Pharmacologic management of gastroesophageal reflux disease

The burden of gastroesophageal reflux disease (GERD) results from its widespread prevalence and the unfavorable impact of its symptoms on well-being and quality of life. Whereas abnormalities of the antireflux barrier (lower esophageal sphincter) are important in the pathophysiology of GERD, pharmacologic therapy for GERD is based on suppression of acid, which is responsible for the majority of the symptoms and for epithelial damage. Proton pump inhibitors (PPIs) are the agents of choice for achieving the goals of medical therapy in GERD, which include symptom relief, improvement in quality of life, and healing and prevention of mucosal injury. As a class, these drugs are extremely safe. The newest PPI, esomeprazole, brings a statistically significant increase in healing of mucosal injury and symptom relief in patients with erosive esophagitis, compared with omeprazole and lansoprazole. This article reviews the role of medical therapy in the short-and long-term management of symptomatic patients with or without erosive esophagitis, including extraesophageal presentations, GERD during pregnancy, and Barrett’s esophagus. Management of refractory patients is addressed.     

Pharmacologic management and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in daily practice. Diagnosis can be made on symptom evaluation, on pH-monitoring or on endoscopic findings. In contrast to commonly held opinion there is no strong evidence that lifestyle factors are a dominant factor in the pathophysiology of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H(2)-blockers and proton pump inhibitors. This article gives an overview of the pharmacological management of GERD and focuses on the differential therapy of endoscopy-negative GERD, GERD with esophagitis and maintenance therapy.     

Step-down management of gastroesophageal reflux disease.

BACKGROUND & AIMS: As the economic burden of gastroesophageal reflux disease (GERD) is largely weighted to maintenance as opposed to initial therapy, switching from more potent to less expensive medication once symptoms are alleviated (step-down therapy) may prove to be most cost-effective. This study aimed to prospectively evaluate the feasibility of step-down therapy in a cohort of patients with symptoms of uncomplicated GERD. METHODS: Patients whose GERD symptoms were alleviated by proton pump inhibitors (PPIs) were recruited from outpatient general medicine clinics. After baseline demographic and quality of life information were obtained, PPIs were withdrawn from subjects in a stepwise fashion. Primary outcome was recurrence of symptoms during follow-up that required reinstitution of PPIs. Secondary outcomes included changes in quality of life and overall cost of management. Predictors of nonresponse to step-down were assessed. RESULTS: Seventy-one of 73 enrolled subjects completed the study. Forty-one of 71 (58%) were asymptomatic off PPI therapy after 1 year of follow-up. Twenty-four of 71 (34%) required histamine 2-receptor antagonists, 5/71 (7%) prokinetic agents, 1/71 (1%) both, and 11/71 (15%) remained asymptomatic without medication. Quality of life did not significantly change, whereas management costs decreased by 37%. Multivariable analysis revealed younger age and a dominant symptom of heartburn to predict PPI requirement. CONCLUSIONS: Step-down therapy is successful in the majority of patients and can decrease costs without adversely affecting quality of life.     

Endoscopic management of refractory gastroesophageal reflux disease

Objective: Despite the therapeutic and surgical interventions for the management of gastroesophageal reflux disease (GERD), yet the high cost and the post-operative complications had led to a significant socioeconomic burden. The aim was to evaluate the safety and efficacy of endoscopic band ligation (EBL) in the management of refractory GERD.

Methods: A total of 150 patients with refractory GERD were assigned to an EBL group (banding was done at four quadrants just at the gastroesophageal junction (GEJ) (n?=?75) or to a control group (optimized dose of PPI, n?=?75). Follow-up for both groups by upper GI endoscopy to evaluate the site of the Z line from the incisors, the width of the GEJ and the coaptation of GEJ around the endoscope on retroflection. PH monitoring was performed every 3 months with GERD- QoL assessment monthly for 1 year.

Results: In EBL group; 58 patients (77.3%) needed 1 session, 17 patients (22.7%) needed 2 sessions. 4 rubber bands were utilized in 44 patients (58.7%), 3 rubber bands in 31 patients (41.3%). Follow-up for 1 year revealed a highly significant improvement of the GERD- QoL score, the site of Z line with significant reduction of reflux episodes and symptom index when compared to the medical treatment group. In EBL group; there were no major adverse events including bleeding, post band ulcers, stenosis at one year follow up.

Conclusion: The current study provides a novel endoscopic intervention to treat refractory GERD, which is safe, cost-effective, with no major adverse effects at one year follow up.     

The pharmacological management of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders, and the pharmacological management of GERD is a topic of intense interest given the sizeable yearly expenditure for antireflux therapies. GERD is primarily a motor disorder of the esophagus, yet pharmacological approaches directed at altering esophageal motility have been only partially effective. Antisecretory therapy is the mainstay of treatment for GERD. Both H2 receptor antagonists (H2RA) and proton pump inhibitors (PPIs) are effective in the treatment of GERD, but PPI therapy is clearly superior in the treatment of severe disease and in the healing of erosive esophagitis. A treatment schema for GERD based on presenting symptoms is outlined, promoting a stepwise approach to the appropriate use of antisecretory therapy.     

Optimal management of severe symptomatic gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common disorder, and empirical proton pump inhibitor (PPI) treatment is often the first step of management; however, up to 40% of patients remain symptomatic despite PPI treatment. Refractory reflux refers to continued symptoms despite an adequate trial of PPI, and management remains challenging. The differential diagnosis is important; other oesophageal (e.g. eosinophilic oesophagitis) and gastroduodenal disorders (e.g. functional dyspepsia) should be ruled out, as this changes management. A combination of clinical assessment, endoscopic evaluation and in selected cases oesophageal function testing can help characterize patients with refractory reflux symptoms into oesophageal phenotypes so appropriate therapy can be more optimally targeted. Medical options then may include adding a H2 receptor antagonist, alginates, baclofen or antidepressant therapy, and there is emerging evidence for bile acid sequestrants and diaphragmatic breathing. The demonstration of a temporal association of symptoms with reflux events on pH-impedance testing (reflux hypersensitivity) serves to focus the management on modulating oesophageal perception and reducing the reflux burden, or identifies those with no obvious pathophysiologic abnormalities (functional heartburn). Anti-reflux surgery based on randomized controlled trial evidence has a role in reflux hypersensitivity or continued pathological acid reflux despite PPI in carefully considered, fully worked up cases that have failed medical therapy; approximately two of three cases will respond but there is a small risk of complications. In patients with persistent volume reflux despite medical therapy, given the lack of alternatives, anti-reflux surgery is a consideration. Promising newer approaches include endoscopic techniques. This review aims to summarize current diagnostic approaches and critically evaluates the evidence for the efficacy of available treatments.     

Key points in the management of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a relatively common condition with a prevalence ranging from 10% to 20% in Western countries and 5% to 10% in Asian populations [1]. In a recent evidence-based consensus [2], GERD was defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms or complications. This global definition emphasizes the syndromic nature of the disease and subdivides the patients in different groups depending on the presence of mucosal complications (ie, esophagitis, metaplasia, stenosis) and on the prevalent clinical manifestations (ie, typical reflux symptoms or extraesophageal/supraesophageal syndromes). General practitioners, gastroenterologists, and specialists from different branches of medicine generally share the management of GERD patients, and basically they need to address the following four issues.     

Endoscopic therapies for the management of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common disorder with rising incidence worldwide and very high medical costs to society. The medical management of the disease i.e. lifestyle modifications and proton pump inhibitors reaches excellent results in most cases, but it needs to be continued, lifelong; the real cure of the disease is nowadays laparoscopic fundoplication, which is effective and safe in over 95% of well selected patients to provide a durable high quality of life. A very attractive alternative to these well established therapies is the endoscopic treatment of GERD, that employs different endoluminal technologic skills: plication of gastric cardia folds by suturing devices, radiofrequencies thermal-induced cardial fibrosis and bulking or sclerosing agents local injections have been recently tried and validated by different very experienced endoscopic groups. Although endoscopic therapy of GERD seems to be safe and feasible, a definite judgement awaits the results of multicentric controlled studies and longer periods of follow-up; for the present they must be restricted to well experienced endoscopists working to these controlled trials.     

胃食管反流病问卷对胃食管反流病的诊断价值

目的 评价胃食管反流病问卷(GerdQ)在胃食管反流病(GERD)患者中的诊断价值,初步探讨中国GERD人群的症状特点.同时探索一种适合中国人群的质子泵抑制剂(PPI)试验的诊断标准.方法 在全国五家医院进行多中心研究.所有入组患者填写GerdQ问卷表.以胃镜检查、24 h食管pH监测和PPI试验其中任何一项阳性作为GERD的诊断标准,评价GerdQ的诊断价值.以拟定PPI试验诊断标准与胃镜和食管pH监测的诊断相比较,并优化PPI试验的诊断标准.结果 拟定PPI试验诊断的敏感度为0.6627,特异度为0.4872.经统计分析,以PPI治疗1周最后3 d烧心、反流症状总评分较治疗前相比下降3分为优化PPI试验诊断标准,诊断的敏感度为0.3787,特异度为0.8077,阳性预测值为0.8101,阴性预测值为0.3750,Youden指数最大为0.1864.经人群矫正,GerdQ取临界值为10分时,Youden指数达到最大0.1080,诊断的敏感度为0.6690,特异度为0.4390.50岁以上女性患者随着评分的增高,问卷诊断价值下降.结论 GerdQ具有肯定的诊断价值.但在临床工作中,对特殊人群中症状突出而PPI诊断性治疗反应不佳的患者,GERD的诊断应慎重.PPI试验的评分以治疗1周最后3 d为佳.     

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan

Background and Aim:  Epidemiological studies have shown that 10–48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects.
Methods:  A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week.
Results:  Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD.
Conclusion:  Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.     

胃食管反流病维持治疗的研究进展

胃食管反流病是一种慢性复发性疾病，大部分患者需经过初始治疗和维持治疗两个阶段。目前维持治疗的方案主要包括持续治疗、间歇治疗和按需治疗，在胃食管反流病维持治疗中需根据具体情况选择适当的治疗方案。     

Dexlansoprazole MR for the management of gastroesophageal reflux disease

Dexlansoprazole modified release (MR; Dexilant?), the R-enantiomer of lansoprazole, was approved in the USA in 2009 for the management of erosive esophagitis and nonerosive reflux disease. Dexlansoprazole MR has a unique dual delayed-release delivery system that was designed to address unmet needs that may accompany the use of single-release proton pump inhibitors (PPIs), specifically, their short plasma half-life and requirement for meal-associated dosing. The delivery technology of dexlansoprazole MR is designed to release the drug in two separate pH-dependent phases, the first in the proximal duodenum and the second in the more distal small intestine. This extends plasma concentration and pharmacodynamic effects of dexlansoprazole MR beyond those of single-release PPIs and allows for dosing at any time of the day without regard to meals. This added convenience, along with excellent healing of esophagitis and symptom relief, substantiate its use in patients with gastroesophageal reflux disease requiring PPI treatment.     

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan

BACKGROUND AND AIM: Epidemiological studies have shown that 10-48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects. METHODS: A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week. RESULTS: Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD. CONCLUSION: Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.     

Duodenogastral reflux burden gastroesophageal reflux disease

The article presents research data of duodenogastral reflux (DGR) role in patients with gastroesophageal reflux disease. It is shown that in the presence DGR, the reflux esophagitis is detected at a higher frequency and outside of esophageal manifestations of the disease. The comorbidities of hepatobiliary zone and pancreas contributes to the DGR development, as well as the syndrome of bacterial overgrowth in the small intestine.     

Pediatric gastroesophageal reflux disease

Gastroesophageal reflux is a recognized clinical problem in infancy. To a great extent it represents a normal behavior that improves with maturation. The identification of appropriate candidates for medical and surgical therapy of GER during infancy is difficult and deserves further study. There are few well-conducted clinical trials of therapy for infantile GER that compare the usual drugs used for adults with GER. Moreover, medications currently licensed for adults are often not approved for pediatric use in the United States. Surgical therapy for GER should be reserved for infants with severe disease that does not respond to medical therapy.     

Pathophysiology of gastroesophageal reflux disease

The pathophysiology of gastroesophageal reflux disease remains incompletely understood. Its hallmark symptom is "heartburn" and, on the basis of endoscopy, those with heartburn are subdivided into nonerosive reflux disease and erosive esophagitis. Although subjects with nonerosive reflux disease have no gross damage on endoscopy, a characteristic histopathologic feature of this disease is present on endoscopic biopsy. This lesion is known as "dilated intercellular spaces," a finding present within squamous epithelium. This report details how acid in contact with a damaged esophageal epithelium leads to heartburn and to the progression of nonerosive reflux disease to erosive esophagitis. It also addresses the fact that esophageal pH monitoring may be normal in a significant number of subjects with heartburn, particularly with nonerosive reflux disease, and details how this observation suggests that in addition to defects in the antireflux barrier, for example, transient lower esophageal sphincter relaxations and low lower esophageal sphincter pressure, defects in tissue resistance created by contact with ingested products may also be etiologic in some subjects with gastroesophageal reflux disease.     

Management of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a chronic condition requiring long-term treatment. Simple lifestyle modifications are the first methods employed by patients and, because of their low cost and simplicity, should be continued even when more potent therapies are initiated. Potent acid-suppressive therapy is currently the most important and successful medical therapy. Whereas healing of the esophageal mucosa is achieved with a single dose of any proton pump inhibitor (PPI) in more than 80% of cases, symptoms are more difficult to control. Patients with persistent symptoms on therapy should be tested (preferably with combined multichannel intraluminal impedance and pH) for association of symptoms with acid, nonacid, or no GER. Long-term follow-up studies indicate that PPIs are efficacious, tolerable, and safe medication. So far, promotility agents have shown limited efficacy, and their side-effect profile outweighs their benefits. Antireflux surgery in carefully selected patients (ie, young, typical GERD symptoms, abnormal pH study, and good response to PPI) is as effective as PPI therapy and should be offered to these patients as an alternative to medication. Still, patients should be informed about the risks of antireflux surgery (ie, risk of postoperative dysphagia; decreased ability to belch, possibly leading to bloating; increased flatulence). Endoscopic antireflux procedures are recommended only in selected patients and given the relative short experience with these techniques, patients treated with endoscopic procedures should be enrolled in a rigorous follow-up program.     

Pathophysiology of gastroesophageal reflux disease

The gastroesophageal junction is structurally complex and functionally designed to ensure the acid secreted by the most proximal gastric mucosa flows towards the stomach and not up onto the oesophageal squamous mucosa. The pattern and mechanism of reflux vary with the severity of reflux disease and this probably represents different ends of a spectrum rather than distinct pathophysiological mechanisms. Nearly all patients with severe reflux disease have hiatus hernia, however, a substantial proportion of patients with mild reflux disease do not, and this may be a result of intermittent or partial hiatus hernia undetectable by current available tools. The acid pocket is an area of post-prandial unbuffered gastric acidity immediately distal to the gastroesophageal junction and which is enlarged in patients with hiatus hernia. The acid pocket provides a reservoir of acid available to reflux when the intrinsic sphincter fails. Central obesity is an important factor in the aetiology of reflux and does this by the increased abdomino-thoracic pressure gradient inducing hiatus hernia and increasing the rate of flow of reflux when sphincter opens. Central obesity also induces short segment intrasphincteric reflux and thereby columnar metaplasia of the most distal oesophagus.