Refractory Gastroesophageal Reflux Disease Research Articles

A meta-analysis of the efficacy of traditional Chinese medicine alone in the treatment of refractory gastroesophageal reflux disease

A meta-analysis of the efficacy of traditional Chinese medicine alone in the treatment of refractory gastroesophageal reflux disease

Outcome of Stretta in a Tertiary Medical Center: A Safe and Effective Non-Surgical Option for Refractory GERD

Outcome of Stretta in a Tertiary Medical Center: A Safe and Effective Non-Surgical Option for Refractory GERD

ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro‐esophageal reflux disease

AbstractUp to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term “refractory GERD” has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD‐related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term “refractory GERD symptoms” only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.

Magnetic Sphincter Augmentation Placement for Recalcitrant Gastroesophageal Reflux Disease Following Bariatric Procedures: A Systematic Review and Bayesian Meta-Analysis.

Background: This study aims to consolidate all available articles on this topic and evaluate MSA effectiveness in the management of gastroesophageal reflux disease (GERD). Matherials and Methods: We conducted an electronic systematic search using MEDLINE databases (PubMed), EMBASE, and Web of Science. An electronic systematic search of articles comparing preoperative and postoperative health-related quality of life (GERD-HRQL) scores in patients who underwent MSA placement for management of GERD following bariatric surgery was performed. Three retrospective studies totaling 33 patients met the inclusion criteria and were included in this meta-analysis. Results: The pooled mean difference in change from preoperative GERD-HRQL score was 17.5 (95% CrI; -22.88 to -12.20) and it was statistically significant. The between-study variability is 3.621 (95% HPD; 1.39 4.99) with low heterogeneity (I2 = 15%; 95% HPD; 2.1 26.2%). Conclusions: MSA for refractory GERD following bariatric surgery appears feasible. Prospective randomized controlled with standardized surgical technique and objective follow-up evaluation is needed to better assess short- and long-term efficacy.

The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health.

Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5-HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5-HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5-HT in esophageal sensitivity in healthy volunteers (HV). Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo-controlled studies. In the first study, the effect of citalopram (40mg; 5-HT reuptake inhibitor; intravenous) was investigated (n=14). In the second study, the effect of buspirone (20mg; 5HT1A agonist; oral) was investigated (n=10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5-HT levels to investigate the effect of reduced 5-HT availability on esophageal sensitivity (n=15). No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p>0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD (p=0.017, Cohen's d+=0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. ATD, which induces 5-HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5-HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies.

Endoscopic gastric plication for the treatment of GERD and underlying class I obesity.

Endoscopic gastric plication for the treatment of GERD and underlying class I obesity.

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.

Gastroesophageal Reflux Disease and Need for Antireflux Surgery in Children with Cystic Fibrosis: A Systematic Review on Incidence, Surgical Complications, and Postoperative Outcomes.

Introduction Gastroesophageal reflux disease (GERD) is associated with accelerated decline in lung health in children with cystic fibrosis (CF). Thus, antireflux surgery (ARS) is offered to a selected CF cohort with refractory GERD, but outcomes remain poorly investigated. This study aimed to determine the incidence of GERD in children with CF and to evaluate complications and outcomes of ARS. Materials and Methods A systematic literature-based search was conducted using various online databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The number of GERD cases in pediatric CF cohorts who underwent diagnostic investigation(s) was recorded. Data on postoperative complications and outcomes (including symptoms, lung function, and nutritional status) following ARS were analyzed. Results Ten articles ( n = 289 patients) met the defined inclusion criteria (51% male; age range, 0.5 month–36 years). The overall incidence of GERD was 46% (range, 19–81%), derived from seven studies ( n = 212 patients). Four publications ( n = 82 patients) reported on ARS due to uncontrolled GERD. All ARSs were Nissen fundoplication (majority with gastrostomy placement). Major postoperative complications occurred in 15 (18%) patients, two required redo-ARS. Median follow-up time was 2 years (range, 3 months–6 years); 59% showed symptom improvement, and pulmonary exacerbations and decline in lung function were reduced. Nutritional status mainly improved in milder CF cases. There were no deaths related to ARS. Conclusion Approximately half of pediatric CF patients have GERD. Published data for children with CF are limited and heterogeneous in terms of GERD diagnosis and outcomes following ARS. However, ARS has shown to slow the deterioration of lung function in CF.

The early therapeutic response at 2weeks is a crucial predictor of proton pump inhibitor-refractory gastroesophageal reflux disease.

In recent years, the prevalence of proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) has been increasing, posing a clinical obstacle to improving the management of GERD patients. The ability of known predictive factors to explain therapeutic response to PPI remains insufficient. Therefore, we examined whether the addition of early therapeutic response to PPI as an explanatory variable may increase the predictive power for PPI-refractory GERD. The severity and therapeutic response of GERD symptoms to PPI were evaluated using the GastroEsophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test (GERD-TEST) questionnaire at baseline and at 2 and 4weeks after treatment. The relevance of the therapeutic effect of PPI at 2weeks compared to that at 4weeks was examined in 301 patients with GERD. Independent predictive factors for refractory GERD at 4weeks of PPI therapy were examined in 182 patients. The effect of various clinical factors, including the early response to PPI, was assessed using multiple regression analysis. The number of PPI-therapy responders increased significantly with the duration of treatment (p < 0.0001). The response to PPI therapy at 2weeks was significantly correlated with that at 4weeks (p < 0.0001). Multiple regression analysis revealed that the therapeutic response to PPI at 2weeks was by far the strongest predictor of the therapeutic effect at 4weeks among all clinical factors. Medication change for PPI-refractory GERD at 2weeks may be an efficacious therapeutic strategy to improve patients' quality of life.

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.

S0354 Outcomes of Anti-Reflux Surgery in Patients With PPI Refractory Erosive and Non-Erosive Gastro-Esophageal Reflux Disease: A Meta-Analysis

INTRODUCTION: The evidence has suggested that anti-reflux surgery is beneficial in patients with proton-pump inhibitor (PPI) refractory erosive gastroesophageal reflux disease (ERD). The outcomes of surgical intervention in patients with PPI refractory non-erosive reflux disease (NERD) compared to ERD remains unclear. METHODS: 5 prospective observational studies investigating the outcomes of anti-reflux surgery in PPI refractory-NERD and -ERD were selected using PubMed, EMBASE and MEDLINE databases (inception April 2020). The primary endpoint was post-surgical GERD symptom resolution. The secondary endpoints were short-term (≤1-year) and long-term (>1-year) mean improvement in quality of life (QOL). The outcomes were measured as relative risk (RR) and standardized mean difference (SMD) with a 95% confidence interval (CI) using the fixed effect model. RESULTS: In analysis comprising of 670 patients with a mean age of 47.6 ± 3.1 years and 60.5% males, the anti-reflux surgery led to significantly higher GERD symptom resolution in the ERD group as compared to the NERD group as shown in Figure 1 (RR: 1.15, 95% Cl 1.01–1.31, P = 0.04, I2 = 0). There was significant improvement in short-term QOL in both NERD (SMD: 0.28, 95% Cl 0.13-0.44, P < 0.001, I2 = 0) and ERD groups (SDM: 0.34, 95% Cl 0.18–0.50, P < 0.001, I2 = 0). Similarly, long-term QOL significantly improved after surgery in both NERD (SDM: 0.30, 95% Cl 0.14–0.45, P < 0.001, I2 = 13) and ERD groups (SDM: 0.23, 95% Cl 0.07–0.39, P = 0.005, I2 = 0). CONCLUSION: Anti-reflux surgery achieved greater GERD symptom resolution in patients with PPI-refractory ERD as compared to NERD, however, improved short- and long-term QOL in PPI refractory GERD irrespective of mucosal changes evidenced on endoscopy. Randomized controlled trials are required to further validate this data.Figure 1.: Forest Plot demonstrating GERD symptom resolution after anti-reflux surgery in PPI refractory non-erosive gastroesophageal reflux disease (NERD) and erosive esophageal reflux disease (ERD).

S3419 Excessive Effervescent Salicylate Use as a Cause for Refractory Esophagitis

INTRODUCTION: Refractory gastroesophageal reflux disease (GERD) is not an uncommon clinical scenario, and many times, these patients do not even have GERD. Patients typically respond to a trial of a proton pump inhibitor (PPI). However, as many as 40% of patients do not improve with PPI alone, which is referred to as refractory esophagitis (RE). These patients may have eosinophilic esophagitis, malignancy, or pill esophagitis. Here we present the case of a man with RE despite multiple endoscopic interventions and medical treatment. CASE DESCRIPTION/METHODS: A 73-year-old man with rheumatoid arthritis presented with several years of dysphagia to solid food with associated burning chest pain after eating. He underwent 3 upper endoscopy procedures in our health system from November 2019 to March 2020. He was found to have Los Angeles grade D esophagitis, large hiatal hernia and mild lower esophageal stenosis with associated ulceration during each scope. He was started on PPI in November 2019 with reported compliance. However, the ulceration persisted and prevented safe dilation of the stricture. Biopsies showed no eosinophilic infiltrate or metaplasia. On further investigation, patient reported he was taking an effervescent medication containing aspirin, sodium bicarbonate, and citric acid (Alka-Seltzer) 6–8 times per day since the Vietnam War for headaches and indigestion. He reluctantly agreed to stop the medication. He reported mild improvement in his symptoms in May 2020, although he admitted to still occasionally taking the antacid. DISCUSSION: This case highlights the importance of taking a detailed history, particularly when patients are not responding to therapy as expected. There are hundreds of drugs, including NSAIDS, known to cause esophagitis. Many patients are unaware of the anti-inflammatory components of common over-the-counter medications, so a careful history is needed. Avoidance of the inciting agent almost always results in resolution of the esophagitis and can prevent more severe complications. The hiatal hernia may also have contributed, but lack of improvement with PPI should have prompted more investigation. A thorough history and better rapport could have prevented his RE from leading to strictures and dysphagia.

S0957 Outcome of Stretta in a Tertiary Medical Center: A Safe and Effective Non-Surgical Option for Refractory GERD

INTRODUCTION: GERD is a common chronic condition that can affect quality of life. For a subset of patients, GERD is refractory to lifestyle changes and medications, including PPIs and H2 receptor blockers. Surgical therapies include Nissen fundoplication, but for patients who have already attempted this or do not wish to have surgery, the Stretta procedure is a valuable option. The Stretta procedure delivers radiofrequency energy along the GE junction through an endoscopic catheter. This mechanically alters the GEJ and modulates neural pathways to reduce the frequency of lower esophageal sphincter relaxation. Successful procedures result in symptom resolution, mucosal healing, and/or increased health-related quality of life (HRQoL). METHODS: Retrospective chart review of all patients who underwent the Stretta procedure for GERD from 2005 to 2019 at our center was conducted. Demographics, clinically noted GERD symptoms, including dysphagia heartburn, reflux, and breakthrough symptoms, and PPI usage at baseline and post-procedure were reviewed. RESULTS: Fifty-nine procedures were performed on 56 patients (average age 52.3 years, range 20–82 years, women = 40) from 2005 to 2019. All procedures were performed in an outpatient endoscopy suite. Five patients were lost to follow-up. At 6-month follow-up, 21/51 patients (41%) successfully reduced their PPI dosage by at least half. Symptom resolution was determined by percentage decrease of number of symptoms. Thirty-four out of 51 patients reported symptom improvement, averaging a 78.5% decrease in number of symptoms. The average symptomatic improvement was a 54% decrease in number of symptoms. One patient who had decrease in 1 out of 3 symptoms underwent a second Stretta and had full response after the subsequent procedure. Seventeen patients experience no improvement. Two of these 17 patients underwent a second procedure without improvement. There were no reported long-term procedure-related complications. CONCLUSION: The Stretta procedure can help patients with severe refractory GERD. In our review, two-thirds of patients had meaningful improvement in symptoms. More than two-fifths of patients were able to reduce their PPI dosage. No long-term procedure-related complications were noted. The strength of the review was limited due to the small number of patients and lack of objective markers, such as first-hand HRQoL questionnaires. This can be utilized on future patients to further assess quality of life improvement with the procedure.

S0918 Transoral Incisionless Fundoplication in a Treatment of Refractory GERD: a Retrospective Experience at a Large Quaternary Care Center

S0918 Transoral Incisionless Fundoplication in a Treatment of Refractory GERD: a Retrospective Experience at a Large Quaternary Care Center

S0388 High Prevalence of Opioid Use Among U.S. GERD Patients With and Without Refractory GERD Symptoms

S0388 High Prevalence of Opioid Use Among U.S. GERD Patients With and Without Refractory GERD Symptoms

Application of magnetic sphincter augmentation for treating gastroesophageal reflux disease

The lower esophageal sphincter incompetent is fundamental pathological abnormality of gastroesophageal reflux disease (GERD). Magnetic sphincter augmentation (MSA) is a magnetic bracelet, which designed to be placed surgically around the exterior surface of the distal esophagus. In the closed position, the highest attractive force between the magnetic beads would reinforce the lower esophageal sphincter to strengthen the antireflux barrier. Animal experiments and clinical trials have verified the safety and efficacy of MSA in GERD patients. For refractory GERD and GERD with huge hernia, MSA can also achieve acceptable clinical effect. Comparative researches appeared that there is no significantly difference in clinical effect between Nissen fundoplication and MSA. MSA could preserve the function of belching and vomiting postoperatively, and it can be implanted with the use of standard laparoscopic techniques. The long-term effect of MSA is satisfactory with less complications, which has been carried out in China since 2018. It can be predicted that MSA will play an important role in the treatment of GERD in the future.

Resolution of Erosive Esophagitis After Conversion from Vertical Sleeve Gastrectomy to Roux-en-Y Gastric Bypass.

BackgroundLaparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, there is one shortcoming of LSG in the long-term follow-up, and this is the onset of gastro-esophageal reflux disease (GERD) and erosive esophagitis (EE). Conversion to Roux-en-Y gastric bypass (RYGB) is considered an option in patients unresponsive to medical therapy. Currently, there is no evidence of EE improvement or resolution after conversion surgery. In this study, we objectively evaluate the effectiveness of RYGB in management of EE with upper endoscopy (EGD) to identify the significant variables in patients with GERD symptoms post LSG refractory to medical therapy and require conversion surgery.MethodsOver a period of 11 years (2008–2019) at Singapore General Hospital, we retrospectively reviewed a prospectively collected database of a cohort of patients whom had conversion surgery to RYGB for refractory GERD and EE after LSG. Patient’s endoscopic findings and demographic and anthropometric data were analyzed.ResultsWe identified a total of 14 patients who underwent LSG to RYGB conversions for endoscopic proven erosive esophagitis in our unit during the study period. Eight patients (57.1%) had concurrent hiatal hernia repaired. Nine (64.3%) patients were females. The median age of patients in this cohort was 44 (range 30–61) years. Mean weight and BMI were 87.7 kg (± 19.2) and 32.8 (± 3.09) kg/m2, respectively, on the day of conversion surgery. The median time between LSG and revision to RYGB was 36 (range 6–68) months. Seven patients (50%) had complete resolution of GERD symptoms after conversion, and 6 patients (42.9%) had partial resolution. Six out of 7 patients had complete resolution of EE. There were 4 anastomotic strictures (28.6%). Older patients, Indian ethnicity, present of hiatal hernia and lower weight loss after initial LSG were more likely to undergo conversion surgery.ConclusionConversion to RYGB after LSG is clinically relevant and may be a feasible solution if patients have ongoing GERD refractory to medical therapy. Ninety-three percent of our patients achieved complete resolution of their GERD symptoms and significant improvement of erosive esophagitis with significant weight loss after conversion. This study has important implications as LSG is increasingly being performed and a proportion of these will need revision surgery for various reasons, particularly GERD which is extremely prevalent.

Efficacy and patient satisfaction of single-session transoral incisionless fundoplication and laparoscopic hernia repair.

Transoral incisionless fundoplication (TIF) is an effective endoscopic treatment for refractory GERD with small or absent hiatal hernia (<2cm in length and width). The single-session laparoscopic hernia repair followed by transoral incisionless fundoplication (HH+TIF) aims to repair mechanical defects in the lower esophageal sphincter that leads to GERD in patients with hiatal hernias≥2cm. The procedure effectively treats GERD without causing added post-surgical dysphagia and gas bloating commonly associated with partial laparoscopic fundoplication. We aimed to assess patient satisfaction, symptom resolution, safety, and proton pump inhibitor use following the HH+TIF procedure. Thirty-three patients underwent single-session laparoscopic hernia repair with intraoperative TIF using the EsophyX Z device (EndoGastric Solutions, Inc.) between June 2015 and June 2018. The presence of GERD and normal esophageal motility were confirmed with pH testing and manometry prior to the procedure. Data were collected on pre- and post-procedure symptoms, patient satisfaction, PPI use, and complications. Median post-procedure follow-up with symptom surveys was 9months (11-29months). Patients reported significant decreases in common GERD symptoms including heartburn, regurgitation, cough, and hoarse voice. Eighty-one percent (27/33) of patients were off daily PPIs. Ninety-four percent (31/33) of patients reported 75% or greater satisfaction with the procedure and outcomes. One patient had a superficial mucosal laceration after the procedure, likely due to vomiting, which was treated conservatively. The majority of patients reported 75% or greater satisfaction with the procedure and had an improvement in GERD symptoms as well as decreased PPI use. There were no serious adverse events.

Antireflux Mucosectomy Band (ARM-b) in Treatment of Refractory Gastroesophageal Reflux Disease After Bariatric Surgery.

Laparoscopic sleeve gastrectomy has become the most commonly used bariatric surgery worldwide. However, there are a proportion of patients who present with a refractory GERD after this procedure. In these patients, when surgical conversion to RYGPB is not possible or declined, we propose to describe the results of an endoscopic antireflux mucosectomy band (ARM-b) technique in 6 LSG patients with refractory GERD. The technical feasibility was 100%; 5 out of 6 patients had a clinical response with a reduction of the GERD-HRQL score of > 50%. Two patients had adverse events: one esophageal stricture and one benign bleeding. ARM-b is feasible and potentially effective to treat patients with refractory GERD after LSG.

New developments in esophageal function testing and esophageal manifestations of connective tissue disorders.

This work summarizes new and emerging metrics and tools in esophageal function testing and their potential clinical impact. Because the diagnostic sensitivity and reliability of conventional impedance-pH variables are suboptimal, several novel impedance parameters, such as the postreflux swallow-induced peristaltic wave index and the mean nocturnal baseline impedance, as well as mucosal impedance, are entering a validation stage prior to general clinical use. The accurate diagnosis of behavioral disorders in patients with rumination syndrome and supragastric belching using ambulatory multiple intraluminal impedance-pH can lead directly to behavioral interventions in patients with refractory gastroesophageal reflux disease (GERD). New provocative measures, such as multiple rapid swallows and the rapid drink challenge, have been developed to overcome the limitations of standard high-resolution esophageal manometry, aiming at further clarifying esophageal dysmotility. Furthermore, the current diagnostic and therapeutic challenges in patients with esophageal involvement in Sjogren's syndrome and scleroderma, who tend to have severe forms of GERD, are entering a new investigative and clinical phase.