Endoscopy-negative Reflux Disease Research Articles

Esophagogastric junction contractile integral (EGJ-CI) complements reflux disease severity and provides insight into the pathophysiology of reflux disease.

Esophagogastric junction contractile integral (EGJ-CI) has not come into routine use due to methodological discrepancies and its unclear clinical utility. We aimed to determine which method of calculating EGJ-CI was best at discriminating between common reflux disease states. High-resolution manometry (HRM) and pH-Impedance measurements were acquired for 100 patients; 25 Barrett's esophagus (>3 cm/acid exposure time (AET) > 6), 25 endoscopy-negative reflux disease (ENRD; AET >6), 25 borderline reflux (AET 4-6), 25 functional heartburn (FH; AET <4), constituting the developmental cohort. EGJ-CI was calculated at 20 mmHg, 2 mmHg, and 0 mmHg isobaric contour. Empirical associations, univariable, multivariable and ROC analyses were performed between EGJ-CI and manometric/pH-impedance metrics. A validation cohort (n = 25) was used to test the new EGJ-CI cutoff. Significant correlations with AET were observed when EGJ-CI was calculated with an isobaric threshold of 20 mmHg (p < 0.001). Significant differences in EGJ-CI were observed between patients with FH and Barrett's esophagus (p = 0.004) and with ENRD (p = 0.01); however, LES basal pressure was unable to differentiate between these disease states (p = 0.09, p = 0.25, respectively). ROC analysis on the developmental cohort found that EGJ-CI 21.2 mmHg.cm demonstrated sensitivity 72% and specificity 72% between patients with reflux (Barrett's esophagus/ENRD) and FH. In the validation cohort, 92.8% with a low EGJ-CI had good/moderate improvement in symptoms following therapy compared to 54.5% with raised EGJ-CI (p = 0.026). This study re-affirms EGJ-CI as a reliable discriminator between reflux disease (Barrett's esophagus/ENRD) and FH. In borderline reflux patients, patients with a lower EGJ-CI score (<21.2 mmHg) appear to respond better to anti-reflux therapies compared to those with a higher value.

Comparison of acid-lowering drugs for endoscopy negative reflux disease: Systematic review and network Meta-Analysis.

The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score. We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated. Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.

Endoscopic correlation of clinical presentation of gastroesophageal reflux disease among patients referred for gastroscopy in a tertiary hospital

Gastroesophageal reflux disease (GERD) is a leading indication for gastroscopy and a common cause of serious complications among patients with dyspeptic symptoms. Ethnic variability, gender and geographical locations are some of the factors that determine severity index and complications of GERD. Upper gastrointestinal endoscopy is a reliable method used in confirming clinical suspicion of GERD. This study aimed to determine the endoscopic correlation of clinical presentations and frequency of complications among patients with clinical diagnosis of GERD referred for gastroscopy. Hospital-based cross sectional study conducted between 1stJanuary, 2013 to 31st December, 2016. Sociodemographic characteristics and clinical diagnosis of GERD were evaluated alongside endoscopic findings. Endoscopic findings of oesophagitis, strictures, Barrett’s oesophagus or oesophageal adenocarcinoma were classified as endoscopy positive while those with symptoms but with normal endoscopic finding were classified as endoscopy negative or Non-erosive reflux Disease. One thousand, five hundred and ninety seven patients were referred for gastroscopy within the study period of which 226 were GERD (14.2%) using the self-administered questionnaire. One hundred and seven (47.3%) were males, with M: F ratio of 1:1.1. Mean age 38.5, SD± 13.1, and range of 15-75 years. The peak age occurred within the fourth decade of life (32.7%). One hundred and seventy seven (78.3%) were endoscopy positive, while 49 (21.7%) were endoscopy negative GERD. Los Angeles grade B was the highest prevalence 41.2%. GERD is not uncommon in our study and younger age groups are particularly more affected. Erosive esophagitis is the commonest complication encountered.

What are the benefits and harms of short-term treatment with proton pump inhibitors, H2-receptor antagonists or prokinetics in people with gastro-esophageal reflux disease-like symptoms and endoscopy negative reflux disease?

What are the benefits and harms of short-term treatment with proton pump inhibitors, H2-receptor antagonists or prokinetics in people with gastro-esophageal reflux disease-like symptoms and endoscopy negative reflux disease?

Convenient Method of Measuring Baseline Impedance for Distinguishing Patients with Functional Heartburn from those with Proton Pump Inhibitor-Resistant Endoscopic Negative Reflux Disease

Background: Combined 24-h intraesophageal pH-multichannel intraluminal impedance (24MII-pH) used for assessing gastroesophageal reflux disease by measuring baseline impedance (BI) requires a 24-h measuring period. In the present study, we developed a quick method of measuring BI and evaluated its usefulness in classifying patients with proton pump inhibitor (PPI)-refractory non-erosive reflux diseases (NERD) as having functional heartburn (FH) or endoscopic-negative reflux disease (ENRD). Methods: Ninety-one NERD patients without esophageal motility disorder underwent 24MII-pH monitoring while on a PPI. The measurements of the mean nocturnal BI (MNBI) and short MNBI were assessed at 3 times (at about 1: 00, 2: 00, and 3: 00 am) for 10 min and 30 s respectively. The measurement of the simple mean BI (MBI) was performed once 30 s at about 11: 00 am. Results: Ninety-one patients were divided into 2 groups: 59 with ENRD and 32 with FH. The cutoff, specificity, and sensitivity for distinguishing patients with FH were as follows: MNBI, 2,874.1 Ω, 72%, and 72%; short MNBI, 2,857.6 Ω, 74%, and 84%; and simple MBI, 2,874.1 Ω, 86%, and 78% respectively. Conclusion: Measuring the simple MBI is a quick method and is useful for distinguishing patients with FH from those in a cohort with PPI-refractory NERD.

Juice Test for Identification of Nonerosive Reflux Disease in Heartburn Patients.

Background/AimsEvaluation of esophageal clearance by orange juice swallowing could be useful to identify different categories of gastroesophageal reflux disease. We determined whether a juice test at the beginning of esophageal pH monitoring can identify nonerosive reflux disease (NERD) among heartburn patients.MethodsMultiple swallows of orange juice (pH 3) were performed at the beginning of esophageal pH monitoring in 71 heartburn patients off acid-suppressive therapy. The area between pH drop below 5 and recovery to 5 was calculated from pH tracings and named Delta5 (mmol·L−1·sec). Fifteen healthy subjects served to determine Delta5 cutoff (95th percentile). Patients were classified as NERD, non-NERD (a mix of reflux hypersensitivity, functional heartburn, and undetermined), and erosive disease depending on acid exposure, reflux symptom analysis, and upper endoscopy.ResultsDelta5 cutoff in healthy subjects was 251 mmol·L−1·sec. Among 71 patients, 23 had NERD, 26 had non-NERD, and 22 had erosive disease. Compared to non-NERD, Delta5 was higher in both NERD (median [interquartile range]: 316 [213–472] vs 165 [105–225]; P < 0.01) and erosive disease (310 [169–625] vs 165 [105–225]; P < 0.01). An elevated Delta5 (> 251 mmol·L−1·sec) showed sensitivity of 74% and specificity of 81% for identification of NERD. Positive and negative likelihood ratios were 3.84 and 0.32 respectively, whereas test accuracy was 78%.ConclusionsA juice test with calculation of Delta5 helps in the identification of true NERD among heartburn patients with endoscopy-negative reflux disease. In these patients, an elevated Delta5 could make prolonged reflux testing unnecessary.

Impaired motility in Barrett's esophagus: A study using high-resolution manometry with physiologic challenge.

Esophageal dysmotility may predispose to Barrett's esophagus (BE). We hypothesized that high-resolution manometry (HRM) performed with additional physiologic challenge would better delineate dysmotility in BE. Included patients had typical reflux symptoms and underwent endoscopy, HRM with single water swallows and adjunctive testing with solids and rapid drink challenge (RDC) before ambulatory pH-impedance monitoring. BE and endoscopy-negative reflux disease (ENRD) subjects were compared against functional heartburn patient-controls (FHC). Primary outcome was incidence of HRM contractile abnormalities with standard and adjunctive swallows. Secondary outcomes included clearance measures and symptom association on pH-impedance. Seventy-eight patients (BE 25, ENRD 27, FHC 26) were included. Water swallow contractility was reduced in both BE (median DCI 87mmHg/cm/s) and ENRD (442mmHg/cm/s) compared to FHC (602mmHg/cm/s; P<.001 and .04, respectively). With the challenge of solid swallows and RDC, these parameters improved in ENRD (solids=1732mmHg/cm/s), becoming similar to FHC (1242mmHg/cm/s; P=.93), whereas abnormalities persisted in BE (818mmHg/cm/s; P<.01 c.f. FHC). In BE and ENRD, reflux events (67 vs 57 events/24hour) and symptom frequency were similar; yet symptom correlation was significantly better in ENRD compared to BE, which was comparable to FHC (symptom index 30% vs 4% vs 0%, respectively). Furthermore, bolus clearance and exposure times were more pronounced in BE (P<.01). Reduced contractile effectiveness persisted in BE with the more representative esophageal challenge of swallowing solids and free drinking; while in ENRD and FHC peristalsis usually improved, demonstrating peristaltic reserve. Furthermore, symptom association and refluxate clearance were reduced in BE. These factors may underlie BE pathogenesis.

Gastroesophageal Reflux Disease and its Association with Body Mass Index: Clinical and Endoscopic Study.

Obesity is rapidly becoming a pandemic and poses a serious health risk to the individuals. Abdominal obesity is quite common in India and is a prime risk factor for diseases like diabetes, coronary artery disease, Gastroesophageal Reflux Disease (GERD), osteoarthritis etc. A complex and multifactorial aetiopathogenesis of GERD exists in presence of obesity. The current study focuses on high Body Mass Index (BMI), a marker of obesity, as a risk factor for GERD and aims for a better understanding of their complex association. To study the association between the BMI and symptoms as well as gross endoscopic appearance of GERD. A prospective cross-sectional study was carried out at a tertiary care hospital in Maharashtra, India, between January 2016 and June 2016. A total of 176 patients referred for upper Gastrointestinal (GI) endoscopy due to dyspeptic symptoms of more than two months duration were selected. BMI (weight in kilograms/square of height in metres) was calculated for all patients and they were classified as normal weight (BMI 18.5 -24.9), overweight (BMI 25-29.9) and obese (BMI≥30). The frequency and severity of GERD symptoms was assessed by a self-administered questionnaire. Data on typical and atypical symptoms of GERD was collected. Upper GI endoscopy was done on all patients. Based on gross endoscopic appearance, the disease was divided as Endoscopy Negative Reflux Disease (ENRD) and true GERD (as per Los Angeles staging system). Association between BMI and frequency, severity and type of symptoms of GERD and also between BMI and gross endoscopic oesophagitis was studied using various statistical tests. All tests were two-tailed with a confidence level of 95%. A p-value < 0.05 was considered to be statistically significant. Typical symptoms of heartburn and acidic regurgitation were present in 71.6% subjects. The frequency and the severity of the dyspeptic symptoms increased significantly with increasing BMI (p<0.05). Based on the endoscopic gross appearance of the oesophageal mucosa, 48.3% participants had ENRD and 51.7% had erosive disease (GERD). High BMI had a statistically significant relationship with occurrence of both ENRD and GERD (p<0.05) but a statistically insignificant relationship with LA classification system for endoscopic oesophagitis. The prevalence, frequency and severity of symptoms of GERD increases with increase in the BMI. Erosive oesophagitis has significant correlation with increasing BMI, but the staging and classification of endoscopic erosive oesophagitis is independent of the BMI of the patients.

Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.

To investigate the pathophysiology of functional heartburn (FH) in Japanese patients. A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria. Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences. Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.

Symptom Characteristics and Psychosomatic Profiles in Different Spectrum of Gastroesophageal Reflux Disease

Background/AimsGastroesophageal reflux disease (GERD) is diagnosed based on symptoms of heartburn and regurgitation but is a heterogeneous condition which can be subclassified according to endoscopy and esophageal reflux monitoring. The aim of this study was to identify differences in demographic characteristics and reflux symptom patterns among patients with various spectrum of GERD.MethodsPatients having weekly heartburn or acid regurgitation were classified into four pathophysiological subgroups according to endoscopy and pH monitoring: reflux esophagitis (RE), endoscopy-negative reflux disease with pathological reflux (PR+), hypersensitive esophagus (HE), and normal acid exposure with negative symptom association (pH-).ResultsA total of 195 patients were enrolled. The numbers of patients in the subgroups were: RE, 39.0%; PR+, 20.0%; HE, 10.3%; and pH-, 30.8%. Grossly, reflux symptom patterns and relieving/exacerbating factors did not differ between subgroups. Prevalence of extraesophageal syndrome was higher in patients with PR+ than in other groups. Overlapping functional dyspepsia was common in all groups. The SCL-90-R depression score was higher in PR+ patients than in RE patients (p<0.05).ConclusionsDemographic characteristics and reflux symptom patterns cannot differentiate pH- group from GERD subtypes. Esophageal pH monitoring could be considered for the initial evaluation of GERD in the tertiary referral setting.

Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease

Approximately 25% of adults regularly experience heartburn, a symptom of gastro-oesophageal reflux disease (GORD). Most patients are treated empirically (without specific diagnostic evaluation e.g. endoscopy. Among patients who have an upper endoscopy, findings range from a normal appearance, mild erythema to severe oesophagitis with stricture formation. Patients without visible damage to the oesophagus have endoscopy negative reflux disease (ENRD). The pathogenesis of ENRD, and its response to treatment may differ from GORD with oesophagitis. Summarise, quantify and compare the efficacy of short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in adults with GORD, treated empirically and in those with endoscopy negative reflux disease (ENRD). We searched MEDLINE (January 1966 to November 2011), EMBASE (January 1988 to November 2011), and EBMR in November 2011. Randomised controlled trials reporting symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be either from an empirical treatment group (no endoscopy used in treatment allocation) or from an endoscopy negative reflux disease group (no signs of erosive oesophagitis). Two authors independently assessed trial quality and extracted data. Thirty-four trials (1314 participants) were included: fifteen in the empirical treatment group, fifteen in the ENRD group and four in both. In empirical treatment of GORD the risk ratio (RR) for heartburn remission (the primary efficacy variable) in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87).In treatment of ENRD, the RR for heartburn remission for PPI versus placebo was 0.71 (ten trials, 95% CI 0.65 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with ENRD, although the magnitude of benefit is greater for those treated empirically.

Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease

Non-specific esophageal dysmotility with impaired clearance is often present in patients with gastro-esophageal reflux disease (GERD), especially those with erosive disease; however the physio-mechanic basis of esophageal dysfunction is not well defined. Retrospective assessment of patients with erosive reflux disease (ERD; n=20) and endoscopy negative reflux disease (ENRD; n=20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n=20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3cm break in 30 mmHg isocontour). Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P<0.023 vs controls, P=0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18%vs 33%, P=0.082) and ENRD (22%vs 54%, P=0.046) but not ERD (62%vs 76%, P=0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P<0.017 vs controls and P<0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r=0.52 vs 0.27). Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate.

Clinical and pathophysiological consequences of on-demand treatment with PPI in endoscopy-negative reflux disease. Is rebound hypersecretion of acid a problem?

Objective. Rebound acid hypersecretion after withdrawal of proton pump inhibitor (PPI) may lead to symptom aggravation and difficulties in withdrawing anti-reflux medication. The aim was to investigate pathophysiological and clinical consequences of on-demand treatment with PPI in patients with endoscopy-negative reflux disease. Material and methods. Twenty-six patients with endoscopy-negative reflux disease were investigated for rebound effects of lansoprazole 15 mg, used on-demand, maximum 4 capsules daily during a 6-month period. P-CgA and s-gastrin were measured before, at termination and 2 weeks after stopping treatment. Symptom score was performed the week before and the second week after treatment, 24-h pH-metry after both periods. Results. Median daily consumption of lansoprazole was 15.1 mg (95% CI: 10.5; 18.8). S-gastrin before treatment was 31.2 pmol/l, 54.8 at the end (p < 0.01), 31.7 two weeks after withdrawal. P-CgA was 16.7 u/l before treatment, 37.5 at the end (p < 0.01), 17.7 two weeks after withdrawal (p = 0.35). A positive correlation was found between total consumption of lansoprazole and CgA increase during treatment (r = 0.44 p = 0.03). There was a reduction in symptom score during the treatment period from 30 (24–38) before, to 20 (15–36) the second week after treatment, p = 0.06. 32% had increase in symptoms. Conclusions. Rebound acid hypersecretion is probably an infrequent problem in on-demand treatment with PPI in patients with endoscopy-negative reflux disease. A significant increase in p-CgA and s-gastrin was found after 6 months treatment. Fourteen days after withdrawal, CgA and gastrin returned to pretreatment levels. Overall, no aggravation of symptoms was found, but 1/3 experienced increased symptoms.

Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease

Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux - is a common relapsing and remitting disease which often requires long-term maintenance therapy. Patients with GORD may have oesophagitis (inflammation of the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or ENRD). To assess the effects of continuous maintenance therapy in adults with GORD (both ENRD and healed oesophagitis). We searched Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982-2003), and the National Research Register (Issue 2, 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. Randomised controlled studies comparing PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo in adults with reflux oesophagitis and ENRD. One author extracted data from included trials and a second author carried out an unblinded check. Two authors independently assessed trial quality. Study authors were contacted for additional information. Maintenance of patients with healed oesophagitis: For a healing dose of PPI (generally the standard dose given by the manufacturer) versus placebo, the relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse effects were also more common and headaches were more common when comparing healing PPIs to H2RAs.For a maintenance dose of PPI (half of the standard dose) versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57) and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects were more common.H2RAs were of marginal help but beneficial for symptomatic relief. Prokinetics and sucralfate were also more effective than placebo.For ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once daily over placebo (RR 0.4; 95% CI 0.29 to 0.53). The findings in this review support the long-term treatment of oesophagitis to prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs are more effective than all other therapies, although there is an increase in overall adverse effects compared to placebo, and headache occurrence compared to H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over placebo, but the former is no longer licenced. There is only limited data for ENRD.

A Comparative Study of Proton-pump Inhibitor Tests for Chinese Reflux Patients in Relation to the CYP2C19 Genotypes

The proton-pump inhibitor (PPI) test has been proposed as a valuable tool for diagnosing gastroesophageal reflux disease in Western populations. We aim to compare the diagnostic accuracy of the PPI test using rabeprazole and pantoprazole in a Chinese population with a higher prevalence of poor PPI metabolization. After diagnostic endoscopy, patients with gastroesophageal reflux disease symptoms were randomly assigned to a 2-week test with rabeprazole (20 mg b.i.d.) or pantoprazole (40 mg b.i.d.). Therapeutic response was assessed with a 5-grade daily record. Genotypes of cytochrome P450 (CYP) 2C19 polymorphism were determined. Of the 178 patients who completed the study, 92 (51.7%) had erosive esophagitis and 78 (48.3%) were endoscopy-negative reflux disease. On the basis of 50% reduction of symptoms, there was a nonsignificant difference of diagnostic performances between rabeprazole and pantoprazole. For the CYP2C19 genotypes, 138 (87.3%) were determined to be extensive metabolizers (EMs) and 20 (12.7%) were poor metabolizers (PMs). When comparing the EMs and PMs, the diagnostic specificity in the prediction of erosive esophagitis was higher in the EMs (57.6% vs. 20.0%, P=0.040), as was the accuracy (74.6% vs. 50.0%, P=0.023). There were no differences in the sensitivity, positive predictive value, or negative predictive value. CYP2C19 genotypic polymorphism was related to a higher possibility of false-positive results for patients who metabolized PPI poorly. High-dose rabeprazole and pantoprazole showed a similar diagnostic performance.

Efficacy of Three Different Dosages of Esomeprazole in the Long-Term Management of Reflux Disease: A Prospective, Randomized Study, Using the Wireless Bravo pH System

Gastroesophageal reflux disease (GERD) is a chronic condition that usually requires long-term maintenance therapy with proton-pump inhibitors (PPIs). In clinical practice, patients receive PPIs at the lowest dose to control symptoms. However, it is not known whether this approach adequately controls acidic esophageal reflux. We sought to investigate the efficacy of three different dosages of esomeprazole in patients receiving maintenance therapy for GERD, using the Bravo pH system. Patients with a previous history of erosive esophagitis A or B (LA classification) that was healed at the time of enrollment or endoscopy-negative reflux disease (ENRD), documented with an abnormal pH study, were randomized to receive maintenance therapy with esomeprazole 40 mg twice daily (group A), once daily (group B), or every other day (group C). Intraesophageal pH was monitored for two consecutive days using the Bravo wireless system, 30 days after randomization. The parameters subjected to analysis were percent of total time pH<4 and the De Meester score. The pH results from 73 patients (group A=24, group B=24, group C=25 patients) were subjected to final analysis. On the first day of the study, the mean (+/-s.d.) percent of total time pH <4 and the De Meester score were group A: 0.9(1.2) and 4.1(4.0); group B: 1.5(1.6) and 7.0(6.9); group C: 1.3(1.0) and 6.0(3.3), respectively (P=0.262 and 0.134, respectively). On the second day of the study, the corresponding values were group A: 0.7(1.0) and 3.9(5.9); group B: 1.5(1.8) and 6.4(6.6); group C: 7.0(4.4) and 29.4(19.4), respectively. The difference was statistically significant (P<0.0001 and <0.0001, respectively). Further analysis showed that patients not receiving PPI had a significantly higher mean percent of total time pH<4 and De Meester score as compared with patients on PPI once or twice daily (P<0.001 and <0.001 respectively). The administration of esomeprazole 40 mg every other day does not control acidic esophageal reflux on the day off PPI. Esomeprazole 40 mg once daily effectively controls reflux of acid in patients with history of mild esophagitis or ENRD, whereas doubling the dose does not seem to confer any further advantage.

Questionnaires in gastroesophageal reflux disease: What do the answers mean?

Questionnaires in gastroesophageal reflux disease: What do the answers mean?

Influence of cytochrome P450 2C19 genetic polymorphism and dosage of rabeprazole on accuracy of proton‐pump inhibitor testing in Chinese patients with gastroesophageal reflux disease

To evaluate the optimal dosage of rabeprazole for proton-pump inhibitor (PPI) testing of gastroesophageal reflux disease (GERD) and to test the influence of cytochrome P450 (CYP) 2C19 polymorphism in a population with a high prevalence of people who metabolize PPI poorly. In this randomized, open-label trial, patients with symptoms suggestive of GERD were randomized to receive a 2-week test with 20- or 40-mg rabeprazole after diagnostic endoscopy. Symptom response was assessed with a four-grade daily record; in addition, DNA from peripheral blood leukocytes was genotyped for CYP2C19 polymorphism with the polymerase chain reaction-restriction fragment length polymorphism technique. Of the 164 patients who completed the study, 69 (42.1%) were endoscopically positive for esophagitis; the remaining 95 (57.9%) were diagnosed with endoscopy-negative reflux disease. Based on the best cut-off value for 50% symptom reduction, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detecting erosive esophagitis were 68%, 70%, 66%, 72%, and 69%, respectively, for the 20-mg regimen, and 84%, 71%, 64%, 88%, and 76%, respectively, for the 40-mg regimen, a non-significant difference. Regarding the genotype, 60 (39%) patients had two wild-type alleles, 63 (40.9%) had one variant allele, and 31 (20.1%) had two variant CYP2C19 alleles. The presence of a variant allele did not alter the diagnostic efficacy of PPI testing. Both dose levels of rabeprazole proved efficacious in the diagnosis of GERD. Various measures of test accuracy were unrelated to the status of the CYP2C19 genotype.

ACG Practice Guidelines: Esophageal Reflux Testing

Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented.

Pantoprazole On-Demand Effectively Treats Symptoms in Patients with Gastro-Oesophageal Reflux Disease

The efficacy of pantoprazole as on-demand therapy for the long-term management of patients with mild gastro-oesophageal reflux disease (GORD) has been demonstrated in clinical studies. In this study, the efficacy of pantoprazole 20mg and esomeprazole 20mg as on-demand therapy for relief of symptoms of mild GORD was compared. Patients with reflux oesophagitis grade A or B (Los Angeles classification) or endoscopy-negative reflux disease (enGORD) were treated with pantoprazole 20mg once daily for 28 days during the acute phase (AP, n = 236). Patients without heartburn during the final 3 days of the AP entered the long-term phase (LTP, n = 199) and were randomised to either pantoprazole 20mg or esomeprazole 20mg as on-demand treatment for 6 months. Antacids were provided as rescue medication during this phase. The mean intensities of the symptoms of heartburn, acid eructation and pain on swallowing, both separately and as a combined symptom score, together with the mean duration of these symptoms during on-demand treatment, were compared between the two treatment groups. The number of tablets taken was also compared. After 4 weeks of treatment with pantoprazole, 87.3% of patients had relief from heartburn, 74.1% from epigastric pain and 80.8% from acid eructation, according to the investigator assessment. A total of 236 patients were eligible for the on-demand phase. Based on patient diary data, on-demand treatment with pantoprazole resulted in significantly lower mean intensity of heartburn compared with that in the esomeprazole group (1.12 for pantoprazole and 1.32 for esomeprazole, respectively [p = 0.012], in the intention-to-treat [ITT] population). The mean symptom intensities of acid eructation and pain on swallowing, together with the duration of these symptoms, were comparable in the two treatment groups. The combined symptom score of the three symptoms heartburn, acid eructation and pain on swallowing was numerically lower in the pantoprazole group compared with the esomeprazole group (1.72 vs 1.99, respectively, in the ITT population). Tablet intake was comparable in both groups. Relief of symptoms in Helicobacter pylori-positive and -negative patients was also similar in both treatment groups. Both treatments were well tolerated with a good safety profile. On-demand therapy with either pantoprazole 20mg or esomeprazole 20mg is a comparably effective treatment strategy for the long-term treatment of non-erosive and mild GORD. However, the mean intensity of heartburn was significantly lower with pantoprazole treatment.