Large animal models, while valuable, are expensive, time-consuming, and limited to discrete interventional or terminal timepoints, while existing benchtop models do not offer an accurate representation of the esophageal environment. Moreover, current pre-clinical models cannot effectively simulate swallowing dysfunction (dysphagia), restricting progress in understanding motility disorders like achalasia and hindering evidence-based dietary recommendations. In response, we present RoboGullet, a biomimetic soft-robotic model with independent localized longitudinal and circumferential muscle actuation, enabling, for the first time, simulation of both normal and diseased esophageal motility. We further enhance realism with a biohybrid variant, RoboGullet + , incorporating porcine esophageal mucosa/submucosa. We demonstrate this platform's versatility through three key applications: assessing stent migration, simulating achalasia I-III within clinical diagnostic criteria, and analyzing bolus swallowing. Our findings reveal that: (1) stent migration increases over fivefold when incorporating longitudinal muscle movement versus isolated circumferential; (2) using a viscous non-Newtonian bolus improves high-resolution manometry diagnostic sensitivity of Achalasia III through increasing the Distal Latency diagnostic metric by 20.83%; and (3) stirring Greek-style yoghurt (common non-Newtonian dietary recommendation) significantly improves bolus transit versus unstirred for Achalasia Types I-II patients. This establishes RoboGullet+ as a powerful translational tool, advancing our understanding of esophageal motility and its therapeutic interventions.
Publications
2026
INTRODUCTION: Concern for gastroesophageal reflux disease (GERD) is the most common reason to consult gastroenterology. We aimed to optimize routine GERD evaluation on cost-effectiveness according to the dominant typical symptom among patients with persistent symptoms failing empiric proton-pump inhibitors (PPI).
METHODS: We developed a decision analytic model evaluating all permutations of GERD diagnostics including empiric trials of PPI optimization or discontinuation, upper endoscopy, wireless pH-monitoring, and pH-impedance monitoring. The model was applied to patients with heartburn, regurgitation, and chest pain in general gastroenterology to identify the appropriate combination and order of testing from insurer and patient perspectives. Health outcomes were informed by systematic reviews of clinical trials. Cost outcomes were informed by Centers for Medicare and Medicaid Services and commercial datasets and national observational studies. The time horizon was 1 year, and willingness-to-pay threshold was $100,000/quality-adjusted life year gained.
RESULTS: For patients with typical persistent GERD symptoms failing empiric PPI, routine up-front ambulatory reflux testing saved $2,500-$4,500 compared with endoscopy alone when no erosive esophagitis is found. The most cost-effective initial ambulatory reflux test was 96-hour wireless pH-monitoring for patients with heartburn and chest pain and 24-hour pH-impedance monitoring for patients with regurgitation, both performed OFF-PPI. Adding ON-PPI pH-impedance monitoring optimized cost-effectiveness for patients with documented evidence of GERD and PPI-refractory symptoms. Patient and insurer perspectives aligned on these optimal diagnostic strategies.
DISCUSSION: Compared with a one-size-fits-all strategy, a tailored approach based on Lyon 2.0 optimizes cost-effective evaluation and management of GERD by phenotyping the appropriate diagnostics to dominant symptom.
BACKGROUND: Since gastroesophageal reflux disease (GERD) manifests typical and atypical symptoms of varying frequency and severity, the dominant symptom needs identification and quantification.
GOALS: We aimed to compare 5-point Likert scales assessing symptom burden to validated GERD questionnaires and outcomes following GERD management.
STUDY: We retrospectively analyzed pooled data from patients undergoing pH-impedance testing for reflux symptoms from 2 centers. Preprocedure questionnaires assessed symptom severity and frequency on 5-point Likert scales (0=not severe, infrequent; 4=extremely severe, multiple daily episodes); the product for the highest scoring symptom constituted the dominant symptom intensity (DSI). DSI was compared against validated instruments [global symptom severity (GSS), GERD questionnaire (GERDQ) and reflux symptom index (RSI)], and pH-impedance parameters per Lyon Consensus 2.0. DSI change after GERD management was compared against GSS and satisfaction with therapy.
RESULTS: Among 808 patients (mean age: 53.8±1.44 y, 65.2% female). DSI significantly correlated with GSS (R=0.682), GERDQ (R=0.414), RSI (R=0.577), acid exposure time (AET) (R=0.175), total reflux episodes (R=0.194) and mean nocturnal baseline impedance (R=-0.157) (P<0.0001 for each comparison). On ROC analyses, DSI (AUROC=0.60) was noninferior to GSS, GERDQ, and RSI in predicting pathologic AET and total reflux episodes, and conclusive GERD. Percentage DSI improvement after antireflux treatment significantly correlated with GSS change (R=0.632, P<0.0001) and treatment satisfaction (R=0.513, P<0.0001) and was an independent predictor of GSS change (β=0.302, P<0.0001), and satisfaction with therapy (β=0.833, P=0.011) on multivariable regression.
CONCLUSIONS: DSI correlates with validated reflux questionnaires and discriminates abnormal from normal reflux burden. DSI change reflects reflux treatment outcome and satisfaction.
BACKGROUND: Erosive esophagitis (EE) is commonly managed with proton pump inhibitors (PPIs), yet many patients experience incomplete healing or recurrence. Potassium-competitive acid blockers (P-CABs) have emerged as potential alternatives, but high-certainty comparative evidence across agents remains limited. We performed a network meta-analysis to evaluate the relative efficacy and safety of P-CABs versus PPIs and to assess the certainty of the evidence.
METHODS: We systematically searched PubMed, the Cochrane Library, and Web of Science from inception through March 1, 2025, for randomized controlled trials (RCTs) comparing P-CAB, PPI, and/or placebo for the treatment of EE. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Key outcomes were 8-week endoscopic healing and 24-week recurrence. Certainty of evidence was evaluated using GRADE. Risk difference (RD) estimates were calculated using random-effects models. The study protocol was registered with PROSPERO (CRD420251116179).
FINDINGS: Thirty-nine RCTs were included; all evaluated once-daily dosing. At 8 weeks, zastaprazan 20 mg, vonoprazan 20 mg, and esomeprazole 40 mg demonstrated moderate-certainty superiority over rabeprazole 20 mg and omeprazole 20 mg with RDs ranging from 0.05 to 0.11, while only vonoprazan 20 mg demonstrated moderate-certainty benefit versus lansoprazole 30 mg (RD: 0.04). In Los Angeles (LA) grade C/D EE, vonoprazan 20 mg, esomeprazole 40 mg, and rabeprazole-ER 50 mg demonstrated moderate-to-high-certainty benefit over lansoprazole 30 mg and omeprazole 20 mg with RDs ranging from 0.05 to 0.15. Vonoprazan 20 mg and rabeprazole-ER 50 mg demonstrated moderate-certainty benefit compared with pantoprazole 40 mg (RDs: 0.12 and 0.09, respectively).At 24 weeks, vonoprazan 10 mg and 20 mg showed moderate-to-high-certainty benefit versus lansoprazole 15 mg (RDs: -0.11 and -0.13, respectively), while in direct comparisons, esomeprazole 20 mg outperformed lansoprazole 15 mg and pantoprazole 20 mg, with approximately 40-50% relative reductions in recurrence. In LA grade C/D EE, vonoprazan 10 mg and 20 mg demonstrated moderate-to-high-certainty superiority over lansoprazole 15 mg and pantoprazole 20 mg with RDs ranging from -0.12 to -0.20. Esomeprazole 20 mg showed a high-certainty benefit compared with pantoprazole 20 mg (RD: -0.16). At 8 and 24 weeks, safety profiles were generally comparable between P-CABs and PPIs.
INTERPRETATION: Among once-daily regimens, vonoprazan 20 mg, zastaprazan 20 mg, and esomeprazole 40 mg were most effective for healing EE, while vonoprazan 10 mg and 20 mg and esomeprazole 20 mg were most effective in preventing recurrence. Benefits were most pronounced in LA grade C/D EE and are supported by moderate to high-certainty evidence. Comparative trials evaluating newer P-CABs against optimized PPI strategies, including twice-daily dosing, are needed to evaluate efficacy and long-term safety, particularly with respect to hypergastrinemia and infection risk.
FUNDING: None was received for the study.
BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a complex, technically demanding endoscopic procedure that requires focused, structured training. While increasingly adopted in both gastroenterology and surgical practice, there has been no consensus-based guidance to establish adequate training standards in POEM. Using a validated consensus methodology, we aimed to define minimum standards for POEM training programs to ensure competence in technical, cognitive, and integrative skills necessary for safe and effective practice.
METHODS: A multidisciplinary expert panel was convened by the American Society for Gastrointestinal Endoscopy. The Research and Development (RAND)/University of California, Los Angeles appropriateness method (RAM) was used to evaluate candidate statements across 5 domains: pretraining activities, structure of training programs, POEM-specific cognitive training, POEM-specific technical training, and assessment of competence. Experts participated in 2 rounds of voting, rating each statement on a 9-point scale from highly inappropriate (1) to highly appropriate (9). For each statement, the median score and mean absolute deviation from the median were calculated. A statement was considered appropriate if it received a median score ≥7 and met the criteria for appropriateness based on the BIOMED, Interpercentile Range Adjusted for Symmetry, and P value methods.
RESULTS: Of the 40 proposed statements, 34 met the criteria as appropriate. Key recommendations included that trainees should undergo POEM training within programs performing at least 40 procedures annually, be mentored by at least 1 trainer with ≥100 prior POEMs, and complete a minimum of 15 POEMs before undergoing milestone assessments with a validated assessment tool. Cognitive requirements included mastery of mediastinal anatomy, GERD management, electrosurgical tools, and interpretation of motility and imaging studies. Simulation model training and exposure to esophageal POEM, gastric POEM, and Zenker POEM were also recommended.
CONCLUSIONS: This consensus effort provides evidence-based minimum standards for POEM training, applicable to both GI and surgical trainees. These recommendations are intended to guide the structure of training programs, ensure safe dissemination of POEM, and support the evolution of competency-based education in third-space endoscopy.
BACKGROUND: Patients with gastroesophageal reflux disease (GERD) are commonly instructed to reduce coffee intake. However, prior studies evaluating the effects of coffee on GERD yielded conflicting results. We aimed to perform a comprehensive systematic review and meta-analysis to assess the association between coffee use and risk of GERD and its complications.
METHODS: A protocolized search strategy was developed for PubMed, EMBASE, and Web of Science databases in accordance with PRISMA and MOOSE guidelines. Measured outcomes for GERD were compared between coffee drinkers and non-drinkers. Dichotomous events between unmatched groups were used to calculate pooled proportions with rates estimated using random effects models and effect size. Heterogeneity was assessed with I2 statistics and publication bias by funnel plot asymmetry and Egger regression.
RESULTS: A total of 40 studies encompassing 122,074 patients were included (85,400 coffee drinkers vs 36,674 non-drinkers). GERD was more common among coffee users than non-users [34.9% (CI:28.5-41.8) vs 30.7% (CI:25.2-36.7); OR:1.18 (CI:1.03-1.36; I2=89.38)]. There was no significant association between coffee intake and Barrett's esophagus [22.1% (CI:12.8-35.4) users vs 17.6% (CI:5.5-43.8) non-users; OR:1.13 (CI:0.79-1.61; I2=55.5)]. There was no evidence of publication bias based on funnel plot and Egger regression testing (p>0.05 for all analyses).
CONCLUSION: Coffee use was associated with a small, statistically significant increased rate of GERD, but not Barrett's. The magnitude of this effect, however, is of unclear clinical significance. The role of routine avoidance/reduction of coffee intake as universal lifestyle modification for GERD needs further evaluation.
BACKGROUND: The value of esophageal baseline impedance (BI) in assessing proximal reflux and laryngopharyngeal symptoms (LPS) is unclear.
METHODS: 208 patients with LPS underwent 24-hour combined hypopharyngeal-esophageal impedance-pH monitoring. Proximal/distal BI were obtained and a slope-and-intercept model of proximal BI contour was constructed.
RESULTS: Proximal BI correlated with proximal/pharyngeal reflux (r=-0.21, p<0.01) and reflux symptom index (r=-0.14, p=0.08). Proximal BI contour model incorporating both BI change (slope) and BI just below upper esophageal sphincter (intercept) outperformed models using individual BI measures in predicting proximal (AIC: 110 vs 251-253) or pharyngeal (AIC: 32 vs 141-148) reflux.
CONCLUSION: Proximal esophageal impedance contour predicts proximal reflux n patients with LPS.
BACKGROUND & AIMS: The impact of the esophageal eosinophilic distribution pattern on treatment outcomes in eosinophilic esophagitis (EoE) is unclear. We aimed to determine if the eosinophil distribution at index endoscopy predicts proton pump inhibitor (PPI) response in EoE.
METHODS: This was a cohort study of newly diagnosed adult patients with EoE from 3 hospitals. All included patients received ≥8-week PPI trial and underwent repeat biopsies to assess response. Primary analyses compared PPI response between isolated distal disease (≥15 eosinophils/hpf on distal but not proximal biopsies) and proximal/diffuse eosinophilia (≥15 eosinophils/hpf on proximal ± distal biopsies). Secondary analyses categorized patients as distal-predominant (distal >proximal eosinophils by ≥10/hpf), proximal predominant (proximal >distal eosinophils by ≥10/hpf), or even distribution pattern. Multivariable analyses were performed using logistic regression, adjusting for potential confounders.
RESULTS: A total of 266 patients (50.8% male; 89.1% White) met inclusion criteria, including 66 with isolated distal and 200 with proximal/diffuse disease. PPI response was higher among patients with isolated distal disease (histologic remission [<15 eosinophils/hpf post-PPI]: 63.6% vs 44.5%; P = .01; deep remission [<6 eosinophils/hpf]: 54.5% vs 31.0%; P = .001; symptom improvement: 92.4% vs 81.0%; P = .03). On multivariable analyses, isolated distal disease remained independently associated with histologic response (adjusted odds ratio [aOR], 2.04; 95% confidence interval [CI], 1.10-3.77; P = .02), deep remission (aOR, 2.46; 95% CI, 1.33-4.54; P = .02), and symptom improvement (aOR, 4.1; 95% CI, 1.4-12.01; P = .01). On secondary analyses, proximal-predominant eosinophilia independently predicted PPI histologic nonresponse compared with distal-predominant (aOR, 0.52; 95% CI, 0.28-0.99; P = .04) or any nonproximal (aOR, 0.54; 95% CI, 0.3-0.97; P = .04) pattern.
CONCLUSIONS: Isolated distal eosinophilia at index endoscopy independently predicted PPI response in patients with EoE, whereas proximal-predominant pattern predicted nonresponse. Patterns of esophageal eosinophilic distribution may reflect different disease phenotypes and help guide management.
INTRODUCTION: The term laryngopharyngeal reflux (LPR) is frequently applied to aerodigestive symptoms despite lack of objective reflux evidence. The aim of this initiative was to develop a modern care paradigm for LPR supported by otolaryngology and gastroenterology disciplines.
METHODS: A 28-member international interdisciplinary working group developed practical statements within the following domains: definition/terminology, initial diagnostic evaluation, reflux monitoring, therapeutic trials, behavioral factors and therapy, and risk stratification. Literature reviews guided statement development and were presented at virtual/in-person meetings. Each statement underwent 2 or more rounds of voting per the RAND Appropriateness Method; statements reaching appropriateness with ≥80% agreement are included as recommendations.
RESULTS: The term laryngopharyngeal symptoms (LPS) applies to aerodigestive symptoms with potential to be induced by reflux and include cough, voice change, throat clearing, excess throat phlegm, and throat pain. Laryngopharyngeal reflux disease (LPRD) refers to patients with LPS and objective evidence of reflux. Importantly, the presence of LPS does not equate to LPRD. Laryngoscopy has value in assessing for nonreflux laryngopharyngeal processes, but laryngoscopic findings alone cannot diagnose LPRD. LPS patients should be categorized as with or without concurrent esophageal reflux symptoms. While lifestyle modification and empiric trials of acid suppression ± alginates are appropriate when esophageal reflux symptoms coexist, upper endoscopy and ambulatory reflux monitoring are required for LPRD diagnosis when symptoms persist, when LPS is isolated, or when management needs to be escalated to include invasive antireflux management. The two recommended ambulatory reflux monitoring modalities, 24-hour pH-impedance and 96-hour wireless pH monitoring, are not mutually exclusive with distinct roles for the evaluation of LPS. Laryngeal hyperresponsiveness and hypervigilance commonly contribute to both LPS and LPRD presentations and are responsive to laryngeal recalibration therapy and neuromodulators.
DISCUSSION: The San Diego Consensus represents the formal modern-day interdisciplinary care paradigm to evaluate and manage LPS and LPRD.