Fass, Ronnie

ABSTRACT Recent advances in the diagnosis and management of reflux disease were the central focus of the inaugural Gatherings in Esophagology (GiE), which convened experts across gastroenterology, surgery, otolaryngology, pulmonology, and basic research. The sessions highlighted innovations in reflux monitoring—including high‐resolution manometry, wireless pH monitoring, and novel salivary biomarkers—while critically evaluating their diagnostic accuracy and clinical utility. Presentations explored the limitations of traditional proton‐pump inhibitor therapy, the emergence of potassium‐competitive acid blockers as a new class of acid suppressants, and the evolving role of adjunctive treatments such as mucosal protectants, reflux reducers, and neuromodulators for refractory symptoms. The discourse extended to advanced interventional procedures, including transoral incisionless fundoplication, magnetic sphincter augmentation, and the RefluxStop device, with discussion of patient selection, efficacy, and complication management. Discussants emphasized the pathophysiology and management of extraesophageal manifestations of reflux, the interplay between reflux and pulmonary disease, and the diagnostic challenges in pediatric populations. The meeting also addressed the integration of behavioral therapies, the role of the microbiome, and the application of artificial intelligence in reflux diagnostics. Collectively, these insights underscore a shift toward precision medicine in reflux disease, emphasizing individualized diagnostic strategies and tailored therapeutic approaches to improve patient outcomes.

AbstractBackground and AimHealing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60–70%). Vonoprazan, a potassium‐competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta‐analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D.MethodsWe searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed‐effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location.ResultsFour randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169–1.433], Week 4 1.160 [1.059–1.270], and Week 8 1.175 [95% CI 1.107–1.247]), but was similar for mild EE at all weeks (P‐interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P‐interaction < 0.01). Any, serious, and drug‐related treatment‐emergent adverse events were comparable between groups.ConclusionVonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

AbstractBackground and AimUp to 40% of gastroesophageal reflux disease (GERD) patients experience inadequate symptom relief with a proton pump inhibitor (PPI), termed PPI‐resistant or refractory GERD. Vonoprazan, a potassium‐competitive acid blocker, has better efficacy than PPI in suppressing gastric acid secretion. This meta‐analysis summarizes the efficacy and safety of vonoprazan for treating PPI‐resistant GERD (both erosive esophagitis [EE] and non‐erosive reflux disease [NERD]).MethodsFour electronic databases (Medline, Embase, SCOPUS, and CENTRAL) were searched for studies indexed until August 1, 2023. Both observational studies and clinical trials assessing the efficacy and safety of vonoprazan in PPI‐resistant GERD were included. Efficacy outcomes included healing and maintenance rates of EE and improvement of the Frequency Scale for Symptoms of GERD (FSSG) scores. Serious adverse events (SAEs) were considered a safety outcome. The modified Newcastle‐Ottawa Scale (NOS) was used to assess study quality.ResultsTwelve studies were included in this meta‐analysis. Healing rates of PPI‐resistant EE with vonoprazan 20 mg were 91.7% (95% CI 86.8–94.8%) and 88.5% (95% CI 69.7–96.2%) at weeks 4 and 8, respectively. For healed PPI‐resistant EE, the overall maintenance rates with vonoprazan 10 mg were 82.6% (95% 61.2–95.0%) at week 8, 86.0% (95% CI 72.1–94.7%) at week 24, and 93.8% (95% CI 69.8–99.8%) at week 48. FSSG scores were improved in 74.6% (95% CI 65.8–81.7%) and 51.9% (95% CI 37.8–65.7%) of patients at weeks 4 and 8. Overall, no SAE was reported.ConclusionVonoprazan demonstrated high efficacy in the healing and maintenance of PPI‐resistant EE and moderate efficacy for the improvement of FSSG score. Vonoprazan was well tolerated in PPI‐resistant GERD patients.

AbstractBackgroundQuestion prompt lists (QPLs) are structured sets of disease‐specific questions, intended to encourage question‐asking by patients and enhance patient‐physician communication. To date, a dysphagia‐specific QPL has not been developed for patients with esophageal dysphagia symptoms. We aim to develop a dysphagia‐specific QPL incorporating both esophageal expert and patient perspectives, applying rigorous methodology.MethodsThe QPL content was generated applying a two‐round modified Delphi (RAND/UCLA) method among 11 experts. In round one, experts provided five answers to the prompts: “What general questions should patients ask when being seen for dysphagia?” and “What questions do I not hear patients asking but, given my experience, I believe they should be asking?” In round two, experts rated proposed questions on a 5‐point Likert scale. Responses rated as “essential” or “important”, determined by an a priori median threshold of ≥4.0, were accepted for inclusion. Subsequently, 20 patients from Stanford Health Care were enrolled to modify the preliminary QPL, to incorporate their perspectives and opinions. Patients independently rated questions applying the same 5‐point Likert scale. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open‐endedly asking “Are there questions we didn't ask, that you think we should?”Key ResultsEleven experts participated in both voting rounds. Of 85 questions generated from round one, 60 (70.6%) were accepted for inclusion, meeting a median value of ≥4.0. Questions were combined to reduce redundancy, narrowing down to 44 questions. Questions were categorized into the following six themes: 1. “What is causing my dysphagia?”; 2. “Associated symptoms”; 3. “Testing for dysphagia”; 4. “Lifestyle modifications”; 5. “Treatment for dysphagia”; and 6. “Prognosis”. The largest number of questions covered “What is causing my dysphagia” (27.3%). Twenty patients participated and modified the QPL. Of the 44 questions experts agreed were important, only 30 questions (68.2%) were accepted for inclusion. Six patients proposed 10 additional questions and after incorporating the suggested questions, the final dysphagia‐specific QPL created by esophageal experts and modified by patients consisted of 40 questions.Conclusions & InferencesIncorporating expert and patient perspectives, we developed a dysphagia‐specific QPL to enhance patient‐physician communication. Our study highlights importance of incorporating patient perspective when developing such a communication tool. Further studies will measure the impact of this communication tool on patient engagement.

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.

AbstractBackgroundThe 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.MethodsEight 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 Pearson's correlation coefficient (PCC). Percentage agreement evaluated inter‐ and intra‐rater reliability for RACs.Key ResultsNovice 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 InferencesNormative 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.

Summary 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) <4.0% on all days of monitoring with negative reflux‐symptom association excludes GERD and does not support ongoing PPI treatment. Conversely, 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 <40 reflux events, AET <2.0% and a negative reflux‐symptom association does not support escalation of anti‐reflux treatment. In contrast, AET > 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.

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions that enhance patient-physician communication by encouraging patients to ask questions during consultations. Aim: The aim of this study was to develop a preliminary achalasia-specific QPL created by esophageal experts. Methods: The QPL content was derived through a modified Delphi method consisting of 2 rounds. In round 1, experts provided 5 answers to the prompts “What general questions should patients ask when given a new diagnosis of achalasia” and “What questions do I not hear patients asking, but given my expertise, I believe they should be asking?” In round 2, experts rated questions on a 5-point Likert scale. Questions considered “essential” or “important” were accepted into the QPL. Feedback regarding the QPL was obtained in a pilot study wherein patients received the QPL before their consultation and completed surveys afterwards. Results: Nineteen esophageal experts participated in both rounds. Of 148 questions from round 1, 124 (83.8%) were accepted into the QPL. These were further reduced to 56 questions to minimize redundancy. Questions were categorized into 6 themes: “What is achalasia,” “Risks with achalasia,” “Symptom management in achalasia,” “Treatment of achalasia,” “Risk of reflux after treatment,” and “Follow-up after treatment.” Nineteen patients participated in the pilot, most of whom agreed that the QPL was helpful (84.2%) and recommended its wider use (84.2%). Conclusions: This is the first QPL developed specifically for adults with achalasia. Although well-received in a small pilot, follow-up studies will incorporate additional patient feedback to further refine the QPL content and assess its usability, acceptability, and feasibility.

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, enhancing the patient-physician communication by encouraging patients to ask relevant questions during a consultation. Recently, a preliminary 78 question gastroesophageal reflux disease (GERD) specific QPL was created by 12 esophageal experts through a modified Delphi (RAND/University of California, Los Angeles) technique. Patients’ perspectives and opinions on each question, however, had not been accounted for in the preliminary expert’ version. Aim: The aim was to modify a preliminary experts’ QPL, specific to adults with GERD, following patient perspectives and opinions. Methods: A preliminary GERD QPL was modified through patient input and opinions. Thirty-eight patients with a clinical diagnosis of GERD followed at Stanford University Esophageal Clinic between January and November 2019 were consented to modify the preliminary 78 question expert QPL version. After receiving the QPL in Qualtrics (Provo, UT) by a direct e-mail invitation, patients independently rated questions on a 5-point Likert scale, where 1=“should not be included,” 2=“unimportant,” 3=“don’t know/depends,” 4=“important,” and 5=“essential.” Questions were accepted for inclusion in the QPL with an a priori interagreement of 80% ranking in the range of 4 to 5. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking “Are there questions we didn’t ask, that you think we should?” Results: Twenty-three patients with GERD (19 female, median age 64) fully participated and modified the existing QPL (60.5%). Of the 78 questions from the preliminary GERD QPL, 66 questions (84.6%) were accepted for inclusion. The question with the highest agreement among patients rating a question as essential consisted of “what habits, food, and drinks do I have to avoid?” (82.6%). Questions eliminated because of disagreement included “What is the natural history of GERD,” “Do I have a high chance to die from my Barrett’s?,” and “Why are you prescribing an antidepressant to treat my GERD?” Nine patients suggested additional questions totaling to 16 separate questions, including “What type of surgeries are there to help GERD?,” “What stage is my GERD?,” “What are the odds/percentage of getting cancer from GERD?” Incorporating the suggested questions, the final GERD QPL—created by esophageal experts and modified by patients—consisted of 82 questions. Conclusion: Esophageal experts and GERD patients have a high level of agreement on important questions, though there is some variation in perspective. Future studies can simplify this list and measure the impact of a shared GERD QPL on patients’ decisional conflict and perceived involvement in care.