An endoscopic scoring system for achalasia: the CARS score.

BACKGROUND AND AIMS: The diagnosis of achalasia is associated with an average delay of 2 years. Endoscopic features may prompt an earlier diagnosis. We aimed to develop and test a novel endoscopic score, CARS, 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 4 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 4 components: Contents, Anatomy, Resistance, and Stasis. In a mixed-effects model, the mean score across raters was higher for achalasia compared with nonachalasia subjects (4.44 vs 0.87; P < .01). In part 2 of the study, achalasia patients had a higher mean CARS score compared with those with no or ineffective motility disorder (mean 4.1 vs 1.3; P < .01). CONCLUSIONS: We developed a CARS score based on reliability performance in a video-based survey and tested the score in a clinical setting. The CARS score performed well in predicting achalasia.

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.

High Diagnostic Yield of Abnormal Endoscopic Findings in the Evaluation of Laryngopharyngeal Reflux.

Esophagogastroduodenoscopy (EGD) is recommended in patients with typical gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation, chest pain) in the setting of proton pump inhibitor (PPI) nonresponse. EGD evaluates for erosive disease, assesses antireflux barrier integrity, excludes non-GERD conditions, and, in the absence of erosive findings, is followed by reflux testing.1,2 The diagnostic utility of EGD is less clear in the evaluation for laryngopharyngeal reflux (LPR), and the current reference standard is ambulatory reflux monitoring.1,3,4 This study of patients referred for evaluation of chronic laryngeal symptoms had the following aims: (1) to characterize endoscopic findings, (2) to discern whether findings differed between patients with or without concomitant esophageal reflux symptoms, and (3) to measure the association between endoscopic findings and objective GERD on ambulatory reflux monitoring.

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.

Composite score of physiomechanical esophageal function using functional lumen imaging probe panometry in eosinophilic esophagitis.

BACKGROUND AND AIMS: The evaluation provided by functional lumen imaging probe (FLIP) panometry includes esophageal distensibility/compliance (mechanics) of the esophageal body and esophagogastric junction (EGJ) and esophageal motility (secondary peristalsis). We developed a composite score using these parameters to characterize physiomechanical function in patients with eosinophilic esophagitis (EoE). METHODS: Two hundred fifteen adult patients with EoE who completed FLIP panometry during sedated endoscopy with esophageal biopsy sampling were included. FLIP metrics of esophageal body Compliance, Contractile response, Distensibility plateau, and maximum EGJ Diameter (C2D2) were scored as 0 for normal versus 1 or 2 for increasing degree of abnormality. Scores were summed to calculate the composite C2D2 score. RESULTS: The C2D2 score had a significant positive correlation with mucosal eosinophil count (ρ = .241) and total Endoscopic EoE Reference Score (ρ = .467). Among 46 patients off treatment at the baseline evaluation, future proton pump inhibitor (PPI) responders (ie, achieved mucosal eosinophil count <15 per high-powered field after PPI treatment) had lower C2D2 scores than PPI nonresponders (median, 2 [interquartile range, 1-3] vs 4 [interquartile range, 2-6], respectively; P = .003). A regression model (that controlled for age, sex, and baseline eosinophil count) showed a C2D2 score ≤3 had an odds ratio of 14.5 (95% confidence interval, 2.6-85) to predict future PPI response. However, total Endoscopic EoE Reference Scores (P = .142) and baseline eosinophil count (P = .480) did not differ between PPI responders and PPI nonresponders. CONCLUSIONS: This composite score of FLIP panometry metrics, the C2D2 score, may facilitate characterizing physiomechanical function in EoE and serve as an objective outcome measure.

Suprabasal cells retain progenitor cell identity programs in eosinophilic esophagitis-driven basal cell hyperplasia.

Eosinophilic esophagitis (EoE) is an esophageal immune-mediated disease characterized by eosinophilic inflammation and epithelial remodeling, including basal cell hyperplasia (BCH). Although BCH is known to correlate with disease severity and with persistent symptoms in patients in histological remission, the molecular processes driving BCH remain poorly defined. Here, we demonstrate that BCH is predominantly characterized by an expansion of nonproliferative suprabasal cells that are still committed to early differentiation. Furthermore, we discovered that suprabasal and superficial esophageal epithelial cells retain progenitor identity programs in EoE, evidenced by increased quiescent cell identity scoring and the enrichment of signaling pathways regulating stem cell pluripotency. Enrichment and trajectory analyses identified SOX2 and KLF5 as potential drivers of the increased quiescent identity and epithelial remodeling observed in EoE. Notably, these alterations were not observed in gastroesophageal reflux disease. These findings provide additional insights into the differentiation process in EoE and highlight the distinct characteristics of suprabasal and superficial esophageal epithelial cells in the disease.

A PhysioMechanical Model of Esophageal Function in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation, but also heterogeneous presentations involving fibrostenotic esophageal remodeling and esophageal dysmotility. We aimed to define and evaluate phenotypes of EoE using functional lumen imaging probe (FLIP) panometry (ie, a PhysioMechanical classification of EoE). METHODS: Patients with EoE who completed FLIP during endoscopy were included in a cross-sectional study. FLIP studies were analyzed for distensibility plateau and compliance of the esophageal body, maximum esophagogastric junction diameter, and contractile response pattern. These FLIP features were then applied to define PhysioMechanical classifications. RESULTS: A total of 215 patients with EoE (mean [standard deviation] age 38 [12] years; 31% female) were included. Seven PhysioMechanical classifications were identified that differed by various clinical characteristics, including symptom duration (P < .001) and Endoscopic EoE Reference Scores (EREFS) (P < .001). In particular, patients with "nonreactive fibrostenosis" (n = 14), had greater symptom duration (median [interquartile range] 20 [10-30] years) and more frequently had EREFS grade 2 or 3 ring scores (14 of 14 patients) than patients with a "normal" PhysioMechanical classification (symptom duration: 3 [1-8] years; 4 of 50 [8%] had EREFS grade 2 or 3 rings). In addition, among patients off treatment at cross-sectional evaluation (n = 46), there was a difference between PhysioMechanical classifications in future proton pump inhibitor (PPI) response rates (ie, achieving peak mucosal eosinophil count <15 per high-powered field after PPI treatment); P = .009. PPI response ranged from 87% (13 of 15 patients) with "isolated esophagogastric junction outflow obstruction" to 11% (1 of 9 patients) with "spastic-reactive fibrostenosis." CONCLUSIONS: Classifying PhysioMechanical esophageal function in EoE based on FLIP panometry features may facilitate defining disease severity and directing management in EoE.

AGA Clinical Practice Update on the Diagnosis and Management of Extraesophageal Gastroesophageal Reflux Disease: Expert Review.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert advice regarding the clinical management of patients with suspected extraesophageal gastroesophageal reflux disease. METHODS: This article provides practical advice based on the available published evidence including that identified from recently published reviews from leading investigators in the field, prospective and population studies, clinical trials, and recent clinical guidelines and technical reviews. This best practice document is not based on a formal systematic review. The best practice advice as presented in this document applies to patients with symptoms or conditions suspected to be related to extraesophageal reflux (EER). This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Gastroenterologists should be aware of potential extraesophageal manifestations of gastroesophageal reflux disease (GERD) and should inquire about such disorders including laryngitis, chronic cough, asthma, and dental erosions in GERD patients to determine whether GERD may be a contributing factor to these conditions. BEST PRACTICE ADVICE 2: Development of a multidisciplinary approach to extraesophageal (EER) manifestations is an important consideration because the conditions are often multifactorial, requiring input from non-gastroenterology (GI) specialties. Results from diagnostic testing (ie, bronchoscopy, thoracic imaging, laryngoscopy, etc) from non-GI disciplines should be taken into consideration when gastroesophageal reflux (GER) is considered as a cause for extraesophageal symptoms. BEST PRACTICE ADVICE 3: Currently, there is no single diagnostic tool that can conclusively identify GER as the cause of EER symptoms. Determination of the contribution of GER to EER symptoms should be based on the global clinical impression derived from patients' symptoms, response to GER therapy, and results of endoscopy and reflux testing. BEST PRACTICE ADVICE 4: Consideration should be given toward diagnostic testing for reflux before initiation of proton pump inhibitor (PPI) therapy in patients with potential extraesophageal manifestations of GERD, but without typical GERD symptoms. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable. BEST PRACTICE ADVICE 5: Symptom improvement of EER manifestations while on PPI therapy may result from mechanisms of action other than acid suppression and should not be regarded as confirmation for GERD. BEST PRACTICE ADVICE 6: In patients with suspected extraesophageal manifestation of GERD who have failed one trial (up to 12 weeks) of PPI therapy, one should consider objective testing for pathologic GER, because additional trials of different PPIs are low yield. BEST PRACTICE ADVICE 7: Initial testing to evaluate for reflux should be tailored to patients' clinical presentation and can include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy. BEST PRACTICE ADVICE 8: Testing can be considered for those with an established objective diagnosis of GERD who do not respond to high doses of acid suppression. Testing can include pH-impedance monitoring while on acid suppression to evaluate the role of ongoing acid or non-acid reflux. BEST PRACTICE ADVICE 9: Alternative treatment methods to acid suppressive therapy (eg, lifestyle modifications, alginate-containing antacids, external upper esophageal sphincter compression device, cognitive-behavioral therapy, neuromodulators) may serve a role in management of EER symptoms. BEST PRACTICE ADVICE 10: Shared decision-making should be performed before referral for anti-reflux surgery for EER when the patient has clear, objectively defined evidence of GERD. However, a lack of response to PPI therapy predicts lack of response to anti-reflux surgery and should be incorporated into the decision process.

An artificial intelligence platform provides an accurate interpretation of esophageal motility from Functional Lumen Imaging Probe Panometry studies.

BACKGROUND: Functional lumen imaging probe (FLIP) Panometry is performed at the time of sedated endoscopy and evaluates esophageal motility in response to distension. This study aimed to develop and test an automated artificial intelligence (AI) platform that could interpret FLIP Panometry studies. METHODS: The study cohort included 678 consecutive patients and 35 asymptomatic controls that completed FLIP Panometry during endoscopy and high-resolution manometry (HRM). "True" study labels for model training and testing were assigned by experienced esophagologists per a hierarchical classification scheme. The supervised, deep learning, AI model generated FLIP Panometry heatmaps from raw FLIP data and based on convolutional neural networks assigned esophageal motility labels using a two-stage prediction model. Model performance was tested on a 15% held-out test set (n = 103); the remainder of the studies were utilized for model training (n = 610). KEY RESULTS: "True" FLIP labels across the entire cohort included 190 (27%) "normal," 265 (37%) "not normal/not achalasia," and 258 (36%) "achalasia." On the test set, both the Normal/Not normal and the achalasia/not achalasia models achieved an accuracy of 89% (with 89%/88% recall, 90%/89% precision, respectively). Of 28 patients with achalasia (per HRM) in the test set, 0 were predicted as "normal" and 93% as "achalasia" by the AI model. CONCLUSIONS: An AI platform provided accurate interpretation of FLIP Panometry esophageal motility studies from a single center compared with the impression of experienced FLIP Panometry interpreters. This platform may provide useful clinical decision support for esophageal motility diagnosis from FLIP Panometry studies performed at the time of endoscopy.

Measuring esophageal compliance using functional lumen imaging probe to assess remodeling in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is associated with fibrostenotic remodeling that can be objectively assessed using the functional lumen imaging probe (FLIP). This is typically done using a metric called distensibility plateau (DP). We aimed to describe a novel measure of compliance of the esophageal body and evaluate the associated clinical characteristics in EoE. METHODS: One hundred seventy-one adult patients with EoE (mean (SD) age 38 (12) years), 31% female and 35 healthy, asymptomatic controls who completed 16-cm functional luminal imaging probe (FLIP) during endoscopy, were evaluated in a cross-sectional study. The esophageal body DP and compliance were measured using a customized analysis program, with compliance calculated as (Δ esophageal body volume)/(Δ pressure) between two FLIP-filled volumes. RESULTS: In controls, the median (5-95th percentile) DP was 19.8 mm (17.9-21) and esophageal body compliance was 0.37 ml/mmHg (0.18-1.1), which was greater than in EoE (DP 19 (11-21)), compliance 0.19 (0.02-0.71), p-values <0.001. Among EoE patients, 70 (41%) had normal compliance (>0.2 ml/mmHg) and normal DP (>17 mm); 11 (6%) had normal compliance and reduced DP; 34 (20%) had reduced compliance and normal DP; and 56 (33%) had reduced compliance and reduce DP. Patients with both reduced compliance and DP had the greatest proportion of severe rings (61% with EREFS score 2-3) and stricture (100%). CONCLUSION: FLIP provides an objective evaluation of biomechanical properties of the esophageal wall that appears enhanced by complementary application of metrics of DP and esophageal body compliance.

Identifying hiatal hernia with impedance planimetry during esophageal distension testing.

INTRODUCTION: Functional luminal imaging probe (FLIP) Panometry evaluates the esophageal response to distension involving biomechanics and motility. We have observed that hiatus hernia (HH) is evident during FLIP studies as a separation between the crural diaphragm (CD) and lower esophageal sphincter (LES) like what is seen with high-resolution manometry (HRM). The aim of this study was to compare FLIP findings to endoscopy and HRM in the detection of HH. METHODS: A total of 100 consecutive patients that completed FLIP during sedated endoscopy and HRM were included. LES-CD separation was assessed on FLIP and HRM with the presence of HH defined as LES-CD ≥1 cm. The agreement was evaluated using the kappa (κ) statistic. RESULTS: Hiatal hernia was detected in 32% of patients on HRM and 44% of patients on FLIP with a substantial agreement between studies (84% agreement; κ = 0.667). On FLIP, a 'new' HH (i.e. HH not observed on HRM) occurred in 14 patients and an "enlarged" HH (i.e., LES-CD ≥2 cm larger than on HRM) occurred in 11 patients. Among patients that also completed, timed barium esophagogram (TBE), delayed esophageal emptying on TBE was more common in patients with new or enlarged HH on FLIP than those without: 7/11 (64%) versus 2/12 (17%); p = 0.017. CONCLUSION: FLIP can detect HH with a substantial agreement with HRM, though esophageal distension with FLIP testing appeared to elicit and/or enlarge a HH in an additional 25% of patients. Although this unique response to esophageal distension may represent a mechanism of dysphagia or susceptibility to reflux, additional study is needed to clarify its significance.

Functional Lumen Imaging Probe Panometry Helps Identify Clinically Relevant Esophagogastric Junction Outflow Obstruction per Chicago Classification v4.0.

INTRODUCTION: Esophagogastric junction (EGJ) outflow obstruction (EGJOO) per Chicago Classification v4.0 (CCv4.0) represents a high-resolution manometry (HRM) diagnosis with uncertain clinical significance. This study aimed to evaluate functional lumen imaging probe (FLIP) panometry among patients with EGJOO on HRM/CCv4.0 to assess clinical/manometric associations and treatment outcomes. METHODS: An observational cohort study was performed on patients who completed FLIP during endoscopy and had an HRM/CCv4.0 diagnosis of EGJOO, i.e., HRM-EGJOO (inconclusive). Abnormal FLIP panometry motility classifications were applied to identify FLIP-confirmed conclusive EGJOO. Rapid drink challenge on HRM and timed barium esophagram were also assessed. Clinical management plan was determined by treating physicians and assessed through chart review. Clinical outcome was defined using the Eckardt score (ES) during follow-up evaluation: ES < 3 was considered a good outcome. RESULTS: Of 139 adult patients with manometric EGJOO (inconclusive per CCv4.0), a treatment outcome ES was obtained in 55 after achalasia-type treatment (i.e., pneumatic dilation, peroral endoscopic myotomy, laparoscopic Heller myotomy, or botulinum toxin injection) and 36 patients after other nonachalasia-type treatment. Among patients with conclusive EGJOO by HRM-FLIP complementary impression, 77% (33/43) had a good outcome after achalasia-type treatment, whereas 0% (0/12) of patients had a good outcome after nonachalasia-type treatment. Of patients with normal EGJ opening on FLIP, one-third of patients treated with achalasia-type treatment had a good outcome, while 9 of the 10 treated conservatively had a good outcome. DISCUSSION: FLIP panometry provides a useful complement to clarify the clinical significance of an HRM/CCv4.0 EGJOO diagnosis and help direct management decisions.

Normative values of intra-bolus pressure and esophageal compliance based on 4D high-resolution impedance manometry.

BACKGROUND: This study aimed to quantify normative values of phase-specific intra-bolus pressure (IBP) and esophageal distensibility using 4D analysis of high-resolution-impedance manometry (HRIM). METHODS: HRIM studies of supine swallows from 34 normal controls were analyzed with respect to the four phases of bolus transit: (1) accommodation, (2) compartmentalization, (3) peristalsis/esophageal emptying, and (4) ampullary emptying. Phase-specific IBP, bolus volume, and distensibility index (DI) in the esophageal body and esophagogastric junction (EGJ) during phases 1-3 were extracted. RESULTS: The median (5-95th/IQR) IBP values were as follows: phase 1: 4.0 (-2.0-10.4/1.9-5.8) mmHg, phase 2: 5.7 (0.2-14.1/3.6-8.9) mmHg, and phase 3: 11.2 (2.9-19.4/7.7-15.1) mmHg. The median bolus volume calculated by integrating impedance planimetry cross-sectional areas was 4.1 ml during the compartmentalization phase. The EGJ-DI at max EGJ diameter during phase 2 and 3 was 2.8 (1.1-9.5/1.8-3.7) mm2 /mmHg and 6.0 (3.2-20.3/5.1-7.8) mm2 /mmHg, respectively. The phase 3 EGJ-DI values (6.0 (3.2-20.3/5.1-7.8) mm2 /mmHg) were similar to those calculated using functional lumen imaging probe (FLIP) at the 60 ml volume on the same subjects (5.8 [3.5-7.2/5.0-6.4] mm2 /mmHg). CONCLUSIONS AND INFERENCES: 4D-HRIM provides a standardized methodology to track the nadir impedance and provide measurements of IBP during maximal distention across phases 1-3 of bolus transit. Median IBP and delta IBP were different across the phases, supporting the need to define IBP by phase. Additionally, the EGJ-DI calculated during phase 3 was similar to the 60-ml EGJ-DI from FLIP in the same subjects suggesting that 4D-HRIM can quantify EGJ opening during primary peristalsis.

Validation of Clinically Relevant Thresholds of Esophagogastric Junction Obstruction Using FLIP Panometry.

BACKGROUND & AIMS: This study aimed to assess the accuracy of functional luminal imaging probe (FLIP) panometry to detect esophagogastric junction (EGJ) obstruction assigned by high-resolution manometry (HRM) and the Chicago Classification version 4.0 (CCv4.0). METHODS: Six hundred eighty-seven adult patients who completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers (controls) were included. EGJ opening was evaluated with 16-cm FLIP during sedated endoscopy via EGJ-distensibility index (DI) and maximum EGJ diameter. HRM was classified according to CCv4.0 and focused on studies with a conclusive disorder of EGJ outflow (ie, achalasia subtypes I, II, or III; or EGJ outflow obstruction with abnormal timed barium esophagogram) or normal EGJ outflow. RESULTS: All 35 controls had EGJ-DI >3.0 mm2/mmHg and maximum EGJ diameter >16 mm. Per HRM and CCv4.0, 245 patients had a conclusive disorder of EGJ outflow, and 314 patients had normal EGJ outflow. Among the 241 patients with reduced EGJ opening (EGJ-DI <2.0 mm2/mmHg and maximum EGJ diameter <12 mm) on FLIP panometry, 86% had a conclusive disorder of EGJ outflow per CCv4.0. Among the 203 patients with normal EGJ opening (EGJ-DI ≥2.0 mm2/mmHg and maximum EGJ diameter ≥16 mm) on FLIP panometry, 99% had normal EGJ outflow per CCv4.0. CONCLUSIONS: FLIP panometry accurately identified clinically relevant conclusive EGJ obstruction as defined by CCv4.0 in patients evaluated for esophageal motor disorders. Thus, FLIP panometry is a valuable tool for both independent and complementary evaluation of esophageal motility.

Esophageal Dysmotility Is Associated With Disease Severity in Eosinophilic Esophagitis.

BACKGROUND & AIMS: An association of eosinophilic esophagitis (EoE) with esophageal dysmotility has been described, however, the related mechanism remains unclear. We aimed to evaluate clinical and physiologic characteristics, including esophageal distensibility, associated with secondary peristalsis in patients with EoE. METHODS: A total of 199 consecutive adult patients with EoE (age, 18-78 y; 32% female) who completed a 16-cm functional luminal imaging probe (FLIP) during endoscopy were evaluated in a cross-sectional study. FLIP panometry contractile response (CR) patterns were classified as normal CR or borderline CR if antegrade contractions were present, and abnormal CRs included impaired/disordered CR, absent CR, or spastic-reactive CR. The distensibility plateau of the esophageal body and esophagogastric junction distensibility was measured with FLIP. RESULTS: FLIP CR patterns included 68 (34%) normal CR, 65 (33%) borderline CR, 44 (22%) impaired/disordered CR, 16 (8%) absent CR, and 6 (3%) spastic-reactive CR. Compared with normal CRs, abnormal CRs more frequently had reduced esophageal distensibility (distensibility plateau <17 mm in 56% vs 32%), greater total EoE reference scores (median, 5; interquartile range [IQR], 3-6 vs median, 4; IQR, 3-5) with more severe ring scores, and a greater duration of symptoms (median, 10 y; IQR, 4-23 y vs median, 7 y; IQR, 3-15 y). Mucosal eosinophil density, however, was similar between abnormal CRs and normal CRs (median, 34 eosinophils/high-power field [hpf]; IQR, 14-60 eosinophils/hpf vs median, 25 eosinophils/hpf; IQR, 5-50 eosinophils/hpf). CONCLUSIONS: Although normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.

Variability in endoscopic assessment of Nissen fundoplication wrap integrity and hiatus herniation.

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.

Deep learning-based artificial intelligence model for identifying swallow types in esophageal high-resolution manometry.

BACKGROUND: This study aimed to build and evaluate a deep learning, artificial intelligence (AI) model to automatically classify swallow types based on raw data from esophageal high-resolution manometry (HRM). METHODS: HRM studies on patients with no history of esophageal surgery were collected including 1,741 studies with 26,115 swallows labeled by swallow type (normal, hypercontractile, weak-fragmented, failed, and premature) by an expert interpreter per the Chicago Classification. The dataset was stratified and split into train/validation/test datasets for model development. Long short-term memory (LSTM), a type of deep-learning AI model, was trained and evaluated. The overall performance and detailed per-swallow type performance were analyzed. The interpretations of the supine swallows in a single study were further used to generate an overall classification of peristalsis. KEY RESULTS: The LSTM model for swallow type yielded accuracies from the train/validation/test datasets of 0.86/0.81/0.83. The model's interpretation for study-level classification of peristalsis yielded accuracy of 0.88 in the test dataset. Among model misclassification, 535/698 (77%) swallows and 25/35 (71%) studies were to adjacent categories, for example, normal to weak or normal to ineffective, respectively. CONCLUSIONS AND INFERENCES: A deep-learning AI model can automatically and accurately identify the Chicago Classification swallow types and peristalsis classification from raw HRM data. While future work to refine this model and incorporate overall manometric diagnoses are needed, this study demonstrates the role that AI will serve in the interpretation and classification of esophageal HRM studies.

Dysphagia: Novel and Emerging Diagnostic Modalities.

Among recent advances in diagnostics for dysphagia and esophageal motility disorders is the update to the Chicago Classification (version 4.0) for interpretation of high-resolution manometry (HRM) and diagnosis of esophageal motility disorders. The update incorporates application of complementary testing strategies during HRM, such as provocative HRM maneuvers, and recommendation for barium esophagram or functional luminal imaging probe (FLIP) panometry to help clarify inconclusive HRM findings. FLIP panometry also represents an emerging technology for evaluation of esophageal distensibility and motility at the time of endoscopy.

Classifying Esophageal Motility by FLIP Panometry: A Study of 722 Subjects With Manometry.

INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0. RESULTS: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. DISCUSSION: Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.

Esophageal Hypervigilance and Symptom-Specific Anxiety in Patients with Eosinophilic Esophagitis.

BACKGROUND & AIMS: Patient symptom reporting often does not correlate with the pathophysiological markers of esophageal disease, including eosinophilic esophagitis (EoE). Esophageal hypervigilance and symptom-specific anxiety are emerging as important considerations in understanding symptom reporting. As such, we aimed to conduct the first study of these constructs in EoE. METHODS: A retrospective review of an EoE patient registry was conducted and included eosinophils per high power field (from esophagogastroduodenoscopy biopsy: proximal, distal), endoscopic reference score, distal distensibility plateau (functional luminal imaging probe), Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, Northwestern Esophageal Quality of Life scale, and the Esophageal Hypervigilance and Anxiety Scale. Correlational and regression analyses evaluated relationships of hypervigilance and anxiety with Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, and Northwestern Esophageal Quality of Life scale when controlling for histology and endoscopic severity. RESULTS: One hundred and three patients had complete data, 69.9% were male, and the mean (SD) age was 40.66 (13.85) years. Forty-one percent had elevated dysphagia and 46% had elevated hypervigilance and anxiety. Esophageal symptom-specific anxiety emerged as the most important predictor of Brief Esophageal Dysphagia Questionnaire severity (44.8% of the variance), Visual Dysphagia Question of EoE Activity Index severity (26%), and poor health-related quality of life (HRQoL) (55.3%). Hypervigilance was also important, but to a lesser extent. Pathophysiological variables did not significantly predict symptoms or HRQoL. Recent food impaction can predict symptom-specific anxiety and proton pump inhibitor use can reduce hypervigilance. CONCLUSIONS: Hypervigilance and symptom-specific anxiety are important for our understanding of self-reported patient outcomes in EoE. These processes outweigh endoscopic and histologic markers of EoE disease activity across dysphagia, difficulty eating, and HRQoL. Clinicians should assess hypervigilance and anxiety, especially in patients with refractory symptoms and poor HRQoL.