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Background: The prevalence of duodenogastroesophageal reflux (DGER) and its effect on symptoms and oesophageal lesions in gastroesophageal reflux disease (GERD) is unclear., Aims: To conduct a systematic review to determine the prevalence of DGER among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER., Methods: We searched Pubmed and MEDLINE for full text, English language articles until October 2020 that evaluated DGER prevalence among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER., Results: We identified 3891 reports and included 35 which analysed DGER prevalence in GERD, 15 which evaluated its effect in non-erosive reflux disease (NERD), 17 on erosive oesophagitis, 23 in Barrett's, and 13 which evaluated the treatment of DGER. The prevalence of DGER, when evaluated by Bilitec, among all GERD patients ranged from 10% to 97%, in NERD 10%-63%, in erosive oesophagitis 22%-80% and in Barrett's 50%-100%. There were no differences in the presence or degree of DGER among patients who were asymptomatic or symptomatic on proton pump inhibitors (PPI). The most commonly evaluated treatments for DGER were PPIs and DGER reduced post-PPI therapy in all studies., Conclusions: The prevalence of DGER increased with more advanced oesophageal lesions and did not explain persisting symptoms among patients taking PPI therapy. PPIs appear to be effective in the treatment of DGER. DGER remains an important consideration in patients with GERD and future therapies deserve more study., (© 2021 John Wiley & Sons Ltd.)

Objectives: Preventive antireflux surgery (ARS) at the moment of congenital diaphragmatic hernia (CDH) repair has been suggested by some authors, particularly in subgroups with a liver herniated in the chest or patch requirement. We evaluated the incidence and associated factors of gastro-oesophageal reflux disease (GERD) and the need for subsequent ARS in our CDH patients., Methods: We retrospectively reviewed our CDH database. Demographics, prenatal assessment of severity, prenatal treatment, type of repair, intraoperative findings and incidences of gastro-oesophageal reflux and ARS were recorded., Results: CDH repair was performed in 77 infants between July 1993 and November 2009. Eight died after repair. Seven were lost to follow-up. The median follow-up was 4.0 (0.16-14.88) years. Fourteen of these 62 patients were prenatally treated with fetoscopic endoluminal tracheal occlusion (FETO) because of severe pulmonary hypoplasia. After CDH repair, GERD was diagnosed in 31 patients. In all of them, medical antireflux treatment was started. Thirteen (42%) patients needed ARS at a median age of 64 (37-264) days. One year after starting medical treatment, 14 (45%) patients were completely off antireflux medication. In CDH subgroups with patch repair, liver herniated in the chest or previous FETO, the incidences of gastro-oesophageal reflux and ARS were 61 and 32%, 73 and 38% and 71 and 43%, respectively. Univariable analysis of associated potentially predisposing factors shows that patch repair, liver herniated in the chest, pulmonary hypertension, high-frequency oscillatory ventilation and FETO are associated with subsequent ARS. On multivariable analysis, liver herniated in the chest was the only independent predictor for both gastro-oesophageal reflux and ARS., Conclusions: Of all CDH patients, 50% developed gastro-oesophageal reflux and 21% required ARS. For both, liver in the chest was the only independent predictor. Routine ARS in certain subgroups at the time of CDH repair seems not to be justified. Foetal endoluminal tracheal occlusion creates a new cohort of survivors with an increased risk for undergoing ARS. The surgical group, in particular, reflects a more complex gastro-oesophageal reflux physiopathology.

Background and Aims: A subset of patients with gastro-oesophageal reflux disease (GORD) with refractory symptoms during therapy with proton pump inhibitors (PPIs), have persistent non-acid duodeno-gastro-oesophageal reflux (duodenal reflux). The aim of the present study was to investigate the effect of the GABA(B) receptor agonist baclofen, which was shown to inhibit the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) in patients with persistent non-acid duodenal reflux during PPI therapy., Methods: Patients were eligible for the study if they had persistent reflux symptoms, normal pH monitoring, and pathological Bilitec monitoring during PPI treatment. Upper gastrointestinal endoscopy and reflux symptom score were performed at the beginning of the study. Baclofen 5 mg three times daily was associated with treatment, and was increased by 5 mg every fourth day until a maintenance dose of 20 mg three times daily was reached. A reflux symptom questionnaire, ambulatory pH monitoring, and Bilitec monitoring were repeated four days later while PPI and baclofen were continued. All data are given as mean (SEM) or median (interquartile range) and were compared using the Student's t test or the Mann-Whitney U test., Results: Sixteen patients (11 women, mean age 46 (3) years) with persistent heartburn or regurgitation for at least three months, in spite of PPI therapy, were included in the study. Erosive oesophagitis was present in seven patients (five with grade 1, two with grade 2). Under PPI therapy alone, all patients had normal acid exposure (0.3 (0.05; 2.2)% of the time) but pathological duodenal reflux exposure (13.8 (11.8; 15.5)% of the time). After addition of baclofen 20 mg three times daily, acid exposure was similar (0.4 (0.15; 2.3)% of the time; NS) but duodenal reflux had significantly decreased (6.1 (0.8; 10.3)% of the time; p<0.05). The number of duodenal reflux episodes and the number of longlasting duodenal reflux episodes (>5 minutes) was decreased, respectively, from 23 (14.5; 34) to 12 (5; 21) (p = 0.06) and from 5 (3; 8) to 2 (0.5;4.5) (p<0.05). The cumulative severity score for 14 reflux symptoms decreased from 10.3 (1.7) to 5.8 (1.3) (p<0.01). Four patients reported mild side effects of nausea or drowsiness., Conclusions: The GABA(B) receptor agonist baclofen improves duodenal reflux and associated reflux symptoms that persist during PPI therapy.

Objective: Minimal invasive antireflux surgery is now a well accepted technique gaining a wide spread popularity. Simultaneously there is a growing tendency to fit all surgical candidates into one single type of operation, i.e. laparoscopic Nissen antireflux operation. This study evaluates the impact of this new technology on the strategy and practice of a major referral centre for antireflux surgery., Methods: An analysis was made of indications for the different types of antireflux techniques performed between July, 1993 and 1995. If on Barium swallow the gastro-oesophageal (GO) junction proved to be reducible, a laparoscopic approach was proposed, if not, an open transthoracic access was preferred., Results: One hundred and fifteen patients were operated. Fifty five patients underwent a minimal invasive approach: 49 Nissen (are the total fundoplication) and 3 Lind (are the partial fundoplication) operations through laparoscopy, 3 Belsey Mark IV through video assisted thoracic surgery (VATS). Sixty patients were treated by open surgery for following reasons: conversion to open surgery in 2 cases, redo surgery in 15 cases, previous other major abdominal surgery in 12, irreducible GO junction in 5, paraoesophageal or mixed type hernia in 12, Barrett and or oesophagitis IV in 4, combined antireflux surgery and feeding gastrostomy in 5, abdominal partial fundoplication by principle in 1, associated motility disorder in 1, combined reflux and gastric ulcer disease in 2, and severe emphysema in 1. In the laparoscopic series reflux control at 1 year post surgery as measured by 24 h pH study in 28 patients was obtained in 89.5%. One patient required a reoperation for symptomatic recurrence., Conclusions: (1) Laparoscopic antireflux surgery is a feasible and well accepted technique; (2) careful study of each individual patient is of paramount importance to choose the correct type of operation and access as well. Therefore, fitting every patient into a single type of operation, i.e. laparoscopic Nissen, should be avoided; (3) thoracic surgeons with a major interest in GO reflux disease should familiarize themselves with laparoscopic antireflux procedures.

Background: 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., Aims: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2022 John Wiley & Sons Ltd.)

Background: Conflicting results exist on the association between Helicobacter pylori infection and gastro-oesophageal reflux (GOR), and its complications, such as erosive oesophagitis (EO) and Barrett's oesophagus (BO)., Aims: To explore the association of H. pylori infection with GOR symptoms and their complications METHODS: We searched Embase, PubMed, Web of Science and Scopus databases through December 2020 for relevant articles. Regarding the association between H. pylori and GOR symptoms (heartburn, regurgitation or reflux), we included observational studies comparing the prevalence of GOR symptoms between H. pylori-positive and -negative individuals. Concerning the association between H. pylori and complications of GOR, we included studies comparing the prevalence of EO or BO between H. pylori-positive and -negative individuals., Results: In total, 36 papers were eligible. Based on seven cross-sectional surveys, H. pylori infection was associated with a lower odds of GOR symptoms (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.61-0.90). However, in four case-control studies, H. pylori infection was not associated with odds of GOR symptoms (OR 1.10, 95% CI 0.85-0.1.43). In 26 cross-sectional studies in patients with GOR symptoms, the OR for EO was 0.70 (95% CI 0.58-0.84) in H. pylori-positive vs -negative cases. Based on nine cross-sectional studies in subjects with GOR complications, no significant association was found between H. pylori infection and either endoscopically-diagnosed (OR 1.84, 95% CI 0.67-5.02) or histologically confirmed (OR 0.85, 95% CI 0.60-1.20) BO., Conclusions: Helicobacter pylori infection appears to be associated with a decreased odds of GOR symptoms and EO. In contrast, H. pylori infection did not seem to affect the odds of BO in patients with GER complications., (© 2021 John Wiley & Sons Ltd.)

Background: The pathogenesis of gastro-oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive-affective evaluation of visceral sensitivity., Aims: To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD., Methods: Patients with chronic reflux symptoms and negative endoscopy underwent 24-hour impedance-pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient-reported outcomes, including EHAS, GERD questionnaire (GERDQ), State-Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded., Results: We enrolled 105 patients, aged 21-64 years (mean, 48.8), of whom 58.1% were female; 27 had non-erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient-reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05)., Conclusions: EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need., (© 2021 John Wiley & Sons Ltd.)

Background: Gastro-oesophageal reflux is considered the main risk factor for Barrett's oesophagus. The role of other potential risk factors for the development of Barrett's oesophagus in patients with gastro-oesophageal reflux symptoms is controversial., Aims: To perform a systematic review and meta-analysis examining risk factors in development of Barrett's oesophagus., Methods: Medline, Embase and Embase Classic were searched (until December 2020) to identify cross-sectional studies reporting prevalence of Barrett's oesophagus based on presence of one or more proposed risk factors in individuals with gastro-oesophageal reflux symptoms. Prevalence of Barrett's oesophagus was compared according to presence or absence of each risk factor in individuals with gastro-oesophageal reflux symptoms., Results: Of 7164 citations evaluated, 13 studies reported prevalence of Barrett's oesophagus in 11 856 subjects. Pooled prevalence of histologically confirmed Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms in all studies was 7.0% (95% CI 4.8% to 9.6%). Prevalence was higher in subjects with hiatal hernia (OR 2.74; 95% CI 1.58 to 4.75) and in those who drank alcohol (OR 1.51; 95% CI 1.17 to 1.95). Other features including non-steroidal anti-inflammatory drugs and/or aspirin use (OR 1.19; 95% CI 1.00 to 1.42), smoking (OR 1.14; 95% CI 0.96 to 1.35) or obesity (OR 1.10; 95% CI 0.92 to 1.33) were not significantly associated with Barrett's oesophagus., Conclusions: The prevalence of Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms was higher in those who drank alcohol, although this association was modest. The strongest association found was between hiatal hernia and Barrett's oesophagus. Other potential risk factors assessed in this study did not appear to be associated with presence of Barrett's oesophagus among individuals with gastro-oesophageal symptoms., (© 2021 John Wiley & Sons Ltd.)

Background: 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. 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

De spite the worldwide decrease in the incidence of gastric cancer, the proportion of occurrence of carcinomas of the esophagogastric junction and proximal third of stomach is on the rise. The cause of this development is believed to lie in an increasing incidence of reflux esophagitis with Barrett's metaplasia and successful eradication of Helicobacter pylori infection. The aim of this work is to present various views on the definition of the esophagogastric junction itself and to give an overview of tumor classification schemes being used (Fig. 2, Ref. 54). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

One potential comorbidity after congenital diaphragmatic hernia (CDH) is gastroesophageal reflux (GER), which can have a substantial effect on patients' quality of life, thriving, and complications later in life. Efforts have been made to reduce gastroesophageal reflux with a preventive anti-reflux procedure at the time of CDH repair. In this follow-up study of neonates participating in a primary RCT study on preventive anti-reflux surgery, symptoms of GER were assessed longitudinally. Long-term data with a median follow-up time of ten years was available in 66 patients. Thirty-one neonates received an initial fundoplication. Secondary anti-reflux surgery was necessary in 18% and only in patients with large defects. It was required significantly more often in patients with intrathoracic herniation of liver (p = 0.015) and stomach (p = 0.019) and patch repair (p = 0.03). Liver herniation was the only independent risk factor identified in multivariate regression analysis. Primary fundopexy and hemifundoplication did not reveal a protective effect regarding the occurrence of GER symptoms, the need for secondary antireflux surgery or the gain of body weight regardless of defect size neither in the short nor in the long term. Symptoms of GER must be assessed carefully especially in children with large defects, as these are prone to require secondary anti-reflux surgery in the long-term. Routine evaluation of GER including endoscopy and impedance measurement should be recommended especially for high-risk patients. [ABSTRACT FROM AUTHOR]

Objective. To investigate the risk factors associated with reflux esophagitis in patients undergoing esophageal cancer surgery and to provide reference for the prevention and treatment of reflux esophagitis. Methods. In the manner retrospective study, the data of 300 patients with esophageal cancer who received the surgical treatment in our hospital (January 2018–December 2020) were retrospectively reviewed. The 300 patients were divided into the occurrence group (n = 45) and nonoccurrence group (n = 255) depending on whether they had reflux esophagitis after surgery. The social demographic data and clinical data of the patients in the two groups were collected. These data were classified into the personal factors and surgical factors. The single-factor analysis method was adopted to analyze the effects of the personal and surgical factors on reflux esophagitis. The factors with statistically significant differences in the single-factor analysis were analyzed by logistic regression to verify the factors were the risk factors associated with reflux esophagitis in patients undergoing esophageal cancer surgery. Results. The differences in the bodyweight, body mass index (BMI), length of the resected esophagus, surgical approach, intraoperative blood loss, gastrointestinal decompression volume, and surgery time between the two groups were of statistical significance (P < 0.05). After being tested by the logistics multivariate analysis, length of the resected esophagus, whole stomach reconstruction, intraoperative blood loss, and surgery time were identified as the risk factors associated with reflux esophagitis in patients undergoing esophageal cancer surgery. Conclusion. The length of the resected esophagus, whole stomach reconstruction, intraoperative blood loss, and surgery time were the risk factors associated with reflux esophagitis in patients undergoing esophageal cancer surgery. It is necessary to choose the appropriate surgical approach according to the patients' conditions in practice and to strengthen the prevention and treatment of reflux esophagitis. [ABSTRACT FROM AUTHOR]

Achalasia cardia is a rare esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter during swallowing and aperistalsis of the esophageal smooth muscles. The treatment approaches to achalasia include nonsurgical treatment with medications (nitrates, calcium channel blockers), endoscopic treatment (balloon pneumatic dilation [PD], botulinum toxin injection [BTI], peroral endoscopic myotomy [POEM]), and surgery (laparoscopic Heller's myotomy [LHM]). The subtype of achalasia (the Chicago Classification) governs the ideal treatment. For the commonly encountered achalasia subtype I and II, PD, LHM, and POEM all have similar efficacy. However, for type III achalasia, POEM seems to be the best line of treatment. Among high-risk elderly patients or those with comorbidities, BTI is preferred. The choice of treatment should be minimally invasive therapy with good short-term and sustained long-term effects with negligible adverse events. POEM seems to be evolving as a first-line therapy among the available therapies. Here, we review the treatment options among achalasia cardia patients with special attention to post-POEM gastroesophageal reflux disease and its management. [ABSTRACT FROM AUTHOR]

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Gastrostomy placement is crucial in neurologically impaired (NI) children to ensure an adequate food intake and a safe route for drugs administration and to reduce the risk of primary aspiration. NI patents are more prone to gastroesophageal reflux. The association with fundoplication is deemed to reduce reflux-related respiratory complications. However, long-term benefits of this approach are not clear. We therefore aimed to compare long-term reflux-related respiratory complications of gastrostomy only (GO) to gastrostomy with fundoplication (GF). We retrospectively reviewed 145 consecutive NI children managed from 2008 to 2018. As long-term outcomes, we analyzed number and length of hospital admissions (Reflux-Related-Hospitalization, RRH) and emergency department accesses (Reflux-Related-Accesses, RRA) due to respiratory problems. Results were analyzed with appropriate statistical method. Median age at referral and at gastrostomy placement were 2.2 and 3.4 years (SD 5.6), respectively. Median follow-up was four years (range 1-12). Anti-reflux procedures were performed in 26/145 patients (18%); tracheotomy in 23/145 (16%). RRH following surgery showed lower number of admissions/year (0.32 vs. 1 for GO vs. GF, p < 0.005) and days hospitalization/year (3 vs. 13, p = 0.08) in GO compared to GF; RRA was similar (0.60 vs. 0.65, p = 0.43). Gastrostomy placement alone appeared not to be inferior to gastrostomy plus fundoplication with respect to long-term respiratory-related outcomes for NI children in our center. [ABSTRACT FROM AUTHOR]

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) characterized by heartburn and/or regurgitation symptoms is one of the most common gastrointestinal disorders managed by gastroenterologists and primary care physicians. There has been an increase in GERD prevalence, particularly in North America and East Asia. Over the past three decades proton pump inhibitors (PPIs) have been the mainstay of medical therapy for GERD. However, recently there has been an increasing awareness amongst physicians and patients regarding the side effects of the PPI class of drugs. In addition, there has been a marked decline in the utilization of surgical fundoplication as well as a rise in the development of nonmedical therapeutic modalities for GERD. This review focuses on different management strategies for GERD, optimal management of refractory GERD with special focus on available endoluminal therapies and the future directions. (Gut Liver 2018;12:7-16) [ABSTRACT FROM AUTHOR]

The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus ( BO) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium ( HET-1A) and BO ( QH) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α3, α4, α5, α6 and αν). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease ( GORD) and in patient tissue microarrays. The bile acid deoxycholic acid ( DCA) specifically reduced adhesion of HET-1A cells to vitronectin and reduced cell-surface expression of integrin-αν via effects on endocytic recycling processes. Increased expression of integrin-αv was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin-αν was observed in QH BO cells compared to HET-1A cells. QH cells were resistant to DCA-mediated loss of adhesion and reduction in cell-surface expression of integrin-αν. We demonstrated that a specific component of the gastric refluxate, DCA, affects the epithelial barrier through modulation of integrin αν expression, providing a novel mechanism for bile acid-mediated erosion of oesophageal squamous epithelium and promotion of BO. Strategies aimed at preventing bile acid-mediated erosion should be considered in the clinical management of patients with GORD. [ABSTRACT FROM AUTHOR]

Knowledge about the association between alcohol and Barrett’s oesophagus and reflux oesophagitis is conflicting. In this case–control study we evaluated the role of specific alcoholic beverages (red and white wine, beer and liquors) in 339 Barrett’s oesophagus and 462 oesophagitis patients compared with 619 endoscopic controls with other disorders, recruited in twelve Italian endoscopic units. Data on alcohol and other individual characteristics were obtained from structured questionnaires. No clear, monotonic significant dose–response relationship was pointed out for red wine. However, a generalised U-shaped trend of Barrett’s oesophagus/oesophagitis risk due to red wine consumption particularly among current drinkers was found. Similar results were also found for white wine. Liquor/spirit consumption seemed to bring about a 1·14–2·30 risk excess, although statistically non-significant, for current Barrett’s oesophagus/oesophagitis drinkers. Statistically significant decreasing dose–response relationships were found in Barrett’s oesophagus for frequency and duration of beer consumption. Similar, but less clear downward tendencies were also found for oesophagitis patients. In conclusion, although often not statistically significant, our data suggested a reduced risk of Barrett’s oesophagus and oesophagitis with a low/moderate intake of wine and beer consumption. A non-significant increased risk of Barrett’s oesophagus/oesophagitis was observed with a higher intake of any type of heavy alcohol consumption, but no conclusion can be drawn owing to the high number of non-spirit drinkers and to the small number of drinkers at higher alcohol intake levels. [ABSTRACT FROM PUBLISHER]

Impaired esophageal mucosal integrity may be an important contributor in the pathophysiology of gastroesophageal reflux disease (GERD). Nevertheless, the effect of potentially harmful agents on epithelial integrity is mainly evaluated in vitro for a short period of time and the possible induction of epithelial apoptosis has been neglected. Our objective was to assess the effect of an acidic and weakly acidic solution containing deoxycholic acid (DCA) on the esophageal epithelium in an in vivo rabbit model of esophageal perfusion and to evaluate the role of the epithelial apoptosis. The esophagus of 55 anesthetized rabbits was perfused for 30 min with different solutions at pH 7.2, pH 5.0, pH 1.0, and pH 5.0 containing 200 and 500 μM DCA. Thereafter, animals were euthanized immediately or at 24 or 48 h after the perfusion. Transepithelial electrical resistance, epithelial dilated intercellular spaces, and apoptosis were assessed in Ussing chambers, by transmission electron microscopy, and by TUNEL staining, respectively. No macroscopic or major microscopic alterations were observed after the esophageal perfusions. The acidic and weakly acidic solution containing DCA induced similar long-lasting functional impairment of the epithelial integrity but different ultrastructural morphological changes. Only the solution containing DCA induced epithelial apoptosis in vivo and in vitro in rabbit and human tissue. In contrast to acid, a weakly acidic solution containing DCA induces epithelial apoptosis and a long-lasting impaired mucosal integrity. The presence of apoptotic cells in the esophageal epithelium may be used as a marker of impaired integrity and/or bile reflux exposure. [ABSTRACT FROM AUTHOR]

Background The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose- response effect of lesogaberan on reflux episodes in partial responders. Methods In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance-pH measurements were taken. Results Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. Conclusions Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. Trial registration ClinicalTrials.gov identifier: NCT01043185. [ABSTRACT FROM AUTHOR]

Background: The Belsey Mark IV operation has been used for the management of hiatal hernia for over 40 years, but with the introduction of laparoscopic techniques its role has become questionable. To determine the current role of this procedure we present a contemporary series of patients. Methods: We reviewed fifteen consecutive patients, mean age of 63 years, who underwent a Belsey Mark IV fundoplication for gastroesophageal reflux in the presence of a hiatal hernia in our Department from January 2005 to March 2011. Indications for the thoracic approach included paraesophageal hernias, recurrent hiatal hernias and previous upper abdominal surgery. Results: There was no operative mortality. Immediate postoperative morbidity included 1 case of bleeding, 1 case of pneumonia and 1 case of atrial fibrillation. The mean length of stay was 5.9 days. After a mean follow-up time of 49 months, all patients reported total or partial alleviation of their symptoms. No hernia recurrence was detected during barium swallow examination. Conclusions: The Belsey approach is a procedure that can be useful as an alternative in selected cases when there are co-morbidities complicating the transabdominal (laparoscopic) approach. [ABSTRACT FROM AUTHOR]

Background/Aims: Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. Methods: We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Results: Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [< 1%]). Acid reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. Conclusions: In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus. [ABSTRACT FROM AUTHOR]

Background/Aims The aim of this study is to investigate the reflux patterns in patients with galbladder stone and the change of reflux patterns after cholecystectomy in such patients. Methods Fourteen patients with cholecystolithiasis and a control group including 10 healthy control subjects were enrolled in this prospective study. Demographical findings, reflux symptom score scale and 24-hour impedance pH values of the 14 cholecystolithiasis cases and the control group were evaluated. The impedance pH study was repeated 3 months after cholecystectomy. Results Age, gender, and BMI were not different between the two groups. Total and supine weakly alkaline reflux time (%) (1.0 vs 22.5, P = 0.028; 201.85 vs 9.65, P = 0.012), the longest episodes of total, upright and supine weakly alkaline reflux mediums (11 vs 2, P = 0.025; 8.5 vs 1.0, P = 0.035; 3 vs 0, P = 0.027), total and supine weakly alkaline reflux time in minutes (287.35 vs 75.10, P = 0.022; 62.5 vs 1.4, P = 0.017), the number of alkaline reflux episodes (162.5 vs 72.5, P = 0.022) were decreased with statistical significance. No statistically significant difference was found in the comparison of symptoms between the subjects in the control group and the patients with cholecystolithiasis, in preoperative, postoperative and postcholecystectomy status. Conclusions Significant reflux symptoms did not occur after cholecystectomy. Post cholecystectomy weakly alkaline reflux was decreased, but it was determined that acid reflux increased after cholecystectomy by impedance pH-metry in the study group. [ABSTRACT FROM AUTHOR]

Background Little is known about the contribution of bile and acid reflux to night-time symptoms generation in patients who failed PPI treatment. Aim To compare the degree of night-time oesophageal acid and bile [by the surrogate duodenogastroesophageal reflux (DGER)] exposure between gastrooesophageal reflux disease (GERD) patients who failed and those who fully responded to PPI once a day while on treatment. Methods Gastro-oesophageal reflux disease patients were assigned to the PPI failure group if they continued to report symptoms ⩾3 / week and to the PPI success group if they were asymptomatic for the last 3 months while on PPI once a day. All patients underwent upper endoscopy and subsequently simultaneous 24-h oesophageal Bilitec and pH testing while on PPI treatment. Results Twenty-three patients were enrolled into the PPI failure group and 24 patients into the PPI success group. The percentage of night-time pH < 4 and the number of night-time acid reflux episodes were significantly higher in the PPI failure group as compared with the PPI success group. All night-time DGER parameters were similar between the PPI failure and PPI success groups. Conclusions Night-time oesophageal acid exposure is significantly higher in the PPI failure group vs. PPI success group. The degree of night-time bile reflux is similar in the two groups of patients with GERD. [ABSTRACT FROM AUTHOR]

Background Transient lower oesophageal sphincter relaxations (TLOSR) are considered the physiological mechanism that enables venting of gas from the stomach and appear as sphincter relaxations that are not induced by swallowing. It has become increasingly clear that most reflux episodes occur during TLOSRs and therefore play a key role in gastro-oesophageal reflux disease (GERD). Aim To describe the current knowledge about TLOSRs and its clinical implications. Methods Search of the literature published in English using the PubMed database and relevant abstracts presented at international conventions. Results Several factors influence the rate of TLOSRs including anti-reflux surgery, meal, body position, nutrition, lifestyle and a wide array of neurotransmitters. Ongoing insights in the neurotransmitters responsible for the modulation of TLOSRs, as well as the neural pathways involved in TLOSR induction, have lead to novel therapeutic targets. These therapeutic targets can serve as an add-on therapy in patients with an unsatisfactory response to proton pump inhibitor by inhibiting TLOSRs and its associated reflux events. However, the TLOSR-inhibiting drugs that are currently available still have significant side effects. Conclusion It is likely that in the future, selected GERD patients may benefit from transient lower oesophageal sphincter relaxation inhibition when compounds are found without significant side effects. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 443–447 Background In patients with Los Angeles (LA) grade C or D oesophagitis, a positive relationship has been established between the duration of intragastric acid suppression and healing. Aim To determine whether there is an apparent optimal time of intragastric acid suppression for maximal healing of reflux oesophagitis. Methods Post hoc analysis of data from a proof-of-concept, double-blind, randomized study of 134 adult patients treated with esomeprazole (10 or 40 mg od for 4 weeks) for LA grade C or D oesophagitis. A curve was fitted to pooled 24-h intragastric pH (day 5) and endoscopically assessed healing (4 weeks) data using piecewise quadratic logistic regression. Results Maximal reflux oesophagitis healing rates were achieved when intragastric pH >4 was achieved for approximately 50–70% (12–17 h) of the 24-h period. Acid suppression above this threshold did not yield further increases in healing rates. Conclusion After 4 weeks’ acid-suppressive therapy for LA grade C or D oesophagitis, successful healing appears to reach a threshold above which improvements are unlikely to be achieved despite an increase in number of hours with intragastric pH >4. [ABSTRACT FROM AUTHOR]

Background and purpose: Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB1/CB2 receptor agonist Δ9-tetrahydrocannabinol (Δ9-THC) on TLESRs in dogs. Based on these findings, the effect of Δ9-THC was studied in healthy volunteers. Experimental approach: In dogs, manometry was used to evaluate the effect of Δ9-THC in the presence and absence of the CB1 receptor antagonist SR141716A on TLESRs induced by gastric distension. Secondly, the effect of 10 and 20 mg Δ9-THC was studied in 18 healthy volunteers in a placebo-controlled study. Manometry was performed before and for 3 h after meal ingestion on three occasions. Key results: In dogs, Δ9-THC dose-dependently inhibited TLESRs and reduced acid reflux rate. SR141716A significantly reversed the effects of Δ9-THC on TLESRs. Similarly, in healthy volunteers, Δ9-THC significantly reduced the number of TLESRs and caused a non-significant reduction of acid reflux episodes in the first postprandial hour. In addition, lower oesophageal sphincter pressure and swallowing were significantly reduced by Δ9-THC. After intake of 20 mg, half of the subjects experienced nausea and vomiting leading to premature termination of the study. Other side-effects were hypotension, tachycardia and central effects. Conclusions and implications: Δ9-THC significantly inhibited the increase in meal-induced TLESRs and reduced spontaneous swallowing in both dogs and humans. In humans, Δ9-THC significantly reduced basal lower oesophageal sphincter pressure. These findings confirm previous observations in dogs and indicate that cannabinoid receptors are also involved in the triggering of TLESRs in humans. Mandarin translation of abstract [ABSTRACT FROM AUTHOR]

Background The development of well-tolerated acid suppressant drugs has stimulated substantial growth in the number of trials assessing therapy options for gastro-oesophageal reflux disease (GERD). Aim To develop consensus statements to inform clinical trial design in adult patients with GERD. Methods Draft statements were developed employing a systematic literature review. A modified Delphi process including three rounds of voting was used to reach consensus. Between voting, statements were revised based on feedback from the Working Group and additional literature reviews. The final vote was at a face-to-face meeting that included discussion time. Voting was conducted using a six-point scale. Results At the last vote, 93% of the final 102 statements achieved consensus (defined a priori as being supported by ≥75% of the votes). The Working Group strongly supported the development of validated patient-reported outcome instruments. Symptom assessments carried out by the investigator were considered unacceptable. There was agreement that exclusion from clinical trials should be minimized to improve generalizability, that prospective evaluation ideally requires electronic timed/dated methods and that endoscopists should be blinded to patient symptom status. Conclusions Implementation of the consensus statements will improve the quality and comparability of trials, and make them compatible with regulatory requirements. [ABSTRACT FROM AUTHOR]

Background and Purpose: Transient lower oesophageal sphincter relaxations (TLESRs) are triggered by activation of mechanosensitive gastric vagal afferents and are the major cause of gastroesophageal reflux and therefore an important target for therapeutic intervention in gastroesophageal reflux disease (GERD). Activation of the metabotropic GABA(B) receptor has shown to inhibit TLESRs. The aim of the present study was to assess the role of the ionotropic GABA(A) receptor in the regulation of TLESRs.Experimental Approach: TLESRs were quantified using Dentsleeve manometry in dogs, and GABA(A) agonists were given i.v. prior to gastric distension. Immunohistochemistry and RT-PCR were used to localize GABA(A) receptors in the dog nodose ganglion, the source of vagal afferents which initiate TLESRs.Key Results: The prototypical GABA(A) agonist muscimol produced a dose-dependent inhibition of TLESRs ranging from 19 to 56%. The two other GABA(A) agonists evaluated, isoguvacine and 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP), as well as the GABA(A) positive allosteric modulator diazepam, had no major effects on TLESRs. Evaluation of higher doses was limited by emesis (THIP and isoguvacine) or restlessness/sedation (diazepam). Of the predominant GABA(A) receptor subunits (alpha, beta and gamma components), alpha and beta but not gamma were detected in the dog nodose ganglion by RT-PCR, while immunohistochemistry in addition demonstrated nerve fibres expressing the gamma subunit.Conclusions and Implications: The present observations demonstrate that GABA(A) receptors exert an inhibitory control of TLESRs. These results warrant further studies using GABA(A) isoform-selective agonists to define the identity of receptors involved. [ABSTRACT FROM AUTHOR]

Background Over the last 10 years a number of endoscopic procedures for treating gastro-oesophageal reflux disease (GORD) have been developed (suturing, injections, implants and radiofrequency ablation), thus obviating the need for long-term proton pump inhibitors (PPI) and the potential morbidity of laparoscopic fundoplication. Aim To present an update of the literature studying the clinical efficacy of endoscopic antireflux procedures, and to discuss further developments. Methods A PubMed search was performed for endoscopic suturing, antireflux treatment, endoscopic gastroplication, polymer injection, radiofrequency ablation of GORD. Own recent research was compared with existing data. Information concerning GORD endotherapy were gathered. Results Uncontrolled studies have reported promising clinical results on the short to intermediate term for most endoscopic GORD procedures, but the placebo effect remained unknown. It is, therefore, commendable that the three main procedures (Endocinch, Stretta and Enteryx) have now all been tested against a sham procedure. Although all three techniques were able to improve symptoms, quality of life and PPI use, oesophageal acid reduction was unremarkable. Endocinch and Stretta are safe outpatient procedures. Concerns about the durability of Endocinch have risen. Polymer injection (Enteryx) and gel prosthesis implantation (Gatekeeper) were recalled for severe complications and lack of efficacy, respectively. Conclusions Endotherapy has shown the potential to treat (uncomplicated) GORD. However, some early procedures have failed or proven unsafe. Further developments and studies are necessary to determine what modifications to these techniques are required to produce optimal efficacy and durability. Until then, widespread clinical use of endotherapy for GORD should probably be avoided. [ABSTRACT FROM AUTHOR]

Background Gastro-oesophageal reflux disease (GERD) is a common condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Aim To review the current knowledge on the underlying factors contributing to GERD, with particular emphasis on the most recent research. Methods Literature searches were conducted in Medline and EMBASE. The abstracts from recent large congresses were also reviewed to ensure coverage of the latest findings. Results The pathophysiological factors causing GERD can be split into those inducing greater exposure of the oesophagus to stomach contents, and those that provide increased perception of reflux or increased mucosal damage. Transient lower oesophageal sphincter relaxations, which are likely to be triggered by gastric distension, appear to be a key physiological cause of GERD. Excessive reflux may also be provoked by impaired oesophageal or gastric clearance mechanisms. Pre-epithelial, epithelial and post-epithelial defences all normally protect the oesophagus from injury, and may be compromised in individuals with GERD. Heartburn could also be caused by oesophageal hypersensitivity as a result of visceral neural pathway dysfunction. Conclusion The pathophysiology of GERD is multifactorial, and abnormalities in the gastro-oesophageal junction, the stomach, the oesophagus and the nervous system may all contribute to this disease state. [ABSTRACT FROM AUTHOR]

Background A number of mechanisms, other than acid reflux, may be responsible for the symptoms of gastro-oesophageal reflux disease. Aim To assess the importance of non-acid reflux mechanisms. Methods This review is based on presentations and discussion at a workshop, where specialists in the field analysed data relating to these mechanisms. Results Weakly acidic reflux, pH (4–7), detected with impedance–pHmetry is associated with regurgitation and atypical gastro-oesophageal reflux disease symptoms. It is not clear whether pepsin and trypsin can elicit symptoms, but bile can elicit heartburn. The magnitude of reflux-induced oesophageal distension can be determined by high frequency ultrasonography and is not reduced by proton pump inhibition, suggesting that persisting symptoms ‘on’ a proton pump inhibitor may still be due to oesophageal distension by non-acidic reflux. Exaggerated longitudinal muscle contraction can induce non-acid-related heartburn. Preliminary studies showed a positive effect of baclofen, surgery or endoscopic procedures to reduce weakly acidic reflux. Conclusion Mechanisms other than acid reflux are involved in some of the symptoms of gastro-oesophageal reflux disease. Controlled outcome studies are needed to clarify their roles and the indications for antireflux procedures in patients with persistent symptoms whilst ‘on’ a proton pump inhibitor. [ABSTRACT FROM AUTHOR]

Background: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. Design and setting: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. Patients and interventions: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. Outcome measures: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. Results: At 3 months, the percentage of patients who had reduced drug use by ⩾50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p=0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n =41), but 29% of patients were retreated in this period. No serious adverse events occurred. Conclusions: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure. [ABSTRACT FROM AUTHOR]

Gastro-oesophageal reflux disease is a multifaceted and multifactorial disorder which results from the reflux of gastric contents into the oesophagus. Animal studies suggest that synergism between acid and pepsin and conjugated bile acids have the greatest damaging potential for oesophageal mucosa, although unconjugated bile acids may be caustic at more neutral pH. Human studies are compatible with a synergistic action between acid and duodenogastric reflux in inducing lesions. During prolonged monitoring studies, typical gastro-oesophageal reflux symptoms are more related to acid reflux events than to non-acid reflux events. However, symptoms that persist during acid suppressive therapy are often related to non-acid reflux events. The therapeutic options for the non-acid component of the refluxate, including acid suppression, prokinetics, baclofen, surgery and mucosal protective agents like alginates, are discussed. [ABSTRACT FROM AUTHOR]

Ambulatory pH monitoring detects abnormal levels of acid reflux in the oesophagus and can be used to correlate patients’ symptoms with oesophageal acid exposure. Catheter-based pH testing has several limitations, including issues of sensitivity, specificity, tolerability and the inability to record non-acid reflux events. In an effort to improve upon these drawbacks, several devices have been introduced, including the Bilitec system for measuring duodenogastro-oesophageal reflux; intraluminal impedance monitoring, which detects the distribution, composition and clearing of both acid and non-acid oesophageal reflux; and a wireless pH monitoring device, the Bravo capsule. Initial investigations using the Bilitec system demonstrated that duodenogastro-oesophageal reflux tracked very closely with acid reflux and decreased with proton-pump inhibitor (PPI) therapy, casting doubt on the clinical utility of Bilitec monitoring. Recent evidence revealed a possible role for duodenogastro-oesophageal reflux in a subset of patients who continue to report reflux symptoms in the setting of normalized oesophageal acid exposure on high-dose PPI therapy. When combined with pH monitoring, impedance monitoring enhances the detection and characterization of gastro-oesophageal reflux and may have a role in the evaluation of certain specific gastro-oesophageal reflux disease (GERD) symptoms that persist despite acid suppression therapy. The utility of the Bravo wireless technology for GERD diagnosis has been validated in several studies, with improvements over catheter-based pH monitoring in tolerability, accuracy and sensitivity, as well as the ability to record periods both off and on PPI therapy in a single study. All three diagnostic modalities have advanced the understanding of GERD pathogenesis, but their impact on the clinical management of GERD is still the focus of active investigation. [ABSTRACT FROM AUTHOR]

Gastro-oesophageal reflux disease is defined as the presence of symptoms or lesions that can be attributed to the reflux of gastric contents into the oesophagus. Aspiration and prolonged monitoring studies in humans have shown that reflux of gastric contents is comprised of both acid and non-acid components, in healthy as well as diseased people. Methods to monitor the non-acid component of the refluxate are described in detail. Experimental models suggest that synergism between acid and pepsin and conjugated bile acids have the greatest damaging potential for oesophageal mucosa, although unconjugated bile acids may be caustic at a more neutral pH. Human studies are compatible with a synergistic action between acid and duodenogastric reflux in inducing lesions. During prolonged monitoring studies, typical gastro-oesophageal reflux disease symptoms are more related to acid reflux events than to non-acid reflux events. However, symptoms that persist during acid-suppressive therapy are often related to non-acid reflux events. The therapeutic options for the non-acid component of the refluxate, including acid suppression, prokinetics, baclofen and surgery, are discussed. [ABSTRACT FROM AUTHOR]

Gastro-oesophageal reflux disease (GERD) is a condition in which the gastro-oesophageal reflux provokes symptoms or complications. Since the majority of patients with heartburn do not have mucosal breaks, expressions such as ‘endoscopy-negative reflux disease’ (ENRD), ‘non-erosive reflux disease’ (NERD), or even ‘reflux-like dyspepsia’ and ‘functional heartburn’ are frequently employed despite the lack of consensus concerning their exact meaning. Moreover, definition of a disease does not mean that precise diagnostic criteria exist. Diagnostic approaches to GERD differ considerably between primary and secondary care. The primary care physician's role is to decide, on the basis of symptoms and clinical examination, if it is likely that the patient has some serious problem which requires urgent investigation and intervention. In practice, a symptom-based diagnosis can often be made reliably because heartburn and regurgitation are very specific for GERD. The secondary care physician has to make a full evaluation of an already highly-selected patient and, as far as possible, to make a comprehensive, accurate diagnosis, using whatever investigative tools are required. However, there is no ‘gold standard’ for the diagnosis of GERD and 24-hour pH monitoring lacks sensitivity in NERD. Recently, impedance-pH monitoring has been introduced and promising results have been reported. However, this new technology needs further validation and technical improvement before being employed in routine clinical investigation. [ABSTRACT FROM AUTHOR]

Proton-pump inhibitor failure has become a common clinical dilemma in gastrointestinal clinics and has been increasingly encountered at the primary care level as well. Underlying mechanisms are diverse and may overlap. Most patients who have proton-pump inhibitor failure are likely to originate from the non-erosive reflux disease phenotype. Currently, available diagnostic modalities provide limited clues to the exact underlying cause. Treatment relies primarily on escalating dosing of proton-pump inhibitors. However, new insights into the pathophysiology of proton-pump inhibitor failure are likely to provide alternative therapeutic options. [ABSTRACT FROM AUTHOR]

Transient lower esophageal sphincter relaxations (TLESRs) are the most important mechanism by which gastroesophageal reflux occurs, and sleeve sensor manometry is the gold standard for detection of TLESRs. The aim of this study was to evaluate manometry with closely spaced sideholes (high-resolution manometry) for the detection of TLESRs as an alternative. In 12 patients with gastroesophageal reflux disease, a 90-min postprandial manometry was performed by using a catheter incorporating both a sleeve sensor and closely spaced sideholes in the esophagogastric junction. TLESRs recorded with both techniques were scored. Reflux during TLESRs was detected by using manometry (common cavity), intraluminal impedance, and pH monitoring. A total of 145 TLESRs were detected by using both techniques, 117 with high-resolution manometry and 108 with sleeve sensor manometry [not significant (NS)]. Manometric signs of reflux during TLESRs detected with high-resolution and sleeve sensor manometry were found in 62.4 and 56.5%, NS, respectively, versus 38.5 and 35.2%, NS on pH-metry and 70.1 and 60.2%, NS on impedance monitoring. TLESRs recognized only with high-resolution manometry were more often accompanied by reflux, as detected with manometry (59.5%) and impedance monitoring (67.6%), than TLESRs recognized only with sleeve sensor manometry (32.1 and 28.6%). Highresolution manometry is at least as accurate as sleeve sensor manometry for the detection of TLESRs. [ABSTRACT FROM AUTHOR]

In patients with gastro-oesophageal reflux disease (GORD), oesophageal and extraoesophageal symptoms are traditionally attributed to increased contact time beiween the mucosa and refluxates. However, the volume of reflux may be important by increasing the total amount of highly concentrated damaging substances, either by prolonging distal mucosal exposure or by expandinq to more proximal areas. To date, it has not been possible to accurately measure the volume of gastro-oesophageal reflux. Determination of the volume of reflux will help to better understand the pathophysiology of GORD and to evaluate the efficacy of antireflux treatments. [ABSTRACT FROM AUTHOR]

Treatment of gastro-oesophageal reflux disease (GERD) with lifestyle changes to avoid the conditions that make the symptoms worse and medication to lower the acid content of the refluxed material are generally very effective therapies. However, some individuals do not benefit enough from these approaches, and surgical intervention is warranted. Laparoscopic surgery is the procedure of choice among surgeons performing operations for reflux disease. This surgical technique allows for shorter hospitalization, fewer post surgical complications and less pain than open surgery while maintaining a high success rate. Data from Japan confirms that laparoscopic fundoplication is a safe and effective technique for controlling both typical and atypical symptoms of GERD. Recently, several endoscopic or luminally delivered techniques have been developed as an alternative to laparoscopic surgery. These new surgical options, currently under evaluation in Japan, may offer a valuable alternative to patients who are not responsive to, or who do not wish to persist with lifelong medical therapy for GERD. [ABSTRACT FROM AUTHOR]

Endoscopic-negative reflux disease (ENRD) is the most common presentation of gastro-oesophageal reflux disease (GERD)—affecting up to 70% of these individuals. In the last three decades therapeutic studies have focused solely on the treatment of patients with erosive oesophagitis. However, more recent studies have shifted our attention to defining, understanding and treating those with ENRD. GERD has traditionally been approached as a spectrum with ENRD at the mild end and complicated GERD (i.e. patients with erosive oesophagitis, stricture and Barrett's oesophagus) being at the other end, suggesting that patients' disease may progress over time along the spectrum. Current data indicate that ENRD should be approached as a unique entity rather than a part of the GERD spectrum and that over time only a few patients with ENRD will develop GERD-related complications. Patients with ENRD are a heterogenous group of patients with different aetiologies for their heartburn symptoms, including motor events, reflux of acidic or nonacidic gastric contents, minute changes in intraesophageal pH (pH < 4), mucosal hypersensitivity, and emotional or psychological abnormalities. By dropping the spectrum concept, which emphasizes oesophageal mucosal injury, we can focus our attention on the specific mechanisms that lead to symptom generation in each of the three unique groups of GERD (ENRD, erosive oesophagitis and Barrett's oesophagus) and on the specific therapeutic modalities that benefit each of these individual groups. Acid suppressive therapy with proton pump inhibitors is highly effective in healing erosions and controlling symptoms in those with erosive oesophagitis. In those with ENRD the resolution or control of heartburn with proton pump inhibitor therapy is greater than that with placebo or H2 receptor antagonist, but not as consistent nor as impressive as the results observed in studies of patients with erosive oesophagitis. By considering the mechanisms involved in ENRD symptom generation, future studies that include high-dose proton pump inhibitors, promotility agents (alone or in combination with proton pump inhibitors), transient lower oesophageal sphincter reducers, or pain modulators (e.g. tricyclic antidepressant agents) may prove beneficial. [ABSTRACT FROM AUTHOR]

Summary Background: The majority of patients with gastro-oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non-erosive gastro-oesophageal reflux disease are less responsive than patients with oesophagitis to acid-suppressive therapy. Aim: To assess the role of acid reflux in gastro-oesophageal reflux disease symptoms. Methods: The spatio-temporal characteristics of reflux events were analysed and related to reflux perception in 45 patients with non-erosive gastro-oesophageal reflux disease and 20 patients with erosive oesophagitis. Results: Compared with healthy controls, all patients showed a higher intra-oesophageal proximal spread of acid, which was prominent in patients with non-erosive gastro-oesophageal reflux disease (> 50% of events lasting for 1–2 min). Irrespective of mucosal injury, the risk of reflux perception was very high when acid reached proximal sensors (odds ratio, 7.6; 95% confidence interval, 4.6–12.5), being maximal in patients with non-erosive gastro-oesophageal reflux disease with normal acid exposure time (odds ratio, 11; 95% confidence interval, 5.2–22.3). Conclusions: Patients with non-erosive gastro-oesophageal reflux disease are characterized by a significantly higher proportion of proximal acid refluxes and a higher sensitivity to short-lasting refluxes when compared with patients with oesophagitis. The highest proximal acid exposure and highest perception occurred in patients with non-erosive gastro-oesophageal reflux disease presenting with a normal pH-metric profile. The assessment of acid distribution and its perception in the oesophageal body can better identify reflux patients who should benefit from acid-suppressive treatment. [ABSTRACT FROM AUTHOR]

Postoperative nausea and vomiting (PONV) are common complications after anesthesia, but no study has considered the effects of a proton pump inhibitor (PPI) and gastroesophageal reflux disease (GERD) on PONV at the same time. Thus, we investigated the effects of a PPI and GERD on PONV. Patients aged ≥18 years who underwent general anesthesia between 2010 and 2019 were enrolled. In total, 202,439 patients were included and 21,361 In a multivariate analysis, the OR for PONV was higher in subjects with GERD (OR, 1.157; 95% CI, 1.032–1.298; p = 0.012). The OR was lower for subjects with taking a PPI (OR, 0.890; 95% CI, 0.832–0.953; p < 0.0001). In patients without GERD, the incidence of PONV was lower when lansoprazole (OR, 0.801; 95% CI, 0.718–0.894; p < 0.0001), pantoprazole (OR, 0.856; 95% CI, 0.748–0.980; p = 0.025) and ilaprazole (OR, 0.391; 95% CI, 0.158–0.966; p = 0.042) were taken. However, in GERD patients, all PPIs did not show reducing the incidence of PONV. Taken together, the results show that a lansoprazole, pantoprazole, and ilaprazole reduced PONV in patients without GERD, and PPI could not reduce PONV in patients with GERD. [ABSTRACT FROM AUTHOR]

OBJECTIVES The 7th edition of American Joint Committee on Cancer (AJCC) staging system of oesophageal cancer and gastro-oesophageal junction has re-staged positive nodes into N1–3 according to the number of invaded lymph nodes (LNs). However, this new classification does not consider the potential negative impact of the extracapsular breakthrough on survival. This study aims at assessing prognosis according to whether LN involvement is intracapsular (ICLNI) or extracapsular (ECLNI) on disease-free survival (DFS) among the three sub-groups of LN-positive patients. METHODS Four hundred and sixteen consecutive R0 patients who underwent transthoracic oesophagectomy for cancer between 1996 and 2011 were retrospectively re-classified using the latest AJCC TNM classification. Among them, 230 (55%) patients have received a neoadjuvant chemoradiotherapy. Prognostic impact of ICLNI and ECLNI on DFS was assessed according to their new LN status. Multivariate analysis was drawn to determine factors affecting DFS. RESULTS Among the 416 patients, there were 138 (33%) patients with positive LN: 79 (57%) with ICLNI and 59 (43%) with ECLNI. The proportion of ECLNI was 21 of 73 (28%), 21 of 41 (51%) and 17 of 24 (70%) in N1, N2 and N3 patients, respectively. In N1 patients, median DFS was 48 months in ICLNI and 13 months in ECLNI (P = 0.068). In N2 patients, median DFS was 19 months in ICLNI and 9 months in ECLNI (P = 0.07). In N3 patients, median DFS was not reached in ICLNI and was 6 months in ECLNI (P = 0.002). On multivariate analysis, the ECLNI (P < 0.001, hazard ratio, HR: 2.51) and the post-T stage (P = 0.03, HR: 1.62) were the two independent factors affecting DFS. CONCLUSIONS Based on our limited study population, the existence of an ECLNI seems to have an additive negative impact on DFS, regardless of the pN stage. This suggests that extracapsular breakthrough status should be added to the new TNM staging system. This information has to be validated by further investigations. [ABSTRACT FROM AUTHOR]