Therapy For Gastroesophageal Reflux Disease Research Articles

Sa1286 CYP2C19 GENOTYPE VARIABILITY IN PATIENTS WITH REFRACTORY GASTROESOPHAGEAL REFLUX AFTER PERORAL ENDOSCOPIC MYOTOMY (POEM)

Gastroesophageal reflux disease (GERD) is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy for GERD; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability. CYP2C19 rapid (RM) or intermediate metabolizer (IM) genotype may be associated with refractoriness to PPI therapy.

Anti-reflux mucosectomy using a cap-assisted endoscopic mucosal resection method for refractory gastroesophageal disease: a prospective feasibility study

Endoscopic therapy of gastroesophageal reflux disease (GERD) overcomes the "treatment gap" for patients with refractory GERD, who are not willing to go into surgery. We propose an easy and efficient technique that is referred to as anti-reflux mucosectomy (ARMS) using cap-assisted endoscopic mucosal resection (EMR-C) which could be called ARMS-C. This study aimed to investigate the short-term outcomes of ARMS-C in GERD patients. From December 2016 to February 2018, we performed ARMS-C in 33 patients with pathologic reflux disease and esophageal hypersensitivity. ARMS-C involved endoscopic mucosal resection at the circumference of the esophagogastric junction (EGJ), resulting in narrowing of the hiatal opening after healing. The GERD symptoms, 24-h pH monitoring results, manometry, endoscopy, and EGJ distensibility were compared before and after the procedure. Six months after ARMS-C, 63% of patients discontinued the use of pump inhibitors (PPIs), while 30% patients reduced their PPI dose. The GERD questionnaire scores significantly decreased after ARMS-C, from 11.0 to 6.0 (P < 0.001). The median DeMeester score and acid exposure time based on pH monitoring also improved after ARMS-C. Furthermore, the median flap valve grade and EGJ distensibility decreased from 3.0 to 1.0 (P < 0.001) and from 19.0 to 13.9 (P < 0.001), respectively. Two patients were treated with balloon dilation due to stricture, but no other serious adverse events were encountered. ARMS-C may be an effective and safe treatment method for GERD in terms of short-term outcomes.

Partial fundoplication may be an effective therapy for gastroesophageal reflux disease for patients with severe esophageal dysmotility

We appreciate Dr. Herbella’s thorough review on our article. Indeed, the updated classification on esophageal dysmotility based on high-resolution manometry brings a new perspective for the treatment of patients with gastroesophageal reflux disease (GERD). Due to the high prevalence of GERD, and its commonly related esophageal conditions, is it crucial to understand not only the benefits of surgical treatment for this disease, but also which surgical technique is most appropriate in this scenario. This is particularly important for patients with severe esophageal dysmotility, who often present with dysphagia after fundoplication, requiring additional postoperative dilations and continuous use of anti-reflux medication (1).

Partial fundoplication may be an effective therapy for gastroesophageal reflux disease for patients with severe esophageal dysmotility

Partial fundoplication may be an effective therapy for gastroesophageal reflux disease for patients with severe esophageal dysmotility

Systematic review with network meta-analysis: indirect comparison of the efficacy of vonoprazan and proton-pump inhibitors for maintenance treatment of gastroesophageal reflux disease

BackgroundLong-term maintenance treatment of gastroesophageal reflux disease (GERD) is important to prevent relapse. Proton-pump inhibitors (PPIs) are used for both treatment and maintenance therapy of GERD. Recently, a potassium-competitive acid blocker vonoprazan was launched in Japan. We evaluated the comparative efficacy of vonoprazan and other PPIs for GERD maintenance.MethodsA systematic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials. Double-blind randomized controlled trials (RCTs) of PPIs, vonoprazan, and placebo for GERD maintenance published in English or Japanese were selected. Among them, studies conducted at the recommended dose and for the recommended use, and containing information on maintenance rate based on endoscopic assessment, were included. The comparative efficacies of treatments were estimated by performing a Bayesian network meta-analysis, which assessed the consistency assumption. Outcomes were number or rate of patients who maintained remission.ResultsOf 4001 articles identified, 22 RCTs were eligible for analysis. One study published as an abstract was hand-searched and added. The consistency hypothesis was not rejected for the analysis. The odds ratio of vonoprazan 10 mg to each PPI was 13.92 (95% credible interval [CI] 1.70–114.21) to esomeprazole 10 mg; 5.75 (95% CI 0.59–51.57) to rabeprazole 10 mg; 3.74 (95% CI 0.70–19.99) to lansoprazole 15 mg; and 9.23 (95% CI 1.17–68.72) to omeprazole 10 mg.ConclusionsThe efficacy of vonoprazan in GERD maintenance treatment may be higher than that of some PPIs. However, a direct comparison of vonoprazan and PPIs is required to confirm these effects.

Correction of psychosomatic status of patients with stable angina of tension and gastroesophageal reflux disease

The relationship between stress, anxiety and depression in patients with cardiovascular diseases, especially in conditions of comorbidity, is a relevant subject for research, and requires to be studed from the standpoint of evidence-based medicine.The aim of the study. To determine the changes in the psycho-emotional state and prolactin level in patients with stable angina of tension (SAT) and gastroesophageal reflux disease (GERD) in the dynamics of treatment.Materials and methods. The study included 88 patients with SAT of I-II functional class with a comorbid, endoscopically positive GERD. In all of the patients including in the study a serum prolactin level was determined prior the beginning of treatment and 30 days later. To identify the presence of anxiety and depression interviews were conducted using the questionnaire “Hospital Anxiety and Depression Scale” (HADS), and an assessment of the quality of life of the ShortFormMedicalOutcomesStudy (SF-36) questionnaire was also performed. The patients were divided into 2 groups, depending on treatment. 1group (43 persons) received baseline treatment of SAT and GERD. Patients from the second group (45 people) received baseline therapy for SAT and GERD, with the exception of prokinetics and NO donors, only nitroglycerin, if needed, and, additionally, meldonium (Vasonat) capsules 500 mg 2 times daily for 30 days. All drugs were prescribed in average therapeutic doses, according to the individual needs.Results. Patients with SAT with comorbid GERD have an elevated level of prolactin, which directly and strongly correlates with the obtained scores of anxiety (anxiety average degree) and depression (subclinical degree depression) of the HADS questionnaire. Before treatment, the quality of life of patients was, in general, at a low level. At day 30 of treatment in group 2, prolactin levels decreased to almost the norm, what was not detected in group 1 as well as scores from the HADS questionnaire, reflecting the positive effect of baseline therapy correction on the tendency for anxiety and depression to decrease among patients with SAT and GERD. The results of the SF-36 group, additionally receiving Vasonat, were significantly higher in all subscales compared to the identical indeced of group 1, what indicates improvement of quality of patients’ life.Conclusion. Correction of the basic therapy of SAT and GERD (no prokinetics and prolonged-acting nitrates; additional administration of meldonium (Vasonate), at a dose of 500 mg 2 times daily) leads to a significant decrease in serum prolactin, reduction of anxiety and depression, according to the HADS questionnaire, as well as improvement of the quality of patients’ life with SAP and GERD compared to the patients receiving basic therapy of these diseases.

Chronic Cough in Adults: Make the Diagnosis and Make a Difference.

Chronic cough is common and impactful, frustrating both patients and clinicians. An empirical trial of therapy is often done with inhaled corticosteroids, but this practice should be replaced with attempting to make an accurate diagnosis. The three most common causes are upper airway cough syndrome, asthma, and gastroesophageal reflux disease (GERD), but there are often multiple causes involved. Minimal investigations after history, physical exam, travel history, and drug history include a chest radiograph and spirometry. Empirical trial of therapy with inhaled corticosteroids is reasonable if there is evidence of eosinophilic inflammation. Empiric therapy for GERD may also be reasonable in those with symptoms. Red flags should especially be considered an urgency to make the correct diagnosis.

Stretta therapy in the management of gastroesophageal reflux disease (GERD)

Treatment of gastroesophageal reflux disease (GERD) includes medical, surgical, and endoscopic intervention. The growing concerns of patients and physicians alike about adverse effects of chronic proton pump inhibitor (PPI) therapy or anti-reflux surgery have positioned endoscopic therapy for GERD on par with other therapeutic interventions. Endoscopic radiofrequency (RF) ablation (Stretta) has been used for more than 15 years and it is the most studied and followed endoscopic procedure for GERD. The technique itself has improved over the years and has been shown to be effective, safe and durable. Several meta-analyses and cohort studies have cemented the efficacy of the technique in improving patients’ health related quality of life, GERD symptoms, PPI consumption and esophageal acid exposure over more than 10 years follow up. Presently, endoscopic RF has been integrated into treatment guidelines of patients with GERD with diverse clinical scenarios.

Advances in the Diagnosis and Treatment of GERD: New Tricks for an Old Disease

Gastroesophageal reflux disease (GERD) is a common diagnosis encountered by both primary care providers and specialists, but despite its prevalence, there are limitations in the current diagnostic tests for GERD. Once an accurate diagnosis is made, treatment options can be offered, and this field continues to burgeon with options. In this review, we seek to review the recent advances in GERD diagnostics and subsequent treatment options. Novel impedance markers and novel techniques (mucosal impedance testing, salivary pepsin, high-resolution manometry, and narrow-band imaging) have shown promise in diagnosing GERD. Advances in medical therapy, including potassium-competitive acid blockers and bile acid sequestrants, along with advances in invasive therapy (transoral incisionless fundoplication, endoscopic radiofrequency, electrical stimulation of the LES, and magnetic sphincter augmentation) have provided additional options for therapy for GERD beyond PPI and anti-reflux surgery. Novel impedance markers and techniques will provide further clarity on mucosal integrity and the barrier function allowing improved diagnostic accuracy of GERD. Improvements in medical and invasive therapy will expand GERD therapy.

СОВРЕМЕННАЯ ДИАГНОСТИЧЕСКАЯ И ЛЕЧЕБНАЯ ТАКТИКА ПРИ ПИЩЕВОДЕ БАРРЕТТА

The article represents the first experience of endoscopic mucosal cap resection of Barrett’s epithelium in Belarus. The implementation of endoscopic treatment of intestinal metaplasia into clinical practice is suggested on the basis of a case report and literature data. The comparison has been drawn between the updated clinical guidelines on the diagnosis and management of Barrett’s esophagus of different gastroenterological societies. It should be noted however that this article covers the aspect of endoscopic surveillance and treatment of esophageal columnar epithelium only. It doesn’t focus on a combination therapy that should include drug therapy of gastroesophageal reflux disease (GERD) and surgery of the lower esophageal sphincter incompetence if need be.

PATHOGENETIC ROLE OF NITROGEN MONOXIDE EFFICIENCY OF PHARMACOTHERAPY IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE AND STABLE ANGINA OF TENSION

Introduction: The search for new mechanisms of their interconnection and effective pharmacological correction of gastroesophageal reflux disease (GERD) for comorbidity with stable angina of tension (SAT). The aim: To establish the role of nitrogen monoxide (NO) in the pathogenesis of GERD in patients with SAT and to study the effectiveness of the correction of the basic therapy of SAT in order to eliminate the clinical manifestations of GERD and prevent its development. Materials and methods: 88 patients with SAT with a comorbid GERD were examined. We determined clinical symptoms, the level of stable NO metabolites, calculated the number of nitroglycerin tablets taken one week. All patients (2 groups) received baseline therapy for GERD and SAT. In this case, the patients of the 2nd group (45 persons) received therapy with the exception of long-acting nitrates and, in addition, meldonium for 30 days. Results:With the exception of the use of nitro-containing drugs and adding to the basic therapy of SAT the drug meldonium we faster (p<0,05) achieved a regression of clinical symptoms of GERD and decrease in the level of metabolites NO molecule in patients with SAT. Conclusion: In the case of the exclusion of the intake of long-acting nitrates with the adding of meldonium to the basal therapy of the SAT and the GERD the content of metabolites of nitrogen monoxide in the blood is more normalized, which correlates with a decrease in the frequency of GERD symptoms in patients with SAT and GERD.

Short-Term Outcomes Predict Long-Term Satisfaction in Patients Undergoing Laparoscopic Magnetic Sphincter Augmentation.

Laparoscopic magnetic sphincter augmentation (MSA) has been shown to be efficacious therapy for gastroesophageal reflux disease (GERD) refractory to maximal medical management. Herein, we present our experience with this procedure and an analysis of our outcomes. Medical records were retrospectively reviewed of 98 patients who underwent laparoscopic MSA for GERD at a single institution from 2012 to 2016. Symptoms were assessed with gastroesophageal reflux disease-health-related quality of life (GERD-HRQL) questionnaire. Objective testing included pH testing, manometry, endoscopy, and upper GI series. Postimplantation interventions were recorded. Median follow-up was 46 months. Median preoperative DeMeester score was 32 (interquartile range 21-46). Esophagitis was present in 18%. Hiatal hernia was present in 59%. Operation required full hiatal dissection in 16%. There were no intraoperative complications. Mean hospital stay postimplantation was 18 hours. Reoperative intervention with device explant was necessary in 5 cases, one of which was for intraluminal device erosion. Median GERD-HRQL scores were 25 preoperatively, 8 in short-term follow-up at median 1 month, and 5 in long-term follow-up at median 46 months. Improvement in GERD-HRQL scores was statistically significant with both short and long term compared with preoperative (P < .05), but no different between short- and long-term follow-up. Daily bothersome dysphagia was present in 19 patients preoperatively and in 9 at long-term follow-up. Laparoscopic MSA is associated with excellent outcomes with decrease in GERD-HRQL scores in short term that are durable to longer term follow-up, and with low rates of new-onset dysphagia.

Electrical neuromodulation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a difficult to treat medical condition. Inadequate symptom control has been cited as one of the main reasons to drive to surgical therapies for GERD. This unmet medical need has led to new attempts at developing less-invasive therapies for the treatment of GERD. Lower esophageal sphincter (LES) electrical neuromodulation has been shown to improve outcomes in GERD, and may represent and alternative of treatment for special subgroups of patients, such as esophageal dysmotility patients, sleeve gastrectomy and lung transplant patients. A concise review of literature was performed through PubMed. We searched to identify published studies reporting on subjective and objective GERD after LES-electrical neuromodulation therapy (ENT). Data evaluated included GERD-health-related quality of life (HRQL), extra esophageal symptoms, PPI discontinuation and patient satisfaction rates, pH-study metrics, severe adverse effects (AEs), and treatment failures. The aim of the review is to summarize the safety and efficacy of LES-ENT in GERD patients reported up to date, including original data from the authors. Two clinical trials have shown safety and efficacy of LES-ENT with both short and long-term follow-up up to 3 years. Results were comparable in a prospective multi-center registry of LES-ENT for GERD with 223 patients from 16 sites in Europe and Latin America with an extended 5-year-follow up. LES-ENT has shown adequate efficacy in symptom control, medication use, acid exposure control, a solid safety profile and may represent an alternative treatment for patients that are not satisfied with PPI therapy, unable to receive a fundoplication or reluctant to undergo reported side effects. LES-ENT allows correction of hiatal hernia when needed, enhancing the effects of neuromodulation that can also be optimized after surgery. This can lead to an expanded indication of surgical therapies for those patients with unmet needs for GERD.

Alternative therapies for GERD: a way to personalized antireflux surgery.

Gastroesophageal reflux disease (GERD) is a common disorder, known to affect about 20% of the Western population. Although conventional medical or surgical treatment has proven effective, there is certainly room for improvements. As only 10% of GERD patients are finally treated by antireflux surgery, a large therapeutic window exists. This treatment gap consists of patients who are not effectively treated with proton pump inhibitor but do not want to run the potential risks of conventional surgery. During the last two decades, several novel and intriguing options for the surgical treatment of GERD have been introduced and found their way into clinical use. The following summary will give an update of certain alternative therapeutic options to treat GERD or its pathological consequences.

Combined therapy in gastro-esophageal reflux disease of term neonates resistant to conservative therapy and monotherapy: a clinical trial

Background: Gastroesophageal reflux disease (GERD) is one of the most common problems in neonates. The main clinical manifestations of neonatal GERD are frequent regurgitation or vomiting associated with irritability, crying, anorexia or feeding refusal, failure to thrive, arching of the back and sleep disturbance. Aims: As no study has compared metoclopramide plus ranitidine with metoclopramide plus omeprazole in the management of neonatal GERD resistant to conservative and monotherapy, this study was carried out. Study design: This study was a randomized clinical trial of term neonates with GERD resistant to conservative and monotherapy admitted to the neonatal ward of Bahrami Children Hospital during 2013-2015. Totally, 116 term neonates (mean age 10.53 ± 8.17 days; girls 50.9%) were randomly assigned to a double blind trial with either oral omeprazole plus metoclopramide (group A) or oral ranitidine plus metoclopramide (group B). The changes of the symptoms and signs were recorded after one week and one month. Results: There was no significant difference in demographic and baseline characteristics between the two groups. The response rate of “omeprazole plus metoclopramide” was significantly higher than “ranitidine plus metoclopramide” (93.74% ± 7.28% vs. 75.43% ± 23.24%, p = 0.028). All clinical manifestations recovered significantly in group A while the response rate of irritability and wheezing was not significant in group B (primary outcome). There were no side effects in either group after one week and one month of treatment (secondary outcome). Conclusions: The response rate was > 70% in each group, but it was significantly higher in group A (> 90%). Combination of each acid suppressant with metoclopramide led to higher response rate in comparison with monotherapy used before intervention.

Opportunities to predict effectiveness of antisecretory therapy in patients with gastroesophageal reflux disease

To determine the factors that affect the effectiveness of gastroesophageal reflux disease therapy, a correlation analysis was performed that included the international GERD questionnaire, the hospital anxiety and depression score (HADS), and data on the polymorphism of cytochrome P450 2C19 in 136 patients with different variants gastroesophageal reflux disease (GERD): reflux esophagitis (RE), non-erosive reflux disease (NERD) and reflux hypersensitivity (RH). The presence of a strong negative relationship between the favorable outcome of PPI therapy and the GERD score was demonstrated after 4 weeks of therapy in the RE, NERD and RH groups (p &lt; 0.001). When analyzing the relationship between the HADS scale and the effectiveness of therapy, a strong negative correlation was found only in the RE group (p &lt; 0.001), the fact that the metabolic rate of the PPI moderately correlated with the favorable outcome of therapy in the RH and NERD groups (p &lt; 0.05).

Endoscopic Treatments of GERD.

PURPOSE OF REVIEW: Endoscopic therapies for gastroesophageal reflux disease (GERD) are minimally invasive techniques which fill the gap between the medical therapy with proton pump inhibitors (PPIs) and surgical fundoplication. The main endoscopic therapies currently available in the USA are transoral incisionless fundoplication (TIF) using EsophyX device or less commonly, Medigus Ultrasonic Surgical Endostapler, and radiofrequency energy delivery to lower esophageal sphincter using Stretta device. Our aim was to examine the available evidence for these therapies. Consistent evidence for subjective improvement is available for fundoplication using EsophyX and Stretta, but improvement in objective parameters for GERD is not seen or evaluated in all the studies. There is a reduction in long-term efficacy seen with TIF and also to a lesser extent with Stretta. Endoscopic therapies do not replace surgical fundoplication and therefore are useful in patients with breakthrough symptoms on PPI such as regurgitation or those reluctant to take long-term PPI. An ideal patient is one who has symptoms and objective evidence of GERD such as abnormal pH study or erosive esophagitis without any significant anatomic distortion such as a hiatal hernia. Since these are endoluminal procedures, they do not address the hiatal hernia reduction or repair of crural defect. Adequate training in the technique and careful patient selection are essential prior to embarking on these procedures.

New Minimally Invasive Endoscopic and Surgical Therapies for Gastroesophageal Reflux Disease (GERD).

GERD has become one of the most frequent pathology of the upper GI tract. It is a spectrum disease and is a progressive disease as well. Serious and severe complications are possible. The mainstream therapy in most of the patients is the medical therapy with PPI's. The most severe cases with an impaired LES (Lower Esophageal Sphincter) function as well as important anatomical disruptions are of surgical indication, the gold standard being laparoscopic fundoplication, an elective therapy with long term follow up outcomes at the expense of de novo symptoms associated with fundoplications in general. 30% to 40% of the patients are PPI refractory with partial symptom control, but they are not willing to go for the laparoscopic fundoplication because of the invasive character and because of potential postfundoplications syndromes. There is a "treatment gap" for these patients with GERD. For a well selected patient population with GERD, with mild forms of the disease, without complications and without major anatomical disruptions (patients with small hiatal hernias), patients who are refractory on PPI medication, there are today new alternative therapies, minimally invasive. These therapies are less aggressive and basically with no side effects or new onset symptoms that Laparoscopic Fundoplications will give. These are endoscopic therapies which improve the LES function: Stretta utilizes radiofrequence therapy, a novel technique describes mucosal resection at the level of the cardia, while a partial fundoplication from within the stomach can be realized with EsophyX, Muse or Gerd-X. Form all these procedures, EsophyX is the most advanced with more than 20,000 patients treated worldwide, with good clinical outcomes and with no de novo symptoms. The laparoscopic techniques treat hiatal hernias larger than 2 cm. Linx utilizes a magnetic ring at the LES level. EndoStim utilizes electrodes in order to stimulate the LES muscle. These procedures are effective on short term and there are few patients treated with Linx or EndoStim. More research for Linx and EndoStim is necessary with randomized clinical trials, with improvement of the devices and with long term follow up.

Acid Suppression for Gastroesophageal Reflux Disease in Infants.

Gastroesophageal reflux is a normal physiologic occurrence that is common throughout infancy and usually resolves on its own. Infrequently, reflux causes complications and turns into gastroesophageal reflux disease (GERD), which may warrant intervention. Available interventions vary in invasiveness and supporting data may be lacking for efficacy and safety. Nonpharmacologic interventions are first-line therapy for GERD in infants, whereas pharmacologic and surgical approaches are controversial. Efficacy data are limited for pharmacologic strategies for infantile GERD and safety data have demonstrated serious risks, especially in younger infants. Utilization of these medications should be approached cautiously in this population, if appropriate diagnostic techniques determine acid suppression could be beneficial. A robust monitoring plan with frequent reassessment of need for therapy may optimize benefit and minimize risk.

Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date.

Potassium-competitive acid blocker (P-CAB) is a class of drug that competitively blocks the potassium-binding site of H+, K+-adenosine triphosphate (ATP)ase. Although the history of this class of drugs started over 30 years ago, clinical use of two P-CABs, revaprazan and vonoprazan, were only recently approved in Korea and Japan, respectively. Among them, vonoprazan has several advantages over conventional proton-pump inhibitors (PPIs), including rapid onset of action, long duration of acid suppression, fewer interindividual variations in terms of acid suppression, and minimum dietary influence on its action. These advantages of vonoprazan have been proved in clinical trials conducted for license approvals for several acid-related diseases. In this review article, current evidence of vonoprazan in the management of gastroesophageal reflux disease (GERD) will be summarized. Since the clinical trial data, as well as postmarketed clinical data, have consistently demonstrated superiority of vonoprazan over conventional PPIs in terms of achieving healing of mucosal breaks and maintaining the healing, it may provide an excellent, if not complete, option for fulfilling some of the unmet needs for current GERD therapy. The safety problem of vonoprazan is also discussed, as more pronounced hypergastrinemia inevitably ensues with its use.