Refractory Gastroesophageal Reflux Disease Patients Research Articles

Short and long term effect of anti-reflux mucosectomy with cap-assisted endoscopic mucosal resection for refractory gastroesophageal disease.

Anti-reflux mucosectomy with cap-assisted endoscopic mucosal resection (ARMS-C) is a safe and effective treatment for managing refractory gastroesophageal reflux disease (GERD). This study aimed to investigate the short and long-term outcomes of ARMS-C. This study was conducted from 2018 to 2022, during which 115 eligible patients underwent ARMS-C. The primary endpoints of this study were to evaluate the GERD-Q questionnaire score and determine the number of patients who reduced their proton pump inhibitor (PPI) dosage or discontinued PPI usage. The secondary endpoints included the evaluation of the DeMeester score, acid exposure time (AET), gastroesophageal flap valve grade (GEFV), lower esophageal sphincter pressure, the rate of successful esophageal peristalsis, and GERD-Q questionnaires. Additionally, we analyzed the long-term efficacy of ARMS-C. Out of the 120 patients, 115 underwent ARMS-C, 96 were followed up for at least six months after the procedure, and 22 were followed up for at least two years. The primary outcome showed a significant improvement in GERD-Q scores, decreasing from 10.67 to 7.55 (p < 0.001). Out of the 96 patients, 36 were able to reduce or completely stop using PPIs. The DeMeester score, GEFV, AET, and the proportion of intact peristalsis also demonstrated improvement. As for the long-term efficacy of ARMS-C, 86% of patients showed improvement in symptoms, and no serious adverse effects were reported after the procedure. ARMS-C is a safe and effective endoscopic technique to treat refractory GERD patients.

Laparoscopic antireflux surgery for refractory gastroesophageal reflux disease: long-term clinical outcomes

Persistent symptoms despite adequate Proton Pump Inhibitors (PPI) treatment are described in up to 40% of patients with Gastroesophageal Reflux Disease (GERD). The efficacy of Laparoscopic Antireflux Surgery (LARS) in PPI non-responder patients is still unclear. This observational study aims to report the long-term clinical outcomes and predictors of dissatisfaction in a cohort of refractory GERD patients submitted to LARS. Patients with preoperative refractory symptoms and objective GERD evidence submitted to LARS between 2008 and 2016 were included in the study. Primary endpoint was overall satisfaction with the procedure, secondary endpoints were long-term GERD symptom relief and endoscopic findings. Univariate and multivariate analyses were performed to compare satisfied and dissatisfied patients, in order to identify preoperative predictors of dissatisfaction. A total of 73 refractory GERD patients who underwent LARS were included in the study. At a mean follow-up of 91.2 ± 30.5 months, the satisfaction rate was 86.3%, with a statistically significant reduction in typical and atypical GERD symptoms. Causes of dissatisfaction were severe heartburn (6.8%), gas bloat syndrome (2.8%), and persistent dysphagia (4.1%). Multivariate analysis showed that a number of Total Distal Reflux Episodes (TDRE) > 75 was a predictive factor of long-term dissatisfaction after LARS while a partial response to PPI was a protective factor against dissatisfaction. LARS guarantees a high level of long-term satisfaction for selected refractory GERD patients. An abnormal TDRE at 24 h-multichannel intraluminal impedance-pH monitoring and the lack of response to preoperative PPI were predictors of long-term dissatisfaction.

Assessment of Esophageal Motility Disorders in Patients With Refractory Gastroesophageal Reflux Disease

There is insufficient data about esophageal body dysmotility in patients with refractory gastroesophageal reflux disease (RGERD) and inadequate response to proton pump inhibitors (PPIs) treatment. This study aimed to assess esophageal motility disorder and reflux parameters among these patients by high-resolution manometry (HRM) and intraluminal impedance and pH (MII‐pH) monitoring after stopping PPI therapy. A retrospective study was conducted among 100 RGERD patients admitted to Taleghani Hospital (Tehran, Iran) for one year. More than half of them were males (55%). Their mean age was 47.10±6.92, and 50% of patients had ineffective esophageal motility (IEM). Middle, distal, and proximal esophageal pressure (MEP, DEP, and PEP), lower esophageal sphincter (LES) basal pressure (LESP), integrated relaxation pressure (IRP), distal contractile integral (DCI), large breaks, upper esophageal sphincter basal pressure (UESP), and LES length (LESL) in IEM patients were significantly lower than the patients with normal esophageal motility (P&lt;0.001). Furthermore, there were more patients in the IEM group with long-term and abnormal weakly acid reflux compared with the non-IEM group (P&lt;0.05). It seems that the evaluation of reflux parameters and esophageal motility could lead to additional insights into the pathophysiological mechanisms of RGERD. Nevertheless, further studies are suggested to evaluate the effects of esophageal motility disorders among RGERD patients.

The prevalence of coronary atherosclerosis in patients with refractory gastroesophageal reflux disease ready for antireflux surgery.

Coronary atherosclerosis (CAS) and gastroesophageal reflux disease (GERD) share common risk factors. The existing CAS may not only increase the possibility of GERD to be refractory GERD (RGERD), but also increase the risk of antireflux surgery for these patients. The aim of this study was to estimate the prevalence of CAS and its potential risk factors in patients with RGERD ready for antireflux surgery. The retrospective analysis was performed in the digestive disease center of Suining Central Hospital, a teritary hospital in Sichuan, China. Records of patients with RGERD admitted to the hospital for antireflux surgery between July 2018, and June 2021 were included. The included patients were divided into the RGERD group and RGERD-CAS group based on the coronary computed tomography angiography (CCTA) results, which were defined as no CAS and CAS (<50% mild stenosis or ≥50% significant stenosis). In total, 448 patients with RGERD qualified for the study. The prevalence of CAS in these patients was 45.1%. Specifically, 246 patients (54.9%) were in the RGERD group, and 202 patients (45.1%) were in the RGERD-CAS group. Among these 202 patients with CAS, 120 patients (59.4%) had mild CAS (<50% stenosis), 82 patients (40.6%) had significant CAS (≥50% stenosis). Five independent risk factors, including male sex, high blood pressure (HBP), diabetes mellitus (DM), Barrett's esophagus (BE) and family history of coronary artery disease were identified for the occurrence of CAS in patients with RGERD ready for antireflux surgery after adjusting for other factors. CAS is prevalent in patients with RGERD ready for antireflux surgery. Routing CTTA was suggested to exclude potential coronary artery disease in RGERD patients ready for antireflux surgery with independent risk factors.

Esophageal chemical clearance and mucosa integrity values in refractory gastroesophageal reflux disease patients with different esophageal dynamics

Objectives Esophageal post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI), novel impedance-based markers of reflux burden, are associated with esophageal dynamics. We aim to investigate the characteristics of PSPWI and MNBI in Chinese refractory gastroesophageal reflux disease (RGERD) patients with different esophageal dynamic changes. Materials and methods 201 RGERD and 76 functional heartburn patients, undergone off-PPI endoscopy, esophageal manometry and impedance-pH monitoring, were included. Comparisons of conventional and novel impedance-pH metrics were made among different esophageal dynamics groups. Receiver operating-characteristic analyses were utilized to evaluate the diagnostic efficacy of PSPWI and MNBI in differentiating abnormal esophageal dynamics. Correlations were used to investigate their associated factors. Results PSPWI and MNBI of RGERD with esophagogastric junction (EGJ) injury and esophageal dysmotility were lower than EGJ injury alone or normal dynamics (p < 0.05 for both comparisons). PSPWI with esophageal peristalsis abnormality was lower than EGJ injury (p = 0.049), while MNBI showed no statistical difference. PSPWI, MNBI and their combination have auxiliary diagnostic values for esophageal peristalsis [area under the curves (AUCs): 0.683, 0.656, 0.708)] while only their combination for EGJ injury (AUC: 0.610). And they positively correlated with esophageal motility while negatively correlated with ineffective swallows and acid reflux events. Conclusions PSPWI and MNBI, indicating impairment of esophageal chemical clearance and mucosa integrity, were lower in RGERD patients with multiple esophageal dynamic injuries than single injuries or normal dynamics. Moreover, they provided useful contributing information for potential dynamic injuries if manometry has already been found normal or marginal.

The effect of a low-nickel diet and nickel sensitization on gastroesophageal reflux disease: A pilot study.

Gastroesophageal reflux disease (GERD) is a common medical condition, frequently refractory to medical therapy. Nickel is a leading cause of allergic contact dermatitis. Although nickel is widely found in foods, the effect of nickel on GERD is unknown. This pilot study sought to evaluate the effect of a low-nickel diet on GERD and determine if epicutaneous patch testing to nickel could predict responsiveness to a low-nickel diet. This prospective, single-site pilot study recruited 20 refractory GERD patients as determined by GERD Health-Related Quality of Life (GERD-HRQL) scores. All patients had epicutaneous patch testing for nickel and were then instructed to follow a low-nickel diet for 8weeks regardless of patch test results. GERD-HRQL was recorded at baseline and following 8weeks of a low-nickel diet. Demographic and clinical data associated with GERD and nickel allergy were recorded. A Wilcoxon signed-rank test and nonparametric analysis of longitudinal data were run to determine statistical significance in pre-and post- GERD-HRQL scores in nickel patch test-positive and negative groups. Nearly all (19/20 [95%]) participants reported reduced GERD symptoms after 8weeks on a low-nickel diet. Mean total GERD-HRQL, regurgitation, and heartburn scores declined (27.05 ± 16.04, 11.45 ± 6.46, 10.85 ± 8.29). Participants with positive vs. negative patch testing to nickel responded equivalently to a low-nickel diet. A low-nickel diet improves GERD symptoms, but responsiveness to a low-nickel diet does not correlate with epicutaneous patch testing to nickel. ClinicalTrials.gov number: NCT03720756.

Clinical characteristics and esophageal function tests of refractory gastroesophageal reflux disease

Objective: To analyze the clinical characteristics and pathogenesis of refractory gastroesophageal reflux disease(RGERD). Methods: The patients with acid regurgitation, heartburn and extraesophageal symptoms were enrolled in the study from November 2015 to September 2017 at Peking University Third Hospital. All the subjects filled the informed consent.Questionnaire, SCL-90, SAS and SDS scales were recorded. A 24 hour pH-impedance monitoring and esophageal high resonance manometry were carried out. According to the response to proton pump inhibitor(PPI), the patients were divided into RGERD and non-RGERD(NRGERD)groups. The clinical characteristics were compared between these two groups. Logistic regression was used to analyze the risk factors of RGERD. Results: One hundred and nineteen patients were finally enrolled in the study including 61 RGERD (51.3%) and 58 NRGERD patients (48.7%).The body mass index (BMI) and rates of, typical GER symptoms including acid regurgitation in RGERD patients were significantly lower than those in NRGERD patients (P<0.05).While the atypical GER symptoms such as poststernal discomfort or chest pain were more common in RGERD group (P<0.05).RGERD patients presented less acid reflux events and lower proximal segment reflux ratio than NRGERD patients. No obvious differences were found in the manometry metrics between these two groups. The scores of somatization, depression and hostility in RGERD patients by SCL-90 scales were significantly higher than those in NRGERD patients (P<0.05), and depression score was an independent risk factor for RGERD [OR=3.915 (95%CI 1.464-10.466), P =0.007]. Conclusions: RGERD patients present more atypical symptoms and pathological non-acid reflux.Depression is an independent risk factor for RGERD.

878 CLINICAL OUTCOMES OF ENDOSCOPIC ANTI-REFLUX TREATMENT METHODS; ANTI-REFLUX MUCOSECTOMY (ARMS) AND ANTI-REFLUX MUCOSAL ABLATION (ARMA)

Gastroesophageal reflux disease (GERD) is a common disorder with an increasing prevalence worldwide. Proton pump inhibitors (PPIs) are effective in achieving symptom control, however, approximately 30-40% of patients are reported to have persistent symptoms despite PPI therapy. While the surgical intervention such as Laparoscopic Nissen Fundoplication remains the gold standard treatment for refractory GERD, minimally invasive anti-reflux therapies are gaining its popularity to fill in the “gap” of conventional medical therapy and surgery. In 2014, we reported Anti-reflux mucosectomy (ARMS) which utilizes ESD or EMR-C to rebuild the flap valve at the gastric cardia by scarring of the artificial ulcer. In 2018, we developed Anti-reflux mucosal ablation (ARMA) where we apply ablation instead of mucosectomy as an alternative therapy for PPI-refractory GERD. The aim of this study is to evaluate the clinical outcomes of ARMS and ARMA. This is a retrospective, single center study from a prospectively collected database performed between April 2012 and November 2019. The indication of ARMS/ARMA is PPI refractory GERD patients without prominent sliding hernia. In ARMS, ESD or EMR-C at the gastric cardia mucosa was performed in order to create artificial ulcer. In ARMA, mucosal ablation using Triangle Tip Knife with spray coagulation mode (50W-120W, effect 2) was utilized to create the ulcer. The efficacy was evaluated by the patient’s symptom score (Frequent Scale for the Symptoms of GERD: FSSG) and the objective findings; Acid Exposure Time (AET) and DeMeester composite score by 24h multi-channel intraluminal impedance-pH monitoring, before and 2-3 months after procedure. A total of 109 patients (Age 54.0±15.7, M:F 63:46) underwent ARMS, and 24 patients (57.6±15.9, M:F 16:8) underwent ARMA. Mean procedure time (minutes) were 54.7 vs. 35.6, respectively. FSSG score improved from 25.1 to 11.6 (p<0.01) by ARMS and from 25 to 10.5 (p<0.01) by ARMA. By ARMS, AET and DeMeester composite score improved from 20.8 to 6.9 (p < 0.01, n=27) and 64.4 to 24.9 (p < 0.01, n=27), respectively. By ARMA, median AET showed a decreasing trend from 9 to 0.5 (p=0.068, n=8), and the DeMeester composite score significantly improved from 33.5 to 2.8 (p<0.05, n=8). Both ARMS and ARMA were effective anti-reflux therapy methods for PPI-refractory GERD which improved GERD related symptoms and objective acid reflux parameters. ARMA may be advantageous on its easiness and simplicity regarding operative time. A larger study with long-term follow-up is required to confirm these results.

Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease

Introduction: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. Methods: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. Results: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0–0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1–3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7–34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4–74.3%], p < 0.01). Conclusions: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

Psychosocial Distress and Quality of Life Impairment Are Associated With Symptom Severity in PPI Non-Responders With Normal Impedance-pH Profiles.

Up to 50% of patients with reflux symptoms do not manifest a satisfactory symptom response to proton pump inhibitor (PPI) therapy. Our primary aim in this study was to identify factors associated with symptom perception among PPI non-responder phenotypes. This prospective observational cohort study was performed from September 2014 to January 2017 at a single academic medical center and included PPI non-responders who underwent 24-h impedance-pH monitoring and completed a questionnaire set measuring patient-reported symptom severity, quality of life (QOL), and psychosocial distress. Participants were separated into cohorts based on impedance-pH results: on PPI: -acid exposure time (AET)/-symptom-reflux association (SRA), +AET, and -AET/+SRA; off PPI: functional (-AET/-SRA), gastroesophageal reflux disease (GERD) (+AET), and reflux hypersensitivity (RHS) (-AET/+SRA). The primary outcome was abnormal GERD symptom severity defined by GerdQ≥8. One hundred and ninety-two participants were included. Impedance-pH on PPI was performed on 125: 72 (58%) -AET/-SRA, 42 (34%) +AET, and 11 (9%) -AET/+SRA. Among the -AET/-SRA group, younger age, higher dysphagia scores, QOL impairment, and higher brief symptom index were associated with GerdQ≥8. Among the +AET group, higher number of reflux-associated symptoms and lower distal contractile integral was associated with GerdQ≥8. Impedance-pH off PPI was performed on 67 participants: 39 (58%) functional, 16 (24%) GERD, and 12 (18%) RHS. Among the functional group, higher QOL impairment and dysphagia scores were seen with GerdQ≥8. Perceptions of reflux symptoms are associated with psychosocial distress, reduced QOL, and sensation of dysphagia among PPI non-responders with normal impedance-pH. Among PPI refractory GERD patients, patient-reported symptom severity is associated with physiological differences, as opposed to psychosocial factors.

Specific dyspeptic symptoms are associated with poor response to therapy in patients with gastroesophageal reflux disease.

In patients with gastroesophageal reflux disease (GORD), co-existence of functional dyspepsia (FD) is known to be associated with poor response to proton pump inhibitors (PPIs), but the contribution of specific dyspepsia symptoms has not yet been systematically investigated. We aimed to characterize the impact of dyspepsia symptoms on response to PPIs in patients with GORD. The enrolled subjects were consecutive patients with a diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on PPI therapy. Patients were divided into two groups, refractory and responders, according to the persistence of GORD symptoms. A standardized questionnaire for FD was also administered to assess presence of dyspepsia symptoms. In the subgroup of refractory patients FD was more prevalent than in responders, with post-prandial fullness, nausea, vomiting, early satiation and epigastric pain being significantly prevalent in refractory GORD patients. In the multivariate analysis only early satiation and vomiting were significantly associated with poor response to PPIs. Co-existence of FD is associated with refractory GORD. We showed that only early satiation and vomiting are risk factors for poor response to therapy with PPIs. Our findings suggest that symptoms of early satiation and vomiting would help to identify the subset of PPI-refractory GORD patients.

Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms.

Background/AimsLittle data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM).MethodsWe retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility.ResultsForty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group (P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function.ConclusionsIEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients.

Role of altered esophageal intraluminal baseline impedance levels in patients with gatroesophageal reflux disease refractory to proton pump inhibitors.

Numerous studies have investigated utility of esophageal intraluminal baseline impedance levels (BILs) in gastroesophageal reflux disease (GERD). However, effect of BILs in refractory GERD (RGERD) has not been well investigated. The aim of this study is to evaluate role of BILs in RGERD patients. Total 62 subjects with refractory gastroesophageal reflux symptoms underwent 24-hour impedance-pH monitoring and gastroendoscopy. Distal BILs in acid reflux type were significantly lower than those in nonacid reflux type and functional heartburn (FH) group. Distal BILs of reflux esophagitis (RE) patients were lower than those of nonerosive reflux disease (NERD) patients, while there were no statistical significance between 2 groups. Patients with severe esophagitis had lower distal BILs than those with mild esophagitis and NERD patients, and patients with severe esophagitis in acid reflux type had the lowest distal BILs. Distal BILs were significantly negatively correlated with DeMeester score, episodes of acid reflux, and acid exposure time, but no correlated with episodes of nonacid reflux. Characteristics of BILs in RGERD patients were similar with those in GERD patients, but might be more complicated. Evaluating BILs in RGERD patients could achieve a better understanding of pathophysiology in RGERD.

Effects of transcutaneous electro acupuncture stimulation on esophageal motility of forty-five patients with refractory gastroesophageal reflux disease

Objective To investigate the effects of transcutaneous electro acupuncture stimulation (TEA) on esophageal motility of patients with refractory gastroesophageal reflux disease (RGERD) by high resolution manometry (HRM), and to provide a new treatment option for RGERD. Methods From February 2014 to June 2015, a total of 45 patients with RGERD were enrolled. TEA instrument was used for electro acupuncture stimulation at the points of Zusanli and Neiguan. HRM was carried out before and after treatment. The changes of HRM parameters such as lower esophageal sphincter pressure (LESP), distal contractile integral (DCI), and amplitude of 3 cm, 7 cm above lower esophageal sphincter (LES), esophageal body velocity and contractile front velocity (CFV) were also compared. The paired-samples t test was performed for statistical analysis. Results According to LESP value, 45 patients were divided into low LESP group (10 patients) and normal LESP group (35 patients). According to parameter of esophageal motility function, patients were divided into esophageal dysmotility group (25 patients) and normal esophageal motility group (20 patients). After TEA treatment, the LESP of lower LESP group was (14.83±4.17) mmHg (1 mmHg=0.133 kPa), which was higher than that before treatment ((9.54±2.42) mmHg), and the difference was statistically significant (t=4.92, P=0.001). LESP of esophageal dysmotility group was (19.04±5.91) mmHg, which was higher than that before treatment ((16.20±6.09) mmHg), and the difference was statistically significant (t=4.92, P=0.001). There was no statistically significant difference in LESP of normal LESP group and normal esophageal motility group before and after treatment (both P>0.05). After treatment, DCI of esophageal dysmotility group was (530.76±215.53) mmHg·cm·s, which was higher than that before treatment ((363.92±279.17) mmHg·cm·s), and the difference was statistically significant (t=2.86, P 0.05). There was no statistically significant difference in all of the esophageal motility parameters in normal esophageal motility group before and after treatment (all P>0.05). Conclusion TEA can increase LESP and DCI in RGERD patients with esophageal motility dysfunction, improve contraction of entire esophagus and raise esophageal clearance capacity. Key words: Refractory gastroesophageal reflux disease; Transcutaneous electro acupuncture stimulation; High resolution manometry, esophageal; Esophageal motility

Tailored therapy for the refractory GERD patients by combined multichannel intraluminal impedance-pH monitoring.

About 30% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI). The reason for the PPI failure in Asian GERD patients has rarely been studied, and the therapy remained unclear. The aims were to explore the possible reasons for PPI failure and to treat these patients with the guidance of 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring. Thirty-nine consecutive patients with refractory GERD were enrolled; 24-h MII-pH monitoring was performed on PPI. The refractory GERD patients were grouped into acid overexposure, non-acid reflux, and functional heartburn after the MII-pH monitoring. Double dose of either PPI or paroxetine was administered to refractory GERD patients within different groups. The number of patients in groups of acid overexposure, non-acid reflux, and functional heartburn was 6, 12, and 21, respectively. The acid overexposure group had the most acid reflux events. Among the acid overexposure group, five (5/6) patients accomplish symptom relief with double dose of esomeprazole. For the patients in non-acid reflux group, double dose of esomeprazole made half (6/12) of the patients obtain symptom relief. For the patients in functional heartburn group, the paroxetine had relieved the symptoms in 14 patients among all the 21 patients. In total, with the guidance of MII-pH monitoring, 64.1% (25/39) of refractory GERD patients accomplished symptom relief. Acid overexposure, non-acid reflux, and functional heartburn were the common reasons for persistent reflux symptoms despite PPI. With the guidance of MII-pH, a tailored therapy could resolve the persistent reflux symptoms among two-third of patients.

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.

6-months follow-up retrospective study of posterior total (NISSEN) fundoplication patients with GERD: Influence of psychiatric co-morbidity and antidepressant co-treatment in therapeutic result outcomes

Background: Surgical methods play a significant role in the treatment of gastroesophageal reflux disease (GERD) refractory to conservative therapy. There is no evidence-based consensus on the best choice of technique, posterior total (360o) Nissen fundoplication is the most widely used antireflux surgery technique worldwide. Therapy dependent and refractory GERD patients with psychiatric co-morbidity and/or antidepressant co-treatment araise challange in choice of best treatment methods. Aim of the study was to compare 6-month-results of Nissen fundoplication of psychiatric co-morbidity (PCM, n = 16) and antidepressant co-treatment (ADT, n = 17) as independent risk factors with general population data in our patients (n = 177) between 2011 – 2015. Results: Postoperative improvement of GERD symptoms occured in 86% (symptom-free ratio was 48.6%), in antidepressant treated group 88.2% (and 41%, respectively) and in case of psychiatric co-morbidity 56.2% (and 31.2%, respectively). Reoperation was needed in 2.82% of patiens (none in PCM or ADT group). Postoperative dysphagia occured in 28.8% (50% with PCM, 29% with ADT). Significant (> 10%) weight loss was measured 6 months after surgery in 24.8% (37.5% with PCM, 17.6% with ADT). Generally intervention because of surgery-associated comlication was needed in 10.2% (18.75% with PCM, 5.9% with ADT). Re-use of proton pump inhibitor (PPI) treatment was needed in 32.8% (62.5% with PCM, 35.3% with ADT) 6 month later. Conclusions: Similar to literature data psychiatric co-morbidity in itself worsens therapeutic results of Nissen fundoplication in objectively diagnosed therapy refractory and dependent GERD patients. However antidepressant use in itself does not seem to be a significant risk factor for it, it may decrease weight loss and some complication risk. More randomized data are needed to clear correlations in the matter.

846 Cost-Effectiveness of Routine Duodenal Biopsy for Celiac Disease Screening in Patients Undergoing Endoscopy for the Evaluation of Refractory Gastroesophageal Reflux

Background: Patients with refractory gastroesophageal reflux disease (GERD) may have undiagnosed celiac disease. These patients often undergo esophagogastroduodenoscopy to determine the etiology and severity of GERD. Because a duodenal biopsy is the gold standard for diagnosing celiac disease and a gluten-free diet is an effective treatment, performing routine duodenal biopsy during endoscopy may result in early diagnosis and symptom improvement, allowing for discontinuation of proton pump inhibitor therapy. We aimed to evaluate the cost-effectiveness of performing routine duodenal biopsy during endoscopy for diagnosing celiac disease in patients with refractory GERD. Methods: We constructed a decision tree using data from published literature to calculate cost-effectiveness of endoscopy with and without duodenal biopsy in a cohort of 10,000 40-year-old patients. Results: We found that the biopsy strategy would detect 70 out of 100 celiac disease patients in a cohort of 10,000 GERD patients undergoing endoscopy if the prevalence of celiac disease was 1% in this cohort. Up-front biopsy would increase the remaining quality-adjusted life years (QALYs) by 0.0032. Testing for celiac disease using this approach would increase the lifetime cost by $389 per patient. Compared with no biopsy, the biopsy strategy cost $55,693 per celiac case detected, and $121,875 per QALY gained. The incremental cost-effectiveness ratio (ICER) met the threshold of 1.8%, the specificity of biopsy was >98%, the cost of gluten-free diet was $5,874 per year. Increasing the sensitivity of duodenal biopsy to 100% did not affect the cost-effectiveness threshold. Conclusion: Esophagogastroduodenoscopy with duodenal biopsy for refractory GERD patients can be a cost-effective approach for screening when the prevalence of celiac disease in this patient population is 1.8% or greater.

847 Evaluation of Antibodies to Cytolethal Distending Toxin B (CdtB) and Vinculin in Celiac Disease

Background: Patients with refractory gastroesophageal reflux disease (GERD) may have undiagnosed celiac disease. These patients often undergo esophagogastroduodenoscopy to determine the etiology and severity of GERD. Because a duodenal biopsy is the gold standard for diagnosing celiac disease and a gluten-free diet is an effective treatment, performing routine duodenal biopsy during endoscopy may result in early diagnosis and symptom improvement, allowing for discontinuation of proton pump inhibitor therapy. We aimed to evaluate the cost-effectiveness of performing routine duodenal biopsy during endoscopy for diagnosing celiac disease in patients with refractory GERD. Methods: We constructed a decision tree using data from published literature to calculate cost-effectiveness of endoscopy with and without duodenal biopsy in a cohort of 10,000 40-year-old patients. Results: We found that the biopsy strategy would detect 70 out of 100 celiac disease patients in a cohort of 10,000 GERD patients undergoing endoscopy if the prevalence of celiac disease was 1% in this cohort. Up-front biopsy would increase the remaining quality-adjusted life years (QALYs) by 0.0032. Testing for celiac disease using this approach would increase the lifetime cost by $389 per patient. Compared with no biopsy, the biopsy strategy cost $55,693 per celiac case detected, and $121,875 per QALY gained. The incremental cost-effectiveness ratio (ICER) met the threshold of 1.8%, the specificity of biopsy was >98%, the cost of gluten-free diet was $5,874 per year. Increasing the sensitivity of duodenal biopsy to 100% did not affect the cost-effectiveness threshold. Conclusion: Esophagogastroduodenoscopy with duodenal biopsy for refractory GERD patients can be a cost-effective approach for screening when the prevalence of celiac disease in this patient population is 1.8% or greater.

Tu1885 Understanding the Cause of Persistent GERD Symptoms Despite Proton Pump Inhibitor Therapy: Impedance-pH Monitoring Revisited

BACKGROUND: Intraluminal impedance baseline (IB) levels are determined by the conductivity of the esophageal wall and have been shown to be decreased in gastro-esophageal reflux disease (GERD) patients. It has been proposed that IB values may be used as a marker of reflux-induced changes in esophageal mucosal integrity (Farre et al. 2011), although there is no complete agreement on the most appropriate time period to assess IB (upright or recumbent). Altered esophageal mucosal integrity has been proposed as one of the pathological mechanisms associated with persisting symptom perception in GERD patients. Nevertheless, possible alterations in mucosal integrity in refractory GERD patients have not been assessed. The aims of the present study were: 1) to test whether IB measurements differ between the upright and recumbent period in healthy volunteers (HV) and refractory GERD patients on PPI and 2) to evaluate whether mucosal integrity is impaired in refractory GERD patients. METHOD: Ambulatory 24-h pH-impedance tracings from 16 refractory GERD patients (46±4 years, 7 male) as well as 20 HV (49±3 years, 11 male) both on proton pump inhibitor (PPI) therapy (40 mg) were retrospectively analyzed. Mean IB levels in the distal at 3 and 5 cm and in the proximal esophagus at 15 cm were assessed in two stable periods of 30 seconds in a time window of 30 minutes (excluding swallows and reflux events), both in the upright and recumbent positions. Values were expressed as mean±SEM. RESULTS: Both in HV and refractory GERD patients on PPI therapy, mean baseline values at 3 and 5 cm were comparable in upright and recumbent position. Moreover, at 15 cm, IB values were significantly lower in the recumbent period only in HV. In the upright position, IB at 3, 5 and 15 cm was significantly lower in GERD patients compared to HV on PPI. In contrast, in the recumbent position there were no significant differences in IB values between GERD patients and HV. Nevertheless, there was a tendency for IB to be lower in patients both at 3 (p=0.06) as well as at 15 cm (p=0.06). CONCLUSIONS: Refractory GERD patients on PPI have an impaired mucosal integrity in the distal and proximal esophagus. IB measurements in the upright period seem superior to evaluate alterations in mucosal integrity in GERD patients and to distinguish them from health.