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Normal esophageal acid exposure on proton pump inhibitor (PPI) therapy: Traditional normal values are not applicable
2229
gastro-esophagealreflux (GER) ii) those with no GER, defined as TPR -<5.78 and DMS -<14.7 Results 1. There was poor intra-class correlation (R-value) betweenthe first and second TPR, in all diagnostic categories, specifically; i) in all diagnoses, irrespective of second diagnosis (R =0.24) ii) in all with no GER, both diagnoses(R =0.20) iii) in all with GER,both diagnoses (R=O.IO). 2.i) With GER as an initial diagnosis, neither TPR nor DMS were predictive, (at any value), ii) TPR and DMS were predictive of an initial diagnosis of no GER changing to GER (see TABLE).Negativepredictive values (NPV) were calculated. Conclusion 1. There is a high degree of intra-patient variation in TPR, irrespectiveof diagnoses. 2.i) There were no predictive criteria, with GER as an initial diagnosis ii) In those initially diagnosed with no GER, an initial TPR ->1.00 is predictive of subsequent change, but has poor specificity. An initial DMS ->5.8 is a sensitive and useful predictor, of a repeatpH study resulting in a change of the initial diagnosis of no GER. It is not worthwhile repeating a pH study in a patient with an initial diagnosis of no GERand DMS <5.8; the probability of the diagnosis being unchanged is 920.
The Symptom Relieving Effect Of Esomeprazole 40 Mg Daily In Patients With Heartburn Folke Johnsson, Lund Univ Hosp, Lund Sweden; Jan G. Hatlebakk,HaukelandHosp, Univ of Bergen, Bergen Norway; Ann-Charlotte Klintenberg, Jonas Roman, AstraZeneca,MOIndal Sweden Introduction: Treatment with proton pump inhibitors (PPIs) leads to healing of esophagitis in a large proportion of patients. Complete relief of reflux symptoms is, however, achieved in a considerably smaller proportion of patients. Aim: To evaluate the symptom relieving effects of the new PPI, esomeprazole,in patients with typical reflux symptoms. Methods: Patients experiencingheartburn as their predominant symptom for at least six months were studied in this prospective, randomized,double-blind, Scandinavian,multicenter study performed at endoscopy units. Following three days of single-blind placebo run-in, 440 patients were randomizedto two weeks treatment with esomeprazole40 mg om, esomeprazole20 mg bid or placebo.Heartburnsymptoms were recordeddaily on a diary card. Gastroesophageal Reflux Disease (GERD) was diagnosed by upper Gi endoscopy prior to treatment and 24hour pH monitoring 2-6 weeks after the treatment period. A diagnosis by pathological pH monitoring was defined as pH<4 for more than 3.4% of the total time or pH<4 for more than 3.2% of the supine time or a correlation between symptoms and reflux episodesduring 24-hour pH monitoring. Results: 240 patients had erosive esophagitis and 142 patients had GERDdefined by pathological pH monitoring only. The proportion of patients with total relief of heartburn increased during the first days of active treatment in the esomeprazolearms and stabilizedafter the fourth day. The daily proportions of patientswith total relief of heartburn rangedbetween67-73%, 63-70%, and 21-32% in the esomeprazole40 mg om, esomeprazole 20 mg bid and placebo groups, respectively. Similar patterns were found for patients with and without esophagitis, although the levels were higher in patients with esophagitis where total relief of heartburn rangedfrom 7f-80% from the fourth day onwards. The corresponding figures in patients without esophagitis were 52-67%. Similarly, in patients diagnosed via pH monitoring, total relief of heartburn was seen in 65-73% and the corresponding figures for patients with a negativediagnosis via pH monitoring were 51-58%. In the placebo group the proportion of patients with total relief of heartburn was 15-32%. Conclusion: Esomeprazole 40 mg om produces total symptom relief in a high proportion of patients with heartburn. Best results are seen in patients with esophagitis and in patients diagnosed via pathological pH monitoring. Oncedaily dosing is recommendedsince no advantagewas gained by splitting the daily dose.
Tableof Pe~licUveValuesfor a RepeatpH StudyChangingthe Diagnosis Cdteda
Value
Sensitivi 95%Cl ty
Specifici 95%CI ty
NPV%
TPR DM
_>1.00 _>5.80
0.82 0.83
0.55 0.86
89 92
+0.18 _+0.30
+0.15 +0.18
2227 Efficacy and Safety of Pantoprozole20mg O.D. (PANTO)for the Acute and Prophylactic Treatment of Mild GERD R Eissele, Philipps-University Marburg, Dept of Internal Medicine, Marburg Germany; I-I Moennikes, Charite Humboldt-University, Dept of Medicine, Berlin Germany; R Arnold, Philipps-University Marburg, Dept of Internal Medicine, Marburg Germany Aim: To determine symptomatic relapse rate after successful treatment with Panto in patients with mild GERD grade O/l. Methods: In the acute phase patients were treated with Panto 20mg o.d. for 4 weeks. The subsequent long-term phase (6 months) was performed as a randomised, multicentre, double-blind, placebo (PLA)-controlled comparison. Only patients free from heartburnafter the acute phasehave been includedand randomly treated with either PANTO or PLA. Patients were provided with magaldrate as rescue medication in the longterm phase. The intensities of leading (heartburn, acid eructation, dysphagia) and further GI symptoms were scored. Symptom relief after the acute phase and symptom relapse rates after 3 and 6 months were analysed.In a self-administeredquestionnairethe impact on quality of life was assessed(GIQLI). H.p. status was determined by rapid ureasetest and/or histology. Results: 575 patients (279 m, 296 f, mean age 53 -+ 14 yrs) were enrolled. After 4 weeks of treatment a significant symptom relief as well as an improvement in quality of life was observed. Relief from the primary symptom heartburn was observed in 91% of patients (ITT) (PP 95%). Thesepatientsenteredthe long-term phase.The PANTOand PLAgroups comprised 266/227 and 2591212 patients (ITT/PP), respectively.After 3 months relapse of heartburn was observed in 13% of patients in the PLA and only in 5% in the PANTOgroup (ITr). After 6 months this difference increasedto 18%, i.e. 25% in the PLA and only 7% in the PANTO group. Relapsewas accompaniedby the reoccurrence of the other leading symptoms, also to a significantly higher extent in the PLA group. Further improvement in quality of life could be observed in the PANTOgroup, with a significant difference to the PLA group (p
2230 Normal Esophageal Acid Exposure on Proton Pump Inhibitor (PPI) Therapy: Traditional Normal Values Are Not Applicable Shuwen Xue, Philip O. Katz, Kafla P. Bolanos, Donald O. Caste,, Graduate Hosp, Philadelphia, PA Background: Normal value for esophagealacid exposure on 24 hr pH study is based on data in normal subjects not taking medication. Evaluating pH control in patients on PPI using these normal values is not appropriate as "normal" esophagealacid exposure (% time pH <4) on medication for 24 hr pH study has not been documented. Aim: To determine 24 hr esophagealacid exposure in normal subjects on PPI therapy. Method: 24 hr pH studies done in 94 normal subjects (mean age 35) analyzedfor esophagealacid exposure, off-therapy at baseline. 106 subjects studied on standard dose PPI (omeprazole(Ome) 20mg, lansoprazole (Lanso) 30mg or pantoprazole(Panto) 40mg qd, mean age 34). 93 subjects on high dose PPI (Ome 40mg qd or 20mg bid, Lanso 30mg bid, mean age 33). 24 hr pH study was performed after 7 days of PPI. Percenttime esophagealpH < 4 in total, upright and recumbent period analyzed.Mealswere excluded.Kruskal-wallistest used for statistical analysis. Median and upper 95% CI reported. Results: 1) There was no significant difference in % time pH < 4 among subjects on Ome 20, Lanso 30 or Panto 40mg qd, therefore data were pooled together as one group (standard dose PPI). Similarly the subjects on Ome 40mg and Lanso 60mg were pooled to represent high dose PPI. 2) % time esophagealpH <4 in total, upright and supine period shown in table. Summary: All subjects tested on medication showed significantly less esophagealacid exposurethan control. No significant difference in esophageal acid exposurewas found betweenstandarddose and high dose PPI. Conclusion:Thesenormal values should be used to assess adequacyof control of esophagealacid exposure in patients having pH monitoring on PPI therapy.
2228 Esophageal Motility Modifications By Laparoscopic Fundoplication Luis O. Soiter, Enrique Sivori, Jorge Olmos, Daniel Peralta, Demefrio Cavadas,Axel Beskow, Hosp Italy, Buenos Aires Argentina
Baseline
INTRODUCTION:Some patientswith gastroesophagealreflux disease(GERD)presenta reduction in peristaltic contraction amplitude of the distal esophagus(ineffective peristalsis). This disorder is probably the result of chronic damage caused by reflux on the mechanisms responsiblefor peristaltic activity. Although laparoscopicfundoplication is the surgical procedure of choice for the treatment or GERD, there is no evidence of it being able to reverse esophageal peristaltic deficiency. AIM: To determine if iaparoscopicfundoplication improves the averageamplitudeof peristaltic wavesin the distal esophagus.MATERIALAND METHODS: Thirty patients (23 F/TM, age 56 -+14) with GERDwho underwent laparoscopicfundoplication (Nissen) were preoperativelyand postoperatively(6-24 months later) evaluatedby esophageal manomefry. The same team of surgeons performed all the procedures. Pre and postoperative averageamplitudes of peristaltic waves measured5 cm abovethe lower esophagealsphincter were compared. T-test for paired data and 95% confidence interval were used to analyzethe results. RESULTS:Overall, there was an increase in peristaltic amplitude in 22/30 (73.3%) patients. Thirteen (43.3%) subjects had previous ineffective peristalsis, in twelve of them (92.3%) peristaltic amplitude was improved. Averagepre and postoperativeperistaltic amplitudes in the whole series were 60.2 -+ 26.37 mm Hg and 67.8 -+ 32.20 mm HO, respectively. There was a significant increase in peristaltic amplitude (p = 0,012) with a postoperative increase ranging8.28-26.32 mm Hg (95% CI). CONCLUSIONS:Surgical interventionincreases significantly the peristaltic amplitude at the distal esophagusin GERDpatients. This could be related to disappearanceof mechanisms that induce esophagealdamage or to a higher flow resistance after fundoplication.
total upright supine
median
95%CI
Standard dose median
1.6 2.1 O.O
3.45 4.35 2.78
0.4* 0.5* 0.0~
95%CI
High dose median
95%CI
0.98* 1.34" 0.65§
0.5* 0.7* 0.0"
1.20" 1.55" 0.78*
Posttest: * p
A-437
gastro-esophagealreflux (GER) ii) those with no GER, defined as TPR -<5.78 and DMS -<14.7 Results 1. There was poor intra-class correlation (R-value) betweenthe first and second TPR, in all diagnostic categories, specifically; i) in all diagnoses, irrespective of second diagnosis (R =0.24) ii) in all with no GER, both diagnoses(R =0.20) iii) in all with GER,both diagnoses (R=O.IO). 2.i) With GER as an initial diagnosis, neither TPR nor DMS were predictive, (at any value), ii) TPR and DMS were predictive of an initial diagnosis of no GER changing to GER (see TABLE).Negativepredictive values (NPV) were calculated. Conclusion 1. There is a high degree of intra-patient variation in TPR, irrespectiveof diagnoses. 2.i) There were no predictive criteria, with GER as an initial diagnosis ii) In those initially diagnosed with no GER, an initial TPR ->1.00 is predictive of subsequent change, but has poor specificity. An initial DMS ->5.8 is a sensitive and useful predictor, of a repeatpH study resulting in a change of the initial diagnosis of no GER. It is not worthwhile repeating a pH study in a patient with an initial diagnosis of no GERand DMS <5.8; the probability of the diagnosis being unchanged is 920.
The Symptom Relieving Effect Of Esomeprazole 40 Mg Daily In Patients With Heartburn Folke Johnsson, Lund Univ Hosp, Lund Sweden; Jan G. Hatlebakk,HaukelandHosp, Univ of Bergen, Bergen Norway; Ann-Charlotte Klintenberg, Jonas Roman, AstraZeneca,MOIndal Sweden Introduction: Treatment with proton pump inhibitors (PPIs) leads to healing of esophagitis in a large proportion of patients. Complete relief of reflux symptoms is, however, achieved in a considerably smaller proportion of patients. Aim: To evaluate the symptom relieving effects of the new PPI, esomeprazole,in patients with typical reflux symptoms. Methods: Patients experiencingheartburn as their predominant symptom for at least six months were studied in this prospective, randomized,double-blind, Scandinavian,multicenter study performed at endoscopy units. Following three days of single-blind placebo run-in, 440 patients were randomizedto two weeks treatment with esomeprazole40 mg om, esomeprazole20 mg bid or placebo.Heartburnsymptoms were recordeddaily on a diary card. Gastroesophageal Reflux Disease (GERD) was diagnosed by upper Gi endoscopy prior to treatment and 24hour pH monitoring 2-6 weeks after the treatment period. A diagnosis by pathological pH monitoring was defined as pH<4 for more than 3.4% of the total time or pH<4 for more than 3.2% of the supine time or a correlation between symptoms and reflux episodesduring 24-hour pH monitoring. Results: 240 patients had erosive esophagitis and 142 patients had GERDdefined by pathological pH monitoring only. The proportion of patients with total relief of heartburn increased during the first days of active treatment in the esomeprazolearms and stabilizedafter the fourth day. The daily proportions of patientswith total relief of heartburn rangedbetween67-73%, 63-70%, and 21-32% in the esomeprazole40 mg om, esomeprazole 20 mg bid and placebo groups, respectively. Similar patterns were found for patients with and without esophagitis, although the levels were higher in patients with esophagitis where total relief of heartburn rangedfrom 7f-80% from the fourth day onwards. The corresponding figures in patients without esophagitis were 52-67%. Similarly, in patients diagnosed via pH monitoring, total relief of heartburn was seen in 65-73% and the corresponding figures for patients with a negativediagnosis via pH monitoring were 51-58%. In the placebo group the proportion of patients with total relief of heartburn was 15-32%. Conclusion: Esomeprazole 40 mg om produces total symptom relief in a high proportion of patients with heartburn. Best results are seen in patients with esophagitis and in patients diagnosed via pathological pH monitoring. Oncedaily dosing is recommendedsince no advantagewas gained by splitting the daily dose.
Tableof Pe~licUveValuesfor a RepeatpH StudyChangingthe Diagnosis Cdteda
Value
Sensitivi 95%Cl ty
Specifici 95%CI ty
NPV%
TPR DM
_>1.00 _>5.80
0.82 0.83
0.55 0.86
89 92
+0.18 _+0.30
+0.15 +0.18
2227 Efficacy and Safety of Pantoprozole20mg O.D. (PANTO)for the Acute and Prophylactic Treatment of Mild GERD R Eissele, Philipps-University Marburg, Dept of Internal Medicine, Marburg Germany; I-I Moennikes, Charite Humboldt-University, Dept of Medicine, Berlin Germany; R Arnold, Philipps-University Marburg, Dept of Internal Medicine, Marburg Germany Aim: To determine symptomatic relapse rate after successful treatment with Panto in patients with mild GERD grade O/l. Methods: In the acute phase patients were treated with Panto 20mg o.d. for 4 weeks. The subsequent long-term phase (6 months) was performed as a randomised, multicentre, double-blind, placebo (PLA)-controlled comparison. Only patients free from heartburnafter the acute phasehave been includedand randomly treated with either PANTO or PLA. Patients were provided with magaldrate as rescue medication in the longterm phase. The intensities of leading (heartburn, acid eructation, dysphagia) and further GI symptoms were scored. Symptom relief after the acute phase and symptom relapse rates after 3 and 6 months were analysed.In a self-administeredquestionnairethe impact on quality of life was assessed(GIQLI). H.p. status was determined by rapid ureasetest and/or histology. Results: 575 patients (279 m, 296 f, mean age 53 -+ 14 yrs) were enrolled. After 4 weeks of treatment a significant symptom relief as well as an improvement in quality of life was observed. Relief from the primary symptom heartburn was observed in 91% of patients (ITT) (PP 95%). Thesepatientsenteredthe long-term phase.The PANTOand PLAgroups comprised 266/227 and 2591212 patients (ITT/PP), respectively.After 3 months relapse of heartburn was observed in 13% of patients in the PLA and only in 5% in the PANTOgroup (ITr). After 6 months this difference increasedto 18%, i.e. 25% in the PLA and only 7% in the PANTO group. Relapsewas accompaniedby the reoccurrence of the other leading symptoms, also to a significantly higher extent in the PLA group. Further improvement in quality of life could be observed in the PANTOgroup, with a significant difference to the PLA group (p
2230 Normal Esophageal Acid Exposure on Proton Pump Inhibitor (PPI) Therapy: Traditional Normal Values Are Not Applicable Shuwen Xue, Philip O. Katz, Kafla P. Bolanos, Donald O. Caste,, Graduate Hosp, Philadelphia, PA Background: Normal value for esophagealacid exposure on 24 hr pH study is based on data in normal subjects not taking medication. Evaluating pH control in patients on PPI using these normal values is not appropriate as "normal" esophagealacid exposure (% time pH <4) on medication for 24 hr pH study has not been documented. Aim: To determine 24 hr esophagealacid exposure in normal subjects on PPI therapy. Method: 24 hr pH studies done in 94 normal subjects (mean age 35) analyzedfor esophagealacid exposure, off-therapy at baseline. 106 subjects studied on standard dose PPI (omeprazole(Ome) 20mg, lansoprazole (Lanso) 30mg or pantoprazole(Panto) 40mg qd, mean age 34). 93 subjects on high dose PPI (Ome 40mg qd or 20mg bid, Lanso 30mg bid, mean age 33). 24 hr pH study was performed after 7 days of PPI. Percenttime esophagealpH < 4 in total, upright and recumbent period analyzed.Mealswere excluded.Kruskal-wallistest used for statistical analysis. Median and upper 95% CI reported. Results: 1) There was no significant difference in % time pH < 4 among subjects on Ome 20, Lanso 30 or Panto 40mg qd, therefore data were pooled together as one group (standard dose PPI). Similarly the subjects on Ome 40mg and Lanso 60mg were pooled to represent high dose PPI. 2) % time esophagealpH <4 in total, upright and supine period shown in table. Summary: All subjects tested on medication showed significantly less esophagealacid exposurethan control. No significant difference in esophageal acid exposurewas found betweenstandarddose and high dose PPI. Conclusion:Thesenormal values should be used to assess adequacyof control of esophagealacid exposure in patients having pH monitoring on PPI therapy.
2228 Esophageal Motility Modifications By Laparoscopic Fundoplication Luis O. Soiter, Enrique Sivori, Jorge Olmos, Daniel Peralta, Demefrio Cavadas,Axel Beskow, Hosp Italy, Buenos Aires Argentina
Baseline
INTRODUCTION:Some patientswith gastroesophagealreflux disease(GERD)presenta reduction in peristaltic contraction amplitude of the distal esophagus(ineffective peristalsis). This disorder is probably the result of chronic damage caused by reflux on the mechanisms responsiblefor peristaltic activity. Although laparoscopicfundoplication is the surgical procedure of choice for the treatment or GERD, there is no evidence of it being able to reverse esophageal peristaltic deficiency. AIM: To determine if iaparoscopicfundoplication improves the averageamplitudeof peristaltic wavesin the distal esophagus.MATERIALAND METHODS: Thirty patients (23 F/TM, age 56 -+14) with GERDwho underwent laparoscopicfundoplication (Nissen) were preoperativelyand postoperatively(6-24 months later) evaluatedby esophageal manomefry. The same team of surgeons performed all the procedures. Pre and postoperative averageamplitudes of peristaltic waves measured5 cm abovethe lower esophagealsphincter were compared. T-test for paired data and 95% confidence interval were used to analyzethe results. RESULTS:Overall, there was an increase in peristaltic amplitude in 22/30 (73.3%) patients. Thirteen (43.3%) subjects had previous ineffective peristalsis, in twelve of them (92.3%) peristaltic amplitude was improved. Averagepre and postoperativeperistaltic amplitudes in the whole series were 60.2 -+ 26.37 mm Hg and 67.8 -+ 32.20 mm HO, respectively. There was a significant increase in peristaltic amplitude (p = 0,012) with a postoperative increase ranging8.28-26.32 mm Hg (95% CI). CONCLUSIONS:Surgical interventionincreases significantly the peristaltic amplitude at the distal esophagusin GERDpatients. This could be related to disappearanceof mechanisms that induce esophagealdamage or to a higher flow resistance after fundoplication.
total upright supine
median
95%CI
Standard dose median
1.6 2.1 O.O
3.45 4.35 2.78
0.4* 0.5* 0.0~
95%CI
High dose median
95%CI
0.98* 1.34" 0.65§
0.5* 0.7* 0.0"
1.20" 1.55" 0.78*
Posttest: * p
A-437