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As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett’s esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett’s esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.

The purpose of this study was to investigate the relationship between bariatric surgery (laparoscopic sleeve gastrectomy [LSG] and laparoscopic Roux-en-Y gastric bypass [LRYGB]) and gastroesophageal reflux disease (GERD). The number of obese patients with newly onset, worsened, or improved GERD after bariatric surgery in each article were extracted. In the pooled analysis, LSG was associated with a higher risk of GERD than LRYGB (odds ratio [OR] = 5.10, 95% confidence interval [CI] 3.60–7.23, p < 0.001). Compared with LSG, LRYGB had a better effect on GERD (OR = 0.19, 95% CI 0.12–0.30, p < 0.001). LRYGB was more effective for treating GERD in obese patients than LSG and the incidence of newly onset GERD after LRYGB was lower.

The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future.

Abstract Background The effect of sleeve gastrectomy (SG) on the prevalence of gastroesophageal reflux disease (GERD) remains unclear. We aimed to outline the currently available literature. Data Sources All relevant databases were searched for publications examining the effect of laparoscopic SG on GERD. Primary outcome measure was change in prevalence of GERD symptoms, antireflux medication use, and esophageal function tests. Secondary outcomes were prevalence of new-onset GERD and esophagitis. Thirty-three articles were included. Eleven studies used questionnaires to assess changes in the prevalence of GERD symptoms, with a risk difference in prevalence of 4.3%. Eight studies used esophageal function tests, with paradoxical results. Pooled incidence of new-onset GERD symptoms was 20%, with a strong suggestion of heterogeneity. New-onset esophagitis ranged from 6.3% to 63.3%. Conclusions Because of high heterogeneity among available studies and paradoxical outcomes of objective esophageal function tests, the exact effect of laparoscopic SG on the prevalence of GERD remains unanswered. Surgeons should carefully evaluate preoperative GERD symptoms when choosing the proper bariatric technique.

ObjectivesGastro-oesophageal reflux symptoms are common in the community, but there has been no definitive systematic review and meta-analysis of data from all studies to estimate their global prevalence, or potential risk factors for them.DesignMedline, Embase and Embase Classic were searched (until September 2016) to identify population-based studies that reported the prevalence of gastro-oesophageal reflux symptoms in adults (≥15 years); gastro-oesophageal reflux was defined using symptom-based criteria or questionnaires. The prevalence was extracted for all studies, and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, OR and 95% CIs were calculated.ResultsOf the 14 132 citations evaluated, 102 reported the prevalence of gastro-oesophageal reflux symptoms in 108 separate study populations, containing 460 984 subjects. Prevalence varied according to country (from 2.5% in China to 51.2% in Greece) and criteria used to define gastro-oesophageal reflux symptoms. When only studies using a weekly frequency of heart burn or regurgitation to define presence were considered, pooled prevalence was 13.3% (95% CI 12.0% to 14.6%). Prevalence was higher in subjects ≥50 years (OR 1.32; 95% CI 1.12 to 1.54), smokers (OR 1.26; 95% CI 1.04 to 1.52), non-steroidal anti-inflammatory drug (NSAID)/aspirin users (OR 1.44; 95% CI 1.10 to 1.88) and obese individuals (OR 1.73; 95% CI 1.46 to 2.06).ConclusionsThe prevalence of gastro-oesophageal reflux symptoms varied strikingly among countries, even when similar definitions were used to define their presence. Prevalence was significantly higher in subjects ≥50 years, smokers, NSAID users and obese individuals, although these associations were modest.

GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symptoms persist and endoscopy does not reveal evidence of GERD, oesophageal function tests are performed, including oesophageal manometry and ambulatory reflux monitoring. However, reflux episodes can be physiological, and some findings on endoscopy and manometry can be encountered in asymptomatic individuals without GERD symptoms. The diagnosis of GERD on the basis of functional oesophageal testing has been previously reported, but no updated expert recommendations on indications and the interpretation of oesophageal function testing in GERD has been made since the Porto consensus over a decade ago. In this Consensus Statement, we aim to describe modern oesophageal physiological tests and their analysis with an emphasis on establishing indications and consensus on interpretation parameters of oesophageal function testing for the evaluation of GERD in clinical practice. This document reflects the collective conclusions of the international GERD working group, incorporating existing data with expert consensus opinion.

Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called ‘PPI-responsive oesophageal eosinophilia’ (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.

Patients who were referred to Veterans Affairs gastroenterology clinics with heartburn unresponsive to a proton-pump inhibitor had comprehensive evaluation for eligibility for a trial comparing Nissen fundoplication surgery with medical therapy. In the minority of patients who were confirmed to have PPI-refractory and reflux-related heartburn, surgery was more effective than medical treatment in controlling reflux symptoms.

ObjectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett’s oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.DesignWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).ResultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.ConclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.