Non-erosive Reflux Disease Patients Research Articles

T1110 Relationship Between Esophageal Acid Exposure and Symptom Association Probability (SAP) Index in Erosive and Non-Erosive Reflux Disease Patients

T1110 Relationship Between Esophageal Acid Exposure and Symptom Association Probability (SAP) Index in Erosive and Non-Erosive Reflux Disease Patients

W1125 Characteristics of Esophageal Motility in Patients With NERD Refractory for PPIs and a Treatment Strategy Using Rikkunshito – A Study Using Combined Multichannel Intraluminal Impedance and Manometry (MII-EM): Part II

Background: More than 50% of non-erosive gastroesophageal reflux disease (NERD) patients have a poor response to proton pump inhibitors (PPIs) treatment. Recently, it was reported that esophageal motility disorder involving a decline in esophageal clearance contributes to refractory for PPIs. However, there was few reports focused to esophageal motility of patients with NERD refractory for PPIs and there is no established strategy for treatment of refractory NERD. Aims: To clarify the characteristic of patients with refractory NERD, we investigated the esophageal function using MII-EM. In addition, we also evaluated the efficacy of rikkunshito which is a gastrointestinal prokinetic agent. Methods: In this study, 24 NERD patients including 15 patients with NERD refractory for PPIs treatment. Refractory NERD was defined as a score of more than 6 points in the QUEST questionnaire after PPI treatment for over than 4 weeks. After wash-out of gastrointestinal-related drugs, all enrolled patients underwent the examinations using MII-EM and then started oral administration of rikkunshito (7.5 g/ day). After rikkunshito treatment for 8 weeks, the examinations using MII-EM was performed again. Also, symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before and 4 weeks / 8 weeks after starting the rikkunshito treatment. Results: At first examination using MII-EM, 71.4% of the refractory NERD patients had peristaltic contraction rate (PC rate) deviating from the standard value (≧80%) and 85.7% of them had a complete bolus transit rate (CBT rate) deviating from the standard value (≧75%). On the other hand, in the 9 patients other than the refractory NERD, the rate of patients with such deviation was 25.0% and 50.0%, respectively. The rate of patients with a resting LES pressure deviating from the standard value was comparable between the two patient groups. Next, we also evaluated the efficacy of rikkunshito in the refractory NERD. Rikkunshito significantly improved the LES residual pressure during swallow from 7.2 ± 5.1 mmHg to 5.2 ± 4.1 mmHg, PC rate from 52.4 ± 34.6% to 75.5 ± 31.1% and CBT rate from 51.5 ± 27.4% to 81.8 ± 16.0%. In assesment of symptoms with GSRS, rikkunshito significantly improved score of acid reflux symptoms, dyspepsia-like symptoms and total gastrointestinal symptoms. Conclusion: These results suggested that the refractory NERD patients had a disorder of esophageal motility and that rikkunshito ameliorated the gastrointestinal symptoms through improvement of the esophageal and LES motility disorder. We propose the application of rikkunshito as a strategy to treat patients with NERD refractory for PPIs.

Abdominal ultrasonography as a new modality for the diagnosis of gastroesophageal reflux disease

Thickening and abnormal architecture of the esophageal wall in gastroesophageal reflux disease (GERD) have been reported using endoscopic ultrasonography (US), but whether extracorporeal abdominal US is a useful diagnostic modality has not been investigated. Subjects were 37 GERD, 24 non-erosive reflux disease (NERD) patients and 32 controls who visited our hospital from 2006-2009 and underwent upper gastrointestinal endoscopy and extracorporeal abdominal US. The US operator was unaware of any clinical information and examined the following: (i) thickness (>or=5 mm) and (ii) architecture of the esophageal wall; and (iii) presence of reflux. GERD was diagnosed when two or more of these items were positive. Thickening of the lower esophageal wall in erosive GERD, NERD and controls was 5.7 +/- 0.6, 4.4 +/- 0.8 and 4.7 +/- 0.9 mm, respectively. The thickness in erosive GERD was significantly greater (P < 0.05) than that in NERD patients and controls. Sensitivity, specificity and accuracy of abdominal US diagnosis for erosive GERD and NERD (vs control) was 84.6% (11/13), 25% (6/24), 91.1% (31/34) and 91.1% (31/34), 89.4% (42/47) and 63.8% (37/58), respectively. Extracorporeal abdominal US could be a new useful modality for diagnosing GERD.

OC-062 Longitudinal analysis of erosive and non-erosive gastro-oesophageal reflux disease: Abstract OC-062

Introduction Gastro-oesophageal reflux disease (GORD) is a common condition with a prevalence of about 20% in Western countries.1 In some patients GORD symptoms are associated with oesophageal mucosal injury, yet in others there is no macroscopic evidence of erosive disease. We sought to assess the natural history of patients with GORD symptoms with respect to the persistence or emergence of erosive disease over time, as well as the development of complications, including oesophageal strictures, Barrett9s epithelium (BE) and oesophageal cancer. Methods We analysed a database of over 50 000 oesophagogastroduodenoscopies (OGDs) performed at our unit between 1985 and 2006. From this database, we identified all patients undergoing OGD for GORD symptoms, who had subsequently undergone at least one further OGD at least 6 months after the index OGD. At the index OGD patients were categorised as having erosive oesophagitis (EE) or non-erosive reflux disease (NERD) based upon the presence or absence of mucosal injury. Changes or persistence of the index phenotype (EE or NERD) during follow-up OGDs were defined, as were the development of strictures, BE or oesophageal cancer. Results We identified 394 patients undergoing at least two OGDs for GORD symptoms. EE was present at the index endoscopy in 38% of patients (50% male, mean age 54 years) and NERD in 62% (53% male, mean age 54 years). Mean follow-up time was 4.8 years for EE and 5.2 years in NERD patients. Results of follow-up OGDs are shown in Abstract 062. Conclusion Patients with symptomatic GORD who undergo repeat OGD, even over extended time periods (mean follow-up 5 years) have a stable phenotype with respect to the persistence of EE or NERD, although NERD is significantly more likely to persist as a phenotype than EE. Patients with EE are significantly more prone to GORD complications.

Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease

Transient receptor potential channel vanilloid subfamily member-1 (TRPV1) may play a role in esophageal perception. TRPV1 mRNA and protein expression were examined in the esophageal mucosa of non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients and correlated to esophageal acid exposure. Seventeen NERD patients, eight EE patients and 10 healthy subjects underwent endoscopy after a 3-week washout from proton pump inhibitors or H2 antagonists. Biopsies, obtained from the distal esophagus, were used for conventional histology, for Western blot analysis and/or quantitative real-time polymerase chain reaction (qPCR). Overall 13 NERD patients, four EE patients and five controls underwent ambulatory pH-testing. TRPV1 expression was increased in all NERD and EE patients, as measured by Western blot analysis (0.65 +/- 0.07 and 0.8 +/- 0.05 VS 0.34 +/- 0.04 in controls; P < 0.01) and by qPCR (1.98 +/- 0.21 and 2.52 +/- 0.46 VS 1.00 +/- 0.06; P < 0.01). Neutrophilic infiltration, in the mucosa, was detected only in EE patients. Non-erosive reflux disease and EE patients presented increased TRPV1 receptors mRNA and protein, although no correlation with acid exposure was demonstrated. Increased TRPV1 in the esophageal mucosa may contribute to symptoms both in NERD and EE patients and possibly account for peripheral mechanisms responsible for esophageal hypersensitivity in NERD patients.

Efficacy of the Addition of Prokinetics for Proton Pump Inhibitor (PPI) Resistant Non-erosive Reflux Disease (NERD) Patients: Significance of Frequency Scale for the Symptom of GERD (FSSG) on Decision of Treatment Strategy

Non-erosive reflux disease (NERD) is a more difficult to treat than reflux esophagitis (RE) due to the high prevalence of PPI resistance. Consequently, the treatment strategy for NERD is yet to be established. Subjects were 467 GERD patients (NERD 349, RE 118, 47.4 +/- 16.7 years) with reflux symptoms such as heartburn. PPI was administered for 2 weeks, and total score (TS) of symptoms, seven items of reflux symptoms e.g. heartburn (reflux score: RS), and five items of dyspeptic symptoms e.g. heavy stomach (dyspeptic score: DS) were assessed using the frequency scale for the symptoms of GERD (FSSG), a GERD-specific questionnaire developed in Japan. Improvement <50% in TS was defined as non-responder. Patients' background, and pretreatment TS, RS, DS, and 12 items of FSSG were assessed. Furthermore, the effect of additional prokinetics (4 weeks) for 117 PPI non-response NERD patients was also examined. Younger age, constipation, higher TS, DS, F2 (bloated stomach), 3 (heavy stomach), 5 (sick feeling after meal), 8 (satiety during meal) in FSSG were factors to be PPI non-responders in NERD. Significant improvement in TS were observed (pretreatment: 17.4 +/- 7.7 vs. 2 weeks 14.6 +/- 6.0 vs. 6 weeks 7.7 +/- 5.2, p<0.0001) after the addition of prokinetics in PPI non-response NERD. Younger age, constipation, dysmotility were factors of PPI non-response in NERD. As high DS is correlated with PPI non-response, it is indicated that patients with strong dysmotility and functional dyspepsia complication might be PPI resistant. The efficacy of additional prokinetics for PPI non-response NERD was observed.

Technical problems produced by the Bravo pH test in nonerosive reflux disease patients

To evaluate the technical failures of the Bravo pH test in a population with nonerosive gastroesophageal reflux disease. Over the course of a year, we prospectively studied a population of 66 nonerosive reflux disease patients who received a Bravo pH test. The number and frequency of all technical failures were documented, quantified and analyzed. A total of 66 patients, with a mean age of 41.7 years, were studied. Technical failures occurred in 15.15% of the sample. The most frequent failures were due to poor data reception (4.5%), early dislodgement (4.5%) and capsule removal (6.1%). The Bravo capsule pH test involves a low but non-negligible rate of technical problems, a fact that must always be considered by physicians.

The prokinetic effect of mosapride citrate combined with omeprazole therapy improves clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying

Previous studies have shown that non-erosive reflux disease (NERD) patients are less sensitive to proton pump inhibitor (PPI) treatment than patients with erosive reflux disease. The aim of this study was to investigate whether treatment with prokinetics in addition to omeprazole therapy would improve clinical symptoms, gastric emptying and esophageal peristalsis in PPI-resistant NERD patients with or without delayed gastric emptying. Subjects were 64 consecutive patients presenting with typical symptoms of PPl-resistant NERD (n = 44) and 20 healthy volunteers. PPI-resistant NERD patients underwent mosapride citrate (15 mg/day) and omeprazole (20 mg/day) co-therapy for 12 weeks. We evaluated the clinical symptoms as well as gastric emptying and esophageal manometry before and after combined therapy. We measured both acylated- and des-acylated plasma ghrelin levels by the ELISA method. The primary endopoint was to investigate whether co-administration of mosapride citrate and omeprazole would improve clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying. T (max) value in PPI-resistant NERD patients was significantly higher than in healthy volunteers. Combination therapy with the prokinetic agent mosapride citrate and omeprazole significantly improved reflux symptoms and T (max) value in T (max) > 65 min NERD patients. Co-therapy also significantly reduced des-acylated-ghrelin levels in NERD patients with delayed gastric emptying. Administration of mosapride citrate in addition to omeprazole improved gastro-esophageal reflux and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying.

Characteristics of Reflux Episodes and Symptom Association in Patients With Erosive Esophagitis and Nonerosive Reflux Disease: Study Using Combined Impedance–pH Off Therapy

We sought to compare reflux and symptom association patterns in patients with nonerosive reflux disease (NERD), erosive esophagitis (EE), and in healthy volunteers (HVs). Patients with EE and NERD underwent combined impedance-pH monitoring. Normal values were defined on the basis of previously collected data from 48 HVs. We evaluated distal esophageal acid exposure time (AET), number and type of reflux episodes (acid, nonacid), acid and bolus clearance times, proximal extension of reflux episodes, and symptom association probability (SAP). Distal AET (percentage time, pH<4) was higher (P<0.01) in 58 EE patients (median 7.4%, 25-75th percentile 4.2-9.9%) compared with 168 NERD patients (4.2% (1.2-6.4%)) and 48 HVs (0.7% (0.2-1.4%)). Patients with EE and NERD had a higher (P<0.01) number of acid reflux episodes compared with HVs (51 (37-66) vs. 34 (22-51) vs. 17 (8-31); P<0.05), but a similar number of nonacid reflux episodes (22 (15-39) vs. 23 (15-38) vs. 18 (14-26); P=NS). The percentage of reflux episodes reaching the proximal esophagus was higher (P<0.01) in EE patients (57% (45-73%)) than in NERD patients (45% (36-60%)) and HVs (33% (19-46%)). A positive SAP for heartburn or regurgitation was found in 161 of 168 (96%) NERD and 54 of 58 (93%) EE patients (P=NS). Acid reflux episodes, volume, and acid clearance are important factors in the pathogenesis of reflux-induced lesions. Nonacid reflux contributes less to esophageal mucosa damage, but is involved in the development of reflux symptoms in both NERD and EE patients.

Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus

BackgroundOesophageal mucosa dilated intercellular spaces (DIS) may be important for symptom perception in non-erosive reflux disease (NERD). Patients with NERD might have DIS even in the proximal oesophagus. We aimed...

Disease Progression in Non-Erosive Reflux Disease (NERD): A Follow-up Report in an Asian Population

Purpose: We investigated the 5-year clinical course in a cohort of patients with typical reflux symptoms and negative endoscopy. We also investigated whether baseline pathological esophageal acid exposure would influence the outcome of the clinical course. Methods: All patients had a 24-H pH evaluation at baseline. Prospective follow-up was conducted in this group of patients with non-erosive reflux disease (NERD) for at least 5 years after initial evaluation with esophageal pH monitoring and upper gastrointestinal endoscopy. Patients were asked to complete a symptomatic questionnaire. Results: Within the last year of follow-up, reflux symptoms occurred in twenty-seven of the thirty patients (90%) whenever active therapy was discontinued. Twenty-five of twenty-seven symptomatic patients (93%) were on acid suppression therapy. The majority of our patients (70%) remained unchanged in endoscopic status over 5 years. The progression to erosive esophagitis occurred in 4 patients with LA A (13%), 3 patients with LA B (10%), and 2 patients with LA C (7%). The presence of initial pathological acid exposure did not alter the presence of reflux symptoms or the use of acid suppression therapy over 5 years. Disease progression to erosive esophagitis occurred more frequently in patients with pathological acid exposure than those without pathological acid exposure (P=0.025). Conclusion: Most NERD patients still have symptoms and require acid suppression therapy 5 years after their initial diagnosis. Initial pathological acid exposure does not influence the use of acid suppression or symptom presentation; however, it does influence the progression of NERD within 5 years of follow-up.

Building a better mousetrap? Impedance measurement in gastroesophageal reflux disease

Building a better mousetrap? Impedance measurement in gastroesophageal reflux disease

Quality of Life in GERD and Barrett's Esophagus Is Related to Gender and Manifestation of Disease

Gastroesophageal reflux disease (GERD) is a common condition that affects patients' health-related quality of life (HRQoL). The HRQoL of Barrett's esophagus (BE) has been less well studied. Furthermore, it is unknown to what extent BE patients suffer from psychological distress as a result of carrying a diagnosis of a premalignant condition. We sought to compare BE and GERD (stratified by erosive reflux disease (ERD) and non-erosive reflux disease (NERD)) with regard to HRQoL and psychological impact. In this single-center study of subjects presenting for elective upper endoscopy, consecutive patients with BE and GERD were enrolled. Participants completed questionnaires assessing generic HRQoL (medical outcomes study short form-36 (SF-36)), disease-specific HRQoL (gastrointestinal quality of life index (GIQLI)), a measure of psychological distress (the Revised Hopkins Symptom Checklist: SCL-90R), and a patient-centered assessment of the impact of disease severity (the GERD health-related quality of life measure (GERD HRQL)). Patients with BE had the lowest symptom severity compared with those suffering from NERD or ERD (GERD HRQL: 13.7 vs. 18 and 15.9, respectively, P<0.01). Those with BE also had better disease-specific quality of life compared with NERD or ERD patients (GIQLI: 137.2 vs. 124.3 and 131.0, respectively, P<0.001). After adjusting for potential confounding variables including symptom severity and gender, BE patients continued to demonstrate better disease-specific HRQoL, scoring 12.2 points higher on the GIQLI than NERD patients (95% confidence interval (CI) 5.1-19.3) and 16.3 points higher than ERD patients (95% CI 5.4-27.3), as well as better generic HRQoL, scoring 4.8 points higher on the SF-36 physical component summary than NERD patients (95% CI 0.8-8.8) and 7.1 points higher than ERD patients (95% CI 1.2-13.1). There were no significant differences between groups in psychological distress, as demonstrated by the SCL-90R global severity index, although BE patients scored lower on the somatization domain compared with NERD and ERD patients. When stratified by gender, females with NERD and BE had worse disease-specific HRQoL than males. Patients with BE have better generic and disease-specific HRQoL when compared with patients suffering from NERD and ERD. This difference is only partially attributable to lower symptom severity amongs BE patients. Psychological distress did not differ significantly amongs groups. Female gender was associated with worsened HRQoL regardless of GERD disease manifestation. Though more precise instruments may aid in detecting any HRQoL decrements in BE patients because of perceived cancer risk or fear of developing or dying from cancer, we were unable to demonstrate an additional decrement in HRQoL because of cancer risk in subjects with BE.

Long-term impact on quality of life in patients with gastroesophageal reflux disease after 52-week rabeprazole treatment

To investigate the longitudinal changes in quality of life (QoL) for gastroesophageal reflux disease (GERD) treated with 52-week rabeprazole over a period of 2-3 years. A multi-center, open-label and randomized 52-week rabeprazole trial was conducted in 67 eosinophilic esophagitis (EE) and 31 non-erosive reflux disease (NERD) patients. The follow-up period is 2-3 years after the treatment. Their QoL were evaluated using SF-36 Health Survey Questionnaire and GERD-HRQL scale. The results were compared with those acquired before and after a 52-week proton pump inhibitor (PPI) treatment. (1) Both EE and NERD patients improved significantly according to GERD-HRQL scale in scores of reflux symptoms as well as overall satisfaction (12.5 vs 3.5, 20.0 vs 14.0, both P < 0.01) versus the pre-therapy baseline. (2) Both EE and NERD patients had no significant difference in the scale of GERD-HRQL (2.0 vs 3.5, 5.0 vs 4.0, both P > 0.05) and most major domains of SF-36 questionnaire versus the post-therapy baseline (53 +/- 17 vs 61 +/- 17, t = -2.143, P = 0.035). (3) The NERD patients had a higher score of reflux symptoms than the EE patients according to the GERD-HRQL Scale (14.0 vs 3.5, Z = 2.377, P = 0.017), however there were no significant differences between NERD and EE in 8 major domains of SF-36 questionnaire (P > 0.05). Long-term and low-dose PPI treatment achieves improvement both in reflux symptoms and QoL in GERD patients and such effects last a long time. At follow-ups, the reflux symptoms of NERD patients are more severe than EE patients. However, the overall QoL has shown little differences between these two subtypes.

Impact of Measurement of Esophageal Acid Exposure Close to the Gastroesophageal Junction on Diagnostic Accuracy and Event-Symptom Correlation

Ambulatory esophageal pH monitoring has limited diagnostic accuracy in patients with gastroesophageal reflux disease (GERD), especially in those with non-erosive reflux disease (NERD). In addition, there is lack of symptom-reflux association in the majority of GERD patients. The aim of this study was to evaluate the impact of measuring acid exposure 1 cm above the gastroesophageal junction (GEJ) on diagnostic accuracy and symptom correlation in GERD patients compared with conventional pH measurements (6 cm above the GEJ) using the wireless pH system. GERD patients and controls as defined by two validated questionnaires (Gastroesophageal Reflux Questionnaire and Reflux Disease Questionnaire) were prospectively enrolled. Under direct endoscopic vision, two wireless pH capsules (BRAVO, Given Imaging, Yokneam, Israel) were placed 6 and 1 cm, respectively, above the GEJ. Receiver operator characteristic curves were constructed, and symptom indexes were calculated separately for pH measurements at 6-cm (proximal) and 1-cm (distal) locations. A total of 40 GERD patients (20 erosive esophagitis (EE) and 20 NERD) and 16 controls were analyzed. Sensitivity and specificity of abnormal acid exposure times in GERD were as follows: proximal: 67 and 66%, distal: 60 and 88%; in EE proximal: 75 and 81%, distal: 84 and 92%; and in NERD proximal: 61 and 67%, distal: 58 and 66%, respectively. The proportion of patients with a positive symptom-reflux correlation in GERD was as follows: symptom index (SI): proximal: 35%, distal: 50%; symptom sensitivity index (SSI): proximal: 25%, distal: 5%; and symptom-associated probability (SAP): proximal: 30% and distal: 35%. The higher proportion of patients with a positive SI distally was due to the EE group (EE, proximal: 35% and distal: 65%; NERD, proximal: 35% and distal: 35%). Compared with the traditional location, measurement of acid reflux 1 cm above the GEJ improved the diagnostic accuracy as well as symptom correlation in EE, but not in NERD patients. Thus, pH monitoring 1 cm above the GEJ for improving the diagnosis of NERD cannot be recommended in clinical practice at this time.

Comparison of the Different Characteristics of Sensed Reflux Events Among Different Heartburn Groups

Presently, there are no studies comparing sensed acid reflux event (SARE) characteristics among different heartburn groups. Our aim was to compare the different esophageal acid reflux characteristics of an SARE among the different heartburn groups. Patients with heartburn underwent endoscopy and pH testing and were stratified into 3 groups: erosive esophagitis (EE), nonerosive reflux disease (NERD), and functional heartburn (FH). Patients underwent esophageal pH testing using a 4-sensor pH probe, with the most distal pH sensor positioned 1 cm> lower esophageal sphincter (LES). Twenty-two patients had EE, 15 NERD, and 13 FH (M/F: 20/2, 12/3, 5/8, mean age: 51.5+/-3.7, 50.1+/-4.2, 50.3+/-3.8, respectively). The percentage of SAREs at 1 cm>LES that had reached 16 cm>LES was significantly higher in the FH group compared with NERD and EE (P<0.05). EE demonstrated the lowest nadir during an SARE and NERD the most acid reflux events before an SARE (up to 4 h). Patients with FH demonstrated the most SAREs that reached the proximal esophagus. EE patients demonstrated the lowest nadir pH during an SARE and NERD patients the most acid reflux events before an SARE, as compared with the other heartburn groups.

Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non‐erosive reflux disease

There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea. To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients. A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up. BMI > or = 25 (OR 3.0, 95% CI 1.1-8.3), alcohol use (OR 2.9, 95% CI 1.0-8.3), hiatal hernia (OR 5.0, 95% CI 1.2-20) and triglyceride > or =150 mg/dL (OR 4.0, 95% CI 1.7-10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group (P < 0.001). The PPI response rates at 8 weeks were different (P = 0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate. These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.

Reflux profile of Chinese gastroesophageal reflux disease patients with combined multichannel intraluminal impedance‐pH monitoring

To investigate the reflux profile of Chinese gastroesophageal reflux disease (GERD) patients with the aid of combined multichannel intraluminal impedance-pH (MII-pH) monitoring technique. Consecutive patients presented with GERD symptoms were enrolled to erosive esophagitis (EE) group, non-erosive reflux disease (NERD) group and functional heartburn (FH) group after upper endoscopy, combined MII-pH monitoring and rabeprazole test. Another 20 healthy controls (HC) were recruited. Sixty-four GERD patients (EE:20, NERD:22, FH:22, HC:20) were enrolled. There were more episodes of liquid reflux and proximal reflux in EE and NERD groups than that in FH and HC groups (P < 0.05). Patients in FH and HC groups had higher proportion of mixed reflux (P = 0.000). The percentage of acid reflux in EE and NERD was much higher, while there was a higher percentage of weakly acidic reflux in FH and HC (P = 0.000). No significant difference was found in MII-pH parameters between groups with and without response to rabeprazole test except recumbent percentage time of esophageal pH value below 4 and episodes of proximal reflux. Erosive esophagitis and NERD patients had more liquid and proximal reflux episodes than FH patients and healthy controls. Acid and liquid reflux was predominant in the former two groups, while weakly acidic and mixed reflux was predominant in the latter two groups.

Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non‐erosive reflux disease

The proportion of patients who respond to proton pump inhibitor (PPI) therapy is about 20% lower in those with non-erosive reflux disease (NERD) than in those with erosive oesophagitis. To assess efficacy and safety of dexlansoprazole MR, a PPI using Dual Delayed Release technology, in NERD patients. In this 4-week, double-blind, placebo-controlled study, 947 NERD patients randomly received dexlansoprazole MR 30 mg, 60 mg or placebo once daily (QD). The percentages of 24-h heartburn-free days (primary) and nights without heartburn (secondary) were assessed from patients' daily diaries. Investigators also assessed symptoms. Patients completed validated quality of life and symptom severity questionnaires. Dexlansoprazole MR provided significantly greater median percentages of 24-h heartburn-free days (54.9% and 50.0% for the 30- and 60-mg doses vs. 17.5% for placebo, P < 0.00001) and nights without heartburn (80.8% and 76.9% vs. 51.7%, P < 0.00001 vs. placebo). Dexlansoprazole MR also reduced symptom severity. Quality of life improvements in patients receiving dexlansoprazole MR were consistent with clinical efficacy endpoints. Percentages of patients experiencing treatment-emergent adverse events were similar among groups. Dexlansoprazole MR 30 and 60 mg were superior to placebo in providing 24-h heartburn-free days and nights in NERD patients. Treatment was well tolerated.

M1877 Two Functional Categories of Reflux-Inhibiting GABA B Receptor Agonists Defined By Their Affinity for the GABA Transporter

Background: Proton pump inhibitors (PPI) are the drug of first choice for treating patients with gastroesophageal reflux disease (GERD). However, about 50% of non-erosive reflux disease (NERD) patients have a poor response to PPI treatment. It is reported that esophageal motility disorder involving a decline in esophageal clearance contributes to the poor PPI response. Accordingly, a drug capable of enhancing esophageal motility would be beneficial in the treatment of NERD patients. Rikkunshito, a gastrointestinal prokinetic agent, is known to improve esophageal clearance in GERD patients and gastric emptying in functional dyspepsia patients and to increase secretion of ghrelin in rats. Aim: To clarify the efficacy of rikkunshito in NERD patients, we evaluated the effects of rikkunshito on esophageal and lower esophageal sphincter (LES) motility and symptoms. Methods: Fifteen patients were enrolled in the study. They were diagnosed as having NERD according to endoscopic testing and the score (6 points or more) obtained on the questionnaire for the diagnosis of reflux disease (QUEST). All patients stopped taking all gastrointestinal-related drugs for over 1 week prior to rikkunshito treatment, and were administered rikkunshito (7.5 g per day, orally) for 8 weeks. Esophageal and LES functions during liquid or semisolid swallow were evaluated using MII-EM following gold standard methods before and after rikkunshitotreatment. Symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before, 4 weeks after, and 8 weeks after treatment. Results: Rikkunshito-treatment significantly improved the mean of complete bolus transit (CBT) during liquid or semisolid swallow from 60.7±7.7% to 90.0±5.8% (p 79%, semisolid: >69%) for CBT decreased from 53.3% to 16.7% and from 60.0% to 33.3% after treatment, respectively. In manometry evaluation, rikkunshito significantly improved the mean of LES residual pressure during liquid swallow from 6.0±1.3 mmHg to 3.8±1.4 mmHg (p<0.05). In addition, rikkunshito significantly ameliorated total GI symptom scores in GSRS (from 2.1±0.2 to 1.6±0.1: (p<0.05)) and showed a tendency toward improvement of subscales for reflux symptoms, abdominal pain and dyspeptic symptoms. Conclusion: We found that rikkunshito improved the esophageal clearance and symptoms in NERD patients through the amelioration of esophageal and LES motility disorder. Thus, rikkunshito may become a useful drug for treating NERD patients.