PUBLICATIONS

2025

Muftah M, Hartnett DA, Hiramoto B, et al. Yield of esophageal biopsy patterns for the diagnosis of eosinophilic esophagitis.. Gastrointestinal endoscopy. 2025;102(2):194-201.e1. doi:10.1016/j.gie.2025.01.018

BACKGROUND AND AIMS: The pattern of inflammation in eosinophilic esophagitis (EoE) is patchy, necessitating multiple biopsies to optimize diagnostic yield. Current consensus-based guidelines recommend 6 total biopsy samples at 2 sites, distal and either middle or proximal esophagus, although this recommendation is based on limited data. We aimed to determine whether this biopsy protocol sufficiently captures EoE diagnoses by evaluating the distribution of eosinophilia in a large EoE cohort.

METHODS: This was a retrospective study of consecutive patients newly diagnosed with EoE with ≥2 esophageal segments biopsied. Demographic variables, clinical characteristics/history, endoscopic findings, and histologic results were manually reviewed. Distribution (proximal, middle, and/or distal) of eosinophilia (>15 eosinophils/high-power field [HPF]) was assessed. Predictors for non-distal disease (<15 eosinophils/HPF on distal biopsy samples) were evaluated by using multivariable logistic regression.

RESULTS: A total of 511 patients newly diagnosed with EoE with ≥2 segments biopsied were included. All patients underwent distal esophageal biopsy. Overall, 286 (56.0%) had ≥1 site with <15 eosinophils/HPF, including 51 (10%) with non-distal disease. Among patients with 3 segments biopsied (n = 60), 19 (31.7%) had eosinophilia at only 1 site, including 6 (10%) with isolated midesophageal disease and no isolated proximal eosinophilia. Discordant mid and proximal biopsy results were found in 18 (30%) patients, with 17 of 18 (94.4%) having mid esophageal eosinophilia. On multivariable analysis, increasing age (odds ratio, 1.02; 95% CI, 1.002-1.04; P = .03) and male sex (odds ratio, 1.89; 95% CI, 1.002-3.55; P = .049) independently predict non-distal disease.

CONCLUSIONS: Isolated segmental eosinophilia is common in EoE, including up to 10% non-distal disease. Discordant mid and proximal biopsy findings are prevalent, with no isolated proximal eosinophilia. Standard protocol should include routine biopsies of both distal and middle esophagus to maximize diagnostic yield.

Jirapinyo P, Leung D, Chan WW, Thompson CC. The Impact of Endoscopic Gastric Remodeling on Gastroesophageal Reflux Disease.. Clinical and translational gastroenterology. 2025;16(8):e00867. doi:10.14309/ctg.0000000000000867

INTRODUCTION: Sleeve gastrectomy is associated with an increased incidence of gastroesophageal reflux disease (GERD). By contrast, the impact of endoscopic gastric remodeling (EGR) on GERD symptoms remains unclear.

METHODS: This prospective study included patients who underwent EGR and completed validated GERD-related patient-reported outcome questionnaires at baseline and 12 months postprocedure.

RESULTS: Fifty patients were included. At 12 months post-EGR, both GERD questionnaire and Reflux Symptom Index scores significantly improved. Proton-pump inhibitor use decreased from 38% at baseline to 20% at 12 months ( P = 0.047). The presence of a hiatal hernia at baseline was associated with greater symptom improvement.

DISCUSSION: EGR improves both typical and atypical GERD symptoms and reduces proton-pump inhibitor dependence. It may represent a preferable treatment option for patients with obesity and concomitant GERD.

Algara MA, Chan WW. Update on laryngopharyngeal reflux disease.. Current opinion in gastroenterology. 2025;41(4):251-259. doi:10.1097/MOG.0000000000001108

PURPOSE OF REVIEW: Chronic laryngopharyngeal symptoms (LPS) are increasingly prevalent presentations to gastroenterologists' offices, and clinicians often make a presumptive diagnosis of laryngopharyngeal reflux disease (LPRD) based on LPS symptoms or laryngoscopic findings alone. Such presumptive diagnoses of LPRD often are incorrect, and establishing the correct diagnosis poses significant challenges for clinicians. This review addresses the timely need for advances in evaluating and managing LPS/LPRD, given their diagnostic complexity and the healthcare burden of ineffective empiric treatments.

RECENT FINDINGS: Recent evidence emphasizes the diverse etiologies of LPS including LPRD, oropharyngeal or other airway pathologies, allergic conditions, and cognitive-affective processes or altered brain-larynx interaction. The diagnostic approach should be individualized and multimodal, including upfront reflux testing over empiric acid suppression trials for possible LPRD, given the poor correlation between LPS and objective evidence of reflux. Predictive models and risk stratification tools such as the COuGH RefluX score show promise to help guide testing and therapeutic strategies. Reflux testing modalities include wireless pH monitoring and impedance-based testing (traditional impedance-pH or combined hypopharyngeal-esophageal reflux monitoring). Biochemical testing for salivary pepsin may also offer adjunctive value. Management should include antireflux strategies for those with objectively-proven LPRD, alongside treatments targeting nonreflux mechanisms of LPS, such as voice therapy, neuromodulation, and behavioral therapy.

SUMMARY: An individualized, multidisciplinary approach is essential in managing LPS/LPRD. Objective reflux testing improves diagnostic accuracy, avoids unnecessary therapies, and enables tailored treatment. Future research should further refine diagnostic thresholds, validate risk stratification tools, and explore novel therapeutic targets to optimize outcomes.

Yadlapati R, Chan WW. Evaluation of Patients With Laryngopharyngeal Symptoms: The Role and Strategy for Reflux Testing. Foregut. 2025;5(2):166-173. doi:10.1177/26345161251339980
Gastroenterologists and otolaryngologists commonly care for patients with laryngopharyngeal symptoms such as voice hoarseness, sore throat, throat clearing and cough. Often symptoms are reflexively attributed to gastro-esophageal reflux disease, although poorly response to traditional anti-reflux management strategies. The current paradigm to evaluate for laryngopharyngeal reflux disease highlights the role of reflux monitoring performed off acid suppression. This review discusses the indications for reflux monitoring and reviews considerations for selection and interpretation of the different modalities of reflux monitoring for diagnosis of laryngopharyngeal reflux disease: prolonged wireless pH monitoring as well as impedance-pH monitoring.
Gyawali P, Marchetti L, Rogers BD, et al. The Lyon Score: A Novel Reflux Scoring System Based on the Lyon Consensus 2.0 That Associates With Treatment Outcome From Antireflux Therapy.. The American journal of gastroenterology. 2025;120(5):1009-1018. doi:10.14309/ajg.0000000000003083

INTRODUCTION: We explored if a score derived from parameters from esophageal testing could increase confidence in diagnosing conclusive gastroesophageal reflux disease and in predicting outcome.

METHODS: A prediction score was developed using metrics based on Lyon Consensus 2.0 thresholds extracted from endoscopy and pH-impedance monitoring. The Lyon score was the sum of weighted scores derived from a logistic regression model. The outcome was response to antireflux therapy, defined as 50% reduction in global symptoms on validated questionnaires. An existing database of endoscopy-negative patients with typical reflux symptoms undergoing esophageal testing from 2 centers (Europe and the United States) constituted the developmental cohort, while 2 separate cohorts (Europe and Asia) served as validation cohorts. Receiver operating characteristics analysis determined performance of the Lyon score in predicting treatment response.

RESULTS: In 281 developmental cohort patients (median age 53 years, 57.7% female), the Lyon score demonstrated an area under the curve (AUC) of 0.819 in predicting 50% symptom improvement ( P < 0.001) on receiver operating characteristics, with an optimal threshold of 6.25 (sensitivity 81.2%, specificity 73.4%). Of the individual components, only acid exposure time (AUC 0.799, P < 0.001), mean nocturnal baseline impedance (AUC 0.785, P < 0.001), and reflux episodes (AUC 0.764, P < 0.001) approached the Lyon score performance. The Lyon score segregated treatment response in both the European (AUC 0.908, P < 0.001) and Asian validation cohorts (AUC 0.637, P < 0.001) and outperformed the DeMeester score in sensitivity for predicting outcome in the developmental and Asian validation cohorts.

DISCUSSION: The novel Lyon score segregates reflux phenotypes and identifies likelihood of symptom response from antireflux therapy.

Carlson DA, Pandolfino JE, Yadlapati R, et al. A Standardized Approach to Performing and Interpreting FLIP Panometry for Esophageal Motility Disorders: The Dallas Consensus.. Gastroenterology. Published online 2025. doi:10.1053/j.gastro.2025.01.234

BACKGROUND AND AIMS: Functional lumen imaging probe (FLIP) Panometry provides assessment of the esophagogastric junction (EGJ) opening and esophageal body contractile activity during an endoscopic procedure and is increasing being incorporated in comprehensive esophageal motility assessments. We aimed to provide a standardized approach and vocabulary to the procedure and interpretation and update the motility classification scheme.

METHODS: A working group of 19 FLIP Panometry experts convened in a modified Delphi consensus process to produce and assess statements on the FLIP Panometry procedure and interpretation. Three rounds of voting were conducted on an agreement scale of 1-9 for appropriateness followed by face-to-face discussions and opportunity for revisions of statements. The "percent agreement" was proportion of votes with score ≥7 indicating level of agreement on appropriateness.

RESULTS: A total of 40 statements were selected for final inclusion for the Dallas Consensus, including FLIP Panometry protocol, interpretation of EGJ opening and contractile response, and motility classification scheme. Key statements included: "FLIP Panometry should be interpreted in the context of the clinical presentation, the accompanying EGD findings and other relevant complementary testing". (Median response 9.0; 100% agreement). "A major motor disorder is unlikely in the setting of a "Normal" FLIP Panometry classification (Median response 9.0; 94% agreement). "Diminished or absent contractile response with reduced esophageal opening [i.e. "non-spastic obstruction] supports the diagnosis of a disorder of EGJ outflow. (Median response 8.5; 94% agreement).

CONCLUSION: The standardized approach for performance and interpretation of the Dallas Consensus can facilitate use of FLIP Panometry in broad clinical settings.

Shah ED, Curley MA, Patel A, Lo WK, Chan WW. Heartburn Relief Is the Major Unmet Need for Drug Development in Gastroesophageal Reflux Disease: Threshold Value Analysis.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2025;23(2):263-271. doi:10.1016/j.cgh.2024.01.049

BACKGROUND AND AIMS: Heartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment.

METHODS: A decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported.

RESULTS: Without insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts.

DISCUSSION: We demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.