Effects of Cholecystokinin on Esophageal Motor Response to Distension in Asymptomatic Volunteers.

Background/Aims: Cholecystokinin (CCK) administration has been shown to reduce lower esophageal sphincter (LES) pressure in normal subjects in manometric studies. Functional luminal imaging probe (FLIP) panometry offers a method to assess esophageal motility in response to sustained distension though mechanisms related to this response remain unexplored. The aim of this study is to evaluate the effect of CCK-8 on the esophageal response to distension in asymptomatic volunteers using FLIP. Methods: Esophageal response to distension was studied in 7 asymptomatic volunteers (mean age ± SD [27 ± 2]; 86% female) before and after CCK-8 administration in a crossover study design. During sedated endoscopy, FLIP was performed twice with CCK-8 administered via intravenous push in one of 2 protocols: during filling (n = 4) or during emptying (n = 3). Esophagogastric junction distensibility index (EGJ-DI) at 60 mL fill volume and esophageal body contractile response patterns were analyzed. Results: During the baseline FLIP study, all subjects had a contractile response with repetitive antegrade contractions both before and after CCK-8 administration. However, a sustained LES contraction or a sustained occluding contraction with esophageal shortening was observed in all subjects in the filling protocol, but in none during the emptying protocol. EGJ-DI was similar before and after CCK-8 during both filling (4.7 ± 1.9 mm2/mmHg vs 4.3 ± 1.8 mm2/mmHg) and emptying protocol (7.5 ± 1.4 mm2/mmHg vs 6.9 ± 0.6 mm2/mmHg). Conclusion: While EGJ-DI appeared unaffected by CCK-8 administration in asymptomatic volunteers, CCK induced spastic-reactive contractions of the LES during distention suggesting that exogenous CCK interferes with normal LES relaxation during secondary peristalsis.

Assessment of colonoscopy skill using machine learning to measure quality: Proof-of-concept and initial validation.

Background and study aims Low-quality colonoscopy increases cancer risk but measuring quality remains challenging. We developed an automated, interactive assessment of colonoscopy quality (AI-CQ) using machine learning (ML). Methods Based on quality guidelines, metrics selected for AI development included insertion time (IT), withdrawal time (WT), polyp detection rate (PDR), and polyps per colonoscopy (PPC). Two novel metrics were also developed: HQ-WT (time during withdrawal with clear image) and WT-PT (withdrawal time subtracting polypectomy time). The model was pre-trained using a self-supervised vision transformer on unlabeled colonoscopy images and then finetuned for multi-label classification on another mutually exclusive colonoscopy image dataset. A timeline of video predictions and metric calculations were presented to clinicians in addition to the raw video using a web-based application. The model was externally validated using 50 colonoscopies at a second hospital. Results The AI-CQ accuracy to identify cecal intubation was 88%. IT ( P = 0.99) and WT ( P = 0.99) were highly correlated between manual and AI-CQ measurements with a median difference of 1.5 seconds and 4.5 seconds, respectively. AI-CQ PDR did not significantly differ from manual PDR (47.6% versus 45.5%, P = 0.66). Retroflexion was correctly identified in 95.2% and number of right colon evaluations in 100% of colonoscopies. HQ-WT was 45.9% of, and significantly correlated with ( P = 0.85) WT time. Conclusions An interactive AI assessment of colonoscopy skill can automatically assess quality. We propose that this tool can be utilized to rapidly identify and train providers in need of remediation.

Esophageal epithelial Ikkß deletion promotes eosinophilic esophagitis in experimental allergy mouse model.

Background: Eosinophilic esophagitis (EoE) is a chronic T helper type 2 (Th2)-associated inflammatory disorder triggered by food allergens, resulting in esophageal dysfunction through edema, fibrosis, and tissue remodeling. The role of epithelial remodeling in EoE pathogenesis is critical but not fully understood. Objective: To investigate the role of epithelial IKKß/NFκB signaling in EoE pathogenesis using a mouse model with conditional Ikk ß knockout in esophageal epithelial cells ( Ikk ß EEC-KO ). Methods: EoE was induced in Ikkß EEC-KO mice through skin sensitization with MC903/Ovalbumin (OVA) followed by intraesophageal OVA challenge. Histological and transcriptional analyses were performed to assess EoE features. Single-cell RNA sequencing (scRNA-seq) was used to profile esophageal mucosal cell populations and gene expression changes. Results: Ikkß EEC-KO /EoE mice exhibited hallmark EoE features, including eosinophil infiltration, intraepithelial eosinophils, microabscesses, basal cell hyperplasia, and lamina propria remodeling. RNA-seq revealed significant alterations in IKKß/NFκB signaling pathways, with decreased expression of RELA and increased expression of IKKß negative regulators. scRNA- seq analyses identified disrupted epithelial differentiation and barrier integrity, alongside increased type 2 immune responses and peptidase activity. Conclusion: Our study demonstrates that loss of epithelial IKKß signaling exacerbates EoE pathogenesis, highlighting the critical role of this pathway in maintaining epithelial homeostasis and preventing allergic inflammation. The Ikkß EEC-KO /EoE mouse model closely mirrors human EoE, providing a valuable tool for investigating disease mechanisms and therapeutic targets. This model can facilitate the development of strategies to prevent chronic inflammation and tissue remodeling in EoE. Key Messages: Critical Role of Epithelial IKKß/NFκB Signaling: Loss of this signaling exacerbates EoE, causing eosinophil infiltration, basal cell hyperplasia, and tissue remodeling, highlighting its importance in esophageal health.Molecular Insights and Therapeutic Targets: scRNA-seq identified disrupted epithelial differentiation, barrier integrity, and enhanced type 2 immune responses, suggesting potential therapeutic targets for EoE. Relevance of the Ikkß EEC-KO /EoE Mouse Model: This model replicates human EoE features, making it a valuable tool for studying EoE mechanisms and testing treatments, which can drive the development of effective therapies. Capsule Summary: This study reveals the crucial role of epithelial IKKß/NFκB signaling in EoE, providing insights into disease mechanisms and potential therapeutic targets, highly relevant for advancing clinical management of EoE.

Enhancing Chicago Classification diagnoses with functional lumen imaging probe-mechanics (FLIP-MECH).

BACKGROUND: Esophageal motility disorders can be diagnosed by either high-resolution manometry (HRM) or the functional lumen imaging probe (FLIP) but there is no systematic approach to synergize the measurements of these modalities or to improve the diagnostic metrics that have been developed to analyze them. This work aimed to devise a formal approach to bridge the gap between diagnoses inferred from HRM and FLIP measurements using deep learning and mechanics. METHODS: The "mechanical health" of the esophagus was analyzed in 740 subjects including a spectrum of motility disorder patients and normal subjects. The mechanical health was quantified through a set of parameters including wall stiffness, active relaxation, and contraction pattern. These parameters were used by a variational autoencoder to generate a parameter space called virtual disease landscape (VDL). Finally, probabilities were assigned to each point (subject) on the VDL through linear discriminant analysis (LDA), which in turn was used to compare with FLIP and HRM diagnoses. RESULTS: Subjects clustered into different regions of the VDL with their location relative to each other (and normal) defined by the type and severity of dysfunction. The two major categories that separated best on the VDL were subjects with normal esophagogastric junction (EGJ) opening and those with EGJ obstruction. Both HRM and FLIP diagnoses correlated well within these two groups. CONCLUSION: Mechanics-based parameters effectively estimated esophageal health using FLIP measurements to position subjects in a 3-D VDL that segregated subjects in good alignment with motility diagnoses gleaned from HRM and FLIP studies.

Age Affects Esophageal Secondary Peristalsis More Than Primary as Assessed by FLIP Panometry and High-resolution Manometry.

Age-related changes in esophageal function involve increased rates of dysmotility with advancing age (sometimes described as presbyesophagus).1-4 Specifically, advanced age has been associated with increased lower esophageal sphincter (LES) pressure and decreased peristaltic vigor.1-4 However, the mechanisms underlying these changes, including the relative relationship of primary peristalsis and secondary peristalsis over the lifespan, remain incompletely understood. Current approaches assess primary peristalsis using high-resolution manometry (HRM), with esophageal motility disorders defined using the Chicago Classification version 4.0 (CCv4.0), and secondary peristalsis using functional lumen imaging probe (FLIP) panometry.5,6 Although HRM and FLIP panometry motility diagnoses are often analogous, they can sometimes differ. For example, abnormal secondary peristalsis can occur when primary peristalsis is normal, which has been associated with reflux and non-obstructive dysphagia.7,8 This study aimed to examine the effect of age on primary peristalsis and secondary peristalsis.

Peroral endoscopic myotomy for hypercontractile (Jackhammer) esophagus: A retrospective multicenter series with long-term follow-up.

INTRODUCTION: Long-term outcome data are limited for non-achalasia esophageal motility disorders treated by peroral endoscopy myotomy (POEM) as a separate group. We investigated a subset of symptomatic patients with hypercontractile esophagus (Jackhammer esophagus). METHODS: Forty two patients (mean age 60.9 years; 57% female, mean Eckardt score 6.2 ± 2.1) treated by primary peroral myotomy for symptomatic Jackhammer esophagus 2012-2018 in seven European centers were retrospectively analyzed; myotomy included the lower esophageal sphincter but did not extend more than 1 cm into the cardia in contrast to POEM for achalasia. Manometry data were re-reviewed by an independent expert. The main outcome was the failure rate defined by retreatment or an Eckardt score >3 after at least two years following POEM. RESULTS: Despite 100% technical success (mean intervention time 107 ± 48.9 min, mean myotomy length 16.2 ± 3.7 cm), the 2-year success rate was 64.3% in the entire group. In a subgroup analysis, POEM failure rates were significantly different between Jackhammer-patients without (n = 22), and with esophagogastric junction outflow obstruction (EGJOO, n = 20) (13.6% % vs. 60%, p = 0.003) at a follow-up of 46.5 ± 19.0 months. Adverse events occurred in nine cases (21.4%). 14 (33.3%) patients were retreated, two with surgical fundoplication due to reflux. Including retreatments, an improvement in symptom severity was found in 33 (78.6%) at the end of follow-up (Eckardt score ≤3, mean Eckardt change 4.34, p < 0.001). EGJOO (p = 0.01) and frequency of hypercontractile swallows (p = 0.02) were predictors of POEM failure. The development of a pseudodiverticulum was observed in four cases within the subgroup of EGJOO. CONCLUSIONS: Patients with symptomatic Jackhammer without EGJOO benefit from POEM in long-term follow-up. Treatment of Jackhammer with EGJOO, however, remains challenging and probably requires full sphincter myotomy and future studies which should address the pathogenesis of this variant and alternative strategies.

Discriminating "impaired" from "disordered" contractile response on FLIP panometry by utilizing pressure measurement.

BACKGROUND: Functional lumen imaging probe (FLIP) panometry evaluates esophageal motility, including the contractile response to distension, that is, secondary peristalsis. Impaired/disordered contractile response (IDCR) is an abnormal, but nonspecific contractile response that can represent either hypomotility or spastic motor disorders on high-resolution manometry (HRM). We hypothesized that FLIP pressure could be incorporated to clarify IDCR and aimed to determine its utility in a cohort of symptomatic esophageal motility patients. METHODS: 173 adult patients that had IDCR on FLIP panometry and HRM with a conclusive Chicago Classification v4.0 (CCv4.0) diagnosis were included and analyzed as development (n = 118) and validation (n = 55) cohorts. FLIP pressure values were assessed for prediction of either hypomotility or spasm, defined on HRM/CCv4.0. KEY RESULTS: HRM/CCv4.0 diagnoses were normal motility in 48 patients (28%), "hypomotility" (ineffective esophageal motility, absent contractility, or Type I or II achalasia) in 89 (51%), and "spasm" (Type III achalasia, distal esophageal spasm, or hypercontractile esophagus) in 36 (21%). The pressure at esophagogastric junction-distensibility index (DI) (60 mL) was lower in hypomotility (median [interquartile range] 34 [28-42] mmHg) than in spasm (49 [40-62] mmHg; p < 0.001) and had an area under the receiver operating characteristic curve of 0.80 (95% CI 0.73-0.88) for hypomotility and 0.76 (0.69-0.83) for spasm. For "spasm" on HRM, a threshold FLIP pressure of >35 mmHg provided 90% sensitivity (47% specificity) while >55 mmHg provided 93% specificity (40% sensitivity). CONCLUSION & INFERENCES: Pressure on FLIP panometry can help clarify the significance of IDCR, with low-pressure IDCR associated with hypomotility and high-pressure IDCR suggestive of spastic motor disorders.

Focal Distal Esophageal Dilation (Blown-Out Myotomy) After Achalasia Treatment: Prevalence and Associated Symptoms.

INTRODUCTION: Peroral endoscopic myotomy (POEM) may result in a distended distal esophagus, referred to as a blown-out myotomy (BOM), the relevance of which is uncertain. The aim of this study was to investigate the prevalence, risk factors, and associated symptoms of BOM after achalasia treatment. METHODS: A data set of the locally treated patients in a randomized controlled trial comparing POEM with pneumatic dilation (PD) was analyzed. A BOM is defined as a >50% increase in esophageal diameter at its widest point in the distal esophagus between the lower esophageal sphincter and 5 cm above. RESULTS: Seventy-four patients were treated in our center, and 5-year follow-up data were available in 55 patients (32 patients [58%] randomized to POEM, 23 [42%] PD). In the group initially treated with POEM, the incidence of BOM increased from 11.5% (4/38) at 3 months, to 21.1% (8/38) at 1 year, 27.8% (10/36) at 2 years, and 31.3% (10/32) at 5 years. None of the patients treated with PD alone developed a BOM. Patients who developed a BOM had a higher total Eckardt score and Eckardt regurgitation component compared with patients who underwent POEM without BOM development (3 [2.75-3.25] vs 2 [1.75-3], P = 0.032, and 1 [0.75-1] vs 0 [0-1], P = 0.041). POEM patients with a BOM more often report reflux symptoms (85% [11/13] vs 46% [2/16], P = 0.023) and had a higher acid exposure time (24.5% [8-47] vs 6% [1.2-18.7], P = 0.027). DISCUSSION: Thirty percent of the patients treated with POEM develop a BOM, which is associated with a higher acid exposure, more reflux symptoms, and symptoms of regurgitation.

The Role of High-Resolution Manometry Prior to and Following Antireflux Surgery: The Padova Consensus.

BACKGROUND: In the last two decades the development of high-resolution manometry (HRM) has changed and revolutionized the diagnostic assessment of patients complain foregut symptoms. The role of HRM before and after antireflux procedure remains unclear, especially in surgical practice, where a clear understanding of esophageal physiology and hiatus anatomy is essential for optimal outcome of antireflux surgery (ARS). Surgeons and gastroenterologists (GIs) agree that assessing patients following antireflux procedures can be challenging. Although endoscopy and barium-swallow can reveal anatomic abnormalities, physiologic information on HRM allowing insight into the cause of eventually recurrent symptoms could be key to clinical decision making. METHOD: A multi-disciplinary international working group (14 surgeons and 15 GIs) collaborated to develop consensus on the role of HRM pre- and post- ARS, and to develop a postoperative classification to interpret HRM findings. The method utilized was detailed literature review to develop statements, and the RAND/University of California, Los Angeles Appropriateness Methodology (RAM) to assess agreement with the statements. Only statements with an approval rate >80% or a final ranking with a median score of 7 were accepted in the consensus. The working groups evaluated the role of HRM prior to ARS and the role of HRM following ARS. CONCLUSION: This international initiative developed by surgeons and GIs together, summarizes the state of our knowledge of the use of HRM pre- and post-ARS. The Padova Classification was developed to facilitate the interpretation of HRM studies of patients underwent ARS.

Four-dimensional impedance manometry volume metrics for predicting abnormal bolus retention.

BACKGROUND: The objective measurement for esophageal bolus volume and bolus clearance could classify abnormal high-resolution manometry (HRM) beyond the current Chicago classification. We aimed to compare the novel four-dimensional impedance manometry (4D HRM) volume metrics with timed barium esophagram (TBE). METHODS: Adults with esophageal symptoms undergoing HRM and TBE were included. A custom-built program for 4D HRM analysis measured esophageal luminal cross-sectional area (CSA) from impedance and subsequently derived esophageal bolus volume and clearance. 4D HRM volume metrics included pre-swallow residual volume, maximal volume, retention volume, and clearance ratio defined as 1.0-retention volume divided by the maximal volume. An abnormal TBE was defined as a column height >5 cm at 1 min or 5 min. KEY RESULTS: A total of 95 patients (normal motility: 33%; ineffective esophageal motility: 12%; absent contractility: 10%; esophagogastric junction outflow obstruction: 30%; type I achalasia: 5%; type II achalasia: 12%) were categorized into normal TBE (58%), abnormal TBE at 1 min (17%), and abnormal TBE at 5 min (25%). The AUROC demonstrated that, among all 4D HRM volume metrics, the clearance ratio had the best performance in predicting abnormal TBE at 5 min (AUROC, 95% confidence interval: 0.89, 0.82-0.96), and exhibited a strong negative correlation with TBE at 5 min (r = -0.65; p < 0.001). CONCLUSIONS & INFERENCES: Novel 4D HRM volume metrics provide objective measurement of esophageal bolus volume and bolus clearance. The clearance ratio has a strong correlation with TBE and could potentially serve as a substitute for TBE to measure esophageal retention.

An Endoscopic Scoring System for Achalasia: The CARS score.

BACKGROUND AND AIMS: The diagnosis of achalasia is associated with an average delay of two years. Endoscopic features may prompt an earlier diagnosis. We aimed to develop and test a novel endoscopic CARS score for the prediction of achalasia. METHODS: Part 1: Twenty endoscopic videos were taken from patients undergoing endoscopy for dysphagia or reflux. A survey with videos and endoscopic criteria options was distributed to 6 esophagologists and 6 general gastroenterologists. Inter-rater reliability (IRR) was measured and logistic regression was used to evaluate predictive performance. Three rounds of review were conducted to select the final score of four components. PART 2: A retrospective review was conducted for consecutive patients who had comprehensive esophageal testing. Each patient had a CARS endoscopic score calculated based on findings reported at endoscopy. RESULTS: From a video review and analysis of score components, IRR ranged from 0.23 to 0.57 for score components. The final CARS score was selected based on the following four components: Contents, Anatomy, Resistance, and Stasis. In a mixed effects model, the mean score across raters was higher for achalasia compared to non-achalasia subjects (4.44 vs. 0.87, p = < 0.01). In part 2 of the study, achalasia patients had a higher mean CARS score compared to those with no / ineffective motility disorder (mean 4.1 vs 1.3, p = < 0.01). CONCLUSIONS: We developed a CARS score based on reliability performance in a video-based survey and tested the score in clinical setting. The CARS score performed well in predicting achalasia.

Neurological disorders leading to mechanical dysfunction of the esophagus: an emergent behavior of a neuromechanical dynamical system.

An understanding how neurological disorders lead to mechanical dysfunction of the esophagus requires knowledge of the neural circuit of the enteric nervous system. Historically, this has been elusive. Here, we present an empirically guided neural circuit for the esophagus. It has a chain of unidirectionally coupled relaxation oscillators, receiving excitatory signals from stretch receptors along the esophagus. The resulting neuromechanical model reveals complex patterns and behaviors that emerge from interacting components in the system. A wide variety of clinically observed normal and abnormal esophageal responses to distension are successfully predicted. Specifically, repetitive antegrade contractions (RACs) are conclusively shown to emerge from the coupled neuromechanical dynamics in response to sustained volumetric distension. Normal RACs are shown to have a robust balance between excitatory and inhibitory neuronal populations, and the mechanical input through stretch receptors. When this balance is affected, contraction patterns akin to motility disorders are observed. For example, clinically observed repetitive retrograde contractions emerge due to a hyper stretch sensitive wall. Such neuromechanical insights could be crucial to eventually develop targeted pharmacological interventions.

Effect of esophageal body recoil on clinical outcomes in non-spastic achalasia.

BACKGROUND: Despite the established efficacy of achalasia treatments on symptomatic outcomes, there are limited data evaluating the treatment effect on esophageal dilatation. This study aimed to assess the effect achalasia treatment on esophageal dilatation and the effect of esophageal width reduction ("recoil") on clinical outcomes. METHODS: Patients with type I or type II achalasia that completed high-resolution manometry (HRM), functional lumen imaging probe (FLIP), and timed barium esophagram (TBE) pre and post treatment were included. Esophageal width was measured using TBE. Focused subgroup analysis was performed on patients with normal posttreatment EGJ opening on FLIP. Good clinical outcomes were defined as barium column height of <5 cm at 5 min and Eckardt Score ≤3. KEY RESULTS: Sixty-nine patients (41% type I and 59% type II) were included. Esophageal width decreased from pre to post treatment mean (SD) 4.2 (1.3) cm-2.8 (1.2) cm; p < 0.01. In the normal post treatment EGJ opening subgroup, esophageal width was less in patients with good TBE outcome compared to poor outcome mean (SD) 2.2 (0.7) cm versus 3.2 (1.4) cm (p < 0.01), but did not differ in good versus poor symptomatic outcome groups. Esophageal width recoil >25% posttreatment was associated with a greater rate of good TBE outcome (71% vs. 50%, p = 0.04) and good symptomatic outcome (88% vs. 50%; p = 0.04). CONCLUSIONS AND INFERENCES: Esophageal recoil was associated with good achalasia treatment outcome in patients without posttreatment EGJ obstruction. This suggests that mechanical properties of the esophageal wall, likely associated with tissue remodeling, play a role in clinical outcomes following achalasia treatment.

Validation of the Laryngeal Cognitive-Affective Tool.

BACKGROUND & AIMS: Cognitive-affective processes, including hypervigilance and symptom-specific anxiety, may contribute to chronic laryngeal symptoms and are potentially modifiable; however, a validated instrument to assess these constructs is lacking. The aims of this study were to develop and validate the Laryngeal Cognitive-Affective Tool (LCAT) instrument. METHODS: This 2-phase single-center prospective study enrolled participants from November 2021 to June 2023. In the initial phase 1:1 patient cognitive interviews and multidisciplinary team consensus were conducted to develop the LCAT. In the second phase asymptomatic and symptomatic participants completed a series of questionnaires to examine psychometric properties of the LCAT. RESULTS: A total of 268 participants were included: 8 in the initial phase and 260 in the validation phase (56 asymptomatic; 204 symptomatic). A 15-item LCAT was developed. In the validation phase, mean total LCAT and hypervigilance/anxiety subscores were significantly higher in symptomatic versus asymptomatic participants (P < .01). The LCAT had excellent internal consistency (α = 0.942) and split-half reliability (Guttman = 0.853). Using a median split, a score of 33 or greater was defined as elevated. CONCLUSIONS: The 15-item LCAT evaluates laryngeal hypervigilance and symptom-specific anxiety among patients with laryngeal symptoms. It has excellent reliability and construct validity. The LCAT highlights burdensome cognitive-affective processes that can accordingly help tailor treatments.

Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX.

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

Dysphagia associated with esophageal wall thickening in patients with nonspecific high-resolution manometry findings: Understanding motility beyond the Chicago classification version 4.0.

BACKGROUND: Previous studies have demonstrated that 50% of patients with normal high-resolution manometry (HRM) findings or ineffective esophageal motility (IEM) may have abnormal functional luminal imaging probe (FLIP) results. However, the specific HRM findings associated with abnormal FLIP results are unknown. Herein, we investigated the relationship between nonspecific manometry findings and abnormal FLIP results. METHODS: We retrospectively analyzed 684 patients who underwent HRM at a tertiary care center in Seoul, Korea, based on the Chicago Classification version 4.0 protocol. KEY RESULTS: Among the 684 patients, 398 had normal HRM findings or IEM. Of these 398 patients, eight showed esophageal wall thickening on endoscopic ultrasonography or computed tomography; however, no abnormalities were seen during esophagogastroduodenoscopy. Among these eight patients, seven showed repetitive simultaneous contractions (RSCs) in at least one of the two positions: 61% (±29%) in 10 swallows in the supine position and 51% (±30%) in five swallows in the upright position. Four patients who underwent FLIP had a significantly decreased esophagogastric junction distensibility index (1.0 ± 0.5 m m 2 mmHg - 1 at 60 mL). Two of these patients underwent per-oral endoscopic myotomy (POEM) due to a lack of response to medication. Esophageal muscle biopsy revealed hypertrophic muscle with marginal eosinophil infiltration. CONCLUSIONS & INFERENCES: A subset of patients (2%) with normal HRM findings or IEM and RSCs experienced dysphagia associated with poor distensibility of the thickened esophageal wall. FLIP assessment or combined HRM and impedance protocols may help better define these patients who may respond well to POEM.

Secondary peristalsis and esophagogastric junction distensibility in symptomatic post-fundoplication patients.

BACKGROUND: The impact of esophageal dysmotility among patients with post-fundoplication esophageal symptoms is not fully understood. This study aimed to investigate secondary peristalsis and esophagogastric junction (EGJ) opening biomechanics using functional lumen imaging probe (FLIP) panometry in symptomatic post-fundoplication patients. METHODS: Eighty-seven adult patients post-fundoplication who completed FLIP for symptomatic esophageal evaluation were included. Secondary peristaltic contractile response (CR) patterns and EGJ opening metrics (EGJ distensibility index (EGJ-DI) and maximum EGJ diameter) were evaluated on FLIP panometry and analyzed against high-resolution manometry (HRM), patient-reported outcomes, and fundoplication condition seen on esophagram and/or endoscopy. KEY RESULTS: FLIP CR patterns included 14 (16%) normal CR, 30 (34%) borderline CR, 28 (32%) impaired/disordered CR, 13 (15%) absent CR, and 2 (2%) spastic reactive CR. Compared with normal and borderline CRs (i.e., CR patterns with distinct, antegrade peristalsis), patients with impaired/disordered and absent CRs demonstrated significantly greater time since fundoplication (2.4 (0.6-6.8) vs. 8.9 (2.6-14.5) years; p = 0.002), greater esophageal body width on esophagram (n = 50; 2.3 (2.0-2.8) vs. 2.9 (2.4-3.6) cm; p = 0.013), and lower EGJ-DI (4.3 (2.7-5.4) vs. 2.6 (1.7-3.7) mm2/mmHg; p = 0.001). Intact fundoplications had significantly higher rates of normal CRs compared to anatomically abnormal (i.e., tight, disrupted, slipped, herniated) fundoplications (9 (28%) vs. 5 (9%); p = 0.032), but there were no differences in EGJ-DI or EGJ maximum diameter. CONCLUSIONS & INFERENCES: Symptomatic post-fundoplication patients were characterized by frequent abnormal secondary peristalsis after fundoplication, potentially worsening with time after fundoplication or related to EGJ outflow resistance.

Latin American consensus on diagnosis of gastroesophageal reflux disease.

BACKGROUND: Diagnosing gastroesophageal reflux disease (GERD) can be challenging given varying symptom presentations, and complex multifactorial pathophysiology. The gold standard for GERD diagnosis is esophageal acid exposure time (AET) measured by pH-metry. A variety of additional diagnostic tools are available. The goal of this consensus was to assess the individual merits of GERD diagnostic tools based on current evidence, and provide consensus recommendations following discussion and voting by experts. METHODS: This consensus was developed by 15 experts from nine countries, based on a systematic search of the literature, using GRADE (grading of recommendations, assessment, development and evaluation) methodology to assess the quality and strength of the evidence, and provide recommendations regarding the diagnostic utility of different GERD diagnosis tools, using AET as the reference standard. KEY RESULTS: A proton pump inhibitor (PPI) trial is appropriate for patients with heartburn and no alarm symptoms, but nor for patients with regurgitation, chest pain, or extraesophageal presentations. Severe erosive esophagitis and abnormal reflux monitoring off PPI are clearly indicative of GERD. Esophagram, esophageal biopsies, laryngoscopy, and pharyngeal pH monitoring are not recommended to diagnose GERD. Patients with PPI-refractory symptoms and normal endoscopy require reflux monitoring by pH or pH-impedance to confirm or exclude GERD, and identify treatment failure mechanisms. GERD confounders need to be considered in some patients, pH-impedance can identify supragrastric belching, impedance-manometry can diagnose rumination. CONCLUSIONS: Erosive esophagitis on endoscopy and abnormal pH or pH-impedance monitoring are the most appropriate methods to establish a diagnosis of GERD. Other tools may add useful complementary information.

Quality Indicator Development for the Approach to Ineffective Esophageal Motility: A Modified Delphi Study.

GOALS: Develop quality indicators for ineffective esophageal motility (IEM). BACKGROUND: IEM is identified in up to 20% of patients undergoing esophageal high-resolution manometry (HRM) based on the Chicago Classification. The clinical significance of this pattern is not established and management remains challenging. STUDY: Using RAND/University of California, Los Angeles Appropriateness Methods, we employed a modified-Delphi approach for quality indicator statement development. Quality indicators were proposed based on prior literature. Experts independently and blindly scored proposed quality statements on importance, scientific acceptability, usability, and feasibility in a 3-round iterative process. RESULTS: All 10 of the invited esophageal experts in the management of esophageal diseases invited to participate rated 12 proposed quality indicator statements. In round 1, 7 quality indicators were rated with mixed agreement, on the majority of categories. Statements were modified based on panel suggestion, modified further following round 2's virtual discussion, and in round 3 voting identified 2 quality indicators with comprehensive agreement, 4 with partial agreement, and 1 without any agreement. The panel agreed on the concept of determining if IEM is clinically relevant to the patient's presentation and managing gastroesophageal reflux disease rather than the IEM pattern; they disagreed in all 4 domains on the use of promotility agents in IEM; and had mixed agreement on the value of a finding of IEM during anti-reflux surgical planning. CONCLUSION: Using a robust methodology, 2 IEM quality indicators were identified. These quality indicators can track performance when physicians identify this manometric pattern on HRM. This study further highlights the challenges met with IEM and the need for additional research to better understand the clinical importance of this manometric pattern.

The Severity of Reduced Esophageal Distensibility Parallels Eosinophilic Esophagitis Disease Duration.

BACKGROUND & AIMS: Chronic inflammation of eosinophilic esophagitis (EoE) results in progressive, fibrostenotic remodeling of the esophageal wall. This study aimed to demonstrate objective changes in esophageal distensibility relative to duration of EoE disease using a functional lumen imaging probe (FLIP). METHODS: Adult patients with EoE who completed a 16-cm FLIP protocol during endoscopy were evaluated in a cross-sectional study. FLIP analysis focused on distensibility plateau (DP) of the esophageal body. The time from onset of symptoms to time of endoscopy with FLIP was assessed, as was time from symptom onset to EoE diagnosis (ie, diagnostic delay). RESULTS: A total of 171 patients (mean age 38 ± 12 years; 31% female) were included; the median symptom duration was 8 (interquartile range, 3-15) years and diagnostic delay was 4 (interquartile range, 1-12) years. At the time of endoscopy with FLIP, there were 54 patients (39%) in histologic remission (<15 eosinophils per high-power field [eos/hpf]). Symptom duration and diagnostic delay were negatively correlated with DP (rho = -0.326 and -0.309; P values < .001). Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years. When stratifying the cohort based on mucosal eosinophil density, patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P = .004), while there was not a significant difference among patients with <15 eos/hpf (P = .060). CONCLUSIONS: Esophageal distensibility objectively measured with FLIP was reduced in EoE patients with greater symptom duration and diagnostic delay. This supports that EoE is a progressive, fibrostenotic disease and that FLIP may be a useful tool to monitor disease progression in EoE.