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Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response.This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks.Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01).This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Limsrivilai et al. report on a randomized control trial (RCT) testing the efficacy of imipramine for treating esophageal hypersensitivity and functional heartburn, the first RCT to test this therapy in this indication. Among 43 functional heartburn and esophageal hypersensitivity patients randomized to treatment with 25 mg qhs imipramine and 40 randomized to matched placebo, the response rates, judged by a 50% reduction in gastroesophageal reflux disease symptoms, were 37.2% and 37.5%, respectively, with no observed difference between patients with hypersensitivity and those with functional heartburn. On the positive side, imipramine treatment was associated with improvement in quality of life as assessed by total SF-36 score. Although negative at first glance, there are several important lessons from this study: (i) low-dose tricyclic is sufficient in these patients; (ii) proton pump inhibitors can (and should) be discontinued when they are ineffective; and (iii) distinguishing between functional heartburn and esophageal hypersensitivity is of unclear clinical relevance.

This study used high-resolution impedance manometry (HRIM) to determine pressure topography thresholds of peristaltic integrity predictive of incomplete esophageal bolus clearance.A total of 16 normal controls and 8 patients with dysphagia were studied using a solid-state HRIM assembly incorporating 36 manometric sensors and 12 impedance segments. Each of the 10 saline swallows in each study was dichotomously scored as either complete or incomplete bolus clearance by impedance criteria, and peristaltic integrity was evaluated using pressure topography isobaric contours ranging from 10 to 30 mm Hg in 5- mm Hg increments. Each isobaric contour plot was characterized by the location and length of breaks in the isobaric contour.All subjects had normal esophagogastric junction (EGJ) relaxation and none met the pressure topography criteria of hiatus hernia. In all, 70 (29%) of the 240 individual swallows had incomplete bolus clearance. In every case, an intactor=20 mm Hg isobaric contour was associated with complete bolus clearance. The largest defect in the 20 and 30 mm Hg isobaric contours associated with complete bolus clearance measured 1.7 and 3.0 cm, respectively, in length, whereas the smallest defect predictive of incomplete bolus clearance measured 2.1 and 3.2 cm, respectively.In individuals with normal EGJ relaxation and morphology, peristaltic contractions with breaks2 cm in the 20 mm Hg isobaric contour or3 cm in the 30 mm Hg isobaric contour are associated with complete bolus clearance, and longer breaks predict incomplete bolus clearance.

OBJECTIVES: AZD0865 is a gastric acid-suppressing agent that has a rapid onset of action and long duration of effect. This double-blind, randomized, multicenter study investigated the efficacy and safety of AZD0865 in the treatment of patients with nonerosive reflux disease (NERD). METHODS: Patients with troublesome heartburn for at least 6 months and no evidence of erosions at endoscopy were randomized to receive AZD0865 (25, 50, or 75 mg/day) or esomeprazole 20 mg/day, for 4 wk. Throughout the treatment period, patients reported the presence and intensity of heartburn and other NERD symptoms twice daily using an electronic diary. Twenty-four-hour ambulatory intraesophageal/intragastric pH monitoring was performed in a subset of patients on day 14. RESULTS: A total of 1,469 patients were randomized. The median time to sustained absence of heartburn (for 7 consecutive days) was approximately 12 days for all treatment groups and did not differ significantly for any of the AZD0865 doses or compared with esomeprazole. There were no significant differences among treatment groups in the cumulative incidence of sustained absence of heartburn during 4 wk treatment (i.e., 65-70%). The percentage of time for which intragastric pH was greater than 4 was significantly greater for AZD0865 75 mg/day compared with esomeprazole 20 mg (75% vs 60%, P < 0.05). AZD0865 was generally well tolerated although reversible elevations of liver transaminases occurred in some patients receiving the agent. CONCLUSIONS: AZD0865 did not provide clinical benefit over esomeprazole 20 mg in the management of patients with NERD.

High-resolution manometry (HRM) provides a spatially enhanced, dynamic representation of the esophagogastric junction (EGJ) high-pressure zone making it possible to isolate the crural diaphragm (CD) contraction from expiratory lower esophageal sphincter (LES) pressure. This study compared CD function of subjects with and without gastroesophageal reflux disease (GERD). METHODS: A total of 75 asymptomatic controls and 156 GERD patients (EGD or pH monitoring positive) underwent HRM. The EGJ axial pressure profile was analyzed over five respiratory cycles to quantify the position and contractile vigor of the CD relative to the LES. Correlations between EGJ HRM attributes and GERD status were examined. RESULTS: GERD patients had significantly greater CD-LES separation compared with either controls or EGD‐/pH‐ patients. GERD patients also had significantly less inspiratory augmentation of EGJ pressure (EGD‐/pH+, 11.5 ± 1.9 mmHg; EGD+, 10.0 ± 1.2 mmHg) compared with controls (16.9 ± 1 mmHg) or EGD‐/pH‐ patients (16.7 ± 0.2 mmHg). Using a logistic regression model that simultaneously examined expiratory LES pressure, LES-CD separation, and inspiratory EGJ augmentation while controlling for age and BMI, only inspiratory augmentation had a significant independent association with GERD. CONCLUSIONS: HRM characterization of EGJ morphology correlates with the objective demonstration of GERD. Although both LES pressure and LES-CD separation are associated with GERD, the strongest association and the only independent predictor of GERD as a categorical outcome in a logistic regression analysis was impaired CD function as indicated by reduced inspiratory augmentation of EGJ pressure. (Am J Gastroenterol 2007;102:1056‐1063)

We compared esophageal acid exposure data obtained during simultaneous esophageal pH studies using the Bravo wireless and the Slimline catheter-Mark III Digitrapper pH systems.Twenty-five asymptomatic subjects underwent endoscopy with endoclip placement at the squamocolumnar junction (SCJ) and manometry to localize the lower esophageal sphincter (LES). A Bravo capsule was placed 6 cm above the SCJ and a Slimline catheter 5 cm above the LES. Relative positions were checked fluoroscopically. Synchronized pH data were compared by manual extraction into Excel spreadsheets. An in vivo pH reference was established with swallows of orange juice (pH 3.88).Median acid exposure time was greater with the Slimline compared to the Bravo system (Slimline, 3.4%; Bravo, 1.76%, p0.05) but electrode positions were similar. The dominant source of discrepancy between systems was an offset in recorded pH values around pH 4 as evidenced by the recorded values of the swallowed orange juice. Bench-top testing suggested that this offset was mainly attributable to the software designed to compensate for the difference in electrode recording characteristics between room and body temperature. After adjusting the pH data sets to accurately reflect actual orange juice pH, acid exposure between systems was similar (Slimline, 0.90%; Bravo, 1.15%).The Slimline system on average over-recorded esophageal acid exposure compared to the Bravo system largely because of a flawed software scheme for electrode thermal calibration. Accuracy of pH data sets from both systems can be improved by scrutiny for artifacts and use of an in vivo pH reference.

Does chronic Helicobacter pylori gastritis prevent gastroesophageal reflux disease (GERD) and its sequelae? Yes, no, life should be so simple. A quick Medline search on the paired terms identified 527 citations since 1988 and that tells you something right there. Evidently, this is a complex relationship and attempting to reduce it to a yes/no answer is just not going to work. Perusing the literature, it becomes apparent that some combination of three component questions are in fact being asked: (i) Is it biologically plausible that H. pylori gastritis will reduce the occurrence of GERD? (ii) Is there an inverse epidemiological relationship between H. pylori infection and GERD? and (iii) Will the eradication of H. pylori unleash an epidemic of GERD? Each of these questions entails a unique set of consideration. We will consider each in turn.

Although reflux esophagitis is a multifactorial disease, the relative importance of these pathogenetic factors has not been clearly established. In this study, regression analysis was used to model the major determinants of esophagitis in patients with symptomatic gastroesophageal reflux disease (GERD).Sixty-six GERD patients and 16 asymptomatic controls were evaluated. All patients underwent upper endoscopy, esophageal manometry, and 24-h pH monitoring. Esophagrams were performed in 38 of the GERD patients and all controls. Stepwise regression was performed using esophagitis severity as the dependent variable. Logistic regression was performed grouping subjects as controls, nonerosive GERD, or erosive esophagitis.Hiatal hernia size, lower esophageal sphincter pressure, esophageal acid exposure, and number of reflux episodes5 min significantly correlated with esophagitis severity. Stepwise regression identified hiatal hernia size (p = 0.0001) and lower esophageal sphincter pressure (p = 0.0024) as significant predictors of esophagitis. Logistic regression also identified hiatal hernia size (chi2 = 17.07, p0.0001) and lower esophageal sphincter pressure (chi2 = 5.97, p = 0.0146) as significant predictors of erosive esophagitis.Esophagitis severity is best predicted by hiatal hernia size and lower esophageal sphincter pressure. Of these, hiatal hernia size is the strongest predictor.

Although esophageal motor disorders are associated with chest pain and dysphagia, minimal data support a direct relationship between abnormal motor function and symptoms. This study investigated whether high-resolution manometry (HRM) metrics correlate with symptoms.Consecutive HRM patients without previous surgery were enrolled. HRM studies included 10 supine liquid, 5 upright liquid, 2 upright viscous, and 2 upright solid swallows. All patients evaluated their esophageal symptom for each upright swallow. Symptoms were graded on a 4-point likert score (0, none; 1, mild; 2, moderate; 3, severe). The individual liquid, viscous or solid upright swallow with the maximal symptom score was selected for analysis in each patient. HRM metrics were compared between groups with and without symptoms during the upright liquid protocol and the provocative protocols separately.A total of 269 patients recorded symptoms during the upright liquid swallows and 72 patients had a swallow symptom score of 1 or greater. Of the 269 patients, 116 recorded symptoms during viscous or solid swallows. HRM metrics were similar between swallows with and without associated symptoms in the upright, viscous, and solid swallows. No correlation was noted between HRM metrics and symptom scores among swallow types.Esophageal symptoms are not related to abnormal motor function defined by HRM during liquid, viscous or solid bolus swallows in the upright position. Other factors beyond circular muscle contraction patterns should be explored as possible causes of symptom generation.

The typical symptoms of gastroesophageal reflux disease (GERD) are heartburn and regurgitation. Extensive analysis has characterized heartburn and its responsiveness to proton pump inhibitor (PPI) therapy, but regurgitation has received relatively little attention. This study aimed to evaluate the response of regurgitation to PPI therapy in GERD trials.Studies were identified by systematic searches in PubMed and Embase, as well as searching congress abstracts and the reference lists of Cochrane reviews.Regurgitation was not an entry criterion or the primary end point in any of the 31 clinical trials reporting the response of regurgitation to PPI treatment in GERD. The definitions of regurgitation and responsiveness varied among trials and over half used investigator assessment of response. Owing to these inconsistencies, no meta-analysis was attempted. In seven placebo-controlled trials of PPI therapy, the therapeutic gain for regurgitation response averaged 17% relative to placebo and was20% less than that observed for heartburn. Studies comparing PPIs with histamine-2 receptor antagonists or prokinetics found the comparator drug response similar to the placebo response rates seen in the placebo-controlled trials.The therapeutic gain with PPIs over placebo or comparator agents for the relief of regurgitation is modest, and considerably lower than for heartburn. Thus, regurgitation is likely to be an important factor for determining incomplete response to PPI treatment in GERD. Future trials would benefit from using regurgitation as a primary end point, applying an unambiguous definition of the symptom and of a positive treatment response, and using a validated patient-reported instrument for regurgitation assessment.

Esophageal manometry is frequently used to assess for weak peristalsis. Although commonly used clinically, there are currently no validated metrics of weak peristalsis in high-resolution esophageal pressure topography (EPT). This study aimed to develop a classification of weak peristalsis in EPT based on a comparative analysis of control subjects and patients with unexplained non-obstructive dysphagia.High-resolution esophageal pressure topography (high-resolution impedance manometry) studies were carried out in 16 control subjects to verify EPT features associated with incomplete bolus transit (IBT). The technique of superimposing EPT plots in a computer simulation was used to derive normal limits of peristaltic integrity in EPT in another 75 control subjects. The occurrence of critical EPT defects was then compared between control subjects and 113 patients with non-obstructive dysphagia identified from a large clinical series.IBT occurred with failed peristalsis or with breaks in the 20 mm Hg isobaric contour occurring at the proximal or distal pressure troughs in EPT plots. The normal range for isobaric contour breaks was 0-20% for large (5 cm) and 0-30% for small (2-5 cm) breaks, with both occurring significantly more frequently in dysphagic patients. Failed peristalsis was not more frequent in dysphagic patients.A classification of weak peristalsis adapted to EPT is proposed based on the occurrence of breaks in the 20 mm Hg isobaric contour wherein weak peristalsis with large breaks is defined by those occurring with20% of swallows and weak peristalsis with small breaks defined by those occurring with30% of swallows.

Two recent studies-one of which is published in this edition of the American Journal of Gastroenterology-have reported that new dyspeptic or reflux symptoms may develop among previously asymptomatic individuals after withdrawal of a short course of a proton pump inhibitor (PPI). It has been suggested that this is attributable to rebound gastric acid hypersecretion, and that the same phenomenon explains why some patients become chronic PPI users and physicians experience "difficulty" in withdrawing PPI treatment from patients. Although we congratulate the authors of both studies for their controlled observations, we question the generalizability of these observations and hypotheses to the clinical domain. PPI treatment continues to be the optimal management strategy for most patients with gastroesophageal reflux disease and is indicated for chronic use as ulcer prophylaxis in nonsteroidal anti-inflammatory drug takers at high risk for bleeding. However, as with all drugs, PPIs should be dosed appropriately, and should be reserved for patients with conditions for which there is clear evidence of benefit from therapy.

This study aimed to devise a scheme for the systematic analysis of esophageal high-resolution manometry (HRM) studies displayed using topographic plotting.A total of 400 patients and 75 control subjects were studied with a 36-channel HRM assembly. Studies were analyzed in a stepwise fashion for: (a) the adequacy of deglutitive esophagogastric junction (EGJ) relaxation, (b) the presence and propagation characteristics of distal esophageal persitalsis, and (c) an integral of the magnitude and span of the distal esophageal contraction.Two strengths of pressure topography plots compared to conventional manometric recordings were: (a) the ability to delineate the spatial limits, vigor, and integrity of individual contractile segments along the esophagus, and (b) the ability to distinguish between loci of compartmentalized intraesophageal pressurization and rapidly propagated contractions. Making these distinctions objectified the identification of distal esophageal spasm (DES), vigorous achalasia, functional obstruction, and nutcracker esophagus subtypes. Applying these distinctions made the diagnosis of spastic disorders quite rare: (a) DES in 1.5% patients, (b) vigorous achalasia in 1.5%, and (c) a newly defined entity, spastic nutcracker, in 1.5%.We developed a systematic approach to analyzing esophageal motility using HRM and pressure topography plots. The resultant scheme is consistent with conventional classifications with the caveats that: (a) hypercontractile conditions are more specifically defined, (b) distinctions are made between rapidly propagated contractions and compartmentalized esophageal pressurization, and (c) there is no "nonspecific esophageal motor disorder" classification. We expect that pressure topography analysis, with its well-defined functional implications, will prove valuable in the clinical management of esophageal motility disorders.

AIM: This study aimed to localize the gastric-to-esophageal pH transition point relative to the squamocolumnar junction (SCJ) and esophagogastric junction (EGJ) high-pressure zone in controls and GERD patients. METHODS: Ten controls and 10 GERD patients were studied. Subjects had an endoclip placed at the SCJ prior to a pH catheter pull-through (upright and supine) during concurrent fluoroscopy before and after consuming a standardized meal. Six controls and 6 GERD patients also underwent concurrent manometry. The relative positions of the SCJ, EGJ high-pressure zone, and pH transition points were analyzed. RESULTS: Most controls and GERD patients exhibited an unbuffered acidified segment in the proximal stomach postprandially. The proximal pH transition point was confined distal to the SCJ in control subjects, regardless of posture or meal state. GERD patients exhibited a more proximal pH transition point, extending above the SCJ and EGJ high-pressure zone in the supine position, especially postprandially. However, the high-pressure zone was intact. CONCLUSION: A short segment of unbuffered acidity of unknown volume exists after meals in the proximal stomach. In controls, the unbuffered acidic segment is contained distal to the SCJ while in the GERD patients it extended into and even across the EGJ high-pressure zone. However, this extension through the EGJ in GERD patients occurred in the context of an intact sphincter suggesting that this is best conceptualized as an acid "film" rather than a "pocket." This observation may help explain the propensity of the distal esophageal mucosa to lesions of reflux disease.

A globally acceptable definition and classification of gastroesophageal reflux disease (GERD) is desirable for research and clinical practice. The aim of this initiative was to develop a consensus definition and classification that would be useful for patients, physicians, and regulatory agencies.A modified Delphi process was employed to reach consensus using repeated iterative voting. A series of statements was developed by a working group of five experts after a systematic review of the literature in three databases (Embase, Cochrane trials register, Medline). Over a period of 2 yr, the statements were developed, modified, and approved through four rounds of voting. The voting group consisted of 44 experts from 18 countries. The final vote was conducted on a 6-point scale and consensus was defined a priori as agreement by two-thirds of the participants.The level of agreement strengthened throughout the process with two-thirds of the participants agreeing with 86%, 88%, 94%, and 100% of statements at each vote, respectively. At the final vote, 94% of the final 51 statements were approved by 90% of the Consensus Group, and 90% of statements were accepted with strong agreement or minor reservation. GERD was defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The disease was subclassified into esophageal and extraesophageal syndromes. Novel aspects of the new definition include a patient-centered approach that is independent of endoscopic findings, subclassification of the disease into discrete syndromes, and the recognition of laryngitis, cough, asthma, and dental erosions as possible GERD syndromes. It also proposes a new definition for suspected and proven Barrett's esophagus.Evidence-based global consensus definitions are possible despite differences in terminology and language, prevalence, and manifestations of the disease in different countries. A global consensus definition for GERD may simplify disease management, allow collaborative research, and make studies more generalizable, assisting patients, physicians, and regulatory agencies.

Intragastric pH monitoring is currently done using catheter-based pH systems. This study assessed the feasibility of proximal intragastric pH recording with the Bravo wireless pH monitoring system using novel methodology.Nine asymptomatic volunteers and 9 symptomatic patients were studied. One pH capsule was positioned under direct endoscopic visualization so that the device straddled the squamocolumnar junction (SCJ) with the attachment well positioned on squamous mucosa and the pH electrode 1.5-2 cm distal to the SCJ. A second capsule was placed 6 cm proximal to the SCJ. The signal from each capsule was recorded by a separate receiver synchronized for time.Successful placement and interpretable recording for42 h from both pH capsules was achieved in 16 (88%) of 18 subjects. Data capture were 98.3% in the cardia and 97.7% in the esophagus. Two failures occurred due to premature capsule detachment (one esophageal and one gastric). The acid environment in the cardia was similar in asymptomatic controls and symptomatic patients and exhibited less meal-related buffering than is typical of more distal intragastric recordings. In addition, nadir gastric cardia pH was almost always less than nadir esophageal pH during reflux events.Twenty-four hour gastric cardia pH monitoring is feasible with the Bravo system and can be added to esophageal pH monitoring to assess concomitant cardia acidity. Instantaneous cardia pH defines the potential nadir esophageal pH during reflux events.

BACKGROUND Although strenuous exercise has been reported to increase gastroesophageal reflux, there are few AND AIM: data exploring the mechanism behind this relationship. The aim of this study was to use vigorous exercise as a provocation for strain-induced reflux and examine the correlation between endoscopically assessed EGJ integrity and exercise-induced reflux. METHODS: Ten controls and 10 GERD patients were studied for a 2-day period using the wireless Bravo pH monitoring system. The subjects were randomly assigned to perform 60 min of exercise on day 1 or 2 consuming the same diet on both days. Exercise consisted of 30 min of running and 30 min of 5 resistance exercises. Subjects underwent endoscopy to grade the EGJ flap valve and manometry to measure basal LES pressure. RESULTS: Nineteen subjects completed the 2-day study with 100% data capture during exercise. Median acid exposure was increased more than threefold for both controls and GERD patients during exercise when compared to nonexercise periods. In addition, a strong correlation existed between EGJ grade and % time pH < 4 during exercise while there was not a significant correlation between LES pressure and EGJ grade. These findings were present even after exclusion of hiatus hernia patients (flap valve grade 4). CONCLUSIONS: Exercise caused a threefold increase in esophageal acid exposure in both controls and GERD patients. The degree of exercise-induced reflux is strongly correlated with EGJ morphology and this supports the hypothesis that anatomical integrity of the EGJ is of cardinal importance in preventing strain-induced reflux.

OBJECTIVES: Little consensus exists regarding the endoscopic assessment of the esophagogastric junction after antireflux surgery. The purpose of this report is to characterize the gastroesophageal valve appearance unique to each type of antireflux procedure and to introduce an endoscopic lexicon by which to describe this anatomic region. METHODS: Endoscopic Images were obtained from patients who had undergone any one of the following procedures: Nissen, Collis-Nissen, Toupet, and Dor fundoplicatlons and Hill repair. Images were excluded if patients had any symptoms of heartburn, regurgitation, dysphagia, chest pain, or gas bloat or if they were using antisecretory medication. Seven photographs per operation type were evaluated by experienced surgeons and gastroenterologists tasked with describing defining characteristics of each procedure. RESULTS: Ten valve criteria were developed to uniquely identify and quantify the ideal endoscopic appearance of each procedure. Illustrations were created to clearly depict those traits. CONCLUSIONS: Using 10 gastroesophageal valve criteria, the key components of a successful functional repair of the esophagogastric junction were defined. These criteria can be employed when evaluating upper gastrointestinal complaints after antireflux surgery and may ultimately serve as a dependable outcome measure.

Limitations of catheter-based esophageal pH monitoring are discomfort, inconvenience, and interference with normal activity. An alternative to conventional pH monitoring is the wireless Medtronic Bravo pH System. The aim of this study was to evaluate the safety, performance, and tolerability of this system.A total of 44 healthy subjects and 41 patients with gastroesophageal reflux disease (GERD) were studied for a 2-day period. The pH telemetry capsule was positioned transorally 6 cm above the squamocolumnar junction using endoscopic measurement. The signal transmitted from the capsule was received and recorded by a small, pager-sized receiver, and pH data were subsequently uploaded to a computer for analysis.Successful 24-h pH studies were completed in 82 subjects (96%). During the 24-h study period the median percentage of the time that pH was4 was 2.3% (95th percentile, 5.9%) in controls and 6.5% (range, 0.8-27.6) in GERD patients. In 76 subjects (89%), 36-48 h recordings were obtained. For the extended period the median percentage of the time that pH was40 was 2.0% (95% percentile, 5.3%) in controls and 6.6% (range, 1.0-26.7) in GERD patients. Capsules required endoscopic removal in three subjects (4%). Optimal sensitivity in distinguishing controls from reflux patients was achieved when analyzed from the perspective of the worst of the 2 days.The wireless Bravo pH System successfully recorded esophageal acid exposure in 96% of the patients during a 24-h period and in 89% of subjects for36 h. The 95th percentile for the 2-day recordings in control subjects was 5.3%, slightly higher than observed with conventional systems.

Esomeprazole, the S isomer of omeprazole, has been shown to have higher healing rates of erosive esophagitis than omeprazole. This study compared esomeprazole with lansoprazole for the healing of erosive esophagitis and resolution of heartburn.This United States multicenter, randomized, double blind, parallel group trial was performed in 5241 adult patients (intent-to-treat population) with endoscopically documented erosive esophagitis, which was graded by severity at baseline (Los Angeles classification). Patients received 40 mg of esomeprazole (n = 2624) or 30 mg of lansoprazole (n = 2617) once daily before breakfast for up to 8 wk. The primary efficacy endpoint was healing of erosive esophagitis at week 8. Secondary assessments included proportion of patients healed at week 4, resolution of investigator-recorded heartburn, time to first and time to sustained resolution of patient diary-recorded heartburn, and proportion of heartburn-free days and nights.Esomeprazole (40 mg) demonstrated significantly higher healing rates (92.6%, 95% CI = 91.5-93.6%) than lansoprazole (30 mg) (88.8%, 95% CI = 87.5-90.0%) at week 8 (p = 0.0001, life-table estimates, intent-to-treat analysis). A significant difference in healing rates favoring esomeprazole was also observed at week 4. The difference in healing rates between esomeprazole and lansoprazole increased as baseline severity of erosive esophagitis increased. Sustained resolution of heartburn occurred faster and in more patients treated with esomeprazole. Sustained resolution of nocturnal heartburn also occurred faster with esomeprazole. Both treatments were well tolerated.Esomeprazole (40 mg) is more effective than lansoprazole (30 mg) in healing erosive esophagitis and resolving heartburn. Healing rates are consistently high with esomeprazole, irrespective of baseline disease severity.

This randomized, double-blind, multicenter study was conducted to confirm a previous finding that lansoprazole relieves heartburn faster than omeprazole in patients with erosive esophagitis.A total of 3510 patients with erosive esophagitis and at least one episode of moderate to very severe daytime and/or nighttime heartburn during the 3 days immediately before the screening visit were randomized to lansoprazole 30 mg once daily or omeprazole 20 mg once daily for 8 wk. Patients recorded the presence and severity of daytime and nighttime heartburn in daily diaries. On treatment days 1-4, patients were telephoned to confirm the completion of their daily diary. The primary efficacy parameters were the percentage of heartburn-free days and heartburn-free nights, as well as the average severity of daytime and nighttime heartburn.During treatment day I and all evaluation time points including the entire 8-wk treatment period, significantly (p0.05) higher percentages of patients treated with lansoprazole than those treated with omeprazole did not experience a single episode of heartburn. Onset of heartburn relief was more rapid in lansoprazole-treated versus omeprazole-treated patients: on day 1, 33% versus 25% of lansoprazole- versus omeprazole-treated patients were heartburn-free. The percentages of heartburn-free days and heartburn-free nights were also significantly (p0.01) greater for patients treated with lansoprazole at all evaluation time points. Heartburn severity was significantly less among those treated with lansoprazole compared with omeprazole. Both treatments were safe and well tolerated.Over 8 wk, lansoprazole 30 mg once daily relieved heartburn symptoms faster and more effectively than omeprazole 20 mg once daily in patients with erosive esophagitis.

OBJECTIVE: Our aim was to assess the efficacy and mechanism of solid bolus transit through the esophagus. METHODS: Eight healthy volunteers were studied with concurrent manometry and videofluoroscopy while swallowing 5 ml liquid barium, a 5–6 mm diameter bread ball, and 4 g chewed bread in both a supine and upright posture. As many as four successive swallows were performed until clearance was achieved. RESULTS: The esophageal clearance of liquid barium was 100% with the first swallow. Clearance of the unchewed bread ball occurred with the first swallow in only 6.7% of trials in the upright posture and 5.9% in the supine posture. After four swallows, clearance was 100% and 52.9% in the upright and supine postures, respectively. Chewed bread was more readily cleared than unchewed bread, with 100% clearance after two swallows in the upright posture and 91% clearance after four swallows in the supine posture. The most common locus of bread stasis was at the aortic arch and carina. The bread boluses were noted to move more effectively when localized in the head as opposed to the tail of the bolus composite. Nonocclusive contractions often occurred at the bolus tail despite the increased peristaltic amplitude seen with the chewed bread. Failed peristalsis, a frequent cause for solid clearance failure, was observed during 30% of all bread swallows. This usually occurred distal to the stopping point of the bolus, suggesting it to be the result rather than the cause of impaired transit. CONCLUSIONS: Although infrequently perceived by these normal subjects and in contradistinction to liquid clearance, bread is rarely cleared from the esophagus with a single swallow. Mastication and an upright posture facilitate the esophageal transport of solids. Bolus composition and impaired bolus transit alter the amplitude and conductance of peristalsis. Manometric data pertaining to liquid clearance through the esophagus do not readily apply to bread.

TO THE EDITOR: We are glad that Dr. Graham read the Montreal definition paper with interest and acknowledges that the outcome is potentially important. We were surprised at his comments regarding advertising and equally surprised that despite his many questions, he has failed to identify any statement in the consensus document that could be construed as a potential conflict of interest. Advertising is defined as "calling public attention to something by emphasizing desirable qualities so as to arouse a desire to buy or patronize" (1). Our paper does not mention any product (e.g., pharmaceutical), medical device, or service and was focused on the intellectual exercise of defining a disease and therefore cannot be construed as an advertisement for anything. There is simply nothing to buy or patronize. Our paper is therefore quite different from the published Canadian gastroesophageal reflux disease Consensus cited by Dr. Graham that does discuss commercial products and services (2).

Two manuscripts in this issue utilize quantitative methods to analyze the association between gastroesophageal reflux disease (GERD) and dilated intercellular spaces (DIS) evident on transmission electron microscopy of the esophageal epithelium. One study of 20 patients found that, irrespective of whether or not a pH study was positive, all GERD patients who had responded to proton pump inhibitors therapy had intercellular space measurements that were at least twice normal. The other study demonstrated that DIS resolved with effective GERD therapy in essentially every instance. Both studies suggest that DIS are an objective structural marker of endoscopy-negative reflux disease.

The cricopharyngeal (CP) bar is a common radiographic finding that can cause oropharyngeal dysphagia (OPD). Treatment options include CP myotomy, which is problematic given that CP bars primarily affect elderly patients with comorbidities who are at higher risk for peri-operative complications. The aim of this study was to examine the effectiveness of endoscopic dilation in the management of dysphagia attributed to a CP bar. Review of upper endoscopic (EGD) and videofluoroscopic swallowing studies from 1999–2002 identified 32 patients with CP bars. CP bar was defined by radiology as a distinct posterior impression in the cervical esophagus inferior to the vocal cords. Six of these patients had dysphagia without any other identifiable cause aside from the CP bar. Each of these six patients underwent EGD with Savary (5) or balloon dilation (1) of the upper esophageal sphincter to a diameter of 51–60 Fr. Short- and long-term follow-up was conducted post-dilation at 1–4 weeks and 10–27 months, respectively. The median age of the 32 patients with CP bars was 63 yrs. The 6 symptomatic patients who underwent endoscopic therapy were women with median age of 62 yrs. Each of the 6 patients experienced immediate improvement in dysphagia. None of the patients developed complications of post-dilation pain, bleeding or perforation. Five patients had continued improvement of their OPD at short-term follow-up. One patient who was dilated to 51 Fr using a Savary dilator experienced return of globus sensation after 48 hours, although dysphagia and regurgitation had resolved. A second Savary dilation, one month after the initial procedure, resulted in complete elimination of symptoms at subsequent short-term follow-up. Four patients had continued complete resolution of OPD at long-term follow-up. The remaining two patients reported the recurrence of significant dysphagia after 6 and 8 months, which they stated was less severe than at initial presentation. None of the patients required surgical or endoscopic myotomy for residual or refractory dysphagia. Every patient was satisfied with the results and stated they would recommend endoscopic dilation to others with the same problem.(1) CP bar is an important cause of dysphagia that affects elderly patients. (2) Endoscopic dilation of symptomatic CP bars can produce long-term relief of dysphagia. (3) Further controlled studies are warranted to better define the efficacy and safety of endoscopic CP bar dilation as an alternative to surgical myotomy in symptomatic patients.