Evidence Of Gastroesophageal Reflux Disease Research Articles

Esophagitis, treatment outcomes, and long-term follow-up in children with esophageal atresia.

Survival rates in children born with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) have improved; however, morbidity associated with the disease remains high. This study aimed to assess the prevalence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), fungal esophagitis, esophageal strictures, and long-term outcomes in children with EA/TEF. We conducted a retrospective chart review on patients with EA/TEF who were seen at Children's Wisconsin from January 2003 to January 2023. Patients born with EA/TEF were included if they underwent at least one endoscopy after 1 year of age. GERD was diagnosed based on abnormal findings on endoscopy, pH-metry, and/or history of fundoplication. EoE and fungal esophagitis were diagnosed based on abnormal endoscopy. Esophageal stricture diagnosis was based on findings on endoscopy and/or esophagram, and clinical symptoms necessitating esophageal dilation. Eighty-five patients (64.7% males, mean age 7.5 years) were included, the majority had type C EA/TEF (90.6%). GERD was diagnosed in 61.1% (n = 52), 49.4% (n = 42) by macro and/or microscopic endoscopic findings, 22.3% (n = 19) by abnormal pH-metry, and 21.1% (n = 18) by the need for fundoplication for refractory reflux and/or esophageal stricture. Risk of GERD increased with lower gestational age (p = 0.0030), lower birth weight (p = 0.023), and long-gap EA (p = 0.034). In children diagnosed with GERD, only 13.4% of patients (n = 7/52) were able to be weaned off proton pump inhibitor (PPI) without disease recurrence. However, overall, at the completion of the study, 44.7% (n = 38) of patients were successfully weaned off PPI without evidence of GERD. EoE was diagnosed in 20% of the patients (n = 17). All patients diagnosed with EoE required escalation of therapy from PPI alone to swallowed corticosteroids in 52.9% (n = 9), dupilumab in 23.5% (n = 4), elemental formula in 17.6% (n = 3), and elemental formula and swallowed steroids in 5.8% (n = 1). Fungal esophagitis was diagnosed in 15.3% of patients (n = 13). An esophageal stricture requiring dilation was diagnosed in 77.6% (n = 66) of patients at a mean age of 28.5 months, with over 60% diagnosed by 24 months of age. Children born with EA/TEF continue to be at high risk of developing GERD, EoE, fungal esophagitis, and esophageal stenosis. Diagnostic and therapeutic endoscopy remains a high-yield test to identify and treat these comorbidities.

455. SHOULD THE DIAGNOSTIC THRESHOLD FOR PH MONITORING IN GASTROESOPHAGEAL REFLUX DISEASE DIFFER BETWEEN THE EAST AND THE WEST?

Abstract Background The Montreal definition's reliance on troublesome typical symptoms alone is inadequate for diagnosing 'actionable' Gastroesophageal Reflux Disease (GERD). Lyon consensus 2.0 updated conclusive evidence of GERD, incorporating Los Angeles grade B or above esophagitis and Acid Exposure Time (AET) exceeding 6% in ambulatory reflux monitoring. The Seoul Consensus 2020 presents varied opinions on applying the same standards to the Asian population. A meta-analysis determined the Asian upper limit of AET as 3.2%. This study aims to compare Lyon 1.0 and 2.0 consensus compositions and assess the sensitivity and specificity of different AET thresholds in predicting Grade B or above esophagitis. Methods Patients with refractory GERD symptoms or considering anti-reflux surgery underwent objective GERD workup, including 24-hour catheter-based or 96-hour wireless ambulatory pH monitoring, High-Resolution Manometry, and upper endoscopy. This retrospective cohort study analyzed patient data from 2011-2023, excluding those with prior anti-reflux surgery, bariatric surgery, or myotomy for achalasia. Patients were categorized based on Lyon Consensus 1.0 and 2.0 as 'Non-GERD,' 'Borderline GERD,' 'Borderline GERD with evidence,' and 'Conclusive GERD.' Sensitivity, specificity, and Area-Under-Curve (AUC) were calculated using AET thresholds of 3.2%, 4%, 6%, and 7.2% to predict Grade B or above esophagitis. Results Between July 2011 and August 2023, 257 patients underwent pH monitoring and were included in the analysis, with 247 (93.8%) being ethnic Chinese. The number of patients categorized as conclusive GERD was significantly higher in Lyon 2.0 (134, 52.1%) compared to Lyon 1.0 (109, 42.4%), p < 0.001. Sensitivity and specificity for predicting Grade B or above esophagitis were as follows: AET 3.2% (83.3%, 48.8%), AET 4% (65.3%, 52.4%), AET 6% (73.8%, 66%), AET 7.2% (69.0, 72.1%). AET 7.2% demonstrated the highest AUC of 70.6% (Figure 1). Among patients classified as conclusive GERD, 67 (50%) underwent antireflux surgery. Conclusion Using the Asian threshold of AET 3.2% yields the highest sensitivity for detecting Grade B or above esophagitis. Additionally, the AUC is higher compared to using AET 4.0%. However, it is important to note that AET alone should not be the sole parameter for diagnosing actionable GERD, as even with the lowest AET threshold of 3.2%, 16.7% of patients with Grade B or above esophagitis would be missed.

Mucosal impedance as a diagnostic tool for gastroesophageal reflux disease: an update for clinicians.

Mucosal impedance is a marker of esophageal mucosal integrity and a novel technique for assessing esophageal function and pathology. This article highlights its development and clinical application for gastroesophageal reflux disease (GERD), Barrett's esophagus, and eosinophilic esophagitis. A narrative review of key publications describing the development and use of mucosal impedance in clinical practice was conducted. A low mean nocturnal baseline impedance (MNBI) has been shown to be an independent predictor of response to anti-reflux therapy. MNBI predicts medication-responsive heartburn better than distal esophageal acid exposure time. Patients with equivocal evidence of GERD using conventional methods, with a low MNBI, had an improvement in symptoms following the initiation of PPI therapy compared to those with a normal MNBI. A similar trend was seen in a post fundoplication cohort. Strong clinical utility for the use of mucosal impedance in assessing eosinophilic esophagitis has been repeatedly demonstrated; however, there is minimal direction for application in Barrett's esophagus. The authors conclude that mucosal impedance has potential clinical utility for the assessment and diagnosis of GERD, particularly when conventional investigations have yielded equivocal results.

P137 A multinational survey to identify the clinicians perspectives concerning proton pump inhibitors in patients with systemic sclerosis

Abstract Background/Aims Proton Pump Inhibitors (PPIs) are widely used in Systemic Sclerosis (SSc) for the treatment of gastroesophageal reflux disease (GERD). However, there is scarce evidence to support their use while long-term safety has been questioned. The aim of our study was to identify healthcare providers’ perspectives and experience regarding PPIs therapy in SSc patients. Methods An online survey in English language targeting clinicians involved in the care of SSc patients, was developed and distributed through social media and international physician networks. The survey was launched on 27th November 2022 and kept open for three weeks. Results Responses from 227 clinicians from 36 countries were recorded: most of them (86%) were between 30-70 years and gender was equally represented (F: 52%; M: 48%). The majority ‘agreed’ (41%) or ‘strongly agreed’ (45%) that GERD is a major cause of morbidity in SSc. Lifestyle modifications and non-pharmacological approaches alone were seldom (16%) considered effective. Only half of respondents ‘agreed’ (43%) or ‘strongly agreed’ (11%) there is solid evidence supporting PPIs efficacy in SSc. A range of PPIs was prescribed by clinicians, most frequently pantoprazole (74%), esomeprazole (72%), omeprazole (72%), and lansoprazole (68%). The most common reasons for PPIs prescription (Table 1) were symptomatic GERD unresponsive to lifestyle modification (95%), objective evidence of GERD (82%), and hoarseness or respiratory symptoms (71%). Multiple concerns were raised about PPI long-term safety. The three highest (mean, 10 being very concerned) reasons were: small intestinal bacterial overgrowth (5.5), osteoporosis (5.4), and drug interactions (5.2). There were significant differences in attitudes towards surgery for refractory GERD: ‘strongly disagreed’ (14%), ‘disagreed’ (26%) ‘neutral’ (52%), ‘agreed’ (13%), ‘strongly agreed’ (3%). Furthermore, half of respondents had concerns about potential complications (i.e., worsening of dysphagia): ‘disagreed’ (26%) or ‘strongly disagreed’ (6%), ‘neutral (52%), ‘agreed’ (13%), ‘strongly agreed’ (3%). Conclusion Our survey confirms that PPIs are frequently prescribed for GERD in SSc patients, despite the absence of randomized clinical trials demonstrating their efficacy and safety. Clinicians are concerned about side effects, especially regarding long-term use. There is significant heterogeneity in attitudes towards surgery for refractory GERD. Future research and practical treatment recommendation are urgently needed. Disclosure G. Bandini: None. A. Alunno: None. F. Oliveira Pinheiro: None. C. Campochiaro: None. I. Galetti: None. P. Matucci Cerinic: None. B. Ruaro: None. A. Moggi Pignone: None. L. Dagna: None. M. Matucci Cerinic: None. Z. McMahan: None. M. Hughes: None.

The role of transoral incisionless fundoplication (TIF) in the management of gastroesophageal reflux disease (GERD) following peroral endoscopic myotomy (POEM): A pilot, prospective, patient-driven study.

Gastroesophageal reflux (GERD) is a concern after peroral endoscopic myotomy (POEM). Transoral incisionless fundoplication (TIF) has been recently described as a possible therapy for post-POEM GERD in case series. We prospectively enrolled patients undergoing POEM who agreed to participate in objective post-procedure GERD evaluation. Patients with objective evidence of GERD and suitable anatomy were offered TIF vs. proton pump inhibitor (PPI) only. Patients who underwent TIF were compared to those on PPI-only therapy after follow-up. Of 21 enrolled POEM patients with objective testing, GERD was found in 11 (52%). Of those eligible for TIF, 4 (40%) opted to pursue TIF and were compared to those on PPI-only therapy ( n = 6). Three months post-TIF, 75% of patients had discontinued or significantly decreased PPI. There were no adverse events. GERD health-related quality of life scores were low and comparable between TIF (3.75 ± 6.2) and those who remained on PPI-only therapy (4.1 ± 5). In this pilot, patient-driven prospective study, 75% of patients with post-POEM GERD undergoing TIF had stopped or significantly reduced PPI use. Post-POEM TIF is safe and effective and may be a viable alternative to PPI for POEM-related GERD; however, future studies should include a control arm and post-intervention pH monitoring.

A multi-national survey to identify clinicians’ perspectives concerning Proton Pump inhibitors in patients with systemic sclerosis

ObjectivesProton Pump Inhibitors (PPIs) are widely used in SSc for gastroesophageal reflux disease (GERD). However, there is little evidence to support their empirical use and long-term safety has been questioned. Our objective was to better describe clinicians’ attitudes toward PPIs prescription and use in SSc patients. MethodsClinicians involved in the care of SSc patients were invited through international physician networks and social media to participate in an online survey. ResultsResponses from 227 clinicians from 36 countries were evaluable. The majority ‘agreed’ (41.4 %) or ‘strongly agreed’ (45.4 %) that GERD is a major cause of morbidity in SSc. Lifestyle modifications are seldom (16 %) considered effective. Only half ‘agreed’ (43 %) or ‘strongly agreed’ (11 %) there is solid evidence supporting PPIs efficacy in SSc. The most common reasons for PPIs prescription were symptomatic GERD unresponsive to lifestyle modification (95 %), objective evidence of GERD (82 %), and hoarseness or respiratory symptoms (71 %). There are variable concerns about PPIs long-term safety in SSc. The three highest (mean) reasons (0–10, here 10 is ‘very concerned’) were: small intestinal bacterial overgrowth (5.5), osteoporosis (5.4), and drug interactions (5.2). There are significant differences in attitudes towards surgery for refractory GERD, and concerns about potential complications. PPIs may have a putative role for disease modification (e.g., ILD and calcinosis), and the role of immunosuppression is uncertain for GI (gastrointestinal) disease in SSc. ConclusionPPIs are frequently prescribed in SSc. Side effects are a recognized concern, especially regarding long-term therapy. There is significant variation in attitudes towards surgical intervention. Future research and practical treatment recommendation for PPIs in SSc are urgently needed.

Refractory Gastroesophageal Reflux Disease: Diagnosis and Management.

Gastroesophageal reflux disease (GERD) is common, with increasing worldwide disease prevalence and high economic burden. A significant number of patients will remain symptomatic following an empiric proton pump inhibitor (PPI) trial. Persistent symptoms despite PPI therapy are often mislabeled as refractory GERD. For patients with no prior GERD evidence (unproven GERD), testing is performed off antisecretory therapy to identify objective evidence of pathologic reflux using criteria outlined by the Lyon consensus. In proven GERD, differentiation between refractory symptoms (persisting symptoms despite optimized antisecretory therapy) and refractory GERD (abnormal reflux metrics on ambulatory pH impedance monitoring and/or persistent erosive esophagitis on endoscopy while on optimized PPI therapy) can direct subsequent management. While refractory symptoms may arise from esophageal hypersensitivity or functional heartburn, proven refractory GERD requires personalization of the management approach, tapping from an array of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barrett's esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD.

Mean nocturnal baseline impedance: Influencing factors and diagnostic value in gastroesophageal reflux disease.

At present, there are few studies related to mean nocturnal baseline impedance (MNBI), esophageal dynamic reflux monitoring, high-resolution esophageal manometry (HRM) parameter indexes, and its diagnostic value in gastroesophageal reflux disease (GERD). To analyze the factors influencing MNBI and examine the diagnostic value of MNBI in GERD. A retrospective analysis on 434 patients with typical reflux symptoms who underwent gastroscopy, 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH) and HRM. They were divided into the conclusive evidence group (103 cases), borderline evidence group (229 cases), and exclusion evidence group (102 cases) according to the level of diagnostic evidence of GERD based on the Lyon Consensus. We analyzed the differences in MNBI, esophagitis grade, MII/pH and HRM index among the groups; the correlation between MNBI and the above indexes and its influence on MNBI; and to evaluate the diagnostic value of MNBI in GERD. There were significant differences in MNBI, Acid Exposure Time (AET) 4%, DeMeester score, and total reflux episodes among the three groups (P< 0.001). EGJ contractile integral (EGJ-CI) of the conclusive evidence group and the borderline evidence group was significantly lower than that in the exclusion evidence group (P< 0.001). MNBI was significantly and negatively correlated with age, BMI, AET 4%, DeMeester score, total reflux episodes, EGJ classification, esophageal motility abnormalities, and esophagitis grade (all P< 0.05), and significantly and positively correlated with EGJ-CI (P< 0.001). Age, BMI, AET 4%, EGJ classification, EGJ-CI, and esophagitis grade had significant effects on MNBI (P< 0.05); MNBI was used to diagnose GERD with a diagnostic cutoff of 2061 Ω, and AUC was 0.792 (sensitivity 74.9%, specificity 67.4%); MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 Ω, AUC was 0.774 (sensitivity 67.6%, specificity 72%). AET, EGJ-CI, and esophagitis grade are the most important influence factors of MNBI. MNBI has good diagnostic value in identifying conclusive GERD.

Chicago Classification v4.0 Stratifies Acid Burden and Abnormal Impedance-pH Variables Better Than Chicago Classification v3.0 Chicago Classification v4.0 and GERD.

Gastroesophageal reflux disease (GERD) severity increases with esophageal body hypomotility, but the impact of Chicago Classification (CC) v4.0 criteria on GERD diagnosis is incompletely understood. In patients with GERD evaluated with high-resolution manometry and pH-impedance monitoring, CCv3.0 and CCv4.0 diagnoses were compared. In 247 patients, hypomotility diagnosis decreased from 45.3% (CCv3.0) to 30.0% (CCv4.0, P < 0.001). In contrast, within patients with ineffective esophageal motility, proportions with pathological acid exposure increased from 38% (CCv3.0) to 88% (CCv4.0); baseline impedance and esophageal clearance demonstrated similar findings ( P < 0.05 for each comparison). CCv4.0 hypomotility criteria are more specific in supporting GERD evidence compared with CCv3.0.

Causal association between obstructive sleep apnea and gastroesophageal reflux disease: A bidirectional two-sample Mendelian randomization study.

Objectives: Correlations between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD) have been detected in previous observational studies. However, this association remains uncertain due to the potential presence of selection and confounding biases. Therefore, this bidirectional two-sample Mendelian randomization (MR) study was conducted to evaluate the causal relationship between OSA and GERD. Methods: In this study, instrumental variables (IVs) for OSA were selected from publicly available genetic summary data (27,207 cases and 280,720 controls). Summary statistics for GERD were obtained from a genome-wide association study of 602,604 individuals. The inverse variance weighted (IVW) method was used as the main MR method. The MR-Egger intercept test, MR pleiotropy residual sum and outlier, and leave-one-out analysis were used to detect pleiotropy. Heterogeneity was detected by Cochran's Q test. Results: The IVW results revealed that OSA [odds ratio (OR): 1.19, 95% confidence interval (CI): 1.11-1.28, p = 8.88E-07] was causally associated with the incidence of GERD. Moreover, there was evidence of GERD leading to OSA in the IVW analysis (OR: 1.44, 95%CI: 1.33-1.57, p = 7.74E-19). No directional pleiotropy was detected by the MR-Egger intercept test (all p > 0.05). Conclusion: This study found that OSA is linked to a higher incidence of GERD, and vice versa. This finding might be helpful for the screening and prevention of these two diseases.

Laparoscopic antireflux surgery for refractory gastroesophageal reflux disease: long-term clinical outcomes

Persistent symptoms despite adequate Proton Pump Inhibitors (PPI) treatment are described in up to 40% of patients with Gastroesophageal Reflux Disease (GERD). The efficacy of Laparoscopic Antireflux Surgery (LARS) in PPI non-responder patients is still unclear. This observational study aims to report the long-term clinical outcomes and predictors of dissatisfaction in a cohort of refractory GERD patients submitted to LARS. Patients with preoperative refractory symptoms and objective GERD evidence submitted to LARS between 2008 and 2016 were included in the study. Primary endpoint was overall satisfaction with the procedure, secondary endpoints were long-term GERD symptom relief and endoscopic findings. Univariate and multivariate analyses were performed to compare satisfied and dissatisfied patients, in order to identify preoperative predictors of dissatisfaction. A total of 73 refractory GERD patients who underwent LARS were included in the study. At a mean follow-up of 91.2 ± 30.5 months, the satisfaction rate was 86.3%, with a statistically significant reduction in typical and atypical GERD symptoms. Causes of dissatisfaction were severe heartburn (6.8%), gas bloat syndrome (2.8%), and persistent dysphagia (4.1%). Multivariate analysis showed that a number of Total Distal Reflux Episodes (TDRE) > 75 was a predictive factor of long-term dissatisfaction after LARS while a partial response to PPI was a protective factor against dissatisfaction. LARS guarantees a high level of long-term satisfaction for selected refractory GERD patients. An abnormal TDRE at 24 h-multichannel intraluminal impedance-pH monitoring and the lack of response to preoperative PPI were predictors of long-term dissatisfaction.

The role of magnetic sphincter augmentation in the gastroesophageal reflux disease treatment pathway: the gastroenterology perspective.

Magnetic sphincter augmentation (MSA) is a surgical intervention for well-characterized gastroesophageal reflux disease (GERD), where the esophagogastric junction barrier is augmented using a bracelet of magnetized titanium beads. MSA could be an attractive option for patients with documented GERD who wish to avoid long-term pharmacologic therapy or whose symptoms are not adequately managed with lifestyle modifications and pharmacologic therapy. The 'ideal' MSA patient is one with prominent regurgitation, without dysphagia or esophageal motor dysfunction, with objective evidence of GERD on upper endoscopy and/or ambulatory reflux monitoring. Appropriate candidates with significant hiatus hernia may pursue MSA with concomitant hiatus hernia repair. The increasing adoption of MSA in the GERD treatment pathway reflects research that shows benefits in long-term outcomes and healthcare costs compared with other established therapies in appropriate clinical settings.

Ambulatory pH-Impedance Findings Confirm That Grade B Esophagitis Provides Objective Diagnosis of Gastroesophageal Reflux Disease.

The Lyon Consensus designates Los Angeles (LA) grade C/D esophagitis or acid exposure time (AET) >6% on impedance-pH monitoring (MII-pH) as conclusive for gastroesophageal reflux disease (GERD). We aimed to evaluate proportions with objective GERD among symptomatic patients with LA grade A, B, and C esophagitis on endoscopy. Demographics, clinical data, endoscopy findings, and objective proton-pump inhibitor response were collected from symptomatic prospectively enrolled patients from 2 referral centers. Off-therapy MII-pH parameters included AET, number of reflux episodes, mean nocturnal baseline impedance, and postreflux swallow-induced peristaltic wave index. Objective GERD evidence was compared between LA grades. Of 155 patients (LA grade A: 74 patients, B: 61 patients, and C: 20 patients), demographics and presentation were similar across LA grades. AET >6% was seen in 1.4%, 52.5%, and 75%, respectively, in LA grades A, B, and C. Using additional MII-pH metrics, an additional 16.2% with LA grade A and 47.5% with LA grade B esophagitis had AET 4%-6% with low mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index; there were no additional gains using the number of reflux episodes or symptom-reflux association metrics. Compared with LA grade C (100% conclusive GERD based on endoscopic findings), 100% of LA grade B esophagitis also had objective GERD but only 17.6% with LA grade A esophagitis ( P < 0.001 compared with each). Proton-pump inhibitor response was comparable between LA grades B and C (74% and 70%, respectively) but low in LA grade A (39%, P < 0.001). Grade B esophagitis indicates an objective diagnosis of GERD.

320. EFFICACY OF LAPAROSCOPIC FUNDOPLICATION IN PATIENTS WITH CHRONIC COUGH AND GASTRO-OESOPHAGEAL REFLUX

Abstract The outcome of anti-reflux surgery in patients with cough suspected to be induced by gastro-oesophageal reflux disease is frequently uncertain. The aims of this study were to assess the efficacy of laparoscopic fundoplication (LF) for controlling cough in a patient population suffering chronic cough when alternative aetiologies (e.g. asthma) had been excluded and pathologic gastro-oesophageal reflux had been confirmed on ambulatory pH monitoring, and to identify predictors of response. From a prospective database of 1,598 patients who had undergone laparoscopic fundoplication, 66 (4%) had a principal presenting symptom of chronic cough as well as objective evidence of gastro-oesophageal reflux disease (GORD). Patients completed questionnaires for GORD symptoms (modified DeMeester score) and severity of cough (visual analog scale) both before and after LF, and had pre-operative gastroscopy and 24-hour pH monitoring before operation. Patients were considered to have responded to LF if they had no cough or the cough had improved by 50% or more after operation. Follow-up data was available for 66/66 patients (100%), with a median follow-up time of 43 months (range 14–104 months) after operation. Cough was relieved in 40/66 (61%), while typical GORD symptoms (heartburn, regurgitation) was relieved in 44/49 (90%). The presence of typical GORD symptoms, oesophagitis, or pH study variables did not predict the response of the cough to LF. At 1 year, 67% of patients were satisfied with the results of their surgery, 20% were not and 13% were unsure. For comparison, the 1430/1598 patients in the database with no laryngopharyngeal symptoms had a satisfaction rate of 94%. Based on our study and available literature, it appears there are no reliable pre-operative clinical predictors of a satisfactory response of cough to LF. This probably reflects a current inability to obtain an accurate aetiological diagnosis of chronic cough, even in the presence of known abnormal gastro-oesophageal reflux disease. Regardless, in a well-chosen cohort of patients with chronic cough, LF can yield good patient satisfaction rates, albeit less than for patients with typical GORD symptoms.

Impact of gastroesophageal reflux disease on idiopathic pulmonary fibrosis and lung transplant recipients.

Idiopathic pulmonary fibrosis (IPF) is a prevalent subset of interstitial lung disease (ILD) that often progresses to require lung transplantation. Gastroesophageal reflux disease (GERD) is common in the IPF population, and GER-related micro-aspiration appears to be an important risk factor for IPF pathogenesis and for the deterioration of transplanted lung function. Many patients with IPF have elevated esophageal acid exposure on reflux testing despite having no or minimal symptoms. Studies on the effects of medical GERD therapy on IPF-related outcomes have had mixed results. Antireflux surgery is safe in appropriately selected IPF patients, and appears to have potential for slowing the decline of lung function. GERD can persist, improve or develop after lung transplantation, and the presence of GERD is associated with allograft injury and pulmonary function decline in lung transplant recipients. Clinicians should have a low threshold to assess for objective evidence of GERD in IPF patients. Antireflux surgery in IPF patients with GERD appears to improve lung function, but further studies are needed before surgical treatment can be recommended routinely in this setting. In lung transplant recipients, reflux testing after transplant is the most accurate way to guide GERD treatment decisions.

Mechanisms for the Sex-Specific Effect of H. Pylori on Risk of Gastroesophageal Reflux Disease and Barrett's Esophagus.

Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.

Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at the CYP2C Locus.

Omeprazole is extensively used to manage gastroesophageal reflux disease (GERD). It is primarily metabolized by CYP2C19. The CYP2C19*17 (rs12248560) allele and the recently described CYP2C:TG haplotype (rs11188059 and rs2860840) are associated with increased enzymatic activity, and may reduce omeprazole exposure. This observational study aimed to investigate the association between these genetic variants and omeprazole treatment failure in GERD. We recruited predominantly New Zealand European GERD patients who either did not respond to omeprazole or experienced breakthrough heartburn symptoms despite at least 8 weeks of omeprazole (≥40 mg/day). The GerdQ score was used to gauge symptomatic severity. A total of 55 cases were recruited with a median age (range) of 56 years (19–82) and GerdQ score of 11 (5–17). Of these, 19 (34.5%) were CYP2C19*17 heterozygotes and two (3.6%) were CYP2C19*17 homozygotes. A total of 30 (27.3%) CYP2C:TG haplotypes was identified in our cohort, with seven (12.7%) CYP2C:TG homozygotes, and 16 (29%) CYP2C:TG heterozygotes. No significant differences were observed for overall CYP2C19*17 alleles, CYP2C19*17/*17, overall CYP2C:TG haplotypes, and CYP2C:TG heterozygotes (p > 0.05 for all comparisons). Gastroscopy and 24-h esophageal pH/impedance tests demonstrated objective evidence of GERD in a subgroup of 39 (71%) cases, in which the CYP2C:TG/TG was significantly enriched (p = 0.03) when compared with the haplotype frequencies in a predominantly (91%) New Zealand European reference population, but not the CYP2C19*17/*17 (p > 0.99), when compared with the allele frequencies for the non-Finnish European subset of gnomAD. We conclude that omeprazole treatment failure in GERD is associated with CYP2C:TG/TG, but not CYP2C19*17.

Applying Lyon Consensus criteria in the work-up of patients with proton pump inhibitory-refractory heartburn.

A hierarchical approach for gastro-oesophageal reflux disease (GERD) diagnosis by impedance-pH monitoring was proposed by the Lyon Consensus, based on acid exposure time (AET) and supportive impedance metrics. To establish the clinical value of Lyon Consensus criteria in the work-up of patients with proton pump inhibitory (PPI)-refractory heartburn. Expert review of off-therapy impedance-pH tracings from unproven GERD patients with PPI-refractory heartburn prospectively evaluated at referral centers. Impedance metrics, namely total reflux episodes, postreflux swallow-induced peristaltic wave index, and mean nocturnal baseline impedance, were assessed. Expert review of on-therapy preoperative impedance-pH tracings from a separate cohort of surgically treated erosive/nonerosive GERD cases. Off-therapy, normal, inconclusive, and abnormal AET was found in 59%, 17%, and 23% of 317 cases. Supportive evidence of GERD was provided by abnormal impedance metrics in up to 22% and 62% of cases in the normal and inconclusive AET groups, respectively. Adding the cases with inconclusive AET and abnormal impedance metrics to the abnormal AET group, a significant increase in GERD evidence was observed (from 23% to 37% of cases, p<0.0002). At the on-therapy presurgical evaluation, abnormal/inconclusive AET and supraphysiological values of impedance metrics showed ongoing reflux in 21% and 90% of 96 cases, respectively (p<0.00001); a relationship between on-therapy ongoing reflux and PPI-refractory heartburn was confirmed by the favorable surgical outcome at 3-year follow-up, 88% of cases being in persistent off-PPI heartburn remission. Impedance-pH monitoring, off- and on-therapy, is of high clinical value in the work-up of patients with PPI-refractory heartburn.

Which is the best algorithm for evaluating a patient’s candidate to sleeve with suspected reflux or hiatal hernia: is manometry or reflux assessment always necessary

Laparoscopic sleeve gastrectomy (SG) has reached wide popularity during the last 15 years, owing to limited morbidity and mortality rates, very successful weight loss results, and impact on comorbidities. However, the postoperative development or worsening of gastroesophageal reflux disease (GERD) is one of the most important drawbacks of this surgical procedure. To date, there is great heterogeneity concerning the definition of GERD, the indication for SG in patients with GERD, and the standardization of pre and postoperative diagnostic pathways. In patients with severe obesity, a strictly symptom-based diagnosis of GERD is unreliable. In fact, a high rate of silent GERD (s-GERD, asymptomatic patients despite objective evidence of GERD) has been reported. Moreover, patients with preoperative s-GERD have a significantly higher risk of experiencing GERD symptoms after SG. For these reasons, the reflux burden and the competence of the anti-reflux barrier should be carefully assessed during the preoperative work-up of patients undergoing SG. Ambulatory pH monitoring (APM) and high-resolution manometry (HRM) are useful diagnostic tools that could provide valuable evidence in the guidance of surgical strategy. In this review, we evaluate the current literature concerning the use of APM and HRM in the diagnostic pathway before SG, as well as their predictive value for the evolution of GERD in the postoperative course. Moreover, we propose a diagnostic algorithm for preoperative GERD assessment, which includes validated symptom questionnaires, upper gastrointestinal endoscopy, APM, and HRM.

Refractory Gastroesophageal Reflux Disease: A Management Update.

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with “reflux-like PPI-refractory symptoms.” Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.