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Introduction: Guidelines advise esophageal motility testing for dysphagia when structural disorders are ruled out, but cost concerns impede adoption. We evaluated cost-effective positioning of esophageal motility testing in the algorithm to evaluate esophageal dysphagia., Methods: We developed a decision analytic model comparing 3 strategies: (i) esophageal manometry, (ii) screening impedance planimetry followed by esophageal manometry if needed, or (iii) nonalgorithmic usual care. Diagnostic test accuracy was adapted to expected rates of esophageal motility disorders in general gastroenterology populations. We modeled routine testing for all patients with nonstructural/mechanical dysphagia compared with selective testing with strong suspicion for achalasia. Cost outcomes were defined on national commercial and Medicare datasets stratified on age and sex. Health outcomes were modeled on populations with achalasia. The time horizon was 1 year., Results: Motility testing was preferred over nonalgorithmic usual care due to cost savings rather than health gains. To commercial insurers, routine esophageal manometry for nonstructural/mechanical dysphagia would be cost-saving below a reimbursed cost of $2,415. Screening impedance planimetry would be cost saving below a reimbursed cost of $1,130. The limit for reimbursed costs would be lower for patients older than 65 years to achieve cost savings mainly due to insurance. Sex did not significantly influence cost-effectiveness. Patients and insurers preferred routine screening impedance planimetry before manometry when the index of suspicion for achalasia was below 6%., Discussion: Aligning with practice guidelines, routine esophageal motility testing seems cost saving to patients and insurers compared with nonalgorithmic usual care to evaluate nonstructural/mechanical dysphagia. Choice of testing should be guided by index of suspicion., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Despite deprescribing initiatives to curb overutilization of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge., Summary: An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction., Key Messages: Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. When commencing a PPI, patients should understand the reason for treatment, planned duration, and review date. PPI use at hospital discharge should not be continued without a recognized indication for long-term treatment. Long-term PPI therapy should be reviewed at least annually. PPI use-reduction should be based on the lack of a rational indication for long-term PPI use, not concern for PPI-associated adverse events. PPI use-reduction strategies involving switching to on-demand PPI or dose tapering, with rescue therapy for rebound symptoms, are more likely to succeed than abrupt cessation., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Patients with reflux-like symptoms (heartburn and regurgitation) are often not well advised on implementing individualised strategies to help control their symptoms using dietary changes, lifestyle modifications, behavioural changes or fast-acting rescue therapies. One reason for this may be the lack of emphasis in management guidelines owing to 'low-quality' evidence and a paucity of interventional studies. Thus, a panel of 11 gastroenterologists and primary care doctors used the Delphi method to develop consolidated advice for patients based on expert consensus. A steering committee selected topics for literature searches using the PubMed database, and a modified Delphi process including two online meetings and two rounds of voting was conducted to generate consensus statements based on prespecified criteria (67% voting 'strongly agree' or 'agree with minor reservation'). After expert discussion and two rounds of voting, 21 consensus statements were generated, and assigned strength of evidence and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) rating. Eleven statements achieved the strongest (100%) agreement: five are related to diet and include identification and avoidance of dietary triggers, limiting alcohol, coffee and carbonated beverages, and advising patients troubled by postprandial symptoms not to overeat; the remaining six statements concern advice around smoking cessation, weight loss, raising the head-of-the-bed, avoiding recumbency after meals, stress reduction and alginate use. The aim of developing the consensus statements is that they may serve as a foundation for tools and advice that can routinely help patients with reflux-like symptoms better understand the causes of their symptoms and manage their individual risk factors and triggers., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Myotomy 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., Methods: This 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 Results: Twenty-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 & Inferences: Length 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., (© 2023 John Wiley & Sons Ltd.)

Introduction: Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE., Methods: We identified adults in the USA with an EE diagnosis between January  1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs., Results: Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs., Conclusions: Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use., (© 2023. The Author(s).)

Background: Non-erosive reflux disease (NERD) symptoms are often episodic, making on-demand treatment an attractive treatment approach., Aims: We compared the efficacy and safety of on-demand vonoprazan versus placebo in patients with NERD., Methods: Patients with NERD, defined as heartburn for ≥6 months and for ≥4/7 consecutive days with normal endoscopy, received once-daily vonoprazan 20 mg during a 4-week run-in period. Patients without heartburn during the last 7 days and with ≥80% study drug and diary compliance were randomised 1:1:1:1 to vonoprazan 10, 20, 40 mg or placebo on-demand for 6 weeks. The primary endpoint was the percentage of evaluable heartburn episodes completely relieved within 3 h of on-demand dosing and sustained for 24 h., Results: Of 458 patients in the run-in period, 207 entered the on-demand period. In the vonoprazan 10 mg group, 56.0% (201/359) of evaluable heartburn episodes met the criteria for complete and sustained relief; 60.6% (198/327) in the 20 mg group; and 70.0% (226/323) in the 40 mg group, compared with 27.3% (101/370) in the placebo group (p < 0.0001 versus placebo for each vonoprazan group). By 1 h post-dose, vonoprazan was associated with complete relief of significantly more heartburn episodes compared with placebo. No serious treatment-emergent adverse events were reported., Conclusion: On-demand vonoprazan may be a potential alternative to continued daily acid suppression therapy for the relief of episodic heartburn in patients with NERD., Clinicaltrials: gov: NCT04799158., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background & Aims: Gaps 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., Methods: We 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., Results: The 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., Conclusions: We developed and validated 2 highly accurate coding algorithms for EoE and established a nationwide VHA cohort of adults with EoE for future studies., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Upon completion of this activity, participants will:Have increased knowledge regarding the Mechanistic differences between proton pump inhibitors (PPIs) and potassium-competitive acid blockers (PCABs) Evidence comparing PPIs with PCABs for the treatment of GERD and EE Have greater competence related to Selecting evidence-based treatments for EE.

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 mm 2 /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 < 0.001). Physiologic success was noted in 43 (91.5%) patients (mean EGJ-DI 6.1 mm 2 /mmHg ± 2.5). Among 4 patients not meeting criteria for physiologic success, EGJ-DI was 2.5-2.6. There was no correlation between post-POEM EGJ-DI and ES in the short term or long term. Significant reflux esophagitis was seen in 6 (12.8%) patients with no difference in mean EGJ-DI with vs without esophagitis (5.9 vs 6.1, p = 0.44)., Conclusion: Post-POEM endoscopy with FLIP is useful to both assess EGJ physiology and to examine for reflux esophagitis. Short interval FLIP has limited utility to predict long-term patient outcomes or risk of acid reflux., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Panesophageal pressurization (PEP) defines type II achalasia on high-resolution-manometry (HRM) but some patients exhibit spasm after treatment. The Chicago Classification (CC) v4.0 proposed high PEP values as predictor of embedded spasm, yet supportive evidence is lacking., Methods: Fifty seven type II achalasia patients (47 ± 18 years, 54% males) with HRM and LIP Panometry before and after treatment were retrospectively identified. Baseline HRM and FLIP studies were analyzed to identify factors associated with post-treatment spasm, defined on HRM per CC v4.0., Results: Seven patients (12%) had spasm following treatment (peroral endoscopic myotomy 47%; pneumatic dilation [PD] 37%; laparoscopic Heller myotomy 16%). At baseline, greater median maximum PEP pressure (MaxPEP) values on HRM (77 vs 55 mmHg, p = 0.045) and spastic-reactive contractile response pattern on FLIP (43% vs 8%, p = 0.033) were more common in patients with post-treatment spasm while absent contractile response on FLIP was more common in patients without spasm (14% vs 66%, p = 0.014). The strongest predictor of post-treatment spasm was the percentage of swallows with MaxPEP ≥70 mmHg (best cut-off: ≥30%), with AUROC of 0.78. A combination of MaxPEP <70 mmHg and FLIP 60 mL pressure < 40 mmHg identified patients with lower rates of post-treatment spasm (3% overall, 0% post-PD) compared to those with values above these thresholds (33% overall, 83% post-PD)., Conclusions: High maximum PEP values, high FLIP 60 mL pressures and contractile response pattern on FLIP Panometry prior to treatment identified type II achalasia patients more likely to exhibit post-treatment spasm. Evaluating these features may guide personalized patient management., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Purpose of Review: While 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 Findings: In 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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2022 by The American College of Gastroenterology.)

Background & Aims: Achalasia 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., Methods: We 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., Results: Three 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., Conclusions: Using 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., (Copyright © 2023. Published by Elsevier Inc.)

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 Pearson's 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 mm 2 /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., (© 2022 John Wiley & Sons Ltd.)

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., (© 2023. The Author(s).)

Aims: The study objectives were to 1) characterize the cost drivers of patients with Helicobacter pylori (HP) and 2) estimate HP-related cost savings following lab-confirmed HP eradication with US guideline-recommended treatment compared to failed eradication., Methods: We identified adults newly diagnosed with HP between 1/1/2016-12/31/2019 in the Veradigm Electronic Health Record Database linked to claims data (earliest HP diagnosis = index date). For the overall costs analysis, we required patients to have data available for ≥12 months before and after the index date. Then, we used multivariable modeling to assess the marginal effects of comorbidities on all cause-healthcare costs in the 12 months following HP diagnosis. For the eradication savings analysis, we identified patients with ≥1 HP eradication regimen, a subsequent HP lab test result, and ≥1 year of data after the test result. Then we used multivariable modeling to estimate HP-related cost while adjusting for eradication status, demographics, post-testing HP-related clinical variables, and the interactions between eradication status and each HP-related clinical variable., Results: The overall cost analysis included 60,593 patients with HP (mean age 54.2 years, 65.5% female). Mean (SD) 12-month unadjusted all-cause costs were $23,693 ($78,089). Rare comorbidities demonstrated the highest marginal effect. The marginal effects of gastric cancer and PUD were $15,705 and $7,323, respectively. In the eradication savings analysis, 1,835 (80.0%) of the 2295 patients had lab test-confirmed HP eradication. Compared to failed eradication, there were significant one-year cost savings among patients with successful HP eradication and select conditions: $1,770 for PUD, $518 for atrophic gastritis, $494 for functional dyspepsia, and $352 for gastritis., Conclusions: The healthcare costs of patients with HP are partially confounded by their burden of high-cost comorbidities. In the subset of patients with available results, confirmed vs. failed eradication of HP was associated with short-term cost offsets among those with specific to HP-related sequelae.

Background: Type 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., Methods: This 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 Results: Of 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 (2.2mm 2 /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 Inferences: We 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., (© 2022 John Wiley & Sons Ltd.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Erosive esophagitis (EE) occurs when refluxate from the stomach causes T-lymphocyte infiltration of the esophageal mucosa, resulting in mucosal breaks. Currently, therapy with proton-pump inhibitors (PPIs) is the standard treatment for EE in the United States, but few comprehensive reviews exist on the efficacy of PPIs in US populations. Here, we present the most contemporary, thorough analysis of PPI efficacy rates, and identify and characterize patient subgroups at risk for poor healing outcomes., Areas Covered: We searched the literature to identify studies reporting rates of endoscopic healing and maintained healing of EE with PPI therapies in the US and found a paucity of recent evidence and real-world evidence. Twenty-two studies from 2009 and earlier were included in the final dataset., Expert Opinion: Rates of EE healing with PPIs were highest after 8 weeks of treatment, with over 80% of patients in most treatment arms demonstrating endoscopic healing, compared to lower efficacy (<80%) at 4 weeks. Rates of maintained healing with PPIs at 6 and 12 months were mostly lower than 80%, although the data were limited. Symptomatic patients and those with severe EE were less likely to achieve healing. Obese patients experienced similar healing rates as non-obese patients.

Introduction: Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response., Methods: This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks., Results: Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01)., Discussion: This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy., (Copyright © 2022 by The American College of Gastroenterology.)

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., (© 2022 John Wiley & Sons Ltd.)

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.

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 <3 cm. Length of myotomy for type 3 achalasia has been tailored to treat the entire length of spastic muscle segment, and the modality to gauge the optimal thickness and length of myotomy in this group has yet to be established. In addition to changes in POEM technique, the postoperative management of POEM has also changed, favoring reduced postprocedure imaging, antibiotic use, and hospitalizations., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 by The American College of Gastroenterology.)

Saliva is a complex physiologic fluid that contains an abundance of biological analytes, or biomarkers. Recent research has shown that these biomarkers may be able to convey the physiologic health of a person. Work has been done linking derangements in these salivary biomarkers to a wide variety of pathologic disorders ranging from oncologic diseases to atopic conditions. The specific area of interest for this review paper is esophageal disorders. Particularly because the diagnosis and management of esophageal disorders often includes invasive testing such as esophagogastroduodenoscopy, prolonged pH monitoring, and biopsy. The aim of this review will be to explore salivary biomarkers (pepsin, bile, epidermal growth factor, and micro-RNA) that are being studied as they relate specifically to esophageal disorders. Finally, it will explore the benefits of salivary testing and identify areas of possible future research., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The 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)., Methods: This 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., Results: Thirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m 2 (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 < 0.01). Compared to non-responders, responders to Device + PPI had a significantly lower BMI (p = 0.02) and higher salivary pepsin concentration (p = 0.01)., Conclusion: This clinical trial highlights the potential efficacy of the external UES compression device (Reflux Band) as an adjunct to PPI for patients with LPR (ClinicalTrials.Gov NCT03619811)., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 (Krippendorf's alpha <0.30), indicating low to no agreement between providers., Conclusion: In this multi-center survey study, GI fellows had the lowest accuracy and confidence in assessing EGD images after Nissen fundoplication, whereas esophagologists had the highest. Diagnostic confidence varied considerably and inter-rater agreement was poor. These findings suggest experience may improve confidence, but highlight the need to improve the evaluation of fundoplication wraps., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (© 2021 New York Academy of Sciences.)

Background & Aims: Heterogeneous 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., Methods: A 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/m 2 ). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups., Results: DAPC 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/m 2 ; 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., Conclusions: DAPC 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., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)