Gastroesophageal reflux disease in pediatric esophageal atresia: Assessment of clinical symptoms and pH-impedance data.

BACKGROUND: Esophageal atresia (EA) is the most common congenital anomaly of the gastrointestinal tract. Gastroesophageal reflux disease (GERD) is a frequent and lifelong problem in these patients. GERD can be asymptomatic and the incidence of esophageal gastric and intestinal metaplasia (Barrett's esophagus) is increased in adults with EA compared with the general population. Timely and accurate diagnosis of GERD is important to reduce long-term problems and this may be achieved by pH-impedance testing. AIM: To assess symptoms and pH-impedance data in children after EA, in order to identify their specific features of GERD. METHODS: This study was conducted from November 2017 to February 2020 and involved 37 children who had undergone EA via open surgical repair (51.35% boys, 48.65% girls; age range: 1-14 years, median: 4.99 years). GERD diagnosis was made based on multichannel intraluminal impedance/pH study and two groups were established: EA without GERD, n = 17; EA with GERD, n = 20. A control group was established with 66 children with proven GERD (68.18% boys, 31.82% girls; median age: 7.21 years), composed of a nonerosive reflux disease (referred to as NERD) group (n = 41) and a reflux esophagitis group (n = 25). Upper gastrointestinal endoscopy with a mucosal esophageal biopsy was performed on all patients. RESULTS: The most frequently observed symptom in EA patients with GERD and without GERD was cough (70% and 76.5% respectively). The number of patients with positive symptom association probability in the EA groups was significantly larger in the EA without GERD group (P = 0.03). In the control reflux esophagitis group, prevalence of gastrointestinal symptoms was significantly higher than in the NERD group (P = 0.017). For both EA groups, there was strong correlation with index of proximal events (IPE) and total proximal events (EA with GERD: 0.96, P < 0.001; EA without GERD: 0.97, P < 0.001) but level of IPE was significantly lower than in GERD patients without any surgical treatment (P < 0.001). Data on distal mean nocturnal baseline impedance were significantly different between the EA with GERD group (P < 0.001) and the two control groups but not between EA without GERD and the two control groups. CONCLUSION: Mean nocturnal baseline impedance may have diagnostic value for GERD in EA children after open surgical repair. IPE might be an additional parameter of pH-impedance monitoring.

Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease.

BACKGROUND AND OBJECTIVES: Weakly acidic reflux has been reported as the major cause of symptom occurrence in patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study is aimed at clarifying whether the pH value of weakly acidic reflux affects the induction of symptoms. METHODS: We retrospectively evaluated the records of combined multichannel intraluminal impedance and pH monitoring in 57 patients with PPI-refractory NERD. Weakly acidic refluxes were divided into 3 categories based on the pH value of the refluxate: pH 4-5, 5-6, and 6-7. RESULTS: A total of 29 patients were positive in the symptom index. The symptom provocation rate in reflux of pH 4-5 (19%) was much higher than in that of pH 5-6 (11%) and pH 6-7 (12%). In the reflux at pH 4-5, the symptom provocation rate in the proximal reflux was higher than that in the distal reflux (p < 0.05), whereas the reflux at pH 5-6 and pH 6-7 was not significantly different in the symptom provocation rate between the proximal and distal refluxes. CONCLUSION: Reflux at pH <5 reaching the proximal esophagus was the main factor in the induced symptoms of patients with PPI-refractory NERD.

Adding Acotiamide to Gastric Acid Inhibitors Is Effective for Treating Refractory Symptoms in Patients with Non-erosive Reflux Disease.

BACKGROUND: Approximately 30% of patients who are treated with proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) experience persistent symptoms. No prokinetic agent regiments are useful for symptom relief. AIMS: This study was conducted to examine the effect of adding acotiamide to PPI or vonoprazan refractory GERD. METHODS: This was a randomized, prospective, double-blind, placebo-controlled trial. Seventy-one patients were enrolled. Patients underwent upper endoscopy before initial therapy [15 reflux esophagitis and 55 non-erosive reflux disease (NERD)]. Patients with persistent reflux symptoms were administered 300 mg/day acotiamide or placebo for 2 weeks. The primary endpoint was overall treatment effect (OTE), and gastrointestinal symptoms were evaluated. High-resolution manometry (HRM) and 24-h multiple intraluminal impedance-pH (MII-pH) monitoring were conducted before and after treatment when possible. RESULTS: Seventy patients were randomized (35 acotiamide and 35 placebo). Sixteen and 10 patients in the acotiamide and placebo groups, respectively, completed MII-pH and HRM. The OTE improvement rates were 28.6% and 14.3% in patients administered acotiamide and placebo, respectively (p = 0.145). In patients with NERD, however, the OTE improvement rate and responder rate for regurgitation in the acotiamide group was significantly higher than those in the placebo group (29.6 vs. 7.1%; p = 0.030, 37.0 vs. 10.7%; p = 0.021, respectively). Acotiamide significantly reduced the total reflux episodes (p = 0.001), acid (p = 0.020), proximal reflux (p = 0.007), and liquid reflux (p = 0.013) episodes. CONCLUSION: Adding acotiamide to gastric acid inhibitors can improve symptoms in patients with refractory NERD.

Liquid-containing Refluxes and Acid Refluxes May Be Less Frequent in the Japanese Population Than in Other Populations: Normal Values of 24- hour Esophageal Impedance and pH Monitoring.

BACKGROUND/AIMS: Twenty-four-hour esophageal impedance and pH monitoring allows detection of all types of reflux episodes and is considered the best technique for identifying gastroesophageal refluxes. However, normative data for the Japanese population are lacking. This multicenter study aimed to establish the normal range of 24-hour esophageal impedance and pH data both in the distal and the proximal esophagus in Japanese subjects. METHODS: Forty-two healthy volunteers (25 men and 17 women) with a mean ± standard deviation age of 33.3 ± 12.4 years (range: 22-72 years) underwent a combined 24-hour esophageal impedance and pH monitoring. According to the physical and pH properties, distal or proximal esophageal reflux events were categorized. RESULTS: Median 45 reflux events occurred in 24 hours, and the 95th percentile was 85 events. Unlike previous reports, liquid-containing reflux events are median 25/24 hours with the 95th percentile of 62/24 hours. Acidic reflux events were median 11/24 hours with the 95th percentile of 39/24 hours. Non-acidic gas reflux events were median 15/24 hours with the 95th percentile of 39/24 hours. Proximal reflux events accounted for 80% of the total reflux events and were mainly non-acidic gas refluxes. About 19% of liquid and mixed refluxes reached the proximal esophagus. CONCLUSIONS: Unlike previous studies, liquid-containing and acidic reflux events may be less frequent in the Japanese population. Non-acidic gas reflux events may be frequent and a cause of frequent proximal reflux events. This study provides important normative data for 24-hour impedance and pH monitoring in both the distal and the proximal esophagus in the Japanese population.

Liquid-containing Refluxes and Acid Refluxes May Be Less Frequent in the Japanese Population Than in Other Populations: Normal Values of 24-hour Esophageal Impedance and pH Monitoring

BACKGROUND/AIMS: Twenty-four-hour esophageal impedance and pH monitoring allows detection of all types of reflux episodes and is considered the best technique for identifying gastroesophageal refluxes. However, normative data for the Japanese population are lacking. This multicenter study aimed to establish the normal range of 24-hour esophageal impedance and pH data both in the distal and the proximal esophagus in Japanese subjects. METHODS: Forty-two healthy volunteers (25 men and 17 women) with a mean ± standard deviation age of 33.3 ± 12.4 years (range: 22–72 years) underwent a combined 24-hour esophageal impedance and pH monitoring. According to the physical and pH properties, distal or proximal esophageal reflux events were categorized. RESULTS: Median 45 reflux events occurred in 24 hours, and the 95th percentile was 85 events. Unlike previous reports, liquid-containing reflux events are median 25/24 hours with the 95th percentile of 62/24 hours. Acidic reflux events were median 11/24 hours with the 95th percentile of 39/24 hours. Non-acidic gas reflux events were median 15/24 hours with the 95th percentile of 39/24 hours. Proximal reflux events accounted for 80% of the total reflux events and were mainly non-acidic gas refluxes. About 19% of liquid and mixed refluxes reached the proximal esophagus. CONCLUSIONS: Unlike previous studies, liquid-containing and acidic reflux events may be less frequent in the Japanese population. Non-acidic gas reflux events may be frequent and a cause of frequent proximal reflux events. This study provides important normative data for 24-hour impedance and pH monitoring in both the distal and the proximal esophagus in the Japanese population.

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients.

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter. RESULTS: In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS). CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.

Alginate controls heartburn in patients with erosive and nonerosive reflux disease.

AIM: To evaluate the effect of a novel alginate-based compound, Faringel, in modifying reflux characteristics and controlling symptoms. METHODS: In this prospective, open-label study, 40 patients reporting heartburn and regurgitation with proven reflux disease (i.e., positive impedance-pH test/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic meal. They were studied for 1 h under basal conditions and 1 h after taking 10 mL Faringel. In both sessions, measurements were obtained in right lateral and supine decubitus positions. Patients also completed a validated questionnaire consisting of a 2-item 5-point (0-4) Likert scale and a 10-cm visual analogue scale (VAS) in order to evaluate the efficacy of Faringel in symptom relief. Tolerability of the treatment was assessed using a 6-point Likert scale ranging from very good (1) to very poor (6). RESULTS: Faringel decreased significantly (P < 0.001), in both the right lateral and supine decubitus positions, esophageal acid exposure time [median 10 (25th-75th percentil 6-16) vs 5.8 (4-10) and 16 (11-19) vs 7.5 (5-11), respectively] and acid refluxes [5 (3-8) vs 1 (1-1) and 6 (4-8) vs 2 (1-2), respectively], but increased significantly (P < 0.01) the number of nonacid reflux events compared with baseline [2 (1-3) vs 3 (2-5) and 3 (2-4) vs 6 (3-8), respectively]. Percentage of proximal migration decreased in both decubitus positions (60% vs 32% and 64% vs 35%, respectively; P < 0.001). Faringel was significantly effective in controlling heartburn, based on both the Likert scale [3.1 (range 1-4) vs 0.9 (0-2); P < 0.001] and VAS score [7.1 (3-9.8) vs 2 (0.1-4.8); P < 0.001], but it had less success against regurgitation, based on both the Likert scale [2.6 (1-4) vs 2.2 (1-4); P = not significant (NS)] and VAS score [5.6 (2-9.6) vs 3.9 (1-8.8); P = NS]. Overall, the tolerability of Faringel was very good 5 (2-6), with only two patients reporting modest adverse events (i.e., nausea and bloating). CONCLUSION: Our findings demonstrate that Faringel is well-tolerated and effective in reducing heartburn by modifying esophageal acid exposure time, number of acid refluxes and their proximal migration.