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Background & aimsDiscerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict the likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms.MethodsThis multicenter international study collected data from adults with chronic laryngeal symptoms who underwent objective testing (upper gastrointestinal endoscopy and/or ambulatory reflux monitoring) between March 2018 and May 2023. The training phase identified a model with optimal receiver operating characteristic curves, and β coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model.ResultsA total of 856 adults, 304 in the training cohort and 552 in the validation cohort, were included. In the training phase, the optimal predictive model (area under the curve, 0.68; 95% CI, 0.62-0.74), was the Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX (COuGH RefluX) score, with a lower threshold of 2.5 and an upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an area under the curve of 0.67 (95% CI, 0.62-0.71), with 79% sensitivity and 81% specificity for proven GERD.ConclusionsThe externally validated COuGH RefluX score is a clinically practical model to predict the likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.

BackgroundMyotomy length in type 3 achalasia is generally tailored based on segment of spasticity on high-resolution manometry (HRM). Potential of length of tertiary contractions on barium esophagram (BE) or length of thickened circular muscle on endoscopic ultrasound (EUS) to guide tailored myotomy is less understood. This study aimed to assess agreement between spastic segments lengths on HRM, BE, and EUS among patients with type 3 achalasia.MethodsThis retrospective study included adults with type 3 achalasia on HRM between November 2019 and August 2022 who underwent evaluation with EUS and/or BE. Spastic segments were defined as HRM-distance between proximal borders of lower esophageal sphincter and high-pressure area (isobaric contour ≥70 mmHg); EUS-length of thickened circular muscle (≥1.2 mm) from proximal border of esophagogastric junction (EGJ) to the transition to a non-thickened circular muscle; BE-distance between EGJ to proximal border of tertiary contractions. Pairwise comparisons assessed for correlation (Pearson's) and intraclass correlation classification (ICC) agreement.Key resultsTwenty-six patients were included: mean age 66.9 years (SD 13.8), 15 (57.7%) male. Spastic segments were positively correlated on HRM and BE with good agreement (ICC 0.751, [95% CI 0.51, 0.88]). Spastic segments were negatively correlated with poor agreement on HRM and EUS (ICC -0.04, [-0.45, 0.39]) as well as BE and EUS (ICC -0.03, [-0.47, 0.42]).Conclusions & inferencesLength of spastic segment was positively correlated on HRM and BE while negatively correlated when compared to EUS, supporting the common use of HRM and highlighting the uncertain role for EUS in tailoring myotomy length for type 3 achalasia.

Background & aimsGaps remain in understanding the epidemiology of eosinophilic esophagitis (EoE). Our aim was to identify and validate a national cohort of individuals with EoE using Veterans Health Administration (VHA) data.MethodsWe used 2 validation strategies to develop algorithms that identified adults with EoE between 1999 and 2020. The first validation strategy applied International Classification of Diseases (ICD) code algorithms to a base cohort of individuals who underwent esophagogastroduodenoscopy with esophageal biopsy specimens. The second applied ICD code algorithms to a base cohort of all individuals in the VHA. For each ICD algorithm applied, a random sample of candidate EoE cases and non-EoE controls were selected and the charts were reviewed manually by a blinded reviewer. Each algorithm was modified iteratively until the prespecified diagnostic accuracy end point (95% confidence lower bound for a positive predictive value [PPV], >88%) was achieved. We compiled individuals from each strategy's maximum performance algorithm to construct the Veterans Affairs Eosinophilic Esophagitis Cohort.ResultsThe maximum performance algorithm from the first validation strategy included 2 or more ICD code encounters for EoE separated by more than 30 days and achieved a 93.3% PPV (lower bound, 88.1%) for identifying true EoE cases. The maximum performance algorithm from the second validation strategy included 4 or more ICD code encounters for EoE in which 2 codes were separated by at least 30 days, and similarly achieved a 93.3% PPV (lower bound, 88.1%). Combining both strategies yielded 6637 individuals, which comprised the Veterans Affairs Eosinophilic Esophagitis Cohort.ConclusionsWe developed and validated 2 highly accurate coding algorithms for EoE and established a nationwide VHA cohort of adults with EoE for future studies.

BACKGROUND: The Eckardt score (ES) is used to assess symptom response to Per-Oral Endoscopic Myotomy (POEM), but reliable methods to assess physiologic success are needed. Functional lumen imaging probe (FLIP) panometry has a potential role in post-POEM follow-up to predict long-term outcomes. The aim of this study was to assess the correlation between clinical success and FLIP parameters following POEM to determine if short interval FLIP could predict long-term outcomes. METHODS: This was a prospective study of adult patients who underwent POEM with short interval follow-up FLIP between 11/2017 and 3/2020. Clinical success was defined as post-procedure ES ≤ 3. Physiologic success was based on an esophago-gastric junction distensibility index (EGJ-DI) > 2.8 mm2/mmHg on FLIP. RESULTS: 47 patients (55% female, mean age 55 years) were included in the study. Clinical success after POEM was seen in 45 (96%) patients (mean ES 6.5 ± 2.2 pre and 0.83 ± 1.0 post-POEM, p

Laryngopharyngeal reflux (LPR) is characterized by the reflux of gastric contents into the pharynx or larynx and often presents with symptoms including but not limited to cough, throat clearing, sore throat, globus, and dysphonia. Unlike gastroesophageal reflux disease (GERD), LPR is a relatively understudied syndrome, and knowledge regarding the diagnostic and treatment strategies, as well as the psychosocial impact continues to evolve. No singular test or procedure currently exists as a gold standard for LPR diagnosis. While laryngoscopy or pH monitoring may be positive, this does not exclude the contribution of non-gastroenterological processes. Prior research into psychosocial impact demonstrates a significant increase in symptom burden when comparing patients with laryngeal symptoms to controls and those with isolated GERD symptoms. However, these data are limited by the absence of physiologic data to correlate with the reported symptoms and survey responses. This knowledge gap highlights the need for further research to investigate the relationship between symptom burden and pathologic acid reflux on quality of life (QOL), anxiety, and depression. Ultimately, future studies to directly analyze these variables will help to guide treatment strategies and improve QOL in these patients.

INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations. METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard. RESULTS: Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%). DISCUSSION: Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.

Purpose of reviewWhile guidelines exist for the evaluation and management of esophageal dysphagia in the general population, dysphagia disproportionately affects the elderly. In this article, we reviewed the literature on evaluating esophageal dysphagia in elderly patients and proposed a diagnostic algorithm based on this evidence.Recent findingsIn older patients, dysphagia is often well compensated for by altered eating habits and physiologic changes, underreported by patients, and missed by healthcare providers. Once identified, dysphagia should be differentiated into oropharyngeal and esophageal dysphagia to guide diagnostic workup. For esophageal dysphagia, this review proposes starting with endoscopy with biopsies, given its relative safety even in older patients and potential for interventional therapy. If endoscopy shows a structural or mechanical cause, then further cross-sectional imaging should be considered to assess for extrinsic compression, and same session endoscopic dilation should be considered for strictures. If biopsies and endoscopy are normal, then esophageal dysmotility is more likely, and high-resolution manometry and additional workup should be performed following the updated Chicago Classification. Even after diagnosis of the root cause, complications including malnutrition and aspiration pneumonia should also be assessed and monitored, as they both result from and can further contribute to dysphagia. The successful evaluation of esophageal dysphagia in elderly patients requires a thorough, standardized approach to collecting a history, selection of appropriate diagnostic workup, and assessment of risk of potential complications, including malnutrition and aspiration.

INTRODUCTION: Despite best practice recommendations for managing eosinophilic esophagitis (EoE), variation in care exists. METHODS: We used established methodology for quality indicator development to identify metrics to define quality for the treatment of EoE. RESULTS: Among 29 proposed quality indicator statements, 9 (31%) were adopted as highly valid across all categories. Two (22%) of these statements were identified as having existing or suspected quality gaps. DISCUSSION: We identified highly valid EoE quality indicators for adult gastroenterologists, which can be used for quality improvement with resulting benefits for patient outcomes.

Background & aimsAchalasia is an esophageal motility disorder associated with significant morbidity, yet achalasia-associated risk factors and outcomes are not well-characterized. Our aim was to establish a national cohort of individuals with achalasia, utilizing Veterans Health Administration (VHA) data.MethodsWe iteratively developed combinations of International Classification of Diseases and Current Procedural Terminology code algorithms to validate an approach for identifying achalasia cases. We assessed algorithm accuracy for achalasia diagnosis through manual chart review of candidate achalasia cases and candidate non-achalasia controls. The prespecified end point chosen to establish algorithm performance success was achieving a 1-sided 95% confidence lower bound for a positive predictive value >85% for a random sample of 100 candidate achalasia cases. Once adequate performance was validated, we queried national VHA data to establish and characterize a cohort of individuals diagnosed with achalasia between 1999 and 2020.ResultsThree rounds of algorithm modification and validation were conducted to achieve the prespecified performance endpoint. In the final round, a combination of 3 or more International Classification of Diseases codes for achalasia in the subject's lifetime and a Current Procedural Terminology code for esophageal manometry achieved an observed 94% positive predictive value (1-sided 95% confidence lower bound of 88.5%) for identifying achalasia. Applying the algorithm to national VHA data identified a cohort of 2100 individuals with achalasia, with a median age 65 years and who were 93% male.ConclusionsUsing a rigorous validation approach, we established a national cohort of 2100 individuals with achalasia within the VHA, one of the largest established to date. This cohort can be utilized to study risk factors for achalasia and outcomes over time.

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time

BACKGROUND: The functional lumen imaging probe (FLIP) evaluates esophagogastric junction (EGJ) opening and esophageal contractility. Both post hoc and real-time analyses are possible, but reproducibility and reliability of analysis remain undefined. This study assesses inter- and intra-rater agreement of normative FLIP measurements among novice and experienced users. METHODS: Eight motility experts from different institutions independently evaluated de-identified video recordings from 27 asymptomatic healthy subjects using FLIP. Interpretation methods simulating a post-procedure and a live procedure setting were tested. Novice FLIP users (n = 3) received training prior to post-procedure interpretation. Experienced FLIP users (n = 5) interpreted using both methods. Users recorded maximum EGJ and distal esophageal body diameter, distensive pressure, and EGJ distensibility index (EGJ-DI), at balloon fill volumes of 50-, 60-, and 70 ml, as well as repetitive antegrade contractions (RACs). Inter- and intra-rater agreements of diameters, distensive pressure and EGJ-DI were assessed by intra-class correlation coefficient (ICC) and Pearsons correlation coefficient (PCC). Percentage agreement evaluated inter- and intra-rater reliability for RACs. KEY RESULTS: Novice and experienced users acquired normative FLIP metrics. Good-to-excellent inter- and intra-rater reliability were achieved for all variables at 60 ml balloon fill volumes. Median parameters at 60 ml balloon fill volume were as follows: EGJ-DI 5.5 mm2 /mmHg, maximum EGJ diameter 18.6 mm, distensive pressure at maximum EGJ diameter 48.1 mmHg, and distal esophageal body diameter 19.5 mm. CONCLUSIONS AND INFERENCES: Normative FLIP parameters can be reliably extracted from FLIP videos using both real-time and post hoc analyses, with high reliability between experienced and novice users.

Approximately 36% of the United States (US) population is infected with Helicobacter pylori (HP), a known major risk factor for peptic ulcer disease and gastric cancer. HP eradication reduces the rate of complications; however, the benefits are undermined by rising rates of HP eradication treatment failure. This real-world observational cohort analysis aims to describe HP diagnostic and treatment patterns among insured patients in the US. Using diagnoses, lab results, and treatment patterns, we identified adults (18+) with new diagnoses of HP in the Veradigm Health Insights EHR Database linked to Komodo claims data (1/1/2016-12/31/2019). Patients were required to have ≥ 12 months of data pre-/post-index. We captured patient characteristics, HP-related diagnostic testing, and the use of US guideline-recommended HP eradication regimens. HP eradication rates following first-line eradication treatment were measured among patients with available lab results. Overall, 31.8% of the 60,593 included patients did not receive guideline-recommended treatment. Among the 68.2% (41,340) with first-line treatment, 80.2% received clarithromycin-based triple therapy, and 6.6% received bismuth quadruple therapy. Of the 4569 patients with a repeated course of eradication therapy, 53.4% received the same regimen as their first-line, the majority (90.7%) of whom received two rounds of clarithromycin-based triple therapy. Among the 2455 patients with results of HP non-serology testing following first-line treatment, the 180-day eradication rate was 80.2% overall, with differences based on treatments and demographics. This study highlights gaps between guideline-recommended HP management and real-world patterns, underscoring the need to improve HP testing, treatment, and follow-up practices.

BackgroundType II achalasia (Ach2) is distinguished from other achalasia sub-types by the presence of panesophageal pressurization (PEP) of ≥30 mmHg in ≥20% swallows on high-resolution manometry (HRM). Variable manometric features in Ach2 have been observed, characterized by focal elevated pressures (FEPs) (focal/segmental pressures ≥70 mmHg within the PEP band) and/or high compression pressures (PEP ≥70 mmHg). This study aimed to examine clinical and physiologic variables among sub-groups of Ach2.MethodsThis retrospective single center study performed over 3 years (1/2019-1/2022) included adults with Ach2 on HRM who underwent endoscopic ultrasound (EUS), functional lumen imaging probe (FLIP), and/or barium esophagram (BE) prior to therapy. Patients were categorized into two overarching sub-groups: Ach2 without FEPs and Ach2 with FEPs. Demographic, clinical, and physiologic data were compared between these sub-groups utilizing unpaired univariate analyses.Key resultsOf 53 patients with Ach2, 40 (75%) were without FEPs and 13 (25%) had FEPs. Compared with the Ach2 sub-group without FEPs, the Ach2 sub-group with FEPs demonstrated a significantly thickened distal esophageal circular muscle on EUS (1.4 mm [SD 0.9] vs. 2.1 [0.7]; p = 0.02), higher prevalence of tertiary contractions on BE (46% vs. 100%; p = 0.0006), lower esophagogastric junction distensibility index (2.2mm2 /mmHg [0.9] vs 0.9 [0.4]; p = 0.0008) as well as higher distensive pressure (31.0 mmHg [9.8] vs. 55.4 [18.8]; p = 0.01) at 60 cc fill on FLIP, and higher prevalence of chest pain on Eckardt score (p = 0.03).Conclusions and inferencesWe identified a distinct sub-group of type II achalasia on HRM, defined as type II achalasia with focal elevated pressures. This sub-group uniquely exhibits spastic features and may benefit from personalized treatment approaches.

BACKGROUND: There is limited evidence on the efficacy of peroral endoscopic myotomy (POEM) in patients with esophageal diverticula. AIMS: This meta-analysis aimed to assess the efficacy and safety profile of POEM in patients with Zenker (ZD) and epiphrenic diverticula. METHODS: With a literature search through August 2020, we identified 12 studies (300 patients) assessing POEM in patients with esophageal diverticula. The primary outcome was treatment success. Results were expressed as pooled rates and 95% confidence intervals. RESULTS: Pooled rate of technical success was 95.9% (93.4%-98.3%) in ZD patients and 95.1% (88.8%-100%) in patients with epiphrenic diverticula. Pooled rate of treatment success was similar for ZD (90.6%, 87.1%-94.1%) and epiphrenic diverticula (94.2%, 87.3%-100%). Rates of treatment success were maintained at 1 year (90%, 86.4%-97.4%) and 2 years (89.6%, 82.2%-96.9%) in ZD patients. Pooled rate of symptom recurrence was 2.6% (0.9%-4.4%) in ZD patients and 0% in patients with epiphrenic diverticula. Pooled rates of adverse events and severe adverse events were 10.6% (4.6%-16.6%) and 3.5% (0%-7.4%) in ZD and 8.4% (0%-16.8%) and 8.4% (0%-16.8%) in epiphrenic diverticula, respectively. CONCLUSION: POEM represents an effective and safe therapy for the treatment of esophageal diverticula.

BACKGROUND: Optimal ambulatory reflux monitoring methodology in symptomatic reflux patients continues to be debated. AIMS: To utilise published literature and expert opinion to develop recommendation statements addressing use of ambulatory reflux monitoring in clinical practice METHODS: The RAND Appropriateness Method (RAM) was utilised among 17 experts with discussion, revision and two rounds of ranking of recommendation statements. Ambulatory reflux monitoring protocol, methodology and thresholds ranked as appropriate by ≥80% of panellists met the criteria for appropriateness. RESULTS: Prolonged (96-h recommended) wireless pH monitoring off proton pump inhibitor (PPI) was identified as the appropriate diagnostic tool to assess the need for acid suppression in patients with unproven gastro-oesophageal reflux disease (GERD) and persisting typical reflux symptoms despite once-daily PPI. Acid exposure time (AET) 6.0% across ≥2 days is conclusive evidence for GERD and supports treatment for GERD, while AET >10% across ≥2 days identifies severe acid burden that supports escalation of anti-reflux treatment. In previously proven GERD, impedance-pH monitoring on PPI is helpful in defining refractory GERD and mechanisms of continued symptoms; the presence of  4.0% and positive reflux-symptom association support escalation of anti-reflux treatment, including use of invasive therapeutics. CONCLUSIONS: Statements meeting appropriateness for average clinical care have been identified when utilising reflux monitoring in patients with typical reflux symptoms and PPI non-response.

Although Barrett's metaplasia of the esophagus (BE) is the only known precursor lesion to esophageal adenocarcinomas (EACs), drivers of cellular transformation in BE remain incompletely understood. We use an artificial intelligence-guided network approach to study EAC initiation and progression. Key predictions are subsequently validated in a human organoid model, in patient-derived biopsy specimens of BE, a case-control study of genomics of BE progression, and in a cross-sectional study of 113 patients with BE and EACs. Our model classified healthy esophagus from BE and BE from EACs in several publicly available gene expression data sets (n = 932 samples). The model confirmed that all EACs must originate from BE and pinpointed a CXCL8/IL8↔neutrophil immune microenvironment as a driver of cellular transformation in EACs and gastroesophageal junction adenocarcinomas. This driver is prominent in White individuals but is notably absent in African Americans (AAs). Network-derived gene signatures, independent signatures of neutrophil processes, CXCL8/IL8 expression, and an absolute neutrophil count (ANC) are associated with risk of progression. SNPs associated with changes in ANC by ethnicity (e.g., benign ethnic neutropenia [BEN]) modify that risk. Findings define a racially influenced immunological basis for cell transformation and suggest that BEN in AAs may be a deterrent to BE→EAC progression.

Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical obstruction in the gastric outflow. This condition is increasingly encountered in clinical practice. These guidelines summarize perspectives on the risk factors, diagnosis, and management of gastroparesis in adults (including dietary, pharmacological, device, and interventions directed at the pylorus), and they represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation process. When the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and failed peristalsis. Common clinical manifestations include dysphagia to solid and liquid foods, chest pain, regurgitation, and weight loss, resulting in significant morbidity and healthcare burden. Historically, surgical Heller myotomy and pneumatic dilation were the first-line therapeutic options for achalasia. This convention was shaken in 2009 when Inoue and colleagues introduced an endoscopic approach to dissect the muscle fibers of the LES, known as peroral endoscopic myotomy (POEM). Since incorporation of POEM into standard practice, the overall myotomy technique has remained unchanged; however, adaptations in the thickness and length of myotomy have evolved. Full-thickness myotomy is recognized to have similar clinical success and faster procedure times compared with selective circular muscle myotomy. Although myotomy length for type 1 and type 2 achalasia has classically been >6 cm, recent studies demonstrated similar outcomes with reduction of myotomy length to

Gastroesophageal reflux disease (GERD) is a common disease affecting a significant number of adults both globally and in the USA. GERD is clinically diagnosed based on patient-reported symptoms, and the gold standard for diagnosis is ambulatory reflux monitoring, a tool particularly utilized in the common scenario of non-response to therapy or atypical features. Over the past 20 years, there has been a shift toward extending the duration of reflux monitoring, initially from 24 to 48 h and more recently to 96 h, primarily based on a demonstrated increase in diagnostic yield. Further, multiple studies demonstrate clinically relevant variability in day-to-day acid exposure levels in nearly 30% of ambulatory reflux monitoring studies. For these reasons, an ongoing clinical dilemma relates to the optimal activities patients should engage in during prolonged reflux monitoring. Thus, the aims of this review are to detail what is known about variability in daily acid exposure, discuss factors that are known to influence this day-to-day variability (i.e., sleep patterns, dietary/eating habits, stress, exercise, and medications), and finally provide suggestions for patient education and general GERD management to reduce variation in esophageal acid exposure levels.

BackgroundThe Reflux Band, an external upper esophageal sphincter (UES) compression device, reduces esophago-pharyngeal reflux events. This study aimed to assess device efficacy as an adjunct to proton pump inhibitor (PPI) therapy in patients with laryngopharyngeal reflux (LPR).MethodsThis two-phase prospective clinical trial enrolled adults with at least 8 weeks of laryngeal symptoms (sore throat, throat clearing, dysphonia) not using PPI therapy at two tertiary care centers over 26 months. Participants used double dose PPI for 4 weeks in Phase 1 and the external UES compression device nightly along with PPI for 4 weeks in Phase 2. Questionnaire scores and salivary pepsin concentration were measured throughout the study. The primary endpoint of symptom response was defined as reflux symptom index (RSI) score ≤ 13 and/or > 50% reduction in RSI.ResultsThirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m2 (5.1). Primary endpoint was met in 11 (35%) participants after Phase 1 (PPI alone) and 17 (55%) after Phase 2 (Device + PPI). Compared to baseline, mean RSI score (24.1 (10.9)) decreased at end of Phase 1 (PPI alone) (21.9 (9.7); p = 0.06) and significantly decreased at end of Phase 2 (Device + PPI) (15.5 (10.3); p

BACKGROUND: Upper endoscopy (EGD) is frequently performed in patients with esophageal complaints following anti-reflux surgery such as fundoplication. Endoscopic evaluation of fundoplication wrap integrity can be challenging. Our primary aim in this pilot study was to evaluate the accuracy and confidence of assessing Nissen fundoplication integrity and hiatus herniation among gastroenterology (GI) fellows, subspecialists, and foregut surgeons. METHODS: Five variations of post-Nissen fundoplication anatomy were included in a survey of 20 sets of EGD images that was completed by GI fellows, general GI attendings, esophagologists, and foregut surgeons. Accuracy, diagnostic confidence, and inter-rater agreement across providers were evaluated. RESULTS: There were 31 respondents in the final cohort. Confidence in pre-survey diagnostics significantly differed by provider type (mean confidence out of 5 was 1.8 for GI fellows, 2.7 for general GI attendings, 3.6 for esophagologists, and 3.6 for foregut surgeons, P = 0.01). The mean overall accuracy was 45.9%, which significantly differed by provider type with the lowest rate among GI fellows (37%) and highest among esophagologists (53%; P = 0.01). The accuracy was highest among esophagologists across all wrap integrity variations. Inter-rater agreement was low across wrap integrity variations (Krippendorfs alpha

Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders.

Background & aimsAs many as one-half of all patients with suspected gastroesophageal reflux disease (GERD) do not derive benefit from acid suppression. This review outlines a personalized diagnostic and therapeutic approach to GERD symptoms.MethodsThe Best Practice Advice statements presented here were developed from expert review of existing literature combined with extensive discussion and expert opinion to provide practical advice. Formal rating of the quality of evidence or strength of recommendations was not the intent of this clinical practice update. BEST PRACTICE ADVICE 1: Clinicians should develop a care plan for investigation of symptoms suggestive of GERD, selection of therapy (with explanation of potential risks and benefits), and long-term management, including possible de-escalation, in a shared-decision making model with the patient. BEST PRACTICE ADVICE 2: Clinicians should provide standardized educational material on GERD mechanisms, weight management, lifestyle and dietary behaviors, relaxation strategies, and awareness about the brain-gut axis relationship to patients with reflux symptoms. BEST PRACTICE ADVICE 3: Clinicians should emphasize safety of proton pump inhibitors (PPIs) for the treatment of GERD. BEST PRACTICE ADVICE 4: Clinicians should provide patients presenting with troublesome heartburn, regurgitation, and/or non-cardiac chest pain without alarm symptoms a 4- to 8-week trial of single-dose PPI therapy. With inadequate response, dosing can be increased to twice a day or switched to a more effective acid suppressive agent once a day. When there is adequate response, PPI should be tapered to the lowest effective dose. BEST PRACTICE ADVICE 5: If PPI therapy is continued in a patient with unproven GERD, clinicians should evaluate the appropriateness and dosing within 12 months after initiation, and offer endoscopy with prolonged wireless reflux monitoring off PPI therapy to establish appropriateness of long-term PPI therapy. BEST PRACTICE ADVICE 6: If troublesome heartburn, regurgitation, and/or non-cardiac chest pain do not respond adequately to a PPI trial or when alarm symptoms exist, clinicians should investigate with endoscopy and, in the absence of erosive reflux disease (Los Angeles B or greater) or long-segment (≥3 cm) Barrett's esophagus, perform prolonged wireless pH monitoring off medication (96-hour preferred if available) to confirm and phenotype GERD or to rule out GERD. BEST PRACTICE ADVICE 7: Complete endoscopic evaluation of GERD symptoms includes inspection for erosive esophagitis (graded according to the Los Angeles classification when present), diaphragmatic hiatus (Hill grade of flap valve), axial hiatus hernia length, and inspection for Barrett's esophagus (graded according to the Prague classification and biopsied when present). BEST PRACTICE ADVICE 8: Clinicians should perform upfront objective reflux testing off medication (rather than an empiric PPI trial) in patients with isolated extra-esophageal symptoms and suspicion for reflux etiology. BEST PRACTICE ADVICE 9: In symptomatic patients with proven GERD, clinicians should consider ambulatory 24-hour pH-impedance monitoring on PPI as an option to determine the mechanism of persisting esophageal symptoms despite therapy (if adequate expertise exists for interpretation). BEST PRACTICE ADVICE 10: Clinicians should personalize adjunctive pharmacotherapy to the GERD phenotype, in contrast to empiric use of these agents. Adjunctive agents include alginate antacids for breakthrough symptoms, nighttime H2 receptor antagonists for nocturnal symptoms, baclofen for regurgitation or belch predominant symptoms, and prokinetics for coexistent gastroparesis. BEST PRACTICE ADVICE 11: Clinicians should provide pharmacologic neuromodulation, and/or referral to a behavioral therapist for hypnotherapy, cognitive behavioral therapy, diaphragmatic breathing, and relaxation strategies in patients with functional heartburn or reflux disease associated with esophageal hypervigilance reflux hypersensitivity and/or behavioral disorders. BEST PRACTICE ADVICE 12: In patients with proven GERD, laparoscopic fundoplication and magnetic sphincter augmentation are effective surgical options, and transoral incisionless fundoplication is an effective endoscopic option in carefully selected patients. BEST PRACTICE ADVICE 13: In patients with proven GERD, Roux-en-Y gastric bypass is an effective primary anti-reflux intervention in obese patients, and a salvage option in non-obese patients, whereas sleeve gastrectomy has potential to worsen GERD. BEST PRACTICE ADVICE 14: Candidacy for invasive anti-reflux procedures includes confirmatory evidence of pathologic GERD, exclusion of achalasia, and assessment of esophageal peristaltic function.

Laryngopharyngeal reflux (LPR) is a syndrome caused by reflux of gastric contents into the pharynx or larynx, which leads to symptoms of throat clearing, hoarseness, pain, globus sensation, cough, excess mucus production in the throat, and dysphonia. LPR is a challenging condition, as there is currently no gold standard for diagnosis or treatment, and thus this presents a burden to the healthcare system. Strategies for treatment of LPR are numerous. Medical therapies include proton pump inhibitors, which are first line, H2 receptor antagonists, alginates, and baclofen. Other noninvasive treatment options include lifestyle therapy and the external upper esophageal sphincter compression device. Endoscopic and surgical options include antireflux surgery, magnetic sphincter augmentation, and transoral incisionless fundoplication. Functional laryngeal disorders and laryngeal hypersensitivity can present as LPR symptoms with or without gastroesophageal reflux disease. Though there are minimal studies in this area, neuromodulators and behavioral interventions are potential treatment options. Given the complexity of these patients and numerous available treatment options, we propose a treatment algorithm to help clinicians diagnose and triage patients into an appropriate therapy.

Barretts esophagus (BE) is a common condition associated with chronic gastroesophageal reflux disease. BE is the only known precursor to esophageal adenocarcinoma, a highly lethal cancer with an increasing incidence over the last 5 decades. These revised guidelines implement Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the definition and diagnosis of BE, screening for BE and esophageal adenocarcinoma, surveillance of patients with known BE, and the medical and endoscopic treatment of BE and its associated early neoplasia. Important changes since the previous iteration of this guideline include a broadening of acceptable screening modalities for BE to include nonendoscopic methods, liberalized intervals for surveillance of short-segment BE, and volume criteria for endoscopic therapy centers for BE. We recommend endoscopic eradication therapy for patients with BE and high-grade dysplasia and those with BE and low-grade dysplasia. We propose structured surveillance intervals for patients with dysplastic BE after successful ablation based on the baseline degree of dysplasia. We could not make recommendations regarding chemoprevention or use of biomarkers in routine practice due to insufficient data.

Background & aimsHeterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes.MethodsA total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups.ResultsDAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P = .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure.ConclusionsDAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

Background and study aims  Colonoscopy inspection quality (CIQ) assesses skills (fold examination, cleaning, and luminal distension) during inspection for polyps and correlates with adenoma detection rate (ADR) and serrated detection rate (SDR). We aimed to determine whether providing individualized CIQ feedback with instructional videos improves quality metrics performance. Methods  We prospectively studied 16 colonoscopists who already received semiannual benchmarked reports of quality metrics (ADR, SDR, and withdrawal time [WT]). We randomly selected seven colonoscopies/colonoscopist for evaluation. Six gastroenterologists graded CIQ using an established scale. We created instructional videos demonstrating optimal and poor inspection techniques. Colonoscopists received the instructional videos and benchmarked CIQ performance. We compared ADR, SDR, and WT in the 12 months preceding (baseline) and following CIQ feedback. Colonoscopists were stratified by baseline ADR into lower (≤ 34 %) and higher-performing (> 34 %) groups. Results  Baseline ADR was 38.5 % (range 26.8 %-53.8 %) and SDR was 11.2 % (2.8 %-24.3 %). The proportion of colonoscopies performed by lower-performing colonoscopists was unchanged from baseline to post-CIQ feedback. All colonoscopists reviewed their CIQ report cards. Post-feedback, ADR (40.1 % vs 38.5 %, P  = 0.1) and SDR (12.2 % vs. 11.2 %, P  = 0.1) did not significantly improve; WT significantly increased (11.4 vs 12.4 min, P

BACKGROUND & AIMS: Identification of postendoscopy esophageal adenocarcinoma (PEEC) among Barretts esophagus (BE) patients presents an opportunity to improve survival of esophageal adenocarcinoma (EAC). We aimed to estimate the proportion of PEEC within the first year after BE diagnosis. METHODS: Multiple databases (Medline, Embase, Scopus, and Cochrane databases) were searched until September 2020 for original studies with at least 1-year follow-up evaluation that reported EAC and/or high-grade dysplasia (HGD) in the first year after index endoscopy in nondysplastic BE, low-grade dysplasia, or indefinite dysplasia. The proportions of PEEC defined using EAC alone and EAC+HGD were calculated by dividing EAC or EAC+HGD in the first year over the total number of EAC or EAC+HGD, respectively. RESULTS: We included 52 studies with 145,726 patients and a median follow-up period of 4.8 years. The proportion of PEEC (EAC) was 21% (95% CI, 13-31) and PEEC (EAC+HGD) was 26% (95% CI, 19-34). Among studies with nondysplastic BE only, the PEEC (EAC) proportion was 17% (95% CI, 11-23) and PEEC (EAC+HGD) was 14% (95% CI, 8-19). Among studies with 5 or more years of follow-up evaluation, the PEEC (EAC) proportion was 10% and PEEC (EAC+HGD) was 19%. Meta-regression analysis showed a strong inverse relationship between PEEC and incident EAC (P < .001). The PEEC (EAC) proportion increased from 5% in studies published before 2000 to 30% after 2015. Substantial heterogeneity was observed for most analyses. CONCLUSIONS: PEEC accounts for a high proportion of HGD/EACs and is proportional to reduction in incident EAC. Using best endoscopic techniques now and performing future research on improving neoplasia detection through implementation of quality measures and educational tools is needed to reduce PEEC.

BACKGROUND AND AIMS: This study aimed to systematically evaluate a classification scheme of secondary peristalsis using functional luminal imaging probe (FLIP) panometry through comparison with primary peristalsis on high-resolution manometry (HRM). METHODS: 706 adult patients that completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers (controls) were included. Secondary peristalsis, that is, contractile responses (CRs), was classified on FLIP panometry by the presence and pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), absent (ACR), or spastic-reactive (SRCR). Primary peristalsis on HRM was assessed according to the Chicago Classification. RESULTS: All 35 of the controls had antegrade contractions on FLIP panometry with either NCR (89%) or BCR (11%). The average percentages of normal swallows on HRM varied across contractile response patterns from 84% in NCR, 68% in BCR, 39% in IDCR, to 11% in ACR, as did the percentage of failed swallows on HRM: 4% in NCR, 12% in BCR, 36% in IDCR, and 79% in ACR. SRCR on FLIP panometry was observed in 18/57 (32%) patients with type III achalasia, 4/15 (27%) with distal esophageal spasm, and 7/15 (47%) with hypercontractile esophagus on HRM. CONCLUSIONS: The FLIP panometry contractile response patterns reflect a pathophysiologic transition from normal to abnormal esophageal peristaltic function with shared features with primary peristaltic function/dysfunction on HRM. Thus, these patterns of the contractile response to distension can facilitate the evaluation of esophageal motility using FLIP panometry.

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

PURPOSE OF REVIEW: Chicago Classification has standardized clinical approach to primary esophageal motility disorders. With new clinical data and advancing treatments, Chicago Classification has undergone multiple revisions to reflect updated findings and enhance diagnostic accuracy. This review will describe the recently published Chicago Classification version 4.0 (CCv4.0), which aimed to enhance diagnostic characterization and limit overdiagnosis of inconclusive esophageal motility diagnoses. RECENT FINDINGS: Key revisions outlined in CCv4.0 include (1) a modified standardized HRM study protocol performed in supine and upright positions, (2) recommended ancillary testing and manometric provocation for inconclusive manometric diagnoses (3) the required presence of obstructive symptoms for conclusive diagnoses of esophagogastric junction outflow obstruction, distal esophageal spasm and hypercontractile esophagus, and (4) requirement of confirmatory testing for esophagogastric junction outflow obstruction. These key modifications aim to improve diagnostic accuracy and consistency of clinically relevant esophageal motility disorders, and subsequently clinical outcomes.

INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers (controls) and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0. RESULTS: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. DISCUSSION: Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.

BACKGROUND: Supragastric belching (SGB) and rumination are behavioral disorders associated with proton pump inhibitor (PPI) non-response and can be diagnosed using multichannel intraluminal impedance-pH (MII-pH) and post-prandial high-resolution impedance manometry (PPHRIM). This pilot study compared diagnostic yield and inter-rater agreement for SGB and rumination using MII-pH and PPHRIM. METHODS: Three esophageal physiologists performed blinded interpretations of MII-pH and PPHRIM in 22 PPI non-responders. Raters selected from 4 diagnostic impressions (normal, GERD, behavioral disorders, GERD+behavioral disorders) without clinical context. Primary outcomes were diagnostic impressions compared against clinical gold standard impression, between raters, and between test modalities. Following a 28-month wash-out period, raters re-interpreted MII-pH with clinical context and under consensus definition of diagnostic criteria. KEY RESULTS: Compared to gold standard, rater accuracy for presence of behavioral disorders ranged from 45 to 77% on MII-pH and 45-59% on PPHRIM. On MII-pH, inter-rater agreement was fair for diagnosis (ĸ0.32, p

Esophagogastric junction (EGJ) barrier function is of fundamental importance in the pathophysiology of gastroesophageal reflux disease. Impaired EGJ barrier function leads to excessive distal esophageal acid exposure or, in severe cases, esophagitis. Hence, proposed high-resolution manometry (HRM) metrics assessing EGJ integrity are clinically important and were a focus of the Chicago Classification (CC) working group for inclusion in CC v4.0. However, the EGJ is a complex sphincter comprised of both crural diaphragm (CD) and lower esophageal sphincter (LES) component, each of which is subject to independent physiological control mechanisms and pathophysiology. No single metric can capture all attributes of EGJ barrier function. The working group considered several potential metrics of EGJ integrity including LES-CD separation, the EGJ contractile integral (EGJ-CI), the respiratory inversion point (RIP), and intragastric pressure. Strong recommendations were made regarding LES-CD separation as indicative of hiatus hernia, although the numerical threshold for defining hiatal hernia was not agreed upon. There was no agreement on the significance of the RIP, only that it could localize either above the LES or between the LES and CD in cases of hiatus hernia. There was agreement on how to measure the EGJ-CI and that it should be referenced to gastric pressure in units of mmHg cm, but the numerical threshold indicative of a hypotensive EGJ varied widely among reports and was not agreed upon. Intragastric pressure was endorsed as an important metric worthy of further study but there was no agreement on a numerical threshold indicative of abdominal obesity.

Symptom severity and prevalence of erosive disease in gastroesophageal reflux disease (GERD) differ between genders. It is not known how gastroenterologists incorporate patient gender in their decision-making process. We aimed to evaluate how gender influences the diagnosis and management recommendations for patients with GERD. We invited a nationwide sample of gastroenterologists via voluntary listservs to complete an online survey of fictional patient scenarios presenting with different GERD symptoms and endoscopic findings. Patient gender for each case was randomly generated. Study participants were asked for their likelihood of a diagnosis of GERD and subsequent management recommendations. Results were analyzed using chi-square tests, Fisher Exact tests, and multivariable logistic regression. Of 819 survey invitations sent, 135 gastroenterologists responded with 95.6% completion rate. There was no significant association between patient gender and prediction for the likelihood of GERD for any of the five clinical scenarios when analyzed separately or when all survey responses were pooled. There was also no significant association between gender and decision to refer for fundoplication, escalate PPI therapy, or start of neuromodulation/behavioral therapy. Despite documented symptomatic and physiologic differences of GERD between the genders, patient gender did not affect respondents estimates of GERD diagnosis or subsequent management. Further outcomes studies should validate whether response to GERD treatment strategies differ between women and men.

Chicago Classification version 4.0 (CC v4.0), published in 2021, presents several modifications largely aimed at minimizing over-diagnosis of inconclusive patterns on high-resolution manometry (HRM). These include: 1) introduction of a standardized HRM protocol for consistency among centers, 2) emphasis on the need for supportive data in instances of inconclusive manometric patterns, 3) required presence of relevant symptoms in certain instances to reduce over-diagnosis and inappropriate interventions, and 4) classification as disorders of EGJ outflow or disorders of peristalsis. These updates aim to improve the clinical application of HRM and patient outcomes.