Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hypersensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients. Accordingly, the reinforcement of protective mechanisms of esophageal mucosa by topical therapies has become a novel treatment target. Alginate, the combination of hyaluronic acid+chondroitin sulphate and Poliprotect have been shown to adhere to esophageal mucosa and to have good protective properties. Several placebo-controlled clinical trials have shown that these compounds, given alone or as add-on therapy for short periods, enable to relieve symptoms and to improve the quality of life in NERD patients. Further studies are needed to confirm the above results and to find new mucosal protectants in order to improve the management of NERD patients.

Non-erosive reflux disease (NERD), the most frequent phenotype of gastroesophageal reflux disease, presents without visible esophageal mucosal damage but significantly impacts patients' quality of life. Current treatments like proton pump inhibitors show limited efficacy for many NERD patients, necessitating alternative approaches. Jianpi Qinghua (JQ) granules, a traditional Chinese medicine, have shown promise in treating NERD by targeting symptoms of spleen deficiency and damp-heat syndrome.

This study aims to evaluate the efficacy and safety of JQ granules in treating patients with NERD characterized by spleen deficiency and damp-heat syndrome.

A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted with a total of 78 NERD patients randomly assigned to receive either JQ granules or placebo for 4 weeks, followed by a 4-week follow-up period.

Seventy-eight NERD patients with spleen deficiency and damp-heat syndrome were recruited and randomly assigned to receive either JQ granules (n = 39) or placebo (n = 39). The trial included a 1-week lead-in, followed by a 4-week double-blind treatment, and a 4-week follow-up. Primary endpoints were the improvement rates of reflux and heartburn symptoms and VAS score changes. Secondary endpoints included atypical symptom scores, total TCM syndrome scores, GERD Health-Related Quality-of-Life (HRQL), and self-rated depression and anxiety scales. Safety assessments involved routine blood, urine, and liver and kidney function tests.

After 4 weeks, the improvement rate for reflux or heartburn symptoms was 79.49% in the JQ group vs. 58.97% in the placebo group (P < 0.05). VAS scores showed significant reductions in both groups but without notable inter-group differences. Total TCM syndrome scores significantly decreased in both groups, with the JQ group showing greater improvement trends. The JQ group had higher rates of effective TCM syndrome improvement and better GERD-HRQL scores. Both groups saw significant reductions in self-rated depression and anxiety scores, with trends favoring JQ granules. Safety assessments were comparable between groups.

JQ granules significantly outperform placebo in treating NERD symptoms and display long-term effectiveness. They effectively address spleen deficiency and damp-heat syndrome, improving patients' social functioning, and have a favorable safety profile.

https://clinicaltrials.gov/study/NCT04324138?term=NCT04324138&rank=1, identifier: NCT04324138.

Refractory gastroesophageal reflux disease (refractory GERD) is a heterogeneous disease characterized by unresponsiveness or poor efficacy to proton-pump inhibitors (PPIs). This chronic disorder substantially weakens patients' mental wellbeing and quality of life, increasing the financial burden on society. Multiple articles have been reported in this area. However, literature involving scientometric analysis of refractory GERD is absent. Therefore, it is necessary to understand the evolution of research themes and the main hotspots of refractory GERD through bibliometric methods.

All documents related to refractory GERD based on the WOS Core Collection from January 2000 to November 2023 were selected for analysis. Citespace V 6.1 R6, VOSviewer V 1.6.20, and Scimago Graphica V 1.0.38 were used to perform bibliometric analysis.

We collected a total of 241 research articles from 36 countries and 322 institutions, contributed by over 1,000 authors. Over the last 20 years, the number of articles in this field has increased year by year, and since 2011, the number of publications has increased dramatically, with 85.89% of the papers. These countries are led by the United States and Japan. GUT had the highest number of citations and DIGESTION had the highest number of publications. Research on standardized diagnosis and management, mechanisms, novel monitoring methods, and innovative drugs and procedures for refractory GERD are the main topics and hotspots in this field. This study also found that neuroimmune interaction is closely related to refractory GERD, which may be a new direction for future mechanism research.

Our study is the first bibliometric analysis of the global literature on refractory GERD. This research provides valuable insights for researchers, enabling them to quickly understand the research frontier and hot topics of this field.

Gastroesophageal reflux disease (GERD) is characterized by prolonged exposure of the esophageal mucosa to gastric content, with esophageal motility playing a pivotal role in its pathophysiology. This study employs a cross-sectional design to investigate the interplay between esophageal motility, the severity of esophagitis, and age in individuals presenting with GERD symptoms.

The primary objective is to assess proximal and distal esophageal contractions in individuals with GERD symptoms, exploring potential correlations with the severity of esophageal lesions and age.

A total of 47 patients reporting heartburn and acid regurgitation underwent diagnostic investigations, including esophageal manometry, radiological examinations, and endoscopy. Patients were categorized into groups based on the presence and severity of esophagitis. Esophageal contractions were monitored using a manometric method at various distances from the UES after swallowing 5 mL of water.

Patients with severe esophagitis (SE) exhibited a reduced distal esophageal contraction amplitude compared to those without esophagitis (WE) or with moderate esophagitis (ME). No significant age-related differences were observed in esophageal contractions. Analyses included contraction amplitude, duration, area under the curve (AUC), and propagation time.

This study provides insights into the nuanced relationship between esophageal motility, esophagitis severity, and age in GERD patients. The findings highlight the significance of distal esophageal contractions in SE cases, suggesting potential implications for disease progression. Age did not emerge as a significant factor influencing esophageal motility in this patient cohort.

Gastroesophageal reflux disease (GERD) is the most common diagnosis seen in outpatient gastroenterology clinics. The diagnosis is made by a variable combination of symptoms, response to acid suppressive therapy, endoscopic evaluation, and pH testing. In this review, we evaluate how to utilize various reflux testing in clinical practice based on current evidence.

Ambulatory reflux monitoring is a recognized diagnostic tool for clinical decision making in patients with/without established GERD, persistent reflux symptoms, and lack of response to proton pump inhibitor (PPI) therapy. Standard evaluation approaches include 24-hour pH or impedance monitoring via transnasal catheter, prolonged (48 to 96 hour) wireless pH monitoring, and the recently developed mucosal integrity testing. Testing using one of these methods allows for measurement of acid exposure, frequency of reflux, and to phenotype patients to personalize treatment recommendations.

The primary goal of future studies should be to simplify ambulatory reflux monitoring, reduce diagnostic latency, improve patient tolerance, and to obtain clinical outcomes-based studies. The current paradigm of reflux testing is vastly complex with multiple modalities and shifting cutoffs of pH abnormality that lead to high economic burden on the society.

Advances in ambulatory esophageal reflux monitoring that incorporated impedance electrodes to pH catheters have resulted in better characterization of retrograde bolus flow in the esophagus. With pH-impedance monitoring, in addition to acid reflux episodes identified by pH drops below 4.0, weakly acid reflux (WAR, pH 4-7) and nonacid reflux (NAR, pH >7.0) are also recognized, although both may be included under the umbrella term NAR. However, despite identification of ambulatory pH-impedance monitoring, data on clinical relevance and prognostic value of NAR are limited. The Lyon Consensus, an international expert review that defines conclusive metrics for gastroesophageal reflux disease (GERD), identifies NAR as "supportive" but not conclusive for GERD.

This review provides perspectives on whether NAR fulfills three criteria for clinical relevance: whether NAR sufficiently explains pathogenesis of symptoms, whether it is associated with meaningful manifestations of GERD, and whether it can predict treatment efficacy.

The last 40 years have seen a remarkable change in our understanding of reflux disease.

These changes encompass disease definition and impact, pathophysiology, diagnostic testing, regulatory oversight of clinical trials, pharmacotherapy, endoscopic, and surgical treatment. We have also seen a number of promising therapies fail.

The future holds the promise of further advances. Adaptive artificial intelligence will take over diagnostics in manometry and pH impedance testing and patient-driven outcomes may be changed by interactions with artificial intelligence rather than humans. Changes in chip technology will allow higher resolution chips to be carried on smaller devices making extra-esophageal areas where reflux may play a role more accessible to prolonged observation and testing.

Studies have demonstrated that non-acid reflux (NAR) is associated with esophageal squamous cell carcinoma (ESCC). Esophageal dysmotility is associated with NAR but few studies have focused on the esophageal motility of ESCC patients. We explored the relationship between ESCC, NAR and esophageal dysmotility with the aid of multichannel intraluminal impedance and pH (MII-pH) and high-resolution manometry (HRM).

From Jan 2021 to Oct 2022, 20 patients with superficial ESCC were enrolled as the ESCC group, while 20 age and gender matched individuals without gastroesophageal reflux disease (GERD) symptoms and 20 age and gender matched patients with GERD symptoms were recruited as the control groups. Patients received 24 h MII-pH and HRM procedure before endoscopic submucosal dissection (ESD), and the data were then collected to identify the type of reflux and esophageal dysmotility.

Prevalence of esophageal dysmotility was significantly different among the three groups, 75.0% in the ESCC group, 35.0% in the non-GERD group and 70.0% in the GERD group (P = 0.029). NAR episodes at 15 cm above the lower esophageal sphincter (LES) in the ESCC group were significantly higher than that in the non-GERD group (6.5 (3.5-9.3) vs 1.0 (0.8-4.0), P = 0.001) and were similar with that in the GERD group (6.5 (3.5-9.3) vs 5.5 (3.0-10.5), P > 0.05). NAR episodes at 5 cm above LES was significantly higher in the ESCC group than that in the non-GERD group (38.0 (27.0-60.0) vs 18.0 (11.8-25.8), P = 0.001) and was significantly higher than that in the GERD group (38.0 (27.0-60.0) vs 20.0 (9.8-30.5)), P = 0.010). Prevalence of pathologic non-acid reflux was significantly different among the three groups, 30.0% in the ESCC group, 0.0% in the non-GERD group and 10.0% in the GERD group (P < 0.001).

Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC.

ChiCTR2200061456.

Gastroesophageal reflux (GER) is one of the most common presenting complaints to pediatric gastroenterologists, and a wide variety of symptoms in children are potentially attributable to typical or atypical GER. While reflux diagnosis and treatment paradigms classically have focused on targeting acid, there is a growing recognition of the prevalence and significance of nonacid GER in both children and adults. This review explores the role of nonacid reflux in pediatric patients, including definitions, associations with symptoms, pathophysiologic mechanisms, and treatment implications.

GERD is a common disorder and is characterized by the presence of typical or atypical symptoms. In GERD patients, the presence of mucosal alterations in endoscopy is detected in up to 30% of individuals. The clinical presentation of GERD patients may be complex and their management is challenging, due to the heterogeneous clinical presentation. The present review has been performed searching all relevant articles in this field, over the past years, using PubMed database.

The diagnosis and management of GERD have been significantly improved in the last years due to the increasing availability of reflux monitoring techniques and the implementation of new procedures in the therapeutic armamentarium. Beside traditional impedance-pH variables, new metrics have been developed, increasing the diagnostic yield of reflux monitoring and better predicting the treatment response. Traditional pharmacological treatments include acid-suppressive-therapy and/or anti-acid. On the other hand, surgical treatment and, more recently, endoscopic procedures represent a promising field in the therapeutic approach.

Diagnosis and treatment of GERD still represent a challenging area. However, we believe that an accurate upfront evaluation is, nowadays, necessary in addressing patients with GERD to a more accurate diagnosis as well as to the best treatment options.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert advice regarding the clinical management of patients with suspected extraesophageal gastroesophageal reflux disease.

This article provides practical advice based on the available published evidence including that identified from recently published reviews from leading investigators in the field, prospective and population studies, clinical trials, and recent clinical guidelines and technical reviews. This best practice document is not based on a formal systematic review. The best practice advice as presented in this document applies to patients with symptoms or conditions suspected to be related to extraesophageal reflux (EER). This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Gastroenterologists should be aware of potential extraesophageal manifestations of gastroesophageal reflux disease (GERD) and should inquire about such disorders including laryngitis, chronic cough, asthma, and dental erosions in GERD patients to determine whether GERD may be a contributing factor to these conditions. BEST PRACTICE ADVICE 2: Development of a multidisciplinary approach to extraesophageal (EER) manifestations is an important consideration because the conditions are often multifactorial, requiring input from non-gastroenterology (GI) specialties. Results from diagnostic testing (ie, bronchoscopy, thoracic imaging, laryngoscopy, etc) from non-GI disciplines should be taken into consideration when gastroesophageal reflux (GER) is considered as a cause for extraesophageal symptoms. BEST PRACTICE ADVICE 3: Currently, there is no single diagnostic tool that can conclusively identify GER as the cause of EER symptoms. Determination of the contribution of GER to EER symptoms should be based on the global clinical impression derived from patients' symptoms, response to GER therapy, and results of endoscopy and reflux testing. BEST PRACTICE ADVICE 4: Consideration should be given toward diagnostic testing for reflux before initiation of proton pump inhibitor (PPI) therapy in patients with potential extraesophageal manifestations of GERD, but without typical GERD symptoms. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable. BEST PRACTICE ADVICE 5: Symptom improvement of EER manifestations while on PPI therapy may result from mechanisms of action other than acid suppression and should not be regarded as confirmation for GERD. BEST PRACTICE ADVICE 6: In patients with suspected extraesophageal manifestation of GERD who have failed one trial (up to 12 weeks) of PPI therapy, one should consider objective testing for pathologic GER, because additional trials of different PPIs are low yield. BEST PRACTICE ADVICE 7: Initial testing to evaluate for reflux should be tailored to patients' clinical presentation and can include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy. BEST PRACTICE ADVICE 8: Testing can be considered for those with an established objective diagnosis of GERD who do not respond to high doses of acid suppression. Testing can include pH-impedance monitoring while on acid suppression to evaluate the role of ongoing acid or non-acid reflux. BEST PRACTICE ADVICE 9: Alternative treatment methods to acid suppressive therapy (eg, lifestyle modifications, alginate-containing antacids, external upper esophageal sphincter compression device, cognitive-behavioral therapy, neuromodulators) may serve a role in management of EER symptoms. BEST PRACTICE ADVICE 10: Shared decision-making should be performed before referral for anti-reflux surgery for EER when the patient has clear, objectively defined evidence of GERD. However, a lack of response to PPI therapy predicts lack of response to anti-reflux surgery and should be incorporated into the decision process.

Epithelial barrier dysfunction is a hallmark of gastroesophageal reflux disease (GERD) related to symptom origination, inflammatory remodeling and carcinogenesis. Alginate-based antireflux medications were previously shown to topically protect against peptic barrier disruption, yet the molecular mechanisms of injury and protection were unclear. Herein, Barrett's esophageal (BAR-T) cells were pretreated with buffered saline (HBSS; control), dilute alginate medications (Gaviscon Advance or Gaviscon Double Action, Reckitt Benckiser), a viscosity-matched placebo, or ADAM10 and matrix metalloproteinase (MMP) inhibitors before exposure to HBSS pH7.4 or pH4 ± 1 mg/mL pepsin for 10-60 min. Cell viability was assessed by ATP assay; mediators of epithelial integrity, E-cadherin, ADAM10, and MMPs were examined by Western blot and qPCR. Alginate rescued peptic reduction of cell viability (p < 0.0001). Pepsin-pH4 yielded E-cadherin fragments indicative of regulated intramembrane proteolysis (RIP) which was not rescued by inhibitors of known E-cadherin sheddases. Transcriptional targets of E-cadherin RIP fragments were elevated at 24 h (MMP-1,2,9,14; p < 0.01). Alginate rescued E-cadherin cleavage, ADAM10 maturation, and MMP induction (p < 0.01). Results support RIP as a novel mechanism of peptic injury during GERD. Alginate residue after wash-out to mimic physiologic esophageal clearance conferred lasting protection against pepsin-induced molecular mechanisms that may exacerbate GERD severity and promote carcinogenesis in the context of weakly acidic reflux.

Gastroesophageal reflux disease (GERD) significantly impacts patient quality of life and is a major risk factor for the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Proton pump inhibitors (PPIs) are the standard-of-care for GERD and are among the most prescribed drugs in the world, but do not protect against nonacid components of reflux such as pepsin, or prevent reflux-associated carcinogenesis. We recently identified an HIV protease inhibitor amprenavir that inhibits pepsin and demonstrated the antireflux therapeutic potential of its prodrug fosamprenavir in a mouse model of laryngopharyngeal reflux. In this study, we assessed the capacity of amprenavir to protect against esophageal epithelial barrier disruption in vitro and related molecular events, E-cadherin cleavage, and matrix metalloproteinase induction, which are associated with GERD severity and esophageal cancer. Herein, weakly acidified pepsin (though not acid alone) caused cell dissociation accompanied by regulated intramembrane proteolysis of E-cadherin. Soluble E-cadherin responsive matrix metalloproteinases (MMPs) were transcriptionally upregulated 24 h post-treatment. Amprenavir, at serum concentrations achievable given the manufacturer-recommended dose of fosamprenavir, protected against pepsin-induced cell dissociation, E-cadherin cleavage, and MMP induction. These results support a potential therapeutic role for amprenavir in GERD recalcitrant to PPI therapy and for preventing GERD-associated neoplastic changes.

The upper gastrointestinal (GI) tract is frequently involved in systemic sclerosis (SSc) and may impact quality of life, physical function and survival. Although we are currently very proactive in terms of screening for heart and lung involvement, patients with SSc are not routinely screened for GI involvement. This review details the available investigations for common upper GI symptoms in SSc, including dysphagia, reflux and bloating and provides advice as to how to integrate these investigations into current clinical care.

The clinical management of nonacid gastroesophageal reflux-induced chronic cough (GERC) is challenging, and patient response to standard antireflux therapy (omeprazole 20 mg twice daily plus mosapride 10 mg thrice daily) is suboptimal. This study aimed to identify predictors of standard antireflux therapy efficacy and provide evidence for standardized management algorithms of nonacid GERC.

A total of 115 nonacid GERC patients who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) were enrolled between March 2017 and March 2021. Retrospective analysis of general information and MII-pH indications were used to establish a regression analysis model for multiple factors affecting standard antireflux therapy efficacy.

90 patients met the inclusion criteria, and the overall response rate to standard antireflux therapy was 55.5% (50/90). The mean nocturnal baseline impedance (MNBI) (1817.75 ± 259.26 vs. 2369.93 ± 326.35, P = 0.030) and proximal MNBI (1833.39 ± 92.16 vs. 2742.57 ± 204.64, P ≤ 0.001) of responders were lower than those of nonresponders. Weakly acid reflux (56.00 (31.70, 86.00) vs. 14.00 (14.00, 44.20), P = 0.022), nonacid reflux (61.35 (15.90.86.50) vs. 21.60 (0.00, 52.50), P = 0.008), and proximal extent (19.00 (5.04, 24.00) vs. 5.50 (2.56, 11.13), P = 0.011) were markedly higher in responders than nonresponders. Proximal MNBI (OR = 0.997, P = 0.042, and optimal cutoff = 2140 Ω) and weakly acid reflux (OR = 1.051, P = 0.029, and optimal cutoff = 45) were independent predictors of standard antireflux therapy efficacy. The combination predictive value did not show better results than either individual predictor.

Proximal MNBI < 2140 Ω may be used to screen patients with nonacid GERC suitable for standard antireflux therapy and in standardized management algorithms for nonacid GERC. In the absence of MNBI, weakly acid reflux > 45 can be used as an auxiliary indicator.

Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are chronic conditions caused by backflow of gastric and duodenal contents into the esophagus and proximal aerodigestive tract, respectively. Mucosal barrier dysfunction resultant from the synergistic actions of chemical injury and the mucosal inflammatory response during reflux contributes to symptom perception. Alginates effectively treat symptoms of mild to moderate GERD and have recently shown benefit for LPR. In addition to forming a "raft" over gastric contents to reduce acidic reflux episodes, alginates have been found to bind the esophageal mucosa thereby preserving functional barrier integrity measured by transepithelial electrical resistance. The aim of this study was to further examine the topical protective capacity of alginate-based Gaviscon Advance (GA) and Double Action (GDA) against pepsin-acid mediated aerodigestive epithelial barrier dysfunction in vitro.

Translational.

Immortalized human esophageal and vocal cord epithelial cells cultured in transwells were pretreated with liquid formula GA, GDA, matched viscous placebo solution, or saline (control), then treated for 1 h with saline, acid (pH 3-6) or pepsin (0.1-1 mg/ml) at pH 3-6. Endpoint measure was taken of horseradish peroxidase (HRP) allowed to diffuse across monolayers for 2 h.

Pepsin (0.1-1 mg/ml) at pH 3-6 increased HRP flux through cultures pretreated with saline or placebo (p < 0.05); acid alone did not. GA and GDA prevented barrier dysfunction.

GA and GDA preserved epithelial barrier function during pepsin-acid insult better than placebo suggesting that protection was due to alginate. These data support topical protection as a therapeutic approach to GERD and LPR. Laryngoscope, 132:2327-2334, 2022.

GERD, or gastroesophageal reflux disease, is a prevalent medical condition that affects millions of individuals throughout the world. Chronic cough is often caused by GERD, and chronic cough caused by GER is defined as GERD-related chronic cough (GERC). It is still unclear what the underlying molecular mechanism behind GERC is. Reflux theory, reflex theory, airway allergies, and the novel mechanism of esophageal motility disorders are all assumed to be linked to GERC. Multichannel intraluminal impedance combined with pH monitoring remains the gold standard for the diagnosis of GERC, but is not well tolerated by patients due to its invasive nature. Recent discoveries of new impedance markers and new techniques (mucosal impedance testing, salivary pepsin, real-time MRI and narrow band imaging) show promises in the diagnosis of GERD, but the role in GERC needs further investigation. Advances in pharmacological treatment include potassium-competitive acid blockers and neuromodulators (such as Baclofen and Gabapentin), prokinetics and herbal medicines, as well as non-pharmacological treatments (such as lifestyle changes and respiratory exercises). More options have been provided for the treatment of GERC other than acid suppression therapy and anti-reflux surgery. In this review, we attempt to review recent advances in GERC mechanism, diagnosis, and subsequent treatment options, so as to provide guidance for management of GERC.

An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.

Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised.

Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO).

This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

Proton pump inhibitors (PPI) have no effect on non-acid reflux events which can continue to provoke gastro-oesophageal reflux disease (GERD) symptoms. Baclofen, a γ-aminobutyric acid agonist, can decrease non-acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied.

To assess the efficacy of baclofen 10 mg t.i.d. vs placebo as add-on therapy in PPI-refractory GERD symptoms, in a randomised, double-blind, placebo-controlled study.

Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10 mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance-pH monitoring on-PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models.

About 60 patients were included (age 47.5 years [range 19-73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen-treated group compared to placebo (p = 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n = 25) group improved significantly with baclofen (p_corr  = 0.02), and worsened with placebo (p_corr  = 0.008). The total number of reflux events decreased over time (p = 0.01), mainly due to the baclofen condition (p_corr  = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (p_corr  = 0.009), but not placebo.

Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH-impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.

Reflux scintigraphy is often used to diagnose gastro-esophageal reflux disease (GERD). However, the efficacy of this study remains controversial. Our aim was to determine the role of reflux scintigraphy in diagnosing GERD by comparing it to 24 h combined pH-impedance study as the gold standard.

Adult patients who presented for investigations of reflux symptoms were prospectively recruited into the study. All patients underwent high resolution esophageal manometry and those with major motor disorders of the esophagus were excluded. Eligible patients immediately underwent reflux scintigraphy following insertion of the pH-impedance catheter.

Thirty patients were included in the study. Using a total acid exposure time (AET) of >4.2% as the reference for abnormal acid reflux, reflux scintigraphy had a sensitivity and specificity of 62.5 and 68.2%, respectively, in detecting acid reflux. When compared to AET >6%, reflux scintigraphy had a sensitivity and specificity of 66.7 and 62.5%, respectively, and a positive predictive value of 30.8% and a negative predictive value of 88.2%. There were no associations between outcomes of reflux scintigraphy and total AET (p = .46), total (acid or non-acid) reflux events (p = 0.11), proximal AET (p = .33) or the number of proximal reflux episodes (p = .75) on 24 h pH-impedance study.

Reflux scintigraphy has limited role in diagnosing GERD when compared to 24 h combined pH-impedance monitoring.

Gastroesophageal reflux disease (GERD) is very common and defined as troublesome symptoms owing to excessive acid reflux. The spectrum of GERD is broad, including not only erosive esophagitis and Barrett's esophagus but also nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. Patients with reflux symptoms despite normal endoscopy remain common clinical presentation, can be heterogeneous overlapping with functional gastrointestinal disorders. Ambulatory esophageal pH monitoring with and without impedance helps the diagnosis of NERD. Metrics such as baseline impedance and postreflux swallow induced peristaltic wave enhance diagnostic accuracy in patients with inconclusive diagnoses. The major treatment of all manifestations of GERD is acid suppression with proton pump inhibitors, while other therapies, such as reflux-reducing agents and adjunctive medications, can be individualized where the response to traditional management is incomplete. GERD patients often need long-term treatment due to frequent relapses. Anti-reflux surgery can be effective too. Endoscopic therapies have some promising results, but long-term outcomes remain to be determined.

This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid blocker (P-CAB) therapy.

This study included 23 patients with reflux-related symptoms despite P-CAB therapy. Esophageal impedance-pH monitoring was performed on P-CAB and the following potential determinants of reflux perception were investigated: reflux nadir pH value; change in pH (baseline-nadir); bolus clearance time; reflux extent; proportions of acid, weakly acidic, and weakly alkaline reflux episodes; and proportions of liquid and mixed reflux episodes.

Overall, ≥ 90% of all and symptomatic reflux episodes were weakly acidic reflux and 63% of symptomatic reflux episodes were reflux episodes with pH ≥ 5. There were no significant differences regarding potential determinants between symptomatic and asymptomatic reflux episodes. However, the proportion of symptomatic reflux episodes was significantly greater with pH < 5 (13.8%) than with pH ≥ 5 (9.5%) (P = 0.0431). In reflux episodes with pH < 5, the proportion of symptomatic reflux episodes was significantly greater in proximal sites (20.6%) than in distal sites (10.6%) (P = 0.0178). Conversely, in reflux episodes with pH ≥ 5, there was no significant difference regarding reflux perception according to reflux extent (proximal: 9.6% vs. distal: 9.0%, P = 0.9337).

In patients with P-CAB-resistant NERD, reflux symptoms were mainly caused by reflux episodes with pH ≥ 5 on P-CAB therapy. The proportions of symptomatic reflux episodes among reflux sites differed according to reflux pH value; thus, the mechanisms of reflux perception may differ according to reflux pH value.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Supragastric belching (SGB) and rumination are behavioral disorders associated with proton pump inhibitor (PPI) non-response and can be diagnosed using multichannel intraluminal impedance-pH (MII-pH) and post-prandial high-resolution impedance manometry (PPHRIM). This pilot study compared diagnostic yield and inter-rater agreement for SGB and rumination using MII-pH and PPHRIM.

Three esophageal physiologists performed blinded interpretations of MII-pH and PPHRIM in 22 PPI non-responders. Raters selected from 4 diagnostic impressions (normal, GERD, behavioral disorders, GERD+behavioral disorders) without clinical context. Primary outcomes were diagnostic impressions compared against clinical gold standard impression, between raters, and between test modalities. Following a 28-month wash-out period, raters re-interpreted MII-pH with clinical context and under consensus definition of diagnostic criteria.

Compared to gold standard, rater accuracy for presence of behavioral disorders ranged from 45 to 77% on MII-pH and 45-59% on PPHRIM. On MII-pH, inter-rater agreement was fair for diagnosis (ĸ0.32, p < 0.01) and suboptimal for presence of behavioral disorders (ĸ0.13, p = 0.14). On PPHRIM, inter-rater agreement was suboptimal for both diagnosis (ĸ0.03, p = 0.34) and presence of a behavioral disorder (ĸ-0.22, p = 0.96). Inter-rater agreement improved in post hoc MII-pH interpretations. Rumination was more frequently identified on PPHRIM (23, 35%) compared to MII-pH (7, 11%).

Diagnostic accuracy and inter-rater agreement are higher for MII-pH than PPHRIM, and behavioral disorders are more frequently identified on PPHRIM. Identifying behavioral disorders on MII-pH and PPHRIM has implications for clinical evaluation of PPI non-response; clinical context is essential for accurate study interpretation. Further work is needed to standardize definitions and interpretations.

Esophagogastric junction contractile integral (EGJ-CI) is a novel indicator to evaluate quantitatively the esophagogastric junction (EGJ) barrier function. We aimed to assess the role of EGJ-CI in patients with refractory gastroesophageal reflux disease (GERD) symptoms and the correlation between EGJ-CI and impedance-pH monitoring characteristics.

In total 82 patients with proton pump inhibitors (PPIs)-refractory gastroesophageal reflux symptoms (heartburn or regurgitation) were enrolled. These patients were further divided into two groups based on their EGJ-CI value (39 mmHg·cm). The mean nocturnal baseline impedance (MNBI) was measured to explore its association with EGJ-CI.

The median EGJ-CI in patients with PPI-refractory symptoms was 30.8 mmHg·cm. EGJ-CI was inversely correlated with acid exposure time and reflux episodes; while it was positively correlated with MNBI, distal contractile integral, lower esophageal sphincter basal pressure and integrated relaxation pressure. Patients were further divided into the high (n = 27) and low (n = 55) EGJ-CI groups using a cut-off value of 39.0 mmHg·cm. Patients with a low EGJ-CI had a lower MNBI level than those with a high EGJ-CI (2703 Ω vs 3545 Ω, P = 0.034).

In patients with PPIs-refractory symptoms, EGJ-CI is associated with acid exposure and conventional high-resolution manometry parameters. EGJ-CI may play an important role in the diagnosis and treatment of patients with refractory GERD.

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered the treatment of choice for obesity with gastroesophageal reflux disease (GERD). There are few reports showing objective data based on esophageal function tests (EFTs). The aim of our study was to evaluate the influence of LRYGB on GERD. Methods: Candidates for laparoscopic sleeve gastrectomy (LSG) underwent preoperative esophageal manometry (EM) and 24-hour pH monitoring. Based on the negative influence of LSG on GERD, patients with abnormal pH were offered LRYGB. Those patients repeated EFTs, esophagogastroduodenoscopy, and symptom questionnaire 1 year after surgery. Results: Two hundred fifty LSG candidates underwent preoperative EFTs; 38% were redirected to LRYGB due to abnormal pH and 13 (18%) completed EFTs postoperatively. In ten women, age: 40 ± 7 years, body mass index: 41 ± 1 kg/m². EM: lower esophageal sphincter (LES) length increased from 2.6 to 2.9 cm (P = not statistically significant [NS]), and LES pressure decreased from 15 to 14.2 mmHg (P = NS). Preoperatively, LES was normotensive in 12 (92%) patients and postoperatively in 11 (85%) (P = NS). DeMeester score decreased from 35.7 to 11 (P < .001). Postoperatively, 9 (69%) patients resolved their GERD, 3 (23%) improved, and 1 (8%) remained the same (P < .001). Symptoms decreased significantly after surgery. Two patients (15%) had Grade A esophagitis. One of them was able to resolve it, while the other 1 remained the same. Conclusions: Our preliminary data showed that after LRYGB, LES pressure remained the same and DeMeester score decreased, while 69% of patients resolved their GERD. Therefore, LRYGB seems to be an excellent option for obesity and GERD.

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

Esophageal acid exposure time (AET) during 24 h pH monitoring is reproducible and predictive outcomes of treatment for gastroesophageal reflux disease. Several small Asian studies have investigated the normal range of the AET; the range may be different from that in Western populations. We evaluated its normal range in healthy Asian compared to Western subjects.

We searched PubMed, Embase, Cochrane Library, and KoreaMed for studies that reported pH monitoring parameters in healthy subjects. Studies that reported the AET values of healthy subjects were eligible for the analyses. The upper limit of normal of the AET was obtained from the 95th percentile of the available raw data or calculated as the mean value +2 standard deviations.

Nineteen Asian and 49 Western studies were assessed. The estimated AET values were analyzed using a bootstrapping technique, weighted according to the sample size. The mean AET was 1.1% and 2.9% in the Asian and Western populations, respectively. The upper limit of the reference range was 3.2% (95% confidence interval [CI], 2.7-3.9%) and 8.2 (95% CI, 6.7-9.9) in the Asian and Western populations, respectively. The normal AET differed between the Asian and Western populations because the CI of the two groups did not overlap.

The upper limit of normal of the AET in healthy Asian subjects was 3.2% (95% CI, 2.7-3.9%), which was lower than that of healthy Western subjects.

Although the efficacy of rikkunshito in patients with treatment-resistant non-erosive gastroesophageal reflux disease (NERD) has been reported, it is unclear for which subgroups of NERD patients (per the Rome IV criteria) rikkunshito is effective. The objective of this study was to investigate the efficacy of rikkunshito in patients with functional heartburn.

Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled. The patients were administered rikkunshito for 8 weeks. The frequency scale for the symptoms of GERD (FSSG), Japanese translation of quality of life in reflux and dyspepsia questionnaire (QOLRAD-J), and hospital anxiety and depression scale (HADS) were evaluated before and 4 and 8 weeks after administration. Overall treatment efficacy (OTE) was evaluated 8 weeks after administration.

One patient was discontinued 4 weeks after administration because of voluntary withdrawal. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score tended to increase 8 weeks after treatment or at discontinuation compared with before treatment, no significant difference was observed. HADS score did not decrease significantly 8 weeks after treatment or at discontinuation compared with before treatment. However, a correlation was found between total FSSG and HADS anxiety scores (correlation coefficient: 0.684, P = 0.027).

This was the first study to investigate the efficacy of rikkunshito in patients with functional heartburn. Rikkunshito may be effective in these patients.

Gastroesophageal reflux disease is characterized by the reflux of gastric contents into the esophagus with an estimated worldwide prevalence of 8%-33%. The current paradigm in gastroesophageal reflux disease diagnosis relies on recognition of symptoms and/or the presence of mucosal disease at the time of esophagogastroduodenoscopy. Recognition of symptoms, however, can arise with challenges, particularly when patients complain of less typical symptoms. Since first reported in 1969 by Spencer et al., the application of prolonged intraesophageal pH monitoring to identify pathologic reflux has evolved considerably. Utility of pH monitoring aims to investigate the degree of acid burden and frequency of reflux episode, and the relationship between symptoms and acid reflux events. This relationship is represented by either the Symptom Index, Symptom Sensitivity Index, Symptom Association Probability, or Ghillebert Probability Estimate. This article reviews symptom-association analysis during esophageal reflux testing, covering the literature on current methods of reflux testing, interpretation of symptom association, and practical issues that can arise during symptom analysis.

As there is a scarcity of data on overall prevalence, risk factors, and health-care utilization of esophageal symptoms using the Rome criteria in the rural population in Asia, we undertook a study with the aims to evaluate: (i) the prevalence of heartburn, chest pain, globus, and dysphagia of presumed esophageal origin; (ii) the prevalence of functional esophageal disorders by Rome III criteria; (iii) the risk factors for esophageal symptoms; and (iv) the health-care utilization.

This door-to-door survey was conducted in three villages (Charcharia, Churain of Dhaka district, and Kharrah of Munshiganj district of Bangladesh) among the adult population (≥18 years) using the translated and validated Enhanced Asian Rome III questionnaire.

Of 3559 individuals, 3351 (94.15%) responded (mean age 40.41 ± 16.04 years, female, 1924 [57.4%]). Heartburn was the most common symptom, 863 (25.8%), followed by chest pain, 367 (11%); globus, 285 (8.5%); and dysphagia, 146 (4.4%). At least one symptom was present in 1108 (33.1%) respondents. Based on Rome III criteria, 428 (12.8%), 41 (1.2%), 49 (1.5%), 26 (0.8%), and 524 (15.6%) had heartburn, chest pain, globus, dysphagia, and at least one functional esophageal disorder, respectively. Female gender, lower family income, presence of functional dyspepsia-irritable bowel syndrome (FD-IBS) overlap, FD only, and psychological distress were found to be risk factors for esophageal symptoms on multivariate analysis. Among the subjects with any esophageal disorders, 156 (14.1%) consulted any health-care provider, and 517 (46.6%) took antisecretory medications.

Esophageal symptoms are common in the rural community of Bangladesh and are associated with substantial health resource utilization.

To determine whether combined multichannel intraluminal impedance and pH (MII-pH) testing led to a change in management of children with gastro-oesophageal reflux disease (GORD).

Retrospective chart review was done in all patients who underwent MII-pH testing for GORD symptoms at Sydney Children's Hospital between 2008 and 2016. Changes to anti-reflux medications and referral for anti-reflux surgery were evaluated.

There were 365 patients, 260 (71.2%) of whom were on acid-suppressing therapy. The median age was 4.1 ± 4.8 years, 205 patients (56%) were males, 83 (22.7%) were infants (<1 year of age) and 145 (39.7%%) had comorbid conditions. We found 72.1% had abnormal MII-pH results, of which 17.5% had abnormal acid reflux, 8.2% had abnormal number of retrograde bolus movements and 46.3% had hypersensitive oesophagus (positive symptom association only). Infants were significantly more likely to have abnormal MII-pH results compared to older children (P = .04). Results of MII-pH testing led to medication changes in 44.7% and referral for anti-reflux surgery in 6.8% of patients.

Combined multichannel intraluminal impedance and pH testing is clinically useful in the management of children with symptoms of GORD and over half the patients had changes to their medical treatment or referral for anti-reflux surgery based on the results of MII-pH testing. It resulted in a treatment change in an additional 32% of patients over traditional pH-metry.

The most recent iteration of the classifications for functional esophageal disorders, Rome IV, proposed relevant modifications of the previous definitions for Rome III. They specifically considered increased esophageal acid exposure as the marker of gastroesophageal reflux disease (GERD), including the remaining part of non-erosive reflux disease patients with normal acid in the group with functional alterations, considering both reflux hypersensitivity and functional heartburn. However, recent pathophysiological and therapeutic data suggest the need for a return to including reflux hypersensitivity in the GERD spectrum. Indeed, physiologic alterations in esophageal mucosal integrity and chemical clearance, the presence of microscopic esophagitis, and strict symptom-reflux association support the concept that reflux hypersensitivity pertains to GERD. Surgical anti-reflux therapy has resulted in positive outcomes, even in the long term, in patients with reflux hypersensitivity and not in those with functional heartburn. Moreover, clinical trials using neuromodulators have been scarce and provided conflicting results. As a result, the real progress of the Rome IV classifications is in dispute. This article aims to summarize the most recent knowledge of non-erosive reflux disease and reflux hypersensitivity to discuss the utility of Rome IV criteria in the identification and management of functional esophageal disorders.

Supragastric 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.

We 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.

Impedance-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).

The 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.

Patients with esophageal symptoms potentially associated with gastroesophageal reflux disease such as heartburn, regurgitation, chest pain, or cough represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal reflux monitoring in clinical practice is: (1) to accurately define reflux burden, (2) to segregate patients according to reflux monitoring results as true GERD, reflux hypersensitivity and functional heartburn, and (3) to establish a treatment plan. With this in mind, in the last decade, investigations and technical advances, with the introduction of impedance-pH monitoring and wireless pH capsule, have enhanced our understanding and management of GERD. The following recommendations were discussed and approved after a comprehensive review of the medical literature pertaining to reflux testing techniques and their recent application. This review created under the auspices of the Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE), Società Italiana di Neuro-Gastro-Enterologia e Motilità (SINGEM) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying reflux studies in the most fruitful manner within the context of their patients with esophageal symptoms.

High-resolution manometry evaluates esophageal motor function using 10 supine water swallows. Superimposing impedance over high-resolution manometry pressure topography assesses the relationship between contraction and bolus propulsion and identifies inadequate clearance. Ancillary techniques and maneuvers augment the standard supine high-resolution manometry evaluation by challenging peristaltic function. Increasing bolus volume (rapid drink challenge) and altering bolus consistency (standardized test meal, solid swallows) enhance identification of esophageal outflow obstruction syndromes. Physiologic maneuvers (multiple rapid swallows, abdominal compression) address the ability of the esophageal smooth muscle to augment contraction vigor. Pharmacologic challenge is less commonly used clinically, and elucidates pathophysiology of esophageal motor disorders.

Oesophageal radiofrequency reduces use of proton pump inhibitors (PPIs) in patients with gastro-oesophageal reflux disease responding to PPIs.

To determine the efficacy of oesophageal radiofrequency in patients with PPI-refractory heartburn.

A randomised, double-blind, sham-controlled multicentre study was designed to assess the efficacy of oesophageal radiofrequency in PPI non-responding patients with heartburn. Patients had moderate-to-severe heartburn defined by at least 3 occurrences a week, and not improved by continuous PPI treatment. The primary endpoint was clinical success at week 24, defined by intake of less than 7 PPI doses over the 2 preceding weeks and adequate symptom control determined by the patient.

Sixty two patients were randomised, 29 to the oesophageal radiofrequency group and 33 to the sham group. Intention-to-treat analysis showed that 1/29 (3.4%) and 5/33 (15.1%) achieved the primary endpoint in the oesophageal radiofrequency and sham groups, respectively (NS). There was no significant difference between oesophageal radiofrequency and sham regarding the number of days without heartburn, days with PPI consumption in the last 2 weeks, and patients not taking PPIs. No pH-impedance parameter was associated with clinical response. The occurrence of adverse events was similar in both groups.

This sham-controlled, randomised study did not demonstrate any efficacy of oesophageal radiofrequency for the treatment of PPI-refractory heartburn regarding symptom relief or consumption of PPIs. ClinicalTrials.gov NCT01682265.

This narrative review focuses on the presentation, contributing factors, diagnosis, and treatment of non-acid reflux. We also propose algorithms for diagnosis and treatment.

There is a paucity of recent data regarding non-acid reflux. The recent Porto and Lyon consensus statements do not fully address non-acid reflux or give guidance on classification. However, recent developments in the lung transplantation field, as well as older data in the general population, argue for the importance of non-acid reflux. Extrapolating from the Porto and Lyon consensus, we generally classify pathologic non-acid reflux as impedance events > 80, acid exposure time < 4%, and positive symptom correlation on a standard 24-h pH/impedance test. Other groups not meeting this criteria also deserve consideration depending on the clinical situation. Potential treatments include lifestyle modification, increased acid suppression, alginates, treatment of esophageal hypersensitivity, baclofen, buspirone, prokinetics, and anti-reflux surgery in highly selected individuals. More research is needed to clarify appropriate classification, with subsequent focus on targeted treatments.

The aim of this paper is to review esophageal electrical impedance technologies and to discuss the use of these technologies for physiological measurements, diagnostics, and therapy of esophageal disease. In order to develop a better understanding of the pathophysiology of and improve the diagnosis of esophageal disorders, such as gastroesophageal reflux disease (GERD) and achalasia, several new diagnostic tests, including intraluminal impedance, esophageal mucosal impedance, and the functional luminal imaging probe, have been developed. These technologies have proven valuable for assessment of the esophagus in recent years. They provide information on esophageal flow properties, mucosal integrity, lumen shape, and distensibility in esophageal disorders, in particular for GERD and achalasia. Despite their promise and novel clinical studies, the potential of these technologies has been far from realized. New multidisciplinary approaches will contribute to our understanding and interpretation of esophageal impedance data and disease mechanisms.