acid exposure but only 9/32 (28%) had nocturnal PAE. 2/ 16(13%)' pts with any nocturnal acid exposure had associated symptoms with symptom indices of 2/2 (lOO%)and 2/9 (22%). Endoscopy reports were available for 20/32 pts with any nocturnal acid exposure and revealedHH in 4/5 pts with noctumal acid exposure and 7/ 15 without nocturnal acid exposure (OR =4.57). Conc/usions:Despite PPI, approximately 1/ 3 of GERDpts still have PAE.Of these, approximately1/2 havesome nocturnal acid exposure, but only 1/4 have nocturnal PAE. The liklehood of nocturnal acid exposure is increased in pts with HH. Nocturnal PAE occurs in the minority of GERD pts with suboptimal response to PPI therapy and few of those have associatedsymptoms. The risk for nocturnal esophageal acid exposure is greatest in pts with HH.

2241 EsophagophanjngealAcid Regurgitation Before And During Treatment With Omeprazale in Patients With Posterior Laryngitis Angel Alvarez-Sanchez,Enrique Roy, Cristina Urbasos, Joaquin Poch-Broto, Manuel DiazRuble, Hosp Clinico San Carlos, Madrid Spain PharyngealpH monitoring has been used to identify gastroesophagealreflux (GER)in patients with posterior laringitis (PL). Empiric antireflux long term therapy with high dose omeprazole has been shown to be effective. AIM: to determine whether high dose omeprazoletherapy had different effect on GER and esophagopharyngealacid regurgitation episodes.METHODS: 16 patientswith PL (diagnosedby videolaryngostmboscopicevaluation)were studied. Patients underwent 24-h ambulatory dual-probe pH monitoring (pharyngeal electrode placed 1 cm above the upper esophagealsphincter and esophagealelectrodeplaced 5 cm abovethe upper border of lower esophagealsphincter) before and during treatment with omeprazole(20 mg twice daily). Pharyngealacid episode was defined as a decreasein pH below 4 at pharyngeal electrode. Gastroesophagealreflux episode (GER) was defined as a decrease in pH below 4 at esophagealelectrode. Esophagopharyngealacid regurgitation was defined as a pharyngeal pH decreasethat ocurred in less than 30 seconds during esophagealacidification. Variables studied were GER episodes, esophagopharyngealacid regurgitation episodes and % GER episodes reaching pharynx. Comparisonswere made by .WilcoxonTest for paired data. Data are expressedas median (interquartile range). RESULTS:table summafises the results: CONCLUSION: treatment with orneprazole decreased the number of GER episodes more than esophagopharingealacid regurgitation episodes in patients with posterior laryngitis. These findings may explain why high dose and long term therapy with omeprazole is required in these patients.

2239 Characterization 0! Patients With Heartburn Who Have A Normal EndoscopyAnd 24 Hour pH Monitoring Tony Lembo, Robin Dann, Beth Israel DeaconessMedical Ctr, Boston, MA; Ronnie Fass, Southern Arizona VA Health Care System, Tucson, AZ Heartburn is most often causedby gastroesophagealreflux disease(GERD),howevera subset of patientswith heartburn has no evidenceof GERD(24 hour pH monitoring and endoscopy). The cause of heartbum in these patients is not known but may be secondaryto unrecognized GERD,hypersensitiveesophagusor other functional bowel disorders. We sought to determine the clinical characteristicsand responseto treatment (proton pump inhibitor) in patients with chronic heartburn who do not have evidenceof GERD in comparison to patients with documented GERD. Methods: Consecutive patients referred to the GI clinics with the primary complaint of heartburn were recruited at 2 major medical centers. All patients completed validated GERD, quality of life and psychological questionnaires. All patients underwent 24hour pH study (off antisecretory medications), upper endoscopy, and a modified Bernstein

Before Treatment Eenphago-phadngesl 2 (1-6.7) acid regurgitation episodes GERepisodes 44.5 (13-71,5) %GERepisodes 5.9 (2.5-26.5) renchin9 phadnx

A-439

Dudn9 Treatment

p

1 (0.25-4)

ns

10.5 (2.2-30,7) 13.8 (1-25.7)

p<0.05 ns

2242

2244

Effect of Pantoprazole on Reflux-Associated Laryngitis: A Placebo-Controlled Crossover Study Andreas J. Eherer, Dept of Internal Medicine, KarI-FranzensUniv, Graz Austria; Walter Habermann, Dept of Oto-Rhino-Laryngology, KarI-FranzensUniv, Graz Austria; Heinz F. Hammer, Dept of Internal Medicine, Kari-Franzens Univ, Graz Austria; Karl Klasler, Gerhard Friedrich, Dept of Oto-Rhino-Laryngology, KarI-FranzensUniv, Graz Austria; Guanter J. Krejs, Dept of Internal Medicine, KarI-FranzensUniv, Graz Austria

Superior Symptom Relief Of Pantoprazole 40mg Compared To Omeprazole MUPS 2Onto In Patients With Severe Heartburn Theo Schoflen, Medical Clin Hosp, Hagen Germany; Gudrun Gatz, Peter Sander, Byk Gulden GmbH, Koostanz Germany; Sander Aims:This randomized,double-blind, muificenter parallal-group study was conducted to obtain a direct comparison of the efficacy of pantoprazole 40rag vs omeprazola (ome)MUPS 20rag with regard to the rate of symptoms relief. Method: A total of 198 men and 162 women (n = 360) with hearthum, acid regurgition and general epigastric discomfort were treated for 4 weeks with either pantoprazol 40mg (n = 185) or ome MUPS 20mg (n = 175). At the start of the study, the intensity of heartburn was essentially the same in both patient groups (baseline). The intensity of the two symptoms heartburn and acid regurgitation was graded according to a score system. On days 2, 4 and 7 (median) of the study, patients were interviewed by phone the symptoms and intensity they had experienced on that day. Results: Using factor analysis, we indentified (among others) a factor consisting of the two symptoms acid regurgitation and heartburn. As measured by the employed score system, patients with severe GERDsymptoms who were treated with pantoprazole experienceda clearly faster rate of symptoms relief than those treated with ome. This was especially evident in patients with severe hoartbum where the pantoprazole group (n=63) scored consistently lower corresponding to less heartburn and less acid regurgitation - than the ome group (n =57) at the first telephone interview: 3.32 vs.3.60,(p=O.472), second interview 2.73 vs. 3.33 (p=0.012) and third interview 2.43 vs. 2.74 (p=0.081). The baseline score was 4.01 for the pantoprazofeand 3.98 for the ome group. Conclusions: In patients with severe heartburn, pantoprazole achieves on day 2 already the same degree of symptom relief that is seen with ome only on day 4, and on day 4 the same that is seen with ome on day 7. Thus, with pantoprazole 4Omg symptoms improve about two times faster than with ome MOPS 20mg.

Purpose: The optimal management of patients with reflux-associated laryngitis is unclear. Uncontrolled studies have suggested that long-term acid supression is beneficial and empiric therapy with PPIs has become customary. We performed a placebo-controlled trial in patients with proven reflux disease and associated laryngitis to determine the effect of PPIs. Methods: From 4/1998 to 10/2000, 61 consecutive nonsmoking patients with hoarseness and proven laryngitis were suspectedto have gastroesophagealreflux as cause of their laryngitis. Objective scores with respect to the condition of the posterior portion of the larynx, the vocal cords and the supra- and subglottal space were determined. Scores for subjective complaints considered heartburn, dysphagia, odynophagia, regurgitation, cough, sore throat, hoarseness, globus sensation and dyspnoe. All patients underwent 24h-pH metry with pH sensors 5 cm above the manometrically determined LES and within 1 to 3 cm above the UES. When the time with pH<4 per 24 h exceeded 4.5% patients were offered a therapeutic trial with pantoprazole (Panto) 4Omg bid / placebo. 21 patients consented to participate in the trial, Panto or placebo was started in a randomized and double-blinded fashion. After 3 months' treatment, laryngeal assessment and symptom scoring were repeated. 1-2 weeks later another pH metry followed and treatment was switched to the other study arm. After another 3 months' treatment the trial was concluded with laryngeal examination and another symptom scoring. Results: 14 patients completed both parts of the trial, 6 allowed the 2~ laryngealexamination but refused the 2ndpH metry. Symptom scores and laryngitis scores of patients starting with either Panto or placebo are shown in the Table median (25%-75%), * denotes p
Sympt Larynx

Before Panto

After Panto

After Plac

Before Plac

Alter Plac

Pento

14 (9-22) 12 (10-15)

3* (1-14) 1* (1-5)

5 (1-10) 0 (0-2)

29 (20-39) 10 (4-13)

9" (5-16) 2" (0-7)

3" (1-5) 1 (0-2}

1.1. 1.4

i!

I

.

.

.

.

~

.

OPaatoproEoie ~ OOBIprl~oll MUP$ ~q

2246 A BMthr O l a i p ~ c A P I ~ O a of Nousardiac Chest Pain Shewn Arezo, William M. Pandak, Sharon Everette, Gall Decosta, Alvin M. Zfass, Virginia Commonwealth Univ, Richmond, VA

2243

Background: Noncardiac chest pain presents as a frequent diagnostic challenge, with patients tending to use a disproportionate level of health care resources. Gastroesophagealreflux has been determined as the most frequent cause of noncardiac chest pain. Specific Aim: To test the efficacy of a potent acid suppressing agent, Omeprazole (OMP), as a diagnostic test in the evaluation of patients with noncardiac chest pain. Methods: 44 negative RESS (resting and exercise Sestamibi Scan) patients were enrolled in a prospective, double-blind, placebocontrolled, cross-over trial using high dose OMP (40 mg PO BID) as compared to endoscopy (EGO), manometry (MAN), and 24 hour 2 channel esophageal pH (24h pH) monitoring. After performing EGD to rule out a gastric or duodenal ulcer, 24h pH monitoring, and MAN were performed. Patients were then randomized to either placebo or OMP for 14 days, washed out for 21 days, and then crossed over. Visual analog symptom assessment was performed pre and post OMP and placebo. Result: In patients with NCCP,70% of the patients responded to OMP, as compared to 18% who responded to placebo. In patients with GERD, as defined by a positive 24h pH test or presence of esophagitis on EGD, treatment with OMP led to a response in 95% of patients. 90% of GERD positive patients treated with placebo did not respond. The combination of a positive 24h pH and presence of esophagitis visualized on EGD did not increase the response rate to OMP (86% vs. 90%). Patients with normal 24h pH, but esophagitis as visualized by EGD, all responded to OMP, whereas none of these patients responded to placebo. However, only 11 out of 38 patients with NCCP were found to have esophagitis by EGO. There was no good correlation in response to OMP in patients who had esophagitis by biopsy alone. Only 40% of these patients responded to OMP vs. 20% who responded to placebo. Finally, 13 out of 16 patients with an abnormal 24h pH responded to OMP. However, 11 out of 22 patients with normal 24h pH also responded to OMP. Conclusion: OMP as a first diagnostic tool in the evaluation of Sestamibi negative NCCP, is sensitive and specific for determining the cause of NCCP.EGD, MAN and 24h pH monitoring were not only less sensitive in making the diagnosis of NCCP, but significantly more invasive and expensive.

Effect of Gender, Age, Hiatus Hernia (HR), and Body Mats Index (BMI) go Hentlq of Erosive Esophagltis (EE) Nimish B. Vakil, Univ of Wisconsin Medical Sch, Milwaukee, WI; Clara Hwang, Jeffrey G. Levine, AstraZeneca LP, Wayne, PA Background: In US clinical trials, more than 90% of patients with EE were healed after once daily treatment with esomeprazolefor 8 weeks. Since the influence of BMI, age, gender, and HH on the severity of EE is controversial, we have now retrospectively examined the impact of these variables on EE healing in patients treated with either esomeprazole or omeprazole. Methods: The impact of these patient characteristics on healing responses was examined using pooled data from multiple US trials that evaluatedup to 4877 patients with endoscopically documented EE. HH was also diagnosed endoscopically at baseline. Patients were treated once daily with either esomeprazole 40 mg (E4O, n = 2446) or omeprazole 20 mg (020, n = 2431) for up to 8 weeks. Risk ratios (RR) and 95% confidence intervals (CI) were calculated by the Cox proportional hazards model from complete data from 4831 p~dents. Results: RR showed that patients treated with E4O were more likely to be healed than those treated with 020 (RR = 1.27 [95% CI, 1.20 to 1.35], p < 0.0001). Females and patients > 50 years responded slightly better to either treatment than males and those -< 50 years of age, respectively, whereas the presence of HH and BMI > 30 had no impact on healing (see table). Healing rates in males treated with E40 were 93.3% v females 93.6% whereas 83.4% of males were healed by 020 compared to 90.8% of females. Similar responses to E4O were also found in both age groups (> 50 = 94.0% v -< 50 = 93.1%) whereas responses to 020 were lower in younger versus older patients, 83.7% and 90.5% respectively. Conclusions: Patients -< 50 years and males were less likely to be healed with omeprazole. The healing rates with esomeprazole were > 90% regardless of patient characteristics. Supported by a grant from AstraZeneca LP, Wayne, PA. The Impactof PaUentCharacteristics on Healing of EE (N = 4831) Vadable

Risk Ratio

95% CI

P-value

Male Gender HH Age > 50 years BMI > 30

0.90 0.97 1.15 1.03

0.85 to 0.96 0.91 to 1.04 1.08 to 1.23 0.97 to 1.10

0.0016 0.36 0.0001 0.38

2246 Quality Of LHe Assessment In Patients With Gustro-OusophagealReflux Disease RandomtsedTo Two Types Of Laparoscopic Fundoplioation. Michael I. Booth, Jane Stratford, Thomas C.B. Dehn, Royal Berkshire Hosp, Reading United Kingdom Objectives: 1). To assess the effect of laparoscopic anti-reflux surgery on the quality of life of patients with gastro-oesophagealreflux disease.2). To compare two laparoscopic anti-reflux procedures. Patientsand Methods: 50 consecutive patients (27 male: 23 female)randomised to laparoscopic total (Nissen) fundoplication (n = 29) or laparoscopic posterior partial (Toupet) fundoplication (n=21). Quality of life assessment by 3 self-administered questionnaires Gastrointestinal Symptom Rating Score (GSRS), Psychological General Well-Being index (PGWB) and Short Form 36 (SF36) - completed pre-operatively (whilst on anti-reflux medication) and 6 months post-operatively. Results: Pre-operative quality of life scores in GORD

A-440