Number Of Acid Reflux Episodes Research Articles

Two-year outcomes of anti-reflux mucosectomy in treating gastroesophageal reflux disease: A Chinese prospective cohort study.

Anti-reflux mucosectomy (ARMS) is an emerging and promising endoscopic treatment for gastroesophageal reflux disease (GERD). In the current study we aimed to evaluate the safety and efficacy of ARMS in treating Chinese GERD patients. This was a single-center prospective cohort study. ARMS was performed in GERD patients by an experienced endoscopist. The patients were required to undergo symptom assessment as well as endoscopic examination, high-resolution manometry (HRM), and impedance-pH monitoring before and after ARMS. Twelve patients were enrolled. Follow-up was completed by all patients at 3 and 6 months, 11 patients at 1 year, and 8 patients at 2 years after ARMS, respectively. Symptom improvement was achieved in 66.7%, 75.0%, 72.7%, and 50.0% of the patients at 3 months, 6 months, 1 year, and 2 years after ARMS, respectively. Postoperative dysphagia was reported by 25.0%, 25.0%, 27.3%, and 25.0% of patients at 3 months, 6 months, 1 year, and 2 years after surgery, none of whom required additional invasive treatment. All patients with preoperative esophagitis healed after ARMS. For impedance-pH monitoring parameters, number of acidic reflux episodes and the proportion of patients with acid exposure time (AET) >4.0% decreased significantly after ARMS. ARMS was safe and effective in Chinese GERD patients. The efficacy of ARMS was not short-term and remained evident throughout the 2-year follow-up. Further multicenter studies with larger sample sizes are needed to verify our findings.

Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease.

The purpose of this study was to examine the characteristics of proximal and distal gastroesophageal reflux in patients with gastroesophageal reflux disorder and analyze their clinical symptoms. A total of 67 patients with typical esophageal symptoms were selected for this study. All participants completed the reflux disease questionnaire and a questionnaire survey of extraesophageal symptoms. Diagnosis was made using a 24-h impedance-pH detection and proton pump inhibitor. The results showed that the proximal reflux group had a higher number of acid reflux episodes compared to the distal reflux group (P < 0.05). Similarly, the proximal reflux group also had a higher number of gas reflux episodes compared to the distal reflux group (P < 0.05). On the other hand, the distal reflux group had a higher number of mixed reflux episodes compared to the proximal reflux group (P < 0.05). These differences were statistically significant. This study revealed that acid reflux and gas reflux were more predominant in the proximal reflux group, while mixed reflux was more predominant in the distal reflux group.

The long-term efficacy of transoral incisionless fundoplication with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease

BackgroundTo evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD).MethodsA total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital （Shanghai, China）from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects.ResultsFollow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference.ConclusionTIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn.Trial RegistrationChiCTR2000034350.

Role of Laryngopharyngeal Reflux Changes in Children with Adenoid Hypertrophy: A Randomized Controlled Prospective Study.

This prospective randomized controlled analysis aimed to assess the changes in laryngopharyngeal reflux (LPR) in children with adenoid hypertrophy (AH). Study design: a prospective, randomized, and controlled analysis. The reflux symptom index (RSI) and the reflux finding score (RFS) scores were used to evaluate the laryngopharyngeal reflux changes in children diagnosed with adenoid hypertrophy. The pepsin concentration in salivary samples was examined, and the positive pepsin was used to assess the sensitivity and specificity of RSI, RFS, and RSI combined with RFS in forecasting LPR. In 43 children with AH, the sensitivity of the RSI and RFS scale (used alone or in combination) in diagnosing pharyngeal reflux in children with adenoid hypertrophy was lower. Pepsin expression was identified in 43 items of salivary samples, with a total positive rate of 69.77%, most of which were optimistic. The expression level of pepsin was positively correlated with the grade of adenoid hypertrophy (r = 0.576, P < 0.01). Based on the positive rate of pepsin, we found that the sensitivity and specificity of RSI and RFS were 5.77%, 35.03%, and 91.74%, 55.89%. Moreover, there was a noticeable distinction in the number of acid reflux episodes between the LPR-positive and LPR-negative groups. There is a special connection between LPR change and children's AH. LPR exerts a crucial role in the progression of children's AH. Because of the low sensitivity of RSI and RFS, it is not suitable for LPR children to choose AH.

Does Sleeve Gastrectomy Increase the Risk of Barret's Esophagus?

Sleeve gastrectomy (SG) is the most commonly performed bariatric surgical procedure worldwide. However, the impact of SG on Barrett's esophagus (BE) remains unknown. The main objective was to determine the rate of BE 5years after SG. Patients, operated in 2012 by SG in one center, who preoperatively and postoperatively (5years) underwent upper gastrointestinal endoscopy (UGIE), 24-h pH monitoring, and esophageal manometry, were included. A total of 59 (81.4% of females) patients were included. Preoperative mean age and body mass index were 45.2 ± 11.7years and 45.2 ± 8.1kg/m2 respectively. Preoperative 24-h pH monitoring reported gastroesophageal reflux disease (GERD) in 18 (30.5%) patients. The mean total body weight loss at 5years was 16.1 ± 11.2%. No significant difference was observed between preoperative and postoperative de Meester's score (20.2 ± 27.1 and 21.0 ± 21.5 respectively (p = 0.91)) nor between preoperative and postoperative number of acid reflux episodes per 24h (65.1 ± < 40.0 and 50.3 ± 40.3 (p = 0.21)). The UGIE revealed 5 patients (8.5%) with endoscopically suspected esophageal metaplasia, without confirmed metaplasia on histologic examination. GERD was diagnosed in 32 patients (54.2%), de novo GERD in 16 (27.1%) patients and esophagitis in 16 (27.1%) patients. At 5years, 25 patients (42.4%) reported a lack of regular medical follow-up. This study highlights the incidence of postoperative GERD and endoscopic lesions following SG. Even though SG is not contraindicated in case of reflux, GERD patients who undergo SG may be supervised by a close endoscopic surveillance.

Laryngeal signs and pH-multichannel intraluminal impedance in infants and children: The missing ring: LPR and MII-pH in children

Objectiveto investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants. Methodspatients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI>13, RFS>7, acid exposure index>7%, total reflux episodes>100/24 h in infants or>70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (</>12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated. Results197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS>7, and in 17/31 with RSI>13. RFS>7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI>13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index. ConclusionsRSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.

Acid and nonacid gastroesophageal reflux after single anastomosis gastric bypass. An objective assessment using 24-hour multichannel intraluminal impedance-pH metry

BackgroundSingle anastomosis gastric bypass (SaGB) was introduced in 2001 as an alternative to “loop” gastric bypass. It was considered as a procedure that would eliminate alkaline reflux and associated esophagitis. ObjectivesExisting evidence about the postoperative incidence of gastroesophageal reflux (GERD) after SaGB is based on studies using symptom questionnaires. The aim of our study was to evaluate GERD 12 months after SaGB by using 24-hour multichannel intraluminal impedance pH metry (24-h MIIpH). SettingSurgical department of a university hospital MethodsMorbidly obese candidates for SaGB underwent 24-hour MIIpH prior and 12 months after their bariatric procedure. ResultsThere were 11 patients included in this prospective study. Results of 24-hour MIIpH revealed that DeMeester score (40.48 versus 24.16, P = .339) had an increasing trend 12 months after SaGB. Acid reflux episodes decreased, whereas nonacid reflux episodes increased postoperatively, both in proximal and distal esophagus. Total median bolus clearance time and acid clearance time increased. De novo GERD developed in 2 patients (28.6%) and worsening of already existing GERD developed in all patients with preoperative evidence of GERD. ConclusionThe use of symptom questionnaires to assess postoperative GERD after SaGB may not accurately depict the real image. Twenty-four–hour MIIpH in 12 months after SaGB revealed an increase of total number of nonacid reflux episodes and a decrease of total number of acid reflux episodes, with longer duration of each acid reflux episode. Close postoperative follow-up with reflux testing and possibly endoscopy could eliminate the risk of complicated GERD.

Longitudinal study of gastroesophageal reflux and erosive tooth wear

BackgroundApproximately 60% of patients presenting to dentists with erosive tooth wear have significant gastroesophageal reflux (GERD), despite minor reflux symptoms. No longitudinal studies of reflux-associated erosive tooth wear and of reflux characteristics have been reported to date.The aim of this study was to characterize the longitudinal course of GERD and of associated erosive tooth wear, as well as factors predictive of its progression, in a large group of patients.MethodsSeventy-two patients presenting to dentists with clinically significant erosive tooth wear and increased esophageal acid exposure by 24-h multichannel intraluminal pH-impedance measurement (MII-pH) were re-assessed clinically and by MII-pH after 1 year treatment with esomeprazole 20 mg twice-daily. Predictive factors for erosive tooth wear were assessed by logistic regression.ResultsAt follow-up, no further progression in erosive tooth wear was observed in 53 (74%) of patients. The percentage of time with a pH < 4, the number of acid reflux episodes and the percentage of proximal esophageal reflux off-PPI did not change significantly after one year, but the number of weakly acidic reflux episodes decreased significantly in the large subgroup without progression. None of the baseline demographic, clinical, endoscopic or esophageal acid exposure characteristics were significantly associated with progression of erosive tooth wear at follow-up.ConclusionsIn this longitudinal study in patients with erosive tooth wear and oligosymptomatic GERD receiving esomeprazole for one year, erosive tooth wear did not progress further in the majority of patients. Background acidic esophageal reflux exposure appeared stable over time, whereas weakly acidic exposure decreased significantly in patients without erosion progression. MII-pH measurements on-PPI and with healthy controls will be useful in the further elucidation of the causal role of reflux in erosive tooth wear.Trial registrationClinicalTrials.gov, retrospectively registered: NCT02087345.

Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD). Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH <4. Secondary end-points were number of acid reflux episodes (pH <4), longest reflux time and DeMeester scores. All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH <4 was 5.1%, significantly less (P = 0.0003) than with placebo (14.8%). DA alginate antacid was statistically significantly superior (P = 0.0290) to placebo (from at least twofold to threefold better) for all other end-points. Two patients reported two mild adverse events (AEs) that resolved within a month of completing the study. No patients had serious and/or severe AEs and none withdrew due to AEs. DA alginate antacid was statistically significantly superior to placebo in reducing post-prandial acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms.

Effects of Transcutaneous Electrical Acustimulation on Refractory Gastroesophageal Reflux Disease.

Objective. To investigate effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) performed by a wearable watch-size stimulator for refractory gastroesophageal reflux disease (RGERD). Methods. Twenty patients diagnosed as RGERD were enrolled in the study and randomly divided into four groups: esomeprazole group (Group A), esomeprazole combined with TEA group (Group B), esomeprazole combined with sham-TEA group (Group C), and esomeprazole combined with domperidone group (Group D). HRM and 24 h pH-impedance monitoring and GerdQ score were used to measure related indexes before and after treatment. Results. (1) TEA significantly increased LESP, compared with PPI treatment only or PPI plus sham-TEA. After pairwise comparison, LESP of Group B was increased more than Group A (P = 0.008) or Group C (P = 0.021). (2) PPI plus TEA decreased not only the number of acid reflux episodes but also the number of weak acid reflux episodes (P = 0.005). (3) Heartburn and reflux symptoms were improved more with PPI + TEA than with PPI treatment only or PPI plus sham-TEA (GerdQ scores, P = 0.001). Conclusion. TEA can improve symptoms in RGERD patients by increasing LESP and decreasing events of weak acid reflux and acid reflux; addition of TEA to esomeprazole significantly enhances the effect of TEA.

Evaluation of antireflux surgery using multichannel intraluminal impedance-pH measurement in neurologically impaired patients.

This study aimed to evaluate esophageal function before and after antireflux surgery (ARS) in neurologically impaired (NI) patients using 24 h multichannel intraluminal impedance (MII)-pH measurement. Seven NI patients (age, 0-33 years; median, 13 years) were assessed before and after ARS using 24 h MII-pH. We described reflux parameters such as pH reflux index, bolus exposure index, number of acidic and nonacidic reflux episodes, mean acid clearance time and median bolus clearance time, and esophageal motility parameters in dry swallows such as bolus presence time (BPT), total bolus transit time (TBTT), and total propagation velocity (TPV). The postoperative reflux parameters such as pH reflux index, acid clearance time, bolus exposure index, and the number of acidic reflux episodes significantly decreased (P < 0.05) compared with the preoperative ones. The esophageal motility parameters including all sites of BPTs, TBTT, and TPV did not change in the MII-pH measurement after ARS (P = non-significant). ARS effectively reduced gastro-esophageal reflux (GER) in NI patients without the impairment of esophageal motility by MII-pH measurement. MII-pH was useful to detect the subtype of GER before and after ARS and appeared to be appropriate for evaluating esophageal motility.

Pharmacokinetics and Acid‐suppressive Effects of Esomeprazole in Infants 1–24 Months Old With Symptoms of Gastroesophageal Reflux Disease

ABSTRACTObjectives:To evaluate the pharmacokinetics and acid‐suppressive effects of esomeprazole in infants with gastroesophageal reflux disease (GERD).Patients and Methods:In this single‐blind, randomized, parallel‐group study, 50 infants 1 to 24 months old with symptoms of GERD, and ≥5% of time with intraesophageal pH &lt;4 during 24‐hour dual pH monitoring, received oral esomeprazole 0.25 mg/kg (n = 26) or 1 mg/kg (n = 24) once daily for 1 week. Intraesophageal and intragastric pH were recorded at 1 week, and blood samples were taken for pharmacokinetic analysis.Results:At baseline, mean percentages of time with intragastric pH &gt;4 and intraesophageal pH &lt;4 were 30.5% and 11.6%, respectively, in the esomeprazole 0.25 mg/kg group and 28.6% and 12.5% in the esomeprazole 1 mg/kg group. After 1 week of treatment, times with intragastric pH &gt;4 were 47.9% and 69.3% in the esomeprazole 0.25 mg/kg and 1 mg/kg groups, respectively (P &lt; 0.001 vs baseline), and times with intraesophageal pH &lt;4 were 8.4% (P &lt; 0.05 vs baseline) and 5.5% (P &lt; 0.001 vs. baseline), respectively. The mean number of acid reflux episodes of &gt;5 minutes duration decreased from 6 at baseline to 3 and 2 with esomeprazole 0.25 mg/kg and 1 mg/kg, respectively. The geometric mean AUC0–t of esomeprazole were 0.24 and 1.79 μmol·h/L for the 0.25 mg/kg and 1 mg/kg dosages of esomeprazole, respectively. Both esomeprazole dosages were well tolerated.Conclusions:Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well tolerated and provided dose‐related acid suppression, dose‐related exposure to esomeprazole, and decreased esophageal acid exposure in infants 1–24 months old with GERD.

Added Value of pH Multichannel Intraluminal Impedance in Adults Operated for Esophageal Atresia.

Gastroesophageal reflux (GER) and dysphagia are common following repaired esophageal atresia (EA). The risk of esophagitis and Barrett esophagus is increased compared with the general population. As yet, the causes are not fully explained. The aim of this study was to investigate how GER, measured by pH multichannel intraluminal impedance (pH-MII), is correlated to the esophageal symptoms and histological findings. Twenty-nine adult subjects operated for EA in Gothenburg from 1968 to 1983 were evaluated with pH-MII, manometry, and gastroscopy. pH-MII was performed in 15, manometry in 19, and gastroscopy in 24 subjects. Eleven subjects displayed pathological reflux parameters of any kind, mainly nonacid reflux (10/15). Dysphagia correlated to the number of weakly acidic reflux episodes. Lower esophageal sphincter (LES) incompetence, which correlated to a pathological number of acid reflux episodes (p = 0.012), was noted in 21/24 subjects, but the majority had a normal resting pressure. Esophagitis was present in 14/24, two of whom had Barrett esophagus. Histological changes correlated to the reflux index and the number of weakly acidic reflux episodes (p = 0.028 and 0.040) and tended to correlate to dysphagia (p = 0.052). pH-MII adds further information when it comes to explaining what causes symptoms and esophageal histological changes in adults operated for EA.

Proton Pump Inhibitors Reduce the Size and Acidity of the Gastric Acid Pocket (Clin Gastroenterol Hepatol 2014;12:1101-1107, e1)

Gastric acid pocket is a portion of unbuffered acid accumulations in the proximal stomach during postprandial period. It could be a reservoir of acid reflux in patients with gastroesophageal reflux disease (GERD). How proton pump inhibitors (PPIs) control the acid pocket is rarely known. Recently, Rohof et al1 reported PPIs might change the size, acidity, or position of the acid pocket, which contribute to the therapeutic effect in patients with GERD. Concurrent high resolution manometry and pH-impedance monitoring were performed in 36 patients with GERD (18 on PPIs and 18 off PPIs) after a standardized meal. The acid pocket was visualized using scintigraphy, and its size and position were measured using radionuclide markers. The pH of acid pocket was measured in its aspirates. In patients on PPIs, the number of acid reflux episodes was reduced, and the acid pocket was smaller and more frequently located below the diaphragm, and the mean pH of acid pocket was significantly higher. The number of reflux events was not altered by PPIs. It is interesting to show the acid pocket itself with and reflux episodes through a large hiatal hernia using scintigraphic images by the 99mTc-pertechnetate-labeling.

Esophageal Intraluminal Baseline Impedance Differentiates Gastroesophageal Reflux Disease From Functional Heartburn

Mucosal integrity can be assessed in patients with gastroesophageal reflux disease (GERD) by measuring intraluminal baseline impedance (BI). However, it is not clear whether BI is abnormal in patients with functional heartburn (FH), or can be used to distinguish them from patients with GERD. We compared differences in BI between patients with FH vs GERD. We performed a prospective study of 52 patients (16 men; mean age, 55 y; range, 23-78 y) seen at a tertiary university hospital from February 2009 through December 2012. Thirty-five patients had GERD (19 had nonerosive reflux disease [NERD], 16 had erosive reflux disease [ERD]) and 17 had FH. All patients discontinued proton pump inhibitor therapy and then underwent esophagogastroduodenoscopy and multichannel intraluminal impedance and pH monitoring. BI was assessed at 3, 5, 7, 9, 15, and 17 cm proximal to the lower esophageal sphincter in recumbent patients. Biopsy specimens were taken from 3 cm above the gastroesophageal junction; histology analysis was performed to identify and semiquantitatively score (scale, 0-3) dilated intercellular spaces. Baseline impedance in the distal esophagus was significantly lower in patients with NERD or erosive reflux disease (ERD) than FH (P= .0006). At a cut-off value of less than 2100 Ω, BI measurements identified patients with GERD with 78% sensitivity and 71% specificity, with positive and negative predictive values of 75%. Also in the proximal esophagus, reduced levels of BI levels were found only in patients with ERD. There were negative correlations between level of BI and acid exposure time (r=-0.45; P= .0008), number of acidic reflux episodes (r=-0.45; P= .001), and proximal extent (r= -0.40; P= .004). Biopsy specimens from patients with NERD or ERD had significant increases in dilation of intercellular spaces, compared with those from patients with FH; there was an inverse association between dilated intercellular spaces and BI in the distal esophagus (r= -0.28; P= .06). Measurement of BI in the lower esophagus can differentiate patients with ERD or NERD from patients with FH (78% sensitivity and 71% specificity), and therefore should be considered as a diagnostic tool for patients with proton pump inhibitor-refractory reflux. Low levels of BI are associated with increased exposure to acid and dilation of intercellular spaces, indicating that BI is a marker of mucosal integrity.

Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study.

BackgroundThe γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose–response effect of lesogaberan on reflux episodes in partial responders.MethodsIn this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance–pH measurements were taken.ResultsTwenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment.ConclusionsLesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events.Trial registrationClinicalTrials.gov identifier: NCT01043185.

Physiological analysis of the effects of rikkunshito on acid and non-acid gastroesophageal reflux using pH-multichannel intraluminal impedance monitoring.

To clarify the effects of rikkunshito on acid reflux, non-acid reflux, and esophageal clearance in patients with gastroesophageal reflux disease (GERD). We enrolled seven patients with vomiting and/or stridor (median 6 years; 1 month-17 years), with a percent total time of esophageal pH <4.0 (reflux index) over 4.0%. Rikkunshito (TJ-43; Tsumura Co, Tokyo, Japan) was given in three divided doses before meals. We retrospectively investigated its efficacy using pH-multichannel intraluminal impedance before and 7 (6-10) days after starting treatment. Statistical analyses were conducted using Wilcoxon signed-rank test. In the pH analyses alone, the median number of acid reflux episodes >5 min (14 versus 10, p = 0.046) and median acid-clearance time (184 versus 134 s, p = 0.03) decreased significantly, although median decrease in reflux index did not reach significance (16.0 versus 17.9%, p = 0.06). In the combined impedance and pH analyses, the median number (36 versus 36, p = 0.03) and median duration (1.9 versus 1.1%, p = 0.046) of acid reflux decreased significantly; non-acid reflux and bolus clearance time did not change. Rikkunshito effectively reduced acid reflux, but not esophageal clearance, in patients with GERD.

Proton Pump Inhibitors Reduce the Size and Acidity of the Acid Pocket in the Stomach

The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P < .001). The pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD.

The influence of the speed of food intake on multichannel impedance in patients with gastro-oesophageal reflux disease.

There is a general belief that gastro-oesophageal reflux increases after meals and especially following a rapid intake. To evaluate the impact of rapid vs. slow food intake on gastro-oesophageal reflux disease (GORD) patients. Forty-six GORD patients with heartburn and / or acid regurgitation once a week or more often common were included in this study. Participants were asked to eat the same standard meal within either 5 or 30 minutes under observation in a random order on 2 consecutive days. A total of 28 hours of recording were obtained by intraoesophageal impedance pH and number of liquid and mixed reflux episodes within 3 hours of the slow- and fast-eating postprandial periods were calculated. While all patients defined GORD symptoms, 10 (21.7%) had pathological 24-h intraoesophageal impedance measurement, 15 (32.6%) had pathological DeMeester and 21.7% had erosive oesophagitis. No difference has been shown according to the eating speed when all reflux episodes were taken together (754 vs. 733). Speed of food intake also did not have an impact on patients with normal vs. pathological 24-h intraoesophageal impedance or erosive vs. non-erosive. During the first postprandial hour, approximately half of the reflux events were non-acid, compared to 34.2% during the second hour and 26.8% during the third hour (p < 0.001). The number of acid reflux episodes was significantly higher than non-acid reflux especially during the second and third hours and in total for 3 hours. This first study addressing the effect of eating speed on reflux episodes in GORD patients did not support the general belief that reflux increases following fast eating. Acid and non-acid reflux were similar at the first postprandial hour, then acid reflux episodes were predominantly higher, which implicate the importance of acid pockets.

Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study

Low basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal. Patients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8mg) or placebo. Before and after 7days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal. A total of 223 patients with GERD [125 (56%) women, mean (SD) age=36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p>0.5); however, significant treatment effects (p<0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2mg (10.8±1.1), 0.5mg (9.5±1.1), and 0.8mg (9.9±1.1) compared with placebo (13.3±1.1). Significant treatment effects (p<0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5mg (10%) and 0.8mg (10%) compared with placebo (16%). In GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1-week treatment period.