Rapid Development of Achalasia After SARS-CoV-2 Infection: Polymerase Chain Reaction Analysis of Esophageal Muscle Tissue.

INTRODUCTION: Achalasia has been linked to viruses. We have observed cases of rapid-developing achalasia post-coronavirus disease 2019 (COVID-19). METHODS: We aimed to prospectively evaluate esophageal muscle for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from patients with rapid-onset achalasia post-COVID-19 and compare them with achalasia predating COVID-19 and achalasia with no COVID-19. RESULTS: Compared with long-standing achalasia predating COVID-19 and long-standing achalasia with no COVID-19, the subjects with achalasia post-COVID-19 had significantly higher levels of messenger RNA for the SARS-CoV-2 nucleocapsid (N) protein, which correlated with a significant increase in the inflammatory markers NOD-like receptor family pyrin domain-containing 3 and tumor necrosis factor. DISCUSSION: SARS-CoV-2, the virus responsible for COVID-19, is a possible trigger for 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.

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.

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.

Management advice for patients with reflux-like symptoms: an evidence-based consensus.

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.

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.

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.

Novel histologic score predicts recurrent intestinal metaplasia after successful endoscopic eradication therapy.

Endoscopic eradication therapy (EET) is an effective treatment for Barrett's esophagus (BE); however, disease recurrence remains problematic requiring surveillance post-treatment. While data regarding predictors of recurrence are limited, uncontrolled reflux may play a significant role. Our aim was to develop a scoring system based on histopathologic reflux in surveillance biopsies following EET to identify patients at high risk for recurrence of BE. Patients were identified from two centers in the treatment with resection and endoscopic ablation techniques for BE consortium. Hematoxylin and eosin-stained slides of surveillance biopsies post-EET were assessed for histologic changes associated with reflux from a cohort of patients who also underwent pH-metry (derivation cohort). We developed a novel scoring system (Recurrent Epithelial Changes from Uncontrolled Reflux [RECUR]) composed of dilated intercellular spaces, epithelial ballooning, basal cell hyperplasia, and parakeratosis, to identify patients with abnormal esophageal acid exposure. This scoring system was then used to grade surveillance biopsies from patients with or without recurrence of BE following EET (validation cohort). Of 41 patients in the derivation cohort, 19.5% had abnormal acid exposure times (AET) while on proton pump inhibitor therapy. The mean (SD) RECUR score for patients with AET <4% was 4.0 (1.6), compared with 5.5 (0.9) for AET ≥4% (P = 0.015). In the validation cohort consisting of 72 patients without recurrence and 64 patients with recurrence following EET, the RECUR score was the only significant predictor of recurrence (odds ratio: 1.36, 95% confidence interval: 1.10-1.69, P = 0.005). Histologic grading of surveillance biopsies using the RECUR scoring system correlates with BE recurrence following EET.

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.

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.

Peroral endoscopic myotomy versus pneumatic dilation in treatment-naive patients with achalasia: 5-year follow-up of a randomised controlled trial.

BACKGROUND: 2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up. METHODS: We did a multicentre, randomised controlled trial in six hospitals in the Netherlands, Germany, Italy, Hong Kong, and the USA. Adults aged 18-80 years with newly diagnosed symptomatic achalasia (based on an Eckardt score >3) were eligible for inclusion. Patients were randomly assigned (1:1) to peroral endoscopic myotomy or pneumatic dilation using web-based randomisation with a random block size of 8 and stratification according to site. Randomisation concealment for treatment type was double blind until official study enrolment. Treatment was unmasked because of the different technical approach of each procedure. Patients in the pneumatic dilation group were dilated with a single series of 30-35 mm balloons. The need for subsequent dilations in the pneumatic dilation group, and the need for dilation after initial treatment in the peroral endoscopic myotomy group, was considered treatment failure. The primary outcome was therapeutic success (Eckardt score ≤3 in the absence of severe treatment-related complications and no need for retreatment). Analysis of the primary outcome was by modified intention to treat, including all patients randomly assigned to a group, excluding those patients who did not receive treatment or were lost to follow-up. Safety was assessed in all included patients. This study is registered at the Dutch Trial Registry, NTR3593, and is completed. FINDINGS: Between Sept 21, 2012, and July 20, 2015, 182 patients were assessed for eligibility, 133 of whom were included in the study and randomly assigned to peroral endoscopic myotomy (n=67) or pneumatic dilation (n=66). 5-year follow-up data were available for 62 patients in the peroral endoscopic myotomy group and 63 patients in the pneumatic dilation group. 50 (81%) patients in the peroral endoscopic myotomy group had treatment success at 5 years, compared with 25 (40%) in the pneumatic dilation group, an adjusted absolute difference of 41% (95% CI 25-57; p<0·0001). Reasons for failure were no initial effect of treatment (one patient in the peroral endoscopic myotomy group vs 12 patients in the pneumatic dilation group) and recurrent symptoms causing treatment failure (11 patients in the peroral endoscopic myotomy group [seven patients between 2 and 5 years] vs 25 patients in the pneumatic dilation group [nine patients between 2 and 5 years]); one patient in the pneumatic dilation group had treatment failure due to an adverse event. Proton-pump inhibitor use (mostly daily) was significantly higher after peroral endoscopic myotomy than after pneumatic dilation among patients still in clinical remission (23 [46%] of 50 patients vs three [13%] of 24 patients; p=0·008). 5-year follow-up endoscopy of patients still in clinical remission showed reflux oesophagitis in 14 (33%) of 42 patients in the peroral endoscopic myotomy group (12 [29%] grade A or B, two [5%] grade C or D) and two (13%) of 16 patients in the pneumatic dilation group (two [13%] grade A or B, none grade C or D; p=0·19). No intervention-related serious adverse events occurred between 2 and 5 years after treatment. The following non-intervention-related serious adverse events occurred between 2 and 5 years: a stroke (one [2%]) in the peroral endoscopic myotomy group; and death due to a melanoma (one [2%]) and dementia (one [2%]) in the pneumatic dilation group. INTERPRETATION: Based on this study, peroral endoscopic myotomy should be proposed as an initial treatment option for patients with achalasia. Although our study has shown that peroral endoscopic myotomy has greater long-term efficacy with a low risk of major treatment-related complications, this should not lead to abandonment of pneumatic dilation from clinical practice. Ideally, all treatment options should be discussed with treatment-naive patients with achalasia and a shared decision should be made. FUNDING: Fonds NutsOhra and European Society of Gastrointestinal Endoscopy.

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.

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.

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.

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.

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.

Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used to treat and prevent acid-related disorders. Despite high efficacy, PPI safety has been increasingly scrutinised. However, no comprehensive review summarising investigations of various adverse events is available. AIMS: To perform an umbrella review to comprehensively assess associations between adverse events and PPI use. METHODS: In accordance with PRISMA, an umbrella review of systematic reviews with meta-analyses was conducted. PubMed and EMBASE were searched from 2015 to July 2019. AMSTAR 2 and GRADE were used to assess quality and certainty of evidence. Author-reported quality assessments were also reviewed. RESULTS: Forty-two systematic reviews with meta-analyses, supported predominantly by observational evidence, were included. The most comprehensive studies reported statistically significant associations with PPI use for several outcomes, including: fractures (eg, hip; RR = 1.20; 95% CI = 1.14-1.28; n = 2 103 800), kidney disease (eg, acute kidney injury; RR = 1.61; 95% CI = 1.16-2.22; n = 2 396 640), infections (eg, Clostridioides difficile; OR = 1.99; 95% CI = 1.73-2.30; n = 356 683), gastric cancer (OR = 2.50; 95% CI = 1.74-3.85; n = 943 070) and gastrointestinal events (eg, fundic gland polyps; OR = 2.46; 95% CI = 1.42-4.27; n = 40 218). No associations with non-gastric cancers, or neurological disease were concluded, with conflicting evidence for cardiovascular outcomes. Certainty based on GRADE was very low for most outcomes. CONCLUSIONS: This review identified several published associations between PPIs and adverse outcomes, however, further investigation is needed to understand their clinical significance and the likelihood of causal relationship. If higher quality evidence is generated substantiating the potential risks, it may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal.

Blown-out myotomy: an adverse event of laparoscopic Heller myotomy and peroral endoscopic myotomy for achalasia.

BACKGROUND AND AIMS: Although laparoscopic Heller myotomy (LHM) or peroral endoscopic myotomy (POEM) is highly effective, 10% to 20% of patients with achalasia remain symptomatic after treatment. In evaluating such patients, we have observed a pattern of failure associated with a pseudodiverticulum, or blown-out myotomy (BOM), in the distal esophagus. We aimed to assess risk factors and patient-reported outcomes associated with a BOM. METHODS: We reviewed our manometry database for patients with achalasia previously treated with LHM or POEM. We included patients who had a post-treatment esophagram within 1 year of their follow-up manometry. A BOM was defined radiographically as a wide-mouthed outpouching (>50% increase in esophageal diameter) in the area of the myotomy. RESULTS: One hundred twenty-nine patients with achalasia who underwent treatment were included; 23 (17.8%) had a BOM. Comparing patients with a BOM with those without, post-treatment Eckardt scores were significantly greater (5 vs 2, P = .002), type III achalasia was more common (39.1% vs 14.2%, P = .005), and LHM was more common than POEM (73.9% vs 26.1%, P = .013). The integrated relaxation pressure was also significantly greater in the BOM group (15.0 mm Hg vs 11.0 mm Hg, P = .025). CONCLUSIONS: BOM is a common adverse event after myotomy for achalasia but is not seen after pneumatic dilation. Pretreatment type III achalasia, LHM as opposed to POEM, and a greater post-treatment integrated relaxation pressure were risk factors for developing a BOM. We speculate that esophageal wall strain in the area weakened by myotomy, whether from residual spastic contractility or continued esophageal outflow obstruction, may be the underlying mechanism of BOM development.