PPI-refractory Gastroesophageal Reflux Disease Research Articles

Multicentric short term and safety study of ineffective esophageal motility patients treated with RefluxStop device

Gastroesophageal reflux disease (GERD) presents a general health problem with a variety of symptoms and an impairment of life quality. Conservative therapies do not offer sufficient symptom relief in up to 30% of patients. Patients who suffer from ineffective esophageal motility (IEM) and also GERD may exhibit symptoms ranging from mild to severe. In cases where surgical intervention becomes necessary for this diverse group of patients, it is important to consider the potential occurrence of postoperative dysphagia. RefluxStop is a new alternative anti-reflux surgery potentially reducing postoperative dysphagia rates. In this bicentric tertiary hospital observational study consecutive patients diagnosed with PPI refractory GERD and IEM that received RefluxStop implantation were included. A first safety and efficacy evaluation including clinical examination and GERD-HRQL questionnaire was conducted. 40 patients (25 male and 15 female) were included. 31 patients (77.5%) were on PPI at time of surgery, with mean acid exposure time of 8.14% ± 2.53. The median hospital stay was 3 days. Postoperative QoL improved significantly measured by GERD HRQL total score from 32.83 ± 5.08 to 6.6 ± 3.71 (p < 0.001). A 84% reduction of PPI usage (p < 0.001) was noted. 36 patients (90%) showed gone or improved symptoms and were satisfied at first follow-up. Two severe adverse events need mentioning: one postoperative slipping of the RefluxStop with need of immediate revisional operation on the first postoperative day (Clavien–Dindo Score 3b) and one device migration with no necessary further intervention. RefluxStop device implantation is safe and efficient in the short term follow up in patients with GERD and IEM. Further studies and longer follow-up are necessary to prove long-lasting positive effects.

Does the presence of an esophageal motor disorder influence the response to anti-reflux mucosectomy (ARMS) for refractory GERD?

Introduction The prevalence of esophageal motor disorders (EMD) in PPI-refractory gastroesophageal reflux disease (GERD) is substantial. However, limited data exist on their impact on the efficacy of endoscopic treatments like anti-reflux mucosectomy (ARMS). This study aimed to evaluate the influence of EMD on ARMS efficacy in patients with PPI-refractory GERD. Method This single-center retrospective study enrolled patients with refractory GERD treated with ARMS-b (anti-reflux mucosectomy band-ligation). High-resolution esophageal manometry (HREM) was conducted before the procedure to identify EMD presence. The primary endpoint was treatment efficacy, defined as >50% improvement in GERD-HRQL score at 1 year. Secondary endpoints included PPI intake, symptom control, ARMS complications, and overall patient satisfaction at 12 months. Results The study included 65 patients, with 41 (63.1%) showing EMD on HREM. Treatment efficacy was achieved by 33.8% (22) of patients, with 8 without EMD, 11 having isolated LES hypotonia, and 3 with both LES hypotonia and esophageal body motor disorder. No significant differences were observed between patients with and without EMD regarding the primary endpoint, PPI use, symptom control, or complications. Dysphagia developed in 52.3% (34) within 6 months, leading to esophageal dilatation in 15.3% (10). Two patients experienced acute hemorrhage, and one had perforation. Conclusion The presence of esophageal motor disorders does not seem to impact ARMS response, suggesting the technique’s consideration in this population. Larger studies are essential for confirming these results and exploring treatment response and post-operative predictors.

Endoscopic Non-ablative Radiofrequency Treatment (Stretta) for Gastroesophageal Reflux Disease (GERD).

Gastroesophageal reflux disease (GERD) is very common in the general population and poses a large societal socio-economic burden. In this article, we review the evidence supporting non-ablative radiofrequency treatment (Stretta) for the endoscopic management of GERD and we compare it to pharmacologic and other minimally invasive and surgical interventions. Proton pump inhibitors (PPI) are a key therapy for GERD. For patients without associated significant sliding hiatal hernia, who have inadequate relief of their reflux symptoms, Stretta and other endoscopic therapies, such as transoral fundoplication (TIF), may improve symptoms and GERD-related quality of life. Unfortunately, there are no recent large randomized controlled trials, and most of the evidence is based on meta-analyses and small scale, prospective and retrospective single center efforts. Comparisons of Stretta efficacy to other anti-reflux endoscopic modalities and anti-reflux surgery (ARS) are also presented. There are several endoscopic and minimally invasive modalities to manage PPI-refractory GERD acting through various mechanisms that have been found effective in managing GERD symptoms and quality of life. Among them, Stretta has the longest track record of efficacy and safety. Larger-scale and longer-term comparative efficacy trials in selected populations of patients with acid reflux with and without hiatal hernia will be needed.

Randomized Controlled Trial of Anti-reflux Mucosectomy Versus Radiofrequency Energy Delivery for Proton Pump Inhibitor-refractory Gastroesophageal Reflux Disease.

The efficacy and safety of anti-reflux mucosectomy (ARMS) or radiofrequency energy delivery in the treatment of gastroesophageal reflux disease (GERD) have been reported, but the difference between the 2 remains unclear. This was a single center, randomized, comparative clinical study. Patients with symptoms of heartburn and/or regurgitation despite proton pump inhibitor treatment were randomly assigned to either ARMS group (n = 20) or radiofrequency group (n = 20). Primary outcome was the standardized GERD questionnaire (GERDQ) at 2 years after the procedures. Secondary outcomes were the proportions of patients with complete proton pump inhibitor (PPI) cessation and patients satisfied with the treatment. A total of 18 patients randomized to ARMS and 16 to radiofrequency were analyzed in this study. The operation success rate of the 2 groups was 100%. In both ARMS and radiofrequency groups, GERDQ scores at 2 years after the procedures were significantly lower than that before operation (P = 0.044 and P = 0.046). At 2 years postoperatively, the scores of GERDQ did not differ between the 2 groups (P = 0.755). There was no significant difference in the rate of discontinuation of PPIs and patient satisfaction in the ARMS and radiofrequency groups (P = 0.642 and P = 0.934). The clinical efficacy of ARMS and radiofrequency for the PPI-refractory GERD is equivalent. ARMS, the efficacy of which could be maintained for at least 2 years, is promising endoscopic management for the treatment of refractory GERD.

Vonoprazan - a new drug for inhibiting gastric acid secretion

Introduction and purpose &#x0D; Vonoprazan is a potassium-competent acid blocker (P-CAB). It has the potential to be an alternative to proton pump inhibitors (PPIs) as it inhibits hydrochloric acid secretion. The mechanism of action is different than PPIs - vonoprazan reversibly inhibits gastric H+, K+-ATPase, while PPIs irreversibly. Vonoprazan is approved for use in Japan and the US. The aim of the study was to review articles on the use of vonoprazan instead of PPIs in the treatment of acid-related gastrological diseases and to present the results obtained. &#x0D; &#x0D; A brief description of the state of knowledge &#x0D; Vonoprazan is used in the treatment of acid-related gastrological diseases. The 20 mg dose is suitable for most diseases, such as treatment of ulcers during low-dose aspirin treatment, post-endoscopic submucosal dissection (post-ESD) ulcers, erosive esophagitis (EE) in gastroesophageal reflux disease (GERD), and Helicobacter pylori eradication. &#x0D; &#x0D; Summary &#x0D; Researches suggest that the drug is an alternative for PPIs and can be used instead of them. The main advantage of this drug over PPIs is that it works faster, more potent and long-lasting. Studies suggest that vonoprazan can be use to treatment of the acid-related diseases and may be a better choice than PPIs. Vonoprazan may have a particular use in the treatment of PPI-refractory GERD. In post-ESD ulcers, a significant benefit in treatment effects of vonoprazan over PPIs cannot be clearly concluded.

Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Bulgaria: An Internet-Based Survey

Background: The global pooled prevalence of gastroesophageal reflux disease (GORD) is approximately 14% and varies significantly according to the country. More population-based studies are needed in regions lacking epidemiological data on the prevalence of GORD, such as Eastern Europe, particularly Bulgaria. This current study aimed to evaluate the prevalence of GORD in Bulgaria and assess the risk factors associated with this disorder. Methods: An internet-based health survey was sent to Bulgarian adults. Individuals were invited to complete an online questionnaire on general and gastrointestinal health. The aim of the study was not explicitly stated. The survey collected data on sociodemographic and behavioral characteristics, validated questions to assess GORD, diagnostic questions based on Rome IV criteria to assess irritable bowel syndrome (IBS) and functional dyspepsia (FD), and questions about antisecretory drugs usage. Results: Data were collected from 1,896 individuals (mean age = 35.5 years, SD = 11.7, 73.1% females). The prevalence of GORD in the study population was 27.5%, while 57.29% of all GORD patients taking PPIs had PPI-refractory GORD. Age (p = 0.02), body mass index (BMI) (p < 0.001), marital status (p = 0.03), occupation (p < 0.001), sexual problems (p < 0.001), FD (p < 0.001), and IBS (p < 0.001) were significantly associated with GORD prevalence. Patients with FD (p < 0.001; OR 5.38), IBS (p = 0.03; OR 1.07), and with higher BMI (p < 0.001, OR 1.05) were at an increased risk of having GORD. Conclusions: The first data on GORD prevalence in the adult population in Bulgaria have been reported. Disorders of gut-brain interaction have a significant impact on the prevalence of GORD.

EZH2-mediated suppression of CLDN1 leads to barrier dysfunction in PPI-refractory gastroesophageal reflux disease.

PPI-refractory gastroesophageal reflux disease (RGERD) is characterized as the existence of reflux symptoms resistant to optimized PPI treatment. Alleviated mucosal integrity has been regarded as one of the mechanisms of RGERD. RNA sequencing analysis and GSEA were performed. Human biopsy samples, cell lines, and rat models were recruited. Trans-epithelial electrical resistance (TEER) was tested and a FITC-dextran flux assay was performed to detect barrier permeability. Tissue morphology was evaluated using HE staining, while gene expression was measured by qRT-PCR, western blotting, flow cytometry, immunofluorescence, immunohistochemistry, and chromatin immunoprecipitation (ChIP) analysis. The tight junction protein Claudin-1 is significantly weakened in the RGERD epithelium, while levels of EZH2-mediated H3K27me3 were increased. Forced EZH2 expression in epithelial cells led to H3K27me3 accumulation and Claudin-1 suppression, which consequently caused epithelial barrier dysfunction. Notably, studies on esophagogastroduodenal anastomosis (EGDA) rat models showed the attenuation of Claudin-1 level and barrier function could be rescued by an Ezh2 inhibitor GSK126. ChIP analysis followed by qPCR (ChIP-qPCR) revealed H3K27me3 suppressed CLDN1 via accumulating at the TSS area. For the first time, we explored the attenuated tight junction of RGERD, demonstrating a potential underlying mechanism that EZH2-mediated H3K27me3 could impair esophageal epithelial barrier function by suppressing the transcription of CLDN1.

Antireflux mucosal intervention (ARMI) procedures for refractory gastroesophageal reflux disease: a systematic review and meta-analysis.

Background:Endoscopic treatments are increasingly being offered for refractory gastroesophageal reflux disease (GERD). Three procedures have similar concepts and techniques: antireflux mucosectomy (ARMS), antireflux mucosal ablation (ARMA), and antireflux band ligation (ARBL); we have collectively termed them antireflux mucosal intervention (ARMI). Here, we systematically reviewed the clinical outcomes and technical aspects.Methods:The PubMed, Embase, and Cochrane Library databases were searched from inception to October 2021. The primary outcome was the clinical success rate. The secondary outcomes were acid exposure time, DeMeester score, need for proton pump inhibitors (PPIs), endoscopic findings, and adverse events.Results:Fifteen studies were included. The pooled clinical success rate was 73.8% (95% confidence interval (CI) = 69%–78%) overall, 68.6% (95% CI = 62.2%–74.4%) with ARMS, 86.7% (95% CI = 78.7%–91.9%) with ARMA, and 76.5% (95% CI = 65%–85.1%) with ARBL. ARMI resulted in significantly improved acid exposure time, DeMeester score, and degree of hiatal hernia. Furthermore, 10% of patients had dysphagia requiring endoscopic dilatation after ARMS or ARMA, and ARMS was associated with a 2.2% perforation rate. By contrast, no bleeding, perforation, or severe dysphagia was noted with ARBL. Severe hiatal hernia (Hill grade III) may predict treatment failure with ARMA.Conclusions:The three ARMI procedures were efficacious and safe for PPI-refractory GERD. ARMA and ARBL may be preferred over ARMS because of fewer adverse events and similar efficacy. Further studies are necessary to determine the optimal technique and patient selection.

Outcomes of endoscopic submucosal dissection for gastroesophageal reflux disease (ESD-G) for medication-refractory gastroesophageal reflux disease: 35 cases underwent ESD-G including 15 cases followed more than 5\xa0years

BackgroundAlthough some kinds of endoluminal surgery for patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) have been reported, there are few reports on their long-term outcomes. In 2014, we reported the effectiveness of endoscopic surgery for PPI-refractory GERD, which we invented and named endoscopic submucosal dissection for GERD (ESD-G) in 2008. Thereafter, we accumulated more cases and monitored the patients’ condition postoperatively and describe the outcomes herein.Patients and methodsThis single-center, single-arm trial was conducted at the Osaka Medical and Pharmaceutical University Hospital. We compared outcomes between before and 3–6 months after ESD-G. Additionally, we investigated the outcomes of patients 5 or more years after ESD-G.ResultsWe performed 42 ESD-G procedures in 35 patients between 2008 and 2020. In seven patients, ESD-G was performed twice for various reasons. The frequency scale for the symptoms of GERD score was significantly improved 3–6 months after ESD-G (22 → 10, p < 0.0001); the Los Angeles classification for reflux esophagitis was clearly improved after ESD-G (p = 0.0423). The number of reflux episodes was not decreased by ESD-G. There was a significant difference in the potency unit of gastric acid secretion suppressants for controlling GERD-related symptoms between baseline and 3–6 months after ESD-G (p = 0.0009). In patients without a history of distal gastrectomy who underwent ESD-G, the potency unit of gastric acid secretion suppressants significantly decreased 5 or more years after ESD-G (p = 0.0121).ConclusionESD-G may be effective in patients with refractory GERD-related symptoms without a history of distal gastrectomy.

CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM).

Background and study aims Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms. Patients and methods This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013–2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily. Results POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8–11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics. Conclusions Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.

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.

Belching in Gastroesophageal Reflux Disease: Literature Review.

Belching is a common phenomenon. However, it becomes bothersome if excessive. Impedance–pH monitoring can classify the belching into two types: gastric belching and supragastric belching (SGB). The former is a physiological mechanism to vent swallowed air from the stomach, whereas the latter is a behavioral disorder. Gastroesophageal reflux disease (GERD) is the most relevant condition in both types of belching. Recent findings have raised awareness that excessive SGB possibly sheds light on the pathogenesis of a part of proton pump inhibitor (PPI) refractoriness in GERD. SGB could cause typical reflux symptoms such as heartburn, regurgitation or chest pain in two ways: SGB-induced gastroesophageal reflux or SGB-induced esophageal distension. In PPI-refractory GERD, it is important to detect hidden SGB as a cause of reflux symptoms since SGB requires psychological treatment instead of high dose PPIs or pain modulators. In the case of PPI-refractory GERD with excessive SGB, recent studies imply that the combination of a psychological approach and conventional treatment can improve treatment outcome.

Supragastric belching in Japan: lower prevalence and relevance for management of gastroesophageal reflux disease compared to United Kingdom

BackgroundSupragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK.MethodsWe re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries.ResultsImpedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P < 0.001). Japanese patients had significantly lower prevalence of excessive SGB (18.5%) than the UK (36.1%) irrespective of reflux phenotype (P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09–7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0–4.9)] compared to the UK [35% (0–54.1)] (P = 0.071).ConclusionsThe prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.

Endoscopic treatment of proton pump inhibitor-refractory gastroesophageal reflux disease with anti-reflux mucosectomy: Experience of 109 cases.

Some patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) therapy. Anti-reflux mucosectomy (ARMS) is a minimally invasive endoscopic procedure for treatment of GERD. In this study, we retrospectively evaluated the outcomes of ARMS performed in patients with PPI-refractory GERD at our institution. A total of 109 patients with PPI-refractory GERD who underwent ARMS were retrospectively reviewed. Pre- and post-ARMS questionnaire scores, acid exposure time (AET), DeMeester score, proximal extent, and PPI discontinuation rate were compared. There was a significant improvement in the symptom score (P<0.01) and 40-50% of patients were able to discontinue PPI after ARMS. In patients who were followed up for 3years, sustained improvement in subjective symptoms was observed. AET and DeMeester score significantly improved after ARMS (P<0.01); however, there was no significant improvement in proximal extent (P=0.0846). Anti-reflux mucosectomy is an effective minimally invasive therapy for patients with PPI-refractory GERD. The therapeutic efficacy is attributable to suppression of acid backflow due to contraction of the scar tissue in cardia.

The Effects of Diaphragmatic Breathing and Omeprazole on Respiratory Indices and Diaphragmatic Excursion in Patients with Gastroesophageal Reflux Disease

Background: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders that can disturb patients’ respiratory indices. Proton pump inhibitors (PPIs) such as omeprazole are currently the most common treatment in the patients. PPI-refractory GERD is a clinical problem constituting around 30% of patients with GERD. Objectives: The aim of this study was to investigate the effects of diaphragmatic breathing (DB) and omeprazole on respiratory indices (RI) and diaphragmatic excursion (DEX) in patients with GERD. Methods: This is a clinical trial conducted for eight weeks among 40 patients with severe GERD in Tehran in 2018. The block randomization method was designed to randomize 40 patients into two groups (DB and control) that resulted in equal sample sizes. The control group received omeprazole 20 mg once daily, and the DB group, in addition to omeprazole, performed DB. Respiratory indices, including (Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), Peak Expiratory Flow (PEF)), and DEX were evaluated before, immediately, and six weeks after the end of intervention by spirometry and ultrasonography; respectively. Results: There was no significant difference in the RI and DEX before the intervention between groups. FVC (P = 0.04) and PEF (P = 0.02) significantly changed in the control group, but FEV1 (P = 0.001), FVC (P = 0.002), PEF (P = 0.001) and DEX (0.001) significantly changed after DB. There was a significant difference in terms of RI between before and followed up in DB. Conclusions: Diaphragmatic breathing with omeprazole had more effects on RI and DEX than omeprazole alone. The positive effects of DB remain at least six weeks after the end of the intervention.

Association of residual gastric acid secretion with persistent symptoms in gastroesophageal reflux disease patients receiving standard-dose proton pump inhibitor therapy.

Although a third of gastroesophageal reflux disease (GERD) patients are refractory to proton pump inhibitor (PPI) therapy, the underlying mechanism of the refractoriness remains unclear. We compared the level of gastric acid suppression during PPI treatment between responders and non-responders by directly measuring gastric acid secretion in GERD patients taking PPIs. Seventy-five consecutive patients receiving standard-dose PPI therapy for GERD were prospectively recruited, irrespective of persistent GERD symptoms. They were asked about their GERD symptoms using a validated questionnaire, and simultaneously underwent both a routine endoscopic examination and a gastric acid secretory testing using an endoscopic gastrin test. Associations between residual gastric acid secretion during PPI treatment and persistent GERD symptoms were analyzed by a logistic regression analysis. Overall, 26 of 75 (34.7%) patients were judged to be positive for persistent GERD symptoms. The patients with and without persistent symptoms showed similar gastric acid secretion levels (1.3 [1.3]mEq/10min vs. 1.4 [2.0]mEq/10min). Sufficient gastric acid suppression, defined as < 0.6, was not significantly associated with persistent GERD symptoms (odds ratio 1.1, 95% confidence interval 0.40-3.5). This study provided solid evidence to support that the gastric acid suppression level during PPI treatment does not differ between patients with and without persistent GERD symptoms. The insignificant role of residual gastric acid in the persistent GERD symptoms suggests that the use of medications other than those that enhance gastric acid inhibitory effects would be an essential approach for the management of PPI-refractory GERD.

A PROSPECTIVE STUDY INVOLVING COMPARISON OF ACOTIAMIDE WITH RABEPRAZOLE VS. DOUBLE DOSE RABEPRAZOLE IN PATIENTS HAVING OVERLAPPING SYMPTOMS OF PROTON PUMP INHIBITOR REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE AND FUNCTIONAL DYSPEPSIA

Introduction: Gastroesophageal reflux disease (GERD) is a digestive disorder that affects the lower esophageal sphincter (LES). Functional dyspepsia (FD) is characterized by troublesome early satiety, epigastralgia or heart burn. It is often overlooked as the symptoms overlap with GERD. This study aims to compare the effectiveness of Acotiamide+Rabeprazole vs. a double dose of Rabeprazole in Indian population.&#x0D; Method: In this study 60 patients diagnosed with PPI refractory GERD (taking PPI&gt;8weeks) and FD with no gastric or duodenal organic abnormalities were randomly allocated in two groups. Group 1 received a combination of Acotiamide (200mg/day) +Rabeprazole (20mg/day) and group 2 received a double dose of Rabeprazole (40mg/day). Follow ups were done every month for 3 consecutive months. The frequency and severity of symptoms were assessed using standard Izumo scale and FSSG scale.&#x0D; Results: The total score and GERD score from the baseline were significantly reduced in group 1 however the reduction in FD score from baseline did not differ significantly in the two treatment groups according to F-scale. The proportion of patients with ≥ 50% reduction in the total score for three upper gastrointestinal symptoms (heart burn, epigastralgia, and epigastric fullness) in the izumo scale was 96.7% in group 1 and 33.3% in group 2. Significant difference were noticed between the two groups. No serious adverse events were observed.&#x0D; Conclusion: The combination group of Acotiamide+Rabeprazole was found to be more effective than double dose of Rabeprazole in reducing the overlapping symptoms of PPI refractory GERD and FD.

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.

Anti-reflux mucosal ablation (ARMA) as a new treatment for gastroesophageal reflux refractory to proton pump inhibitors: a pilot study.

Background The incidence of proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) has been increasing. While surgical intervention with Laparoscopic Nissen Fundoplication remains the gold standard, less invasive anti-reflux interventions are desired. We have developed a minimally invasive anti-reflux mucosal ablation (ARMA) treatment. Herein, we report its technical details and describe its feasibility, safety, and efficacy in PPI-refractory GERD. Methods We conducted a prospective single-center single-arm interventional trial evaluating the outcome of ARMA in 12 patients with PPI-refractory GERD. GERD-Health Related Quality of Life Questionnaire (GERD-HRQL) evaluation, Frequency Scale for the Symptoms of GERD (FSSG) assessment, and impedance-pH monitoring were performed at baseline and at 2 months post-ARMA. Results A total of 12 patients underwent ARMA with a median follow-up duration of 9 months (range: 6 – 14 months). Median GERD-HRQL score significantly improved from 30.5 to 12 ( P = 0.002); median FSSG score significantly improved from 25 to 10.5 ( P = 0.002), and median DeMeester score decreased from 33.5 to 2.8 ( P = 0.049) at 2 months follow-up. No immediate complications were observed. Conclusion Our pilot study has shown that ARMA, a new endoscopic treatment for PPI-refractory GERD, is simple, safe, and improves GERD-related symptoms and objective acid reflux parameters.

Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor-Refractory Symptoms

There are few data on the prevalence of gastroesophageal reflux disease (GERD) in the United States. We performed a population-based study to determine the prevalence of GERD symptoms and persistent GERD symptoms despite use of proton pump inhibitors (PPIs). We conducted the National Gastrointestinal Survey in 2015 using MyGiHealth, an app that guides participants through National Institutes of Health gastrointestinal Patient-Reported Outcomes Measurement Information System surveys. Primary outcomes were prevalence of GERD symptoms in the past and persistence of GERD symptoms (heartburn or regurgitation 2 or more days in past week) among participants taking PPIs. Population weights were applied to the data and multivariable regression was used to adjust for confounding. Among 71,812 participants, 32,878 (44.1%) reported having had GERD symptoms in the past and 23,039 (30.9%) reported having GERD symptoms in the past week. We also found that 35.1% of those who had experienced GERD symptoms were currently on therapy (55.2% on PPIs, 24.3% on histamine-2 receptor blockers, and 24.4% on antacids). Among 3229 participants taking daily PPIs, 54.1% had persistent GERD symptoms. Younger individuals, women, Latino individuals, and participants with irritable bowel syndrome or Crohn's disease were more likely to have continued symptoms, even when taking PPIs. Using a population-based survey, we found GERD symptoms to be common: 2 of 5 participants have had GERD symptoms in the past and 1 of 3 had symptoms in the past week. We also found that half of PPI users have persistent symptoms. Given the significant effect of GERD on quality of life, further research and development of new therapies are needed for patients with PPI-refractory GERD symptoms.