Non-erosive Gastroesophageal Reflux Disease Patients Research Articles

Herbal Medicine Hewei Jiangni Decoction Is Noninferior to Oral Omeprazole for the Treatment of Nonerosive Gastroesophageal Reflux Disease: A Randomized, Double-Blind, and Double-Dummy Controlled Trail.

Objectives Conventional approaches for patients with nonerosive gastroesophageal reflux disease (NERD) were not satisfactory. This study aimed to evaluate the effectiveness and mechanisms of Chinese herbal medicine Hewei Jiangni Decoction (HWJND) as a novel and promising regimen for NERD. Methods A total of 128 patients with NERD were randomly assigned to the Treatment group and Control group. The patients from the Treatment group were administered HWJND (81 g) plus dummy omeprazole (20 mg) daily for 8 weeks, and the others were given dummy HWJND granules (81 g) plus omeprazole (20 mg). The clinical efficacy was assessed using the gastroesophageal reflux disease questionnaire (GERD-Q) scale, patient reported outcomes (PRO) scale, and short form health survey 36 (SF-36) scale at week 4. Moreover, its pharmacological and molecular mechanisms were elucidated based on network pharmacology and molecular docking. Results Due to case shedding and other reasons, 109 patients, including 56 in the Treatment group and 53 in the Control group completed this study. Our results showed that HWJND significantly improved heartburn, regurgitation, epigastric pain, nausea, and sleep disturbance, which led to a significant reduction of GERD-Q scores in NERD patients. In addition, PRO scores of NERD patients with HWJND administration were improved, and sufficient relief of physical role, body pain, general health, social function, and mental health on the SF-36 scale was also observed in patients after HWJND treatment. We further showed that the curative effect of HWJND was close to that of omeprazole, except for the better improvement of general health and social function. What's more, the main active ingredients of HWJND included quercetin, beta-sitosterol, naringenin, baicalein, and kaempferol were retrieved, and the protective effects of HWJND against NERD may be closely related to targets such as TNF, IL6, IL1B, MMP9, CXCL8, and EGFR, which were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. Conclusion Our findings demonstrate that HWJND is noninferior to oral omeprazole for the treatment of patients with NERD, plays a therapeutic role through multiple targets and diverse pathways, and holds promise for complementary and alternative therapy for the treatment of NERD. This trial is registered with http://www.chictr.org.cn, Chinese Clinical Trials Registry [ChiCTR2200055960].

Efficacy of Rikkunshito for Functional Heartburn: A Prospective Pilot Study.

Although rikkunshito was reported to be effective for treatment-resistant nonerosive gastroesophageal reflux disease (NERD), it is unclear which Rome IV subgroups of NERD patients benefit fromrikkunshito. This study investigated the efficacy of rikkunshito in patients with functional heartburn. Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled and received rikkunshito for 8 weeks. The Frequency Scale for Symptoms of GERD (FSSG), the Japanese translation of the Quality of Life in Reflux and Dyspepsia (QOLRAD-J) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) before, and 4 and 8 weeks after, administration were evaluated. Overall treatment efficacy (OTE) was evaluated at 8 weeks after administration. One patient voluntarily withdrew from treatment at 4 weeks. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score was higher 8 weeks after treatment or at discontinuation than before treatment, the difference was not significant different. HADS score was not significantly lower 8 weeks after treatment or at discontinuation, as compared with before treatment. However, total FSSG and HADS anxiety scores were positively correlated (correlation coefficient: 0.684, P = 0.027). The findings from this first study of the efficacy of rikkunshito for functional heartburn suggest that it might be effective in such patients.

Acute Effects of Red Chili, a Natural Capsaicin Receptor Agonist, on Gastric Accommodation and Upper Gastrointestinal Symptoms in Healthy Volunteers and Gastroesophageal Reflux Disease Patients.

The effects of chili on gastric accommodation (GA) in gastroesophageal reflux disease (GERD) patients have not been explored. Methods: In total, 15 healthy volunteers (HV) and 15 pH-positive non-erosive GERD (NERD) patients underwent single-photon emission computed tomography after ingesting 2 g of chili or placebo in capsules in a randomized double-blind crossover fashion with a one-week washout period. GA was the maximal postprandial gastric volume (GV) after 250 mL of Ensure® minus the fasting GV. Upper gastrointestinal symptoms were evaluated by using a visual analog scale. Results: NERD patients but not HV had significantly greater GA after chili compared to a placebo (451 ± 89 vs. 375 ± 81 mL, p < 0.05). After chili, the postprandial GVs at 10, 20, and 30 min in NERD patients were significantly greater than HV (10 min, 600 ± 73 vs. 526 ± 70 mL; 20 min, 576 ± 81 vs. 492 ± 78 mL; 30 min, 532 ± 81 vs. 466 ± 86 mL, all p < 0.05). In NERD, chili was associated with significantly less satiety, more severe abdominal burning (p < 0.05), and a trend of more severe heartburn (p = 0.06) compared to the placebo. In HV, postprandial symptoms after chili and placebo ingestion were similar (p > 0.05). Conclusions: Chili enhanced GA in NERD patients but not in HV. This suggests that the modulation of GA in NERD is abnormal and likely involves transient receptor potential vanilloid 1 (TRPV1) sensitive pathways.

The Effect of Diet Composition Change on High-Resolution Oesophageal Manometry Metrics in Non-Erosive Gastroesophageal Reflux Disease Patients

Abstract Objectives To evaluate the influence of change of diet composition on esophageal manometry metrics. Methods The data of 43 NERD patients with low (&amp;lt;20 g/day) baseline dietary fiber intake served as a source data. These patients were examined with the use of standard food frequency questionnaire and high-resolution esophageal manometry. Thirty of them received psyllium 5.0 g TID 10 days in addition of their usual diet within registered clinical trial (NCT01882088). The other 13 were found in the database by diagnosis; their data were eligible in case of the presence of repeated high-resolution esophageal manometry examination and dietary assessments at the same time point and if no significant change in diet composition was revealed. The changes were assessed in accordance to Chicago classification 3.0. Non-parametric statistics (Wilcoxon matched pairs test, Mann-Whitney U-test) were used to assess the change in HRM metrics in these groups. Results In those who received psyllium, significant increase of minimal lower esophageal resting pressure at rest and after 10 water swallows was registered: 5.41 ± 10.1 vs 11.3 ± 9.4 mm Hg, P = 0.023 and 14.1 ± 8.0 vs 14.9 ± 6.4 mm Hg, P = 0.008, accordingly. No significant difference was found in the group with no change of diet composition by these parameters. At baseline, ineffective esophageal motility was found in 46.7% patients of the study group and 53.8% in the control group (P = 0.7). Esophageal motility became normal in 71.4% of those who had IEM initially in the study group after 10 days of treatment, and in 14.3% among the controls (P = 0.0135). This type of peristaltic abnormality was found not changed in 28.6% of the study group and in 85.7% among the control group, P = 0.014. New cases of ineffective esophageal motility revealed in 12.5% of the study group and 16.7% among the controls (P = 0.8) Conclusions Change of diet composition by additional quantity of psyllium may result in the improvement of esophageal motility. Funding Sources Federal Research Center of Nutrition and Biotechnology.

Characteristics of different phenotypes of refractory non-erosive gastroesophageal reflux disease

Objective: To investigate the characteristics of different phenotypes of refractory non-erosive gastroesophageal reflux disease (NERD), the types of esophageal motility and the related factors of symptoms. Methods: A retrospective analysis was made of the patients with refractory NERD of Beijing Tongren Hospital affiliated to Capital Medical University from September 2015 to August 2017. All patients underwent electronic gastroscopy, esophageal manometry and 24-hour dynamic esophageal pH impedance monitoring. They were divided into four phenotype groups according to the results. Results: A total of 231 patients were enrolled in the study. There were 111(48.1%)cases in phenotype 1 group, 9 (3.9%)cases in phenotype 2 group, 100 (43.3%)cases in phenotype 3 group and 11 (4.8%) cases in phenotype 4 group. Compared with the other three groups, the number of weak acid reflux [(86±55) vs (37±8), (70±52), (31±9) times] and the number of gas reflux [(86±76) vs (38±13), (58±57), (26±10)] in phenotype 1 group increased significantly (allP<0.005). Dynamics disorders were common in refractory NERD patients (139/231, 60.2%). Mild esophageal dynamics disorder was the main type of dynamics disorder (118/139, 84.9%). There was no significant difference among the phenotype groups. Multivariate unconditional Logistic regression analysis showed that the risk factors for reflux-related symptoms were female ratio, Chicago power classification, gas reflux and weak acid reflux (OR=3.731, 2.452, 1.036 and 1.037, P<0.05). Conclusions: The characteristics of gastroesophageal reflux and the types of motility disorders are different in different phenotype groups of refractory NERD patients. The risk factors of reflux-related symptoms are female ratio, Chicago motility classification, gas reflux and the frequency of weak acid reflux.

RA06.07: PSYLLIUM SUPPLEMENTATION EFFECT ON ESOPHAGEAL FUNCTION TESTING AND SYMPTOMS IN PATIENTS WITH NON-EROSIVE GERD

Abstract Background Epidemiological data showed negative correlation between heartburn frequency and amount of dietary fiber consumed. However no interventional study was performed to prove clinically beneficial effect of dietary fibers in gastroesophageal reflux disease (GERD) patients. The aim of the study was to investigate the effect of dietary fiber on symptoms and esophageal function testing parameters in non-erosive GERD patients (NCT01882088) Methods Thirty six NERD patients were examined using food frequency questionnaire and in case of less than 20 g/day dietary fibre intake underwent high-resolution esophageal manometry and 24-hours esophageal pH-impedance. Language-specific GERD-Q questionnaire was used to assess symptoms. Repeated examinations were performed after 10 days of usual diet supplemented by psyllium 15.0 gram a day. Complete data of 30 NERD patients were available for the final analysis. Study design is shown in a figure 1. Wilcoxon matched pairs test was used to assess changes in the studied parameters Results The decrease in proportion of patients experiencing heartburn as well as GERD-Q score decrease were found. Minimal resting lower esophageal sphincter pressure increased from 5.41 ± 10.1 to 11.3 ± 9.4, P = 0.023. No change in residual LES pressure and mean resting pressure was found. Total number of gastroesophageal refluxes decreased from 67.9 ± 17.7 to 42.4 ± 13.5, P &lt; 0.001 (Table 1). Conclusion Supplementation of diet with psyllium 5.0 gram TID in NERD patients led to significant increase of minimal esophageal resting pressure, decrease of number of gastroesophageal refluxes and frequency of heartburn per week. The work was supported by Federal Agency of Scientific Organizations of Russia (0529–2017-0057) Disclosure All authors have declared no conflicts of interest.

521 Differences in Resting State Connectivity of the Homeostatic Interoceptive Network in Erosive as Well as Non-Erosive GERD Patients and Healthy Controls

521 Differences in Resting State Connectivity of the Homeostatic Interoceptive Network in Erosive as Well as Non-Erosive GERD Patients and Healthy Controls

Treatment Option for Patients with Non-Erosive Gastroesophageal Reflux Disease Refractory to a Standard Proton Pump Inhibitor

Background: Non-erosive gastroesophageal reflux disease (NERD) resists treatment with standard proton pump inhibitor (PPI) doses in about 50% of patients. However, physicians do not have clear choices available for selecting alternative treatments for the refractory patients. Therefore, we investigated the effectiveness of double-dose PPI or a 5-hydroxytryptamine receptor antagonist (5HTRA) given with the standard PPI dose. Methods: We treated 10 NERD patients resistant to 10mg rabeprazole (RPZ) [RPZ(10)] with 20mg od RPZ [RPZ(20)] or 10mg od RPZ plus 5mg tid mosapride (RPZ-MOS) for 14-days in a cross-over manner. All patients' pHs were monitored for 24h and they were given a ＂Frequency Scale for the Symptoms of GERD＂ (FSSG) questionnaire to document their NERD symptoms, both on day 14. Results: The median FSSG score was significantly lowered by RPZ-MOS [7.0 (4-16), p＜0.01] and RPZ (20) [10.5 (1-28), p＜0.01] regimens compared with that for RPZ (10) [13.5 (10-31)]. However, FSSG scores were not significantly different between both regimens. The FSSG score was significantly associated with intragastric pH (p=0.02). The RPZMOS regimen's FSSG score was significantly correlated with RPZ (20) treatment (p=0.02). The FSSG scores of RPZ (10) in patients responsive to both regimens improved ≧30% compared with control scores. Conclusions: NERD patients whose FSSG score failed to decrease ≧30% after RPZ 10mg od treatment would be refractory to additional PPI or 5HTRA doses. FSSG scores after RPZ 10mg od treatment may provide a guideline for optimally treating NERD patients with a PPI.

Tu1105 Gastric Acid Output Suppression in Response to Proton Pump Inhibitor Therapy in Symptomatic Versus Asymptomatic GERD Patients: Results of a Prospective Study Measuring Control and Meal-Stimulated Gastric Acid Secretion

Background: Gastro-esophageal reflux disease (GERD) is a common acid-related disorder affecting 10-20% of people. GERD is often under-investigated and over-treated, especially in refractory cases. Symptoms are used to guide management despite data showing many acid reflux events are asymptomatic, and many symptomatic events are unrelated to acid reflux. Proton pump inhibitors (PPIs) effectively treat GERD, but are often over-prescribed as non-invasive, accurate methods to measure gastric acid output (GAO) and guide PPI therapy are lacking. Such data might enhance management of patients who remain symptomatic despite appropriate PPI therapy. Recently, a new method for measuring meal-stimulated GAO using a wireless pH-sensing capsule, SmartPill (SP), was validated (Weinstein et al. Aliment Pharmacol Ther 2013). Aim: To evaluate the control and stimulated GAO of GERD patients who are symptomatic (SX) vs. asymptomatic (ASX) on PPI therapy, using traditional aspiration methods and SP, respectively. Methods: A prospective, single center study of symptoms and GAO response to PPI therapy was conducted in non-erosive GERD patients with typical GERD symptoms. GERD symptoms, duration (months) and PPI use were historically recorded. Fasting serum gastrin (pg/mL) was determined. Patients withGI surgery, motility disorders, or H. pylori infection were excluded. Control acid output (CAO; mEq/ hr) was determined by titration of gastric secretions collected by nasogastric tube or EGD just prior to the next PPI dose. Fasting patients ingested a SP, followed by Ensure Plus (240 ml) (EP) diluted to either 1⁄2 or 1⁄4 strength. Meal stimulated acid output, (SP GAO (mEq/ hr)) was calculated from the time to acidify the EP meal from pH 5 to 2. Gastric emptying time (GET; minutes) was measured by SP. Results: Twenty four patients taking PPIs were enrolled; 16 had SX GERD. Mean age was similar for SX vs ASX (44.6 vs 46.1, p=0.75). SX and ASX groups did not differ in mean values for GERD duration (71.4 vs 111.4, p= 0.40), fasting gastrin (149.9 vs 157.8, p=0.90), or GET (135.3 vs 118.8, p=0.63). A nonsignificant trend toward a higher mean PPI dose was seen in SX patients (1.31 vs 1.25 X the standard dose of PPI, p=0.86). Mean CAO (2.31 vs 1.16, p=0.40) and SP GAO (28.2 vs 44.6, p=0.2) were similar in SX and ASX GERD patients. Compared to normal untreated volunteers, SP GAO was significantly lower in both SX (53 vs 28.3, p=0.0004) and ASX (53 vs 30, p=0.0095) groups. Conclusions: SX and ASX GERD patients on PPI therapy have similar CAO and SP GAO, which are significantly lower than untreated volunteers. This suggests less acid suppression is required to relieve symptoms in a subset of GERD patients, who may be less sensitive to acid reflux. Therefore, higher PPI doses may be needed to further suppress acid and relieve symptoms in unresponsive patients.

Recurrence of gastroesophageal reflux disease correlated with a short dinner‐to‐bedtime interval

Gastroesophageal reflux disease (GERD) can be classified into erosive reflux disease (ERD) and nonerosive gastroesophageal reflux disease (NERD). We aimed to compare the recurrence rates of ERD and NERD and determine the risk factors related to the recurrence. This prospective study comprised 337 consecutive adults who completed questionnaires on their GERD symptoms, height, weight, sleeping position, dinner time, and bedtime. During upper gastrointestinal endoscopy, the presence of a hiatal hernia and mucosal breaks in the low esophagus, esophageal length (the distance between the Z-line and the incisors), and the esophageal length-to-height ratio were recorded. Recurrence was diagnosed when the patient required additional proton pump inhibitor medication after initial recovery with 4-8 weeks of treatment. Recurrence was experienced by 47 (26.0%) of 181 GERD patients. The recurrence rate did not differ between the 48 ERD (27.1%) and 133 NERD (25.6%) patients (P = 0.849). Of the various factors studied, recurrence was found to be correlated with a dinner-to-bedtime interval of less than 3 h (P = 0.002), globus sensation (P = 0.031), and old age (P = 0.047). Logistic regression analysis revealed that a short interval between dinner and bedtime was the only factor significantly related to the recurrence (P = 0.002). Both ERD and NERD patients who sleep within 3 h after eating have a higher risk of GERD recurrence. Our findings highlight the impact of a short dinner-to-bedtime interval on the recurrence of GERD (ClinicalTrials.gov ID: KCT0000134).

Issue Highlights

Issue Highlights

964 A Novel Device Measuring Esophageal Mucosal Consequences of Chronic GERD

INTRODUCTION: Gastroesophageal reflux disease (GERD) afflicts more than 100 million US adults, significantly impacts quality of life and imposes >$9 billion/yr in total cost upon our healthcare system. Current GERD diagnostics are suboptimal due to limited sensitivity and specificity, and they are constrained by measurement of esophageal reflux during a single time point at a specified location. They measure presence of reflux but do not measure the long-term mucosal consequences of GERD, a significant limitation of existing platforms. Thus, the aim of our study was to develop and test a novel, minimally invasive technology to assess esophageal mucosal conductivity changes as a result of chronic mucosal exposure to gastroduodenal reflux. METHODS: A single channel mucosal impedance(MI) measuring rings separated by 0.4mm with a 360 degree circumferential design were mounted on a catheter, which could be easily traversed through the working channel of an upper endoscope. 53 patients along the spectrum of GERD were enrolled: Barrett's esophagus (BE) (n=12); Erosive Esophagitis (E+) (n=16); pH+/Non-erosive GERD (pH+) (n=11) and pH-/non-erosive subjects (pH-) (n=14). All pts underwent endoscopy and wireless 48-hour pH monitoring 10-days off PPI tx. During index endoscopy, MI were measured from the site of injury (Barrett's epithelium or esophagitis) as well as 2-, 5and 10-cm above squamocolumnar junction (SCJ). In those without mucosal injury, measurements were taken from 2-, 5and 10-cm above the SCJ. MI measurements (ohms) were obtained continuously for 5 seconds at each location by direct application of the impedance rings to the mucosal surface and the mean of the 5-second measurements for each location was used for analysis. RESULTS: Median (IQ) mucosal measurements were significantly (p=0.001) lower at the site of Barrett's [765 (512-953)] and erosive esophageal mucosa [1147 (530-1307)] than non-erosive regions at the same level [3654 (2315-6146)]. There was a significant (p=0.004) and graded increase in median (IQ) MI axially along the esophagus from distal (2 cm above the SCJ) to proximal (10 cm above the SCJ) (Figure 1). Importantly, there was a graded increase in MI axially along the esophagus in pts with BE, E+ and pH+, which was not present in subjects with visually normal esophageal mucosa and normal acid exposure (E-) (non-GERD) (Figure2). CONCLUSIONS: 1) Esophageal mucosal erosion due to GERD, on average has 81% lower MI than normal tissue. 2) Non-erosive GERD patients show similar pattern of MI along the axial distribution of esophagus as those with erosive disease. 3) This pattern does not exist in those without GERD. 4) These encouraging data show feasibility of the MI concept in providing an alternative and innovative method for detecting chronic consequence of GERD on esophageal mucosal.

The Therapeutic and Diagnostic Value of 2-week High Dose Proton Pump Inhibitor Treatment in Overlapping Non-erosive Gastroesophageal Reflux Disease and Functional Dyspepsia Patients

Background/AimsTo evaluate the value of a 2-week high dose proton pump inhibitor (PPI) treatment on patients with overlapping non-erosive gastroesophageal reflux disease (NERD) and functional dyspepsia (FD).MethodsSixty overlapping NERD and FD patients with symptom onset > 3 months prior underwent 24-hour esophageal pH monitoring studies. All patients received rabeprazole 20 mg b.i.d. for 2 weeks. The reflux and dyspeptic symptoms were evaluated using a symptom questionnaire with 4-point Likert scales before and at the end of treatment. A positive PPI test was defined as score improvement in ≥ 50% from the baseline in the typical reflux symptoms.ResultsThe prevalence of each reflux and dyspeptic symptom did not differ significantly between patients with positive and negative pH tests. After the PPI treatment, epigastric burning, acid regurgitation, heartburn, nausea, vomiting and chest discomfort scores were significantly improved compared to pretreatment values (P < 0.05), whereas postprandial abdominal fullness, early satiation, belching and food regurgitation were not. The proportion of patients who responded to the PPI treatment did not differ significantly between patients with positive and negative pH tests. The sensitivity, specificity, PPV, NPV and accuracy of 2-week high dose rabeprazole treatment for diagnosing gastroesophageal reflux disease were 47%, 38%, 50%, 35% and 43%, respectively.ConclusionsThe two-week high dose PPI treatment was not effective for early satiation, postprandial abdominal fullness, regurgitation or belching symptoms in patients with overlapping NERD and FD. Acid exposure in the distal esophagus could not predict the response of symptoms to PPI. In addition, the 2-week PPI test provided limited value for gastroesophageal reflux disease diagnosis in patients with overlapping NERD and FD.

Halitosis and tongue coating in patients with erosive gastroesophageal reflux disease versus nonerosive gastroesophageal reflux disease

The aim of this study was to investigate whether patients with diagnosed erosive gastroesophageal reflux disease (ERD) have an increased probability of halitosis and tongue coating compared to patients with nonerosive gastroesophageal reflux disease (NERD). Sixty-six patients (33 males and 33 females) were recruited for the study and received an upper gastrointestinal endoscopy. The presence of ERD (n = 31) and NERD (n = 35) was classified based on the Los Angeles classification for erosive changes in the esophagus. Additionally, the patients filled in a questionnaire regarding their subjective assessment of halitosis, and an organoleptic assessment of halitosis, a measurement of oral volatile sulfur compounds (VSC) with the Halimeter, and a tongue coating index were performed. ERD and NERD subjects were compared with regard to Halitosis-related clinical and anamnestic findings. No statistically significant difference could be found between ERD and NERD patients regarding tongue coating index, organoleptic scores, and VSC values as well as self-perceived bad taste, tongue coating, and bad breath. These data suggest that halitosis is not typically associated with erosive gastroesophageal reflux disease and the presence of esophageal mucosal damage (ERD patients). The data of this investigation support the findings of interdisciplinary bad breath clinics that gastroesophageal reflux disease is not a leading cause for halitosis.

Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan

To seek a promising therapeutic regimen for proton pump inhibitor (PPI)-refractory patients with gastroesophageal reflux disease (GERD) after the standard PPI treatment, we compared the efficacies of rikkunshito (a Japanese traditional medication) combined with rabeprazole (RPZ) and a double dose of RPZ in a prospective randomized multicenter trial in Japanese PPI-refractory GERD patients. One hundred and four patients with GERD symptoms remaining after 4-week treatment with RPZ (10 mg/day) were randomly assigned to 4 weeks of either combination therapy [rikkunshito (7.5 g/day) with a standard dose of RPZ (10 mg/day)] or a double dose of RPZ (20 mg/day). The primary endpoint was the improvement rate, calculated based on the frequency scale for the symptoms of GERD (FSSG) before and after treatment. Subgroup analysis was also performed with respect to each subject's background factors such as reflux esophagitis (RE)/non-erosive GERD (NERD), age, gender, and body mass index (BMI). Four-week treatment with rikkunshito combined with RPZ significantly decreased the FSSG score from 17.6 ± 6.5 to 12.0 ± 6.9, similar to the decrease seen on treatment with a double dose of RPZ. Regarding the therapeutic improvement rate, there were also significant effects in both groups. However, in the subgroup analysis based on RE/NERD, the improvement rate of male NERD patients in the rikkunshito group was significantly greater than that of such patients in the other group (P < 0.05). In the rikkunshito group, the treatment was more effective in NERD patients with a low BMI than in those with a high BMI (P < 0.05). Rikkunshito combined with standard-dose RPZ therapy may be a useful new strategy for PPI-refractory GERD patients.

Curry Induces Acid Reflux and Symptoms in Gastroesophageal Reflux Disease

There are limited data on the effect of curry on gastroesophageal reflux disease (GERD). Our objective was to study the effects of curry on GERD. Symptomatic non-erosive gastroesophageal reflux disease (NERD) patients and healthy volunteers underwent ambulatory 24-h esophageal pH monitoring before consumption of either 400 or 800 ml of curry; they were monitored for 3 h thereafter for changes in esophageal pH and upper abdominal symptoms. Selected volunteers were monitored similarly after water ingestion. In total, 25 NERD patients (23 males; mean age, 45 years) and 19 volunteers (13 males; mean age, 22 years) participated. In both patients and volunteers, curry ingestion induced more esophageal acid exposure than did ingestion of a similar volume of water. Curry induced significantly more esophageal acid exposure in NERD patients than in volunteers. Upper abdominal symptoms and esophageal acid exposure were more severe and persisted longer in patients than in volunteers. Curry induced more acid reflux and caused worse symptoms in patients with NERD than in healthy individuals. Patients with NERD should be advised to avoid curry ingestion.

Is it possible to clinically differentiate erosive from nonerosive reflux disease patients? A study using an artificial neural networks-assisted algorithm

The use of either symptom questionnaires or artificial neural networks (ANNs) has proven to improve the accuracy in diagnosing gastroesophageal reflux disease (GERD). However, the differentiation between the erosive and nonerosive reflux disease based upon symptoms at presentation still remains inconclusive. To assess the capability of a combined approach, that is, the use of a novel GERD questionnaire - the QUestionario Italiano Diagnostico (QUID) questionnaire - and of an ANNs-assisted algorithm, to discriminate between nonerosive gastroesophageal reflux disease (NERD) and erosive esophagitis (EE) patients. Five hundred and fifty-seven adult outpatients with typical GERD symptoms and 94 asymptomatic adult patients, were submitted to the QUID questionnaire. GERD patients were then submitted to upper gastrointestinal endoscopy to differentiate them between EE and NERD patients. The QUID score resulted significantly (P<0.001) higher in GERD patients versus controls, but it was not statistically significantly different between EE and NERD patients. ANNs assisted diagnosis had greater specificity, sensitivity and accuracy compared with the linear discriminant analysis only to differentiate GERD patients from controls. However, no single technique was able to satisfactorily discriminate between EE and NERD patients. Our study suggests that the combination between QUID questionnaire and an ANNs-assisted algorithm is useful only to differentiate GERD patients from healthy individuals but fails to further discriminate erosive from nonerosive 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.

Impaired gastric motility and its relationship to reflux symptoms in patients with nonerosive gastroesophageal reflux disease

More than half of patients with refluxrelated symptoms have no endoscopic evidence of mucosal breaks. These patients are considered to have nonerosive gastroesophageal reflux disease (NERD). The pathogenesis of NERD may be multifactorial, but the role played by gastric motility in symptom generation in patients with NERD has not been examined. In this study, we elucidate gastric motility in patients with NERD and the efficacy of a prokinetic agent in the treatment of NERD. Gastric motility was evaluated with electrogastrography (EGG) and by measurement of gastric emptying using the acetaminophen method in 26 patients with NERD and in 11 matched healthy controls. NERD patients were treated with a prokinetic agent (mosapride 15 mg, orally three times daily) for a period of 4 weeks, after which gastric motility was measured again. Compared with the healthy controls, the NERD patients showed a significantly lower percentage of normogastria, a lower power ratio in EGG, and delayed gastric emptying. Ten patients had normal gastric motor function (group A), and 16 showed abnormalities of either gastric myoelectrical activity or gastric emptying (group B). After treatment with mosapride, gastric motility improved significantly in both groups of patients compared with pretreatment values. The subjective assessment by the patient after the treatment was improved in 20.0% of group A versus 62.5% of group B patients (P < 0.05). Gastric hypomotility appears to be an important factor in reflux symptom generation in some NERD patients.

Bowel Symptoms in Nonerosive Gastroesophageal Reflux Disease

Nonerosive gastroesophageal reflux disease (NERD) patients frequently show features of the irritable bowel syndrome (IBS). To investigate the prevalence and intensity of bowel symptoms and their relationship to esophageal acid exposure in NERD patients. Bowel and reflux symptoms and IBS status were assessed in NERD patients (normal upper endoscopy; esophageal pH <4 for >or= 5% of the time on 24-h pH monitoring; n=326), in relation to nonpatient controls. Bowel symptoms were scored on the 3 scales: diarrhea, constipation, and pain/gas symptoms. NERD and age were independently associated with bowel symptoms. NERD patients scored significantly higher than controls on all bowel scales. In a multivariate analysis, the scores on the pain/gas scale were independently associated with NERD. In NERD patients, reflux symptoms independently predicted the bowel symptoms while acid exposure did not. Forty-nine percent of the NERD patients and 18% of the controls met the criteria for IBS [IBS(+)NERD]. IBS(+)NERD patients scored significantly higher than those not meeting IBS criteria [IBS(-)] on all bowel scales. Yet IBS(-) patients scored significantly higher than controls on the scales of constipation and pain/gas. IBS(+)NERD patients scored higher than IBS(-) also on the GERD symptoms scale. (1) NERD patients scored significantly higher than controls on all the bowel scales; (2) Bowel symptoms were associated with reflux symptom scores, but not with acid exposure. (3) The presence of IBS features in a large proportion of NERD patients reflects a high prevalence of visceral hypersensitivity that may aggravate acid reflux symptoms.