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Esophageal achalasia is an uncommon disease in pediatrics. With an insidious clinical presentation, diagnosis is delayed. Here we describe a case of esophageal achalasia in a 16-year-old girl, with the typical delay in consultation and diagnosis. Although pneumatic balloon dilatation has been described as the best therapeutic option for type II achalasia, it was ineffective in our patient and she required Heller extramucosal myotomy with gastroesophageal fundoplication for reflux., (Sociedad Argentina de Pediatría.)

Background/Objective: Multiple system atrophy (MSA) is often associated with dysphagia and esophageal dysmotility (ED). However, ED in patients with MSA is poorly understood. To assess the relationship between ED, dysphagia, and other clinical findings in such patients and investigate the details of ED in MSA using high-resolution manometry (HRM). Methods: Patients from The University of Tokyo Hospital with MSA who underwent swallowing examinations, esophagography, and HRM between 2017 and 2022 were enrolled. A retrospective chart review of patients' backgrounds, swallowing function, and esophageal motility was performed. ED was evaluated using the Chicago Classification version 4.0. Results: Seventy-four patients with MSA were identified. The median age was 64 years, 48 patients (65%) were male, and the cerebellar variant type was predominant (69%). Abnormal upper esophageal sphincter (UES) resting pressure was observed in 34 patients (46%) and intraesophageal stasis in 65 (88%). High-severity MSA was a risk factor for developing dysphagia, vocal fold movement impairment, and abnormal UES function ( p < 0.05). However, no overt clinical risk factors for ED were identified. Various types of ED were detected using HRM, and ineffective esophageal motility was the most frequent disorder. Conclusions: ED is a common occurrence in patients with MSA. Although a high-severity MSA may be a risk factor for developing dysphagia and vocal fold motion impairment, ED can occur regardless of clinical severity. Since ED is rarely detected based on subjective symptoms, careful evaluation of esophageal motility by esophagography or HRM is warranted in patients with MSA.

Background/aims: Pharyngeal pump, esophageal peristalsis, and phrenic ampulla emptying play important roles in the propulsion of bolus from the mouth to the stomach. There is limited information available on the mechanism of normal and abnormal phrenic ampulla emptying. The goal of our study is to describe the relationship between bolus flow and esophageal pressure profiles during the phrenic ampulla emptying in normal subjects and patient with phrenic ampulla dysfunction., Methods: Pressure (using topography) and bolus flow (using changes in impedance) relationship through the esophagus and phrenic ampulla were determined in 15 normal subjects and 15 patients with retrograde escape of bolus from the phrenic ampulla into esophagus during primary peristalsis., Results: During the phrenic ampulla phase, 2 high pressure peaks (proximal, related to lower esophageal sphincter and distal, related to crural diaphragm) were observed in normal subjects and patients during the phrenic ampulla emptying phase. The proximal was always higher than the distal one in normal subjects; in contrast, reverse was the case in patients with the retrograde escape of bolus from the phrenic ampulla into the esophagus., Conclusions: We propose that a strong after-contraction of the lower esophageal sphincter plays an important role in the normal phrenic ampullary emptying. A defective lower esophageal after-contraction, along with high crural diaphragm pressure are responsible for the phrenic ampulla emptying dysfunction.

BACKGROUND AND OBJECTIVES: Achalasia has several treatment modalities. We aim to compare the efficacy and safety of laparoscopic Heller myotomy (LHM) with those of pneumatic dilatation (PD) in adult patients suffering from achalasia., Methods: We searched Cochrane CENTRAL, PubMed, Web of Science, SCOPUS and Embase for related clinical trials about patients suffering from achalasia. The quality appraisal and assessment of risk of bias were conducted with GRADE and Cochrane's risk of bias tool, respectively. Homogeneous and heterogeneous data was analyzed under fixed and random-effects models, respectively., Results: The pooled analysis of 10 studies showed that PD was associated with a higher rate of remission at three months, one year, three years and five years (RR = 1.25 [1.09, 1.42] (p = 0.001); RR = 1.13 [1.05, 1.20] (p = 0.0004); RR = 1.48 [1.19, 1.82] (p = 0.0003); RR = 1.49 [1.18, 1.89] (p = 0.001)), respectively. LHM was associated with lower number of cases suffering from adverse events, dysphagia and relapses (RR = 0.50 [0.25, 0.98] (p = 0.04); RR = 0.33 [0.16, 0.71] (p = 0.004); RR = 0.38 [0.15, 0.97] (p = 0.04)), respectively. There is no significant difference between both groups regarding the lower esophageal pressure, perforations, remission rate at two years, Eckardt score after one year and reflux., Conclusion: PD had higher remission rates than LHM at three months, one year and three years, but not at two years or five years. More research is needed to determine whether PD has a significant advantage over LHM in terms of long-term remission rates., (© 2024. Indian Society of Gastroenterology.)

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., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Introduction: Currently there is little information in Latin America on the clinical outcome and manometric evolution of patients with Achalasia undergoing peroral endoscopic myotomy (POEM)., Primary Outcome: Evaluate the manometric and clinical changes in adult patients with achalasia after peroral endoscopic myotomy at a referral center in Bogotá, Colombia., Methods: Observational, analytical, longitudinal study. Adult patients with achalasia according to the Chicago 4.0 criteria were included. Sociodemographic, clinical and manometric variables were described. To compare the pre- and post-surgical variables, the Student's or Wilcoxon's t test was used for the quantitative variables according to their normality, and McNemar's chi-square for the qualitative variables., Results: 29 patients were included, 55.17% (n=16) women, with a mean age at the time of surgery of 48.2 years (±11.33). The mean post-procedure evaluation time was 1.88±0.81 years. After the procedure, there was a significant decrease in the proportion of patients with weight loss (37.93% vs 21.43% p 0.0063), chest pain (48.28% vs 21.43, p 0.0225) and the median Eckardt score (8 (IQR 8 -9) vs 2(IQR 1-2), p <0.0001). In addition, in fourteen patients with post-surgical manometry, significant differences were found between IRP values (23.05±14.83mmHg vs 7.69±6.06mmHg, p 0.026) and in the mean lower esophageal sphincter tone (9.63±7.2mmHg vs 28.8±18.60mmHg, p 0.0238)., Conclusion: Peroral endoscopic myotomy has a positive impact on the improvement of symptoms and of some manometric variables (IRP and LES tone) in patients with achalasia., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background/aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM., Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis., Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR ( P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar , and enriched Fusobacterium nucleatum . In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded., Conclusions: In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

The aim of this review is to provide an overview of per-oral endoscopic myotomy (POEM) and its utilization in non-achalasia disorders of the esophagus. POEM, a relatively novel endoscopic technique, involves submucosal tunneling to access esophageal muscle layers, enabling selective myotomy and mitigating the consequences of motor disorders of the esophagus. POEM is an effective treatment modality for diffuse esophageal spasm providing resolution of chest pain and dysphagia in a majority of patients who have refractory symptoms despite medical therapy. The results of POEM are more equivocal compared to esophagogastric junction outflow obstruction (EGJOO). POEM in EGJOO has been shown to have a 93% clinical success rate in 6 months. POEM appears to be more effective in motor disorders that affect the lower esophageal sphincter, such as EGJOO and opioid-induced esophageal dysfunction. While the current data for POEM in other entities such as DES and HE are positive, more supportive data are required to make POEM a consistent recommendation for patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diffuse esophageal spasm (DES) is a rare esophageal motility disorder characterized by abnormal contractions of the esophagus, leading to curling of the esophagus. The classic finding on barium swallow resembles that of the turns of a corkscrew. This case report presents a case of DES with impressive imaging and an alternative treatment approach. There are no well-established guidelines for the treatment of DES. Treatment options include surgical myotomy, oral medications to aid in smooth muscle relaxation, esophageal dilation, and several newer approaches such as endoscopic botulinum toxin injections. There is a need for less invasive treatment modalities that provide a solution, longer than the duration of action of an oral medication in patients who are not candidates for surgical intervention. This case report presents a complex and challenging case of DES in the context of multiple complicating comorbidities. This case is unique in demonstrating the successful management of a rare esophageal motility disorder in a high-risk patient using a more traditional, less invasive treatment approach. This case report presents a 91-year-old cachectic female with DES in the context of various comorbidities. Given her age, comorbidities, and current status, she was not a candidate for surgical intervention. After attempts at pharmacological therapy, the patient's dysphagia continued to worsen. Upper gastrointestinal endoscopy with pneumatic esophageal dilation was performed. The patient's swallowing improved in the days following endoscopic dilation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Allen et al.)

Objectives: The inability to burp, known as retrograde cricopharyngeal dysfunction (R-CPD), was initially described in adults. The proposed clinical diagnostic criteria for R-CPD include belching inability, abdominal bloating and discomfort/nausea, postprandial chest pain, and involuntary noises. Botulinum toxin injection to the cricopharyngeal muscle has been reported to be beneficial. High-resolution esophageal impedance-manometry (HRIM) features in adolescent patients with R-CPD have not been described yet.  The aim of our study was to describe the clinical and HRIM findings of pediatric patients with R-CPD., Methods: Clinical and manometric features of five pediatric patients diagnosed with R-CPD were reviewed. HRIM study protocol was modified to include the consumption of carbonated drink to provoke symptoms and distinctive manometric features., Results: We report five female patients aged 15-20 years who presented with an inability to burp and involuntary throat sounds. HRIM revealed normal upper esophageal sphincter (UES) relaxation during swallowing, but abnormal UES relaxation with concurrent high esophageal impedance reflecting air entrapment and secondary peristalsis following the carbonated drink challenge. Four patients exhibited esophageal motility disorder. All patients reported improvement or resolution of symptoms after botulinum toxin injection to the cricopharyngeus muscle., Conclusions: Adolescents with an inability to burp, reflux-like symptoms, bloating, and involuntary throat noises should be assessed for R-CPD by pediatric gastroenterologists with HRIM. The relatively recent recognition of this novel condition is the likely reason for its under- and misdiagnosis in children., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background/aims: There is an increased incidence of gastroesophageal reflux disease (GERD) after lung transplantation (LT) that can be associated with graft dysfunction. It is unclear if the underlying esophageal motility changes in GERD are different following LT. This study aimed to use esophageal high-resolution manometry (HRM) to explore GERD mechanisms in LT recipients compared to matched controls., Methods: This was a retrospective study including patients with pathologic acid reflux who underwent HRM and pH testing at our healthcare facility July 2012 to October 2019. The study included 12 LT recipients and 36 controls. Controls were matched in a 1:3 ratio for age, gender, and acid exposure time (AET)., Results: LT recipients had less hypotensive esophagogastric junction (EGJ) (mean EGJ-contractile integral 89.2 mmHg/cm in LT vs 33.9 mmHg/cm in controls, P < 0.001). AET correlated with distal contractile integral and total EGJ-contractile integral only in LT group ( r = -0.79, P = 0.002 and r = -0.57, P = 0.051, respectively)., Conclusions: Following LT, acid reflux is characterized by a less hypotensive EGJ compared to controls with similar AET. The strongest correlation with AET after LT was found to be esophageal peristaltic vigor. These results add to the understanding of reflux after LT and may help tailor an individualized treatment plan.

High-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders, yet it can be poorly tolerated and technically challenging. Epiphrenic diverticula (ED) are located in the distal esophagus and are associated with underlying motility disorders. ED patients (2008-2022) were retrospectively compared to achalasia patients (2008-2022) and all other patients (2021-2022) who underwent HRM at a single center. Complete success was defined as at least 7 interpretable swallows including measurements throughout the esophagus into the stomach. HRM studies involving children, previously treated achalasia, and sedation or endoscopic-assistance were excluded. 20 ED patients (mean age 66; 60% female) were compared to 76 achalasia patients and 199 controls. HRM was completely successful in 70.0% of ED patients, 85.5% of achalasia (p = 0.106 vs ED), and 91.0% of controls (p = 0.004 vs ED). Most failures in the ED and achalasia groups were due to inability to traverse the esophagogastric junction (EGJ), while patient intolerance was the main reason in controls. Half of the ED group had motility disorders (25% achalasia, 15% hypercontractile esophagus, 10% absent contractility). Large diverticulum size was inversely associated with technical success compared to small diverticulum size (40% vs 100%, p = 0.013), while the presence of a motility disorder did not significantly affect success (60% vs 88.9%, p = 0.303). In conclusion, ED is a predictor of unsuccessful HRM. This appears to be mainly related to an inability to traverse the EGJ due to the size of the diverticulum. Consideration should be given to alternative means of evaluating motility, such as endoscopy-assisted HRM, given the high likelihood of failure with traditional HRM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Major esophageal disorders involve obstructive transport of bolus to the stomach, causing symptoms of dysphagia and impaired clearing of the refluxed gastric contents. These may occur due to mechanical constriction of the esophageal lumen or loss of relaxation associated with deglutitive inhibition, as in achalasia-like disorders. Recently, immune inflammation has been identified as an important cause of esophageal strictures and the loss of inhibitory neurotransmission. These disorders are also associated with smooth muscle hypertrophy and hypercontractility, whose cause is unknown. This review investigated immune inflammation in the causation of smooth muscle changes in obstructive esophageal bolus transport. Findings suggest that smooth muscle hypertrophy occurs above the obstruction and is due to mechanical stress on the smooth muscles. The mechanostressed smooth muscles release cytokines and other molecules that may recruit and microlocalize mast cells to smooth muscle bundles, so that their products may have a close bidirectional effect on each other. Acting in a paracrine fashion, the inflammatory cytokines induce genetic and epigenetic changes in the smooth muscles, leading to smooth muscle hypercontractility, hypertrophy, and impaired relaxation. These changes may worsen difficulty in the esophageal transport. Immune processes differ in the first phase of obstructive bolus transport, and the second phase of muscle hypertrophy and hypercontractility. Moreover, changes in the type of mechanical stress may change immune response and effect on smooth muscles. Understanding immune signaling in causes of obstructive bolus transport, type of mechanical stress, and associated smooth muscle changes may help pathophysiology-based prevention and targeted treatment of esophageal motility disorders. NEW & NOTEWORTHY Esophageal disorders such as esophageal stricture or achalasia, and diffuse esophageal spasm are associated with smooth muscle hypertrophy and hypercontractility, above the obstruction, yet the cause of such changes is unknown. This review suggests that smooth muscle obstructive disorders may cause mechanical stress on smooth muscle, which then secretes chemicals that recruit, microlocalize, and activate mast cells to initiate immune inflammation, producing functional and structural changes in smooth muscles. Understanding the immune signaling in these changes may help pathophysiology-based prevention and targeted treatment of esophageal motility disorders.

Background: There are frequent discrepancies among high-resolution manometry (HRM), functional lumen imaging probe (FLIP), and esophagram in identifying lower esophageal sphincter (LES)-related obstruction. We aimed to determine the frequency of those discrepancies and how they influenced clinical treatment/outcomes., Methods: We identified patients who had all three tests (HRM, FLIP, and esophagram) and endoscopy performed for evaluation of esophageal symptoms in our Center for Esophageal Diseases. Discrepancies among the tests for the presence of LES obstruction were noted, and the performance of individual tests was compared against a consensus opinion rendered by a panel of esophagologists. Binary logistical regression was performed, and ROC curves were generated for prediction of the consensus clinical diagnosis of LES obstruction., Key Results: A total of 126 patients (mean age 57.9 ± 17.0 years; 67% female) met inclusion criteria. All three tests agreed on the presence or absence of LES obstruction in only 72 (57%) patients [no LES obstruction in 57 (45%), LES obstruction in 15 (12%)]. Thirteen patients (10%) had a change in management based on additional findings on FLIP +/- esophagram not seen on HRM with 69% having symptomatic improvement after LES-directed intervention. FLIP was the strongest predictor of a consensus diagnosis of LES obstruction by logistic regression and ROC (OR 23.36, AUC 0.796), followed by HRM (OR 15.41, AUC 0.764)., Conclusions & Inference: High-resolution manometry, functional lumen imaging probe, and esophagram each have considerable limitations for identifying LES obstruction, and discrepancies among these tests occur frequently. Multimodal testing is often required for adequate evaluation of LES-related obstruction., (© 2023 John Wiley & Sons Ltd.)

Absent contractility (AC), a motility disorder characterized by the absence of esophageal contractions while maintaining normal lower esophageal sphincter relaxation, is recognized as a distinctive major disorder of peristalsis on esophageal high-resolution manometry that warrants comprehensive understanding. This unique motility disorder often co-occurs with connective tissue, rheumatologic or autoimmune diseases, with scleroderma being the classic example. Symptoms of gastroesophageal reflux are common. AC can profoundly impact patients' lives and result in a spectrum of complications, including erosive esophagitis, esophageal candidiasis, Barrett's esophagus, and malnutrition. To address the intricate complexities of AC and its multifaceted complications, a multidisciplinary approach is paramount. This approach considers the distinct clinical presentation and underlying rheumatologic conditions of the individual patient, recognizing the inherent diversity within this disorder. While medical management of gastroesophageal reflux remains the cornerstone of AC treatment, emerging surgical and endoscopic interventions offer additional therapeutic options for those grappling with this challenging condition. This comprehensive review provides an in-depth evaluation of recent advances in our understanding of AC and its management. It endeavors to offer valuable insights into therapeutic strategies for AC and its associated issues., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Secondary achalasia or pseudoachalasia is a clinical presentation undistinguishable from achalasia in terms of symptoms, manometric, and radiographic findings, but associated with different and identifiable underlying causes., Methods: A literature review was conducted on the PubMed database restricting results to the English language. Key terms used were "achalasia-like" with 63 results, "secondary achalasia" with 69 results, and "pseudoachalasia" with 141 results. References of the retrieved papers were also manually reviewed., Results: Etiology, diagnosis, and treatment were reviewed., Conclusions: Pseudoachalasia is a rare disease. Most available evidence regarding this condition is based on case reports or small retrospective series. There are different causes but all culminating in outflow obstruction. Clinical presentation and image and functional tests overlap with primary achalasia or are inaccurate, thus the identification of secondary achalasia can be delayed. Inadequate diagnosis leads to futile therapies and could worsen prognosis, especially in neoplastic disease. Routine screening is not justifiable; good clinical judgment still remains the best tool. Therapy should be aimed at etiology. Even though Heller's myotomy brings the best results in non-malignant cases, good clinical judgment still remains the best tool as well., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Gastroesophageal reflux disease (GERD) is characterized by prolonged exposure of the esophageal mucosa to gastric content, with esophageal motility playing a pivotal role in its pathophysiology. This study employs a cross-sectional design to investigate the interplay between esophageal motility, the severity of esophagitis, and age in individuals presenting with GERD symptoms., Objective: The primary objective is to assess proximal and distal esophageal contractions in individuals with GERD symptoms, exploring potential correlations with the severity of esophageal lesions and age., Methods: A total of 47 patients reporting heartburn and acid regurgitation underwent diagnostic investigations, including esophageal manometry, radiological examinations, and endoscopy. Patients were categorized into groups based on the presence and severity of esophagitis. Esophageal contractions were monitored using a manometric method at various distances from the UES after swallowing 5 mL of water., Results: Patients with severe esophagitis (SE) exhibited a reduced distal esophageal contraction amplitude compared to those without esophagitis (WE) or with moderate esophagitis (ME). No significant age-related differences were observed in esophageal contractions. Analyses included contraction amplitude, duration, area under the curve (AUC), and propagation time., Conclusion: This study provides insights into the nuanced relationship between esophageal motility, esophagitis severity, and age in GERD patients. The findings highlight the significance of distal esophageal contractions in SE cases, suggesting potential implications for disease progression. Age did not emerge as a significant factor influencing esophageal motility in this patient cohort., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Fernandes et al.)

Introduction: Epiphrenic diverticulum is a rare disease caused by mucosa and submucosa herniation through the muscular layers of the esophageal wall. This study presents a case of a patient with a symptomatic epiphrenic diverticulum treated with surgery under endoscopic assistance. A review of the literature on this unusual condition was conducted, focusing on the pathogenesis, presentation, and surgical challenges. Methods: A 75-year-old woman who underwent an esophagogastroduodenoscopy (EGD) after experiencing worsening dysphagia for food and liquids. The EGD revealed a large epiphrenic diverticulum 36 cm from the upper incisor teeth. The presence of a diverticulum was verified by barium swallow, which revealed a 6 cm diameter epiphrenic diverticulum on the right side of the esophagus. Results: Patient underwent laparoscopic diverticulectomy associated with Heller's myotomy and anterior partial fundoplication. A gastroscope was placed intraoperatively to calibrate the esophagus to prevent stenosis during diverticulectomy, and it was also used to check the integrity of the esophageal wall. The patient tolerated clear liquids on postoperative day 2. Postoperative course was complicated by right pleural effusion and fever managed with antibiotics and pleural drainage. Conclusion: Epiphrenic diverticulectomy in conjunction with management of the underlying motor dysfunction and avoidance of gastroesophageal reflux disease is an effective procedure. Laparoscopy is considered the approach of choice for the majority of patients. Endoscopic assistance during surgery can help the identification of the diverticulum and verify the integrity of the staple line.

Background: Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility., Methods: We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high-resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed., Key Results: Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm 2 ) and EGJOO (1.2 mmHg/mm 2 ) versus type 2 (2.3 mmHg/mm 2 ) and type 1 achalasia (2.9 mmHg/mm 2 )., Conclusions: Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation., (© 2023 John Wiley & Sons Ltd.)

Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. While the infection is eventually resolved, genetically susceptible individuals may still be at risk of developing achalasia. This study aimed to determine whether immunological and physiological networks differ between male and female patients with achalasia. This cross-sectional study included 189 preoperative achalasia patients and 500 healthy blood donor volunteers. Demographic, clinical, laboratory, immunological, and tissue biomarkers were collected. Male and female participants were evaluated separately to determine the role of sex. Correlation matrices were constructed using bivariate relationships to generate complex inferential networks. These matrices were filtered based on their statistical significance to identify the most relevant relationships between variables. Network topology and node centrality were calculated using tools available in the R programming language. Previous occurrences of chickenpox, measles, and mumps infections have been proposed as potential risk factors for achalasia, with a stronger association observed in females. Principal component analysis (PCA) identified IL-22, Th2, and regulatory B lymphocytes as key variables contributing to the disease. The physiological network topology has the potential to inform whether a localized injury or illness is likely to produce systemic consequences and the resulting clinical presentation. Here we show that immunological involvement in achalasia appears localized in men because of their highly modular physiological network. In contrast, in women the disease becomes systemic because of their robust network with a larger number of inter-cluster linkages., (© 2024. The Author(s).)

Background/aims: While surgery remains a standard treatment for primary esophageal motility disorders (PEMDs), per-oral endoscopic myotomy (POEM) has recently evolved as an alternative. Systematic data on current trends of invasive procedures for PEMDs in Germany are missing., Methods: Hospital discharge data were used to evaluate trends and mortality of invasive treatment options for PEMDs in Germany between 2011 and 2019., Results: 4543 cases of PEMDs (achalasia: n = 4349, dyskinesia of the esophagus: n = 194) receiving open surgery (n = 200), minimal invasive surgery (n = 2366), or POEM (n = 1977) were identified. The relative proportion of POEM significantly increased from 10.9% (2011) to 65.7% (2019). Hospital mortality was 0.2%. The median duration of mechanical ventilation was significantly lower in POEM patients (29.4 hours) compared to open (274.0 hours) or minimal invasive (91.9 hours) surgery. The duration of hospitalization was lowest among POEM patients (5.7 days) compared to surgical procedures (13.7 and 7.7 days)., Conclusion: While the low in-hospital mortality of all procedures combined confirms the solid safety profile of invasive procedures in general, our findings show that POEM has the lowest duration of mechanical ventilation and hospitalization compared to invasive surgical options., Competing Interests: Tom Lüdde received lecture fees from Abbvie, BMS and Gilead as well as travel support from Gilead and Abbvie. Jennis Kandler, Tobias Essing, David Schöler, Georg Flügen, Wolfram T. Knoefel, Christoph Roderburg and Sven H. Loosen have no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Kandler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Study Aims: Peroral endoscopic myotomy (POEM) is the preferred technique for the treatment of esophageal motility disorders and is less invasive than surgery. This study was performed to compare two university centers in the practice of POEM, in terms of efficacy and adverse events, for the treatment of esophageal motility disorder., Patients and Methods: Retrospective comparative study of patients undergoing a POEM between September 2020 and December 2022 from the University Hospital of Liège (Belgium) and Besançon (France). The clinical success was defined by an Eckardt score ≤ 3 after the procedure., Results: Fifty-five patients were included. In both centers, 87,3% of the patients had achalasia (mostly type II), and 12,7% had another esophageal motility disorder. The use of antibiotic prophylaxis was systematic in Liège center but not in Besançon center (100% and 9.1% respectively). The mean value of the post-operative Eckardt score was 1.55± 2.48 in both center with 93.2% of patients with a score ≤ 3 (92% in Besançon and 94.74% in Liège). The rate of adverse event was generally low. There were two minor adverse events more frequent in Liège, clinical capnomediastinum and pain at day one, but they were managed with conservative treatment. Only 7.3% of the total patients had an infectious phenomenon that did not correlate with the use of antibiotic prophylaxis., Conclusion: The post-operative Eckardt score and the adverse event rate were comparable between the university centers. This study confirmed that POEM is a safe and effective technique. It also showed that using an antibiotic prophylaxis does not influence the development of infectious adverse events., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Introduction: The insertion of a high-resolution manometry (HRM) catheter into the stomach is essential for accurate manometric diagnoses; however, it is impossible in some cases due to the inability to traverse the esophagogastric junction (EGJ). Predictive factors for these patients have not been investigated in detail, necessitating time-consuming and burdensome procedures for investigators and patients. Therefore, the present study investigated the percentage of and risk factors for failed intubation at the EGJ., Methods: We initially reviewed the medical charts of consecutive HRM procedures performed at our hospital between September 2018 and January 2023. Patient characteristics and the findings of endoscopy and esophagography (where available) were compared between successful and failed procedures. A multivariate logistic regression analysis was conducted to identify predictive factors for the inability to traverse the EGJ. We then validated the predictive factors identified by reviewing consecutive procedures performed between February 2023 and August 2023., Results: Among the 781 procedures performed, 55 (7.0%) failed due to the inability to traverse the EGJ. Achalasia was the most common disorder in these procedures. An older age and dilated esophagus of &gt;34 mm were independent predictive factors for the inability to traverse the EGJ in patients with treatment-naïve achalasia. In the validation study, 7 out of 68 procedures (10.3%) failed due to the inability to traverse the EGJ. A flowchart using the findings of endoscopy and an esophageal diameter of &gt;34 mm predicted the inability to traverse the EGJ with a sensitivity of 71.4% and specificity of 86.9%., Conclusion: Based on an esophageal diameter &gt;34 mm and endoscopic findings, we predicted the inability to traverse the EGJ in more than 70% of patients. A multi-center prospective study is warranted in the future., (© 2023 S. Karger AG, Basel.)

The lungs and esophagus have a close anatomical and physiological relationship. Over the years, reflux-induced pulmonary injury has gained wider recognition, but the full effects of pulmonary disease on esophageal function are still unknown. Intrathoracic pressure dynamics potentially affect esophageal function, especially in patients with end-stage lung disease, both obstructive and restrictive. Lung transplantation is the only viable option for patients with end-stage pulmonary disease and has provided us with a unique opportunity to study these effects as transplantation restores the intrathoracic environment. Esophageal and foregut functional testing before and after transplantation provide insights into the pathophysiology of the foregut-pulmonary axis, such as how underlying pulmonary disease and intrathoracic pressure changes affect esophageal physiology. This review summarizes the available literature and shares the research experience of a lung transplant center, covering topics such as pre- and posttransplant foregut function, esophageal motility in lung transplant recipients, immune-mediated mechanisms of graft rejection associated with gastroesophageal reflux, and the role of antireflux surgery in this population., Competing Interests: Declaration of Competing Interest No funding was received for the preparation of this manuscript. None of the authors have a conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypercontractile esophagus (HE) is a disorder of increased esophageal body contractile strength on high-resolution esophageal manometry (HREM). Compartmentalized pressurization (CP) is a pattern with an isobaric contour of >30 mmHg extending from the contractile front to the lower esophageal sphincter on HREM. The relevance of CP to HE has yet to be explored., Methods: A retrospective review was performed on 830 HREM studies of patients to identify HE. HE patients' CP status and symptoms by Eckardt score (ES) were reviewed. Diagnoses were made using Chicago Classification (CC) v4.0., Key Results: Forty-seven patients (5.6%) were identified as having HE by CCv3, 30 (3.6%) of which had HE by CCv4. 11/30 HE patients had CP, and 19/30 did not. CP was associated with chronic opioid use (36.4% vs. 5.3% p = 0.047). Presenting ES was greater for HE patients with CP (7 vs. 4). Seven HE patients with CP and 11 without CP were managed medically. ES after medical therapy was higher in HE patients with CP compared to those without CP (9 vs. 0). No HE patients with CP responded to medical therapy. Kaplan-Meier analysis demonstrated significance of this association over time. 83% of all HE patients had all-cause symptom remission., Conclusions & Inferences: HE patients with CP are associated with a higher presenting ES. HE patients with CP do not respond to medical therapy, while HE patients without CP frequently do respond. CP in HE may have prognostic value in determination of treatment strategy for patients with HE., (© 2023 John Wiley & Sons Ltd.)

Background & Aims: Achalasia has been assumed to be an autoimmune disease targeting esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes might be allergy-driven, caused by a form of eosinophilic esophagitis (EoE) in which activated eosinophils and/or mast cells infiltrating esophageal muscle release products that disrupt motility and damage myenteric neurons. To seek epidemiologic support for this hypothesis, we identified patients with achalasia in the Utah Population Database, and explored their frequency of having EoE and other allergic disorders., Methods: We used International Classification of Diseases codes to identify patients with achalasia and allergic disorders including EoE, asthma, atopic dermatitis, contact dermatitis, allergic rhinitis, allergic conjunctivitis, hives/urticaria, and anaphylaxis. We calculated relative risk (RR) for each allergic disorder by comparing the number observed in patients with achalasia with the expected number in individuals matched for birthyear and sex, and we performed subanalyses for patients age ≤40 versus age >40 years., Results: Among 844 patients with achalasia identified (55% female; median age at diagnosis, 58 years), 402 (47.6%) had ≥1 allergic disorder. Fifty-five patients with achalasia (6.5%) had EoE (1.67 EoE cases expected), for a RR of 32.9 (95% confidence interval, 24.8-42.8; P < .001). In 208 patients with achalasia age ≤40 years, the RR for EoE was 69.6 (95% confidence interval, 46.6-100.0; P < .001). RR also was increased significantly for all other allergic disorders evaluated (all greater than 3-fold higher than population rates)., Conclusions: Achalasia is strongly associated with EoE and other allergic disorders. These data support the hypothesis that achalasia sometimes might have an allergic etiology., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions, resulting in dysphagia and noncardiac chest pain. High-resolution manometry (HRM) is essential for the diagnosis of primary EMD; however, the recognition of EMD and HRM by general practitioners in Japan is limited. This review summarizes the diagnosis of and treatment strategies for EMD., Summary: HRM is a specific test for the diagnosis of EMD, whereas endoscopy and barium swallow as screening tests provide characteristic findings (i.e., esophageal rosette and bird's beak sign) in some cases. It is important to note that manometric diagnoses apart from achalasia are often clinically irrelevant; therefore, the recently updated guidelines suggest additional manometric maneuvers, such as the rapid drink challenge, and further testing, including functional lumen imaging, for a more accurate diagnosis before invasive treatment. Endoscopic/surgical myotomy, pneumatic dilation, and botulinum toxin injections need to be considered for patients with achalasia and clinically relevant esophagogastric junction outflow obstruction., Key Message: Since the detailed pathophysiology of EMD remains unclear, their diagnosis needs to be cautiously established prior to the initiation of invasive treatment., (© 2023 S. Karger AG, Basel.)

Background: Endoluminal functional impedance planimetry and panometry assesses secondary peristalsis in response to volumetric distention under sedation. We hypothesize that impedance planimetry and panometry can replace high-resolution manometry in the preoperative assessment prior to anti-reflux surgery., Methods: Single institution prospective data were collected from patients undergoing anti-reflux surgery between 2021 and 2023. A 16-cm functional luminal imaging probe (FLIP) assessed planimetry and panometry prior to surgery under general anesthesia at the start of each case. Panometry was recorded and esophageal contractile response was classified as normal (NCR), diminished or disordered (DDCR), or absent (ACR) in real time by a single panometry rater, blinded to preoperative HRM results. FLIP results were then compared to preoperative HRM., Results: Data were collected from 120 patients, 70.8% female, with mean age of 63 ± 3 years. There were 105 patients with intraoperative panometry, and 15 with panometry collected during preoperative endoscopy. There were 60 patients (50%) who had peristaltic dysfunction on HRM, of whom 57 had FLIP dysmotility (55 DDCR, 2 ACR) resulting in 95.0% sensitivity. There were 3 patients with normal secondary peristalsis on FLIP with abnormal HRM, all ineffective esophageal motility (IEM). No major motility disorder was missed by FLIP. A negative predictive value of 91.9% was calculated from 34/37 patients with normal FLIP panometry and normal HRM. Patients with normal HRM but abnormal FLIP had larger hernias compared to patients with concordant studies (7.5 ± 2.8 cm vs. 5.4 ± 3.2 cm, p = 0.043) and higher preoperative dysphagia scores (1.5 ± 0.7 vs. 1.1 ± 0.3, p = 0.021)., Conclusion: Impedance planimetry and panometry can assess motility under general anesthesia or sedation and is highly sensitive to peristaltic dysfunction. Panometry is a novel tool that has potential to streamline and improve patient care and therefore should be considered as an alternative to HRM, especially in patients in which HRM would be inaccessible or poorly tolerated., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Per-oral endoscopic myotomy (POEM) has become an accepted minimally invasive alternative to Heller myotomy for the treatment of achalasia and other disorders of esophageal dysmotility. One associated adverse event is the inadvertent creation of capnoperitoneum. A proposed mechanism is that extension of the submucosal tunnel below the esophageal hiatus and onto the gastric wall leads to transmural perforation. We hypothesized that the use of impedance planimetry with the endoscopic functional luminal imaging probe (EndoFLIP) more accurately identifies the esophagogastric junction and helps to better define the myotomy's ideal limits, thus lowering the incidence of inadvertent capnoperitoneum., Methods: This is a single-center, retrospective review of consecutive POEM cases from 06/11/2011 to 08/08/2022, with EndoFLIP introduced in 2017. Patient and procedural characteristics, including the incidence of clinically significant capnoperitoneum and decompression, were analyzed using univariate and multivariable linear regression statistics., Results: There were 140 POEM cases identified, 74 (52.9%) of which used EndoFLIP. Clinically significant capnoperitoneum was encountered in 26 (18.6%) cases, with no differences in patient characteristics between those who had capnoperitoneum and those who did not. There was a decreased incidence of capnoperitoneum in cases using EndoFLIP compared to those without (n = 6, 23% vs n = 20, 77%, p = 0.001), with zero instances in the final 56 cases. After adjusting for potentially confounding factors, EndoFLIP use was associated with a - 15.93% (95% confidence interval - 30.68%, - 1.18%) decrease in procedure duration., Conclusions: The routine use of EndoFLIP during POEM was associated with decreased incidence of clinically significant capnoperitoneum, potentially due to improved myotomy tailoring and decreased duration of insufflation with shorter procedure times., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Per-oral endoscopic myotomy (POEM) is a minimally invasive procedure that is very effective in the treatment of achalasia, a rare esophageal motility disorder. POEM has become the first-line treatment for achalasia, with high success rates reported in the literature. However, a known complication of POEM is gastroesophageal reflux disease (GERD). The exact cause and risk factors of post-POEM GERD are not fully understood; however, a number of factors have played a role in its development. The management of post-POEM GERD is mainly by conservative measures, such as lifestyle changes and medications, like proton pump inhibitors (PPI), which are often the first-line method of treatment. However, surgical procedures, such as fundoplication, may be necessary in some patients. This literature review will discuss the effectiveness of the use of PPIs as a management strategy for post-POEM GERD, the factors that lead to PPI-resistant GERD, and other management strategies utilized in these cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nagi et al.)

The Eating Assessment Tool (EAT-10) detects swallowing impairments (dysphagia) self-reported by patients according to their perception. This noninvasive, inexpensive, self-administered instrument is quickly and easily filled out. The objective of this investigation was to evaluate the scores, sensitivity, and specificity of the method to define self-reported dysphagia in Brazilians. EAT-10 scores were evaluated in 443 healthy individuals (273 women and 170 men), aged 20 to 84 years, with no swallowing difficulties or diseases, and 72 patients with diseases that cause dysphagia (35 women and 37 men), aged 29 to 88 years. Each of the 10 instrument items has a 0-4 rating scale, in which 0 indicates no problem and 4, a severe problem; total results range from 0 to 40. The median EAT-10 score of healthy subjects was 0 (range: 0-20), and that of patients was 14.5 (range: 1-40). Considering a ≥ 3 cutoff score to define dysphagia risk, it was self-reported by 97.2% of patients with dysphagia and 9.5% of no-disease individuals (97.2% sensitivity and 90.7% specificity). The positive predictive value of the test was 63% and the negative predictive value was 99.5%. Healthy women had higher scores (median 0, range: 0-20) than healthy men (median 0, range: 0-8, p < 0.01) and more results indicative of self-reported dysphagia (11.7%) than healthy men (5.9%). The EAT-10 cutoff score to detect self-reported dysphagia in Brazilians should be 3, as previously considered. Healthy women complain more of self-reported dysphagia than healthy men. The test has high sensitivity and specificity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In high resolution manometry (HRM), distal contractile integral post multiple rapid swallow augmentation is considered as contraction reserve. The relationship between contraction reserve and esophageal acid reflux remains unclear. The aim of this study was to explore the correlation between contraction reserve and esophageal acid exposure in ineffective esophageal motility (IEM) and normal HRM., Methods: Patients who underwent HRM and ambulatory reflux monitoring were retrospectively screened. Those with diagnosis of normal HRM or IEM were included in the analysis. The proportion of patients with abnormal acid exposure time (AET) was compared between patients with and without contraction reserve. Multivariate regression analysis was performed to determine the predictors of abnormal AET and contraction reserve., Results: A total of 338 patients, including 264 normal HRM and 74 IEM, were included in the analysis. In patients with normal HRM, proportion of abnormal total AET (AET > 6.0%) was significantly lower in patients with supine contraction reserve than patients without contraction reserve (13.85% vs. 24.63%, p = 0.027). Multivariate regression analysis showed that supine contraction reserve could independently predict abnormal total AET (OR = 0.468, 95% CI: 0.249-0.948, p = 0.034), while upright contraction reserve trended strongly (OR = 0.558, 95% CI: 0.290-1.071, p = 0.079). Subgroup analysis showed that upright contraction reserve was an independent predictor of abnormal total AET in patients with 50-70% infective swallows (OR = 0.205, 95% CI: 0.051-0.821, p = 0.025), whereas supine contraction reserve did not have predictive value (p = 0.359)., Conclusions: Supine contraction reserve correlates with esophageal acid reflux in patients with normal HRM, while only upright contraction reserve correlates with esophageal acid reflux in patients with infective swallows of 50-70%., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The esophageal response to stepwise distension during the functional lumen imaging probe (FLIP) Panometry study often parallels high-resolution manometry (HRM) motility diagnoses. This study aimed to describe the changes in FLIP metrics during FLIP emptying, that is, reduced volume distension., Methods: Adult patients who completed FLIP and HRM for esophageal motility evaluation were included. Esophagogastric junction (EGJ) opening parameters were assessed during stepwise FLIP filling to volumes of 60 mL ("filling 60 mL"), then 70 mL, and then back to 60 mL ("emptying 60 mL"). HRM studies were analyzed per Chicago classification version 4.0 (CCv4.0)., Key Results: Among 265 patients included, HRM/CCv4.0 diagnoses included achalasia in 80 patients (30%), normal motility in 70 (26%), and ineffective esophageal motility (IEM) in 43 (16%). EGJ-distensibility index (DI) and EGJ diameter were greater during emptying 60 mL than filling 60 mL in achalasia, normal motility, and IEM (p values <0.002). If applying the emptying 60 mL EGJ-DI (vs. filling 60 mL EGJ-DI), EGJ opening classification changed from reduced EGJ opening to borderline EGJ opening in 31% of achalasia patients and in 2% of patients with normal motility or IEM. EGJ opening classification was unchanged in 69% achalasia and 96% of normal motility/IEM., Conclusions and Inferences: This study suggests that isotonic or auxotonic relaxation of the lower esophageal sphincter occurs with reduced volume distension in patients with achalasia and normal motility. The study also supports the importance of utilizing a standardized FLIP motility study protocol (i.e., controlled, stepwise filling to 50 mL, 60 mL, then 70 mL) to provide reliable and generalizable FLIP metrics to facilitate diagnosis of esophageal motility disorders., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter relaxation and peristalsis of the esophageal body. With the increasing prevalence of achalasia, interest in the role of endoscopy in its diagnosis, treatment, and monitoring is also growing. The major diagnostic modalities for achalasia include high-resolution manometry, esophagogastroduodenoscopy, and barium esophagography. Endoscopic assessment is important for early diagnosis to rule out diseases that mimic achalasia symptoms, such as pseudo-achalasia, esophageal cancer, esophageal webs, and eosinophilic esophagitis. The major endoscopic characteristics suggestive of achalasia include a widened esophageal lumen and food residue in the esophagus. Once diagnosed, achalasia can be treated either endoscopically or surgically. The preference for endoscopic treatment is increasing owing to its minimal invasiveness. Botulinum toxins, pneumatic balloon dilation, and peroral endoscopic myotomy (POEM) are important endoscopic treatments. Previous studies have demonstrated excellent treatment outcomes for POEM, with >95% improvement in dysphagia, making POEM the mainstay treatment option for achalasia. Several studies have reported an increased risk of esophageal cancer in patients with achalasia. However, routine endoscopic surveillance remains controversial owing to the lack of sufficient data. Further studies on surveillance methods and duration are warranted to establish concordant guidelines for the endoscopic surveillance of achalasia.

We define mixed esophageal disease (MED) as a disorder of esophageal structure and/or function that produces variable signs or symptoms, simulating-fully or in part other well-defined esophageal conditions, such as gastroesophageal reflux disease, esophageal motility disorders, or even neoplasia. The central premise of the MED concept is that of an overlap syndrome that incorporates selected clinical, endoscopic, imaging, and functional features that alter the patient's quality of life and affect natural history, prognosis, and management. In this article, we highlight MED scenarios frequently encountered in medico-surgical practices worldwide, posing new diagnostic and therapeutic challenges. These, in turn, emphasize the need for better understanding and management, aiming towards improved outcomes and prognosis. Since MED has variable and sometimes time-evolving clinical phenotypes, it deserves proper recognition, definition, and collaborative, multidisciplinary approach, be it pharmacologic, endoscopic, or surgical, to optimize therapeutic outcomes, while minimizing iatrogenic complications. In this regard, it is best to define MED early in the process, preferably by teams of clinicians with expertise in managing esophageal diseases. MED is complex enough that is increasingly becoming the subject of virtual, multi-disciplinary, multi-institutional meetings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

A novel treatment method for achalasia of the esophagus and related disorders is known as peroral endoscopic myotomy (POEM). This study aimed to calculate the resting energy expenditure (REE) and evaluated the degree of physical invasiveness based on metabolic changes during the perioperative period of POEM. Fifty-eight patients who underwent POEM were prospectively enrolled; REE, body weight (BW), and basal energy expenditure were measured on the day of POEM, postoperative day 1 (POD 1), and three days after POEM (POD 3). The median REE/BW increased from 19.6 kcal/kg on the day of POEM to 24.5 kcal/kg on POD 1. On POD 3, it remained elevated at 20.9 kcal/kg. The stress factor on POD 1 was 1.20. Among the factors, including the Eckardt score, operation time, and the length of myotomy, the length of myotomy was associated with changes in REE/BW. During the perioperative period of POEM, the level of variation in energy expenditure was lower than that of esophageal cancer surgeries performed under general anesthesia. However, because the length of myotomy is a factor affecting changes in energy expenditure, careful perioperative management is desirable for patients with longer myotomy lengths.

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc. The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the HRM with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total score ≥ 7 was considered predictive of ILD, while a score ≥ 10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement. Forty-two patients were included. We found a score ≥ 7 in 11 patients with aperistalsis, in 6 subjects with IEM and in 6 patients with a normal manometry. Otherwise, a score < 7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with IEM and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline LESP and greater HrCT scores at follow-up evaluation were significantly correlated. This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prevailing methods for esophageal motility assessments, such as perfusion manometry and probe-based function imaging, frequently overlook the intricate stress fields acting on the liquid-filled balloons at the forefront of the probing device within the esophageal lumen. To bridge this knowledge gap, we innovatively devised an infusible flexible balloon catheter, equipped with a quartet of PVDF piezoelectric sensors. This design, working in concert with a bespoke local key-node analytical algorithm and a sensor array state analysis model, seeks to shed new light on the dynamic mechanical characteristics at pivotal esophageal locales. To further this endeavor, we pioneered a singular closed balloon system and a complementary signal acquisition and processing system that employs a homogeneously distributed PVDF piezoelectric sensor array for the real-time monitoring of dynamic mechanical nuances in the esophageal segment. An advanced analytical model was established to scrutinize the coupled physical fields under varying degrees of balloon inflation, thereby facilitating a thorough dynamic stress examination of local esophageal nodes. Our rigorous execution of static, dynamic, and simulated swallowing experiments robustly substantiated the viability of our design, the logical coherence of our esophageal key-point stress analytical algorithm, and the potential clinical utility of a flexible esophageal key-node stress detection balloon probe outfitted with a PVDF array. This study offers a fresh lens through which esophageal motility testing can be viewed and improved upon.

Background: Ethnic differences in achalasia presentations have scarcely been described. The association between achalasia and immunologic HLA haplotypes suggests that there may be a genetic predisposition. We aimed to evaluate differences in demographic, clinical, endoscopic, and manometric findings between two distinct ethnic groups with achalasia-Israeli Arabs (IA) and Israeli Jews (IJ)., Methods: A retrospective study was performed at two medical centers. High-resolution manometry (HRM) reports were reviewed for newly-diagnosed achalasia patients. Demographic data, clinical presentations, endoscopy reports, and HRM metrics including the integrated relaxation pressure (IRP) were all reviewed., Results: Overall, 94 achalasia patients were included (53.2% male; mean age 54.5 ± 18.0). 43 patients were IA (45.7%). Body mass index (BMI) was similar in both groups. Compared to IJ, the IA patients had more esophageal dysphagia (100% vs. 88.2%; P = 0.022), chest pain (46.5% vs. 25.5%; P = 0.033), and a tortuous esophagus on endoscopy (23.3% vs. 3.9%; p = 0.005). IA patients were also diagnosed at a younger age than IJ patients (50.9 ± 17.5 vs. 57.5 ± 18.0; p = 0.039). Furthermore, IRP values were higher among IA patients than IJ patients (32.2 ± 13.8 vs. 23.3 ± 8.4; p < 0.001). A regression model analysis found that ethnicity significantly predicted IRP (β = - 10, p < .001)., Conclusion: Ethnicity appears to affect achalasia clinical presentation and HRM findings. IA achalasia patients are diagnosed at a younger age, present with more severe esophageal symptoms, and have a higher IRP compared to IJ patients. Additional studies of diverse, multiethnic populations, especially with genetic evaluations, are required to further assess the role of ethnicity in achalasia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Relieving esophagogastric junction (EGJ) obstruction has been the focus of treatment for achalasia cardia. The recovery of peristalsis has been an elusive goal. Studies analyzing post-intervention peristaltic recovery have several limitations such as the use of conventional manometry or lack of standard definitions of peristalsis. Accordingly, we undertook this study to analyze frequency and pattern of peristaltic recovery following treatment for achalasia cardia on high-resolution manometry (HRM) and standard Chicago definition of peristalsis., Methods: Pre and post-intervention HRM records of 71 treatment-naive patients diagnosed as achalasia cardia were retrospectively analyzed. Records with pre and post-intervention HRM on different systems (e.g. solid state and water perfusion) and those with inadequate information were excluded. All HRMs were interpreted as per Chicago classification version 3.0. After pneumatic dilation (PD) or laparoscopic Heller's myotomy (LHM), pseudorecovery of peristalsis was defined as any contraction at least 3 cm in length along 20 mmHg isobaric contour with a distal latency of less than 4.5 seconds. True recovery and premature contractions were defined by standard Chicago classification v3.0 criteria., Results: Change in diagnosis was observed in 38 of 71 (53.5%) patients after intervention. While pseudo-peristaltic recovery occurred in 11 of 71 (15.5%) patients, only three (4.2%) had a true recovery. Another nine (12.7%) patients showed new premature contractions., Conclusion: True peristaltic recovery is uncommon in achalasia cardia following intervention, particularly PD. Pseudo-peristaltic recovery is more common. Further research is warranted on this issue., (© 2023. Indian Society of Gastroenterology.)

Esophageal high-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders. As this is performed without sedation, it may be poorly tolerated by patients. Additionally, advancing the catheter tip until the stomach may also be difficult, especially if there is a disease affecting the esophagus or esophagogastric junction which may lead to coiling of the catheter. Currently, there are no guidelines as to who can perform HRM. An expert opinion has recommended minimum numbers of cases for the operator to perform in order to obtain and maintain competency. Several studies have reported on the rates of flawed HRM studies with approximately 20% being imperfect, including about 3% with critical flaws. The presence of a large hiatal hernia and achalasia have been identified as predictors of technical failure. Studies with minor flaws are usually still interpretable and clinically useful. Reports have also described several techniques for sedation-assisted placement of the HRM catheter, and this appears to be a promising alternative in cases of failed HRM, especially as sedation does not appear to significantly affect HRM measurements. An algorithm on how to proceed after a technically imperfect HRM study is proposed. Further research in this field is warranted including confirmation of the recommended competency numbers, assessing for quality measures in performing HRM such as technical success rate, identifying additional predictors of technical failure, standardization of the terminology, and qualifying the benefit of sedation-assisted HRM., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Microorganisms provide various benefits to their human hosts, including assisting with digestion, synthesizing certain vitamins, developing the gastrointestinal and immune systems, regulating metabolism, and protecting against some pathogens. However, microbial imbalances can cause tissue damage and contribute to inflammatory disorders and cancers. Microbial dysbiosis refers to an imbalance or disruption in the normal composition and function of the microbial communities that inhabit various body parts, including the gut, oral cavity, skin, and reproductive tract. Emerging research suggests that microbial dysbiosis plays a significant role in cancer development and progression. This issue is particularly relevant in achalasia, in which food stasis, changes in endoluminal pH, and poor esophageal clearance might contribute to esophageal microbial dysbiosis. This study aimed to evaluate the association between dysbiosis and esophageal cancer development, focused on esophageal dysmotility disorders., Methods: This study is a critical review, gathering the current evidence for the association between dysbiosis and the development of esophageal cancer., Results: Studies have shown that microbiota play a role in cancer development, although the mechanisms for how they do so are not yet fully understood. One possible explanation is that microbiota alterations can lead to chronic inflammation, promoting cancer cell growth. Additionally, some bacteria produce toxins that can damage DNA and cause genomic instability, and certain bacterial products can promote tumor growth., Conclusion: Despite the close relationship between dysbiosis and cancer development in esophageal dysmotility disorders, further investigations are still needed to elucidate the precise mechanisms by which dysbiosis contributes to cancer development and to identify potential therapeutic interventions targeting the microbiota to prevent or treat cancer.

Background: We have determined that the impaired accommodation of the lower esophageal sphincter (LES) underlies the pathogenesis of esophagogastric junction outflow obstruction (EGJOO). We have also found that acotiamide may treat EGJOO by improving impaired LES accommodation. The effects of acotiamide in patients with EGJOO need to be further confirmed in a prospective study., Methods: This trial is a multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of acotiamide (300 mg/day or 600 mg/day) with those of a placebo in the treatment of patients with EGJOO. The primary endpoint will be the proportion of patients who report an improvement in symptom of food sticking in the chest after 4 weeks of treatment period 1. The secondary endpoints will be the proportion of patients with normalized integrated relaxation pressure (IRP), the value of change from baseline in the distal contractile integral, basal LES pressure, EGJOO-quality of life score, Gastrointestinal Symptom Rating Scale, and the correlation between IRP and each symptom score. During the 2-year trial period, 42 patients from five institutions will be enrolled., Discussion: This trial will provide evidence to clarify the efficacy and safety of acotiamide as a treatment for patients with EGJOO. Acotiamide might help improve the quality of life of patients with EGJOO and is expected to prevent the progression of EGJOO to achalasia., Trial Registration: This study was approved by the Institutional Review Board (IRB) of Kyushu University Hospital as well as the local IRBs of the participating sites for clinical trials and registered in the Japan Registry of Clinical Trials (jRCT: 2071210072). The registration date is on October 11, 2021., (© 2023. The Author(s).)

Background: The Chicago classification primarily utilizes ten 5 mL liquid swallows in a supine position as the standard high-resolution esophageal manometry (HRM) protocol. HRM can be performed with varying volumes and consistencies and in an upright position. We aimed to determine the impact on HRM results by (1) position, (2) swallows of differing volume and consistency, and (3) perception of bolus passage., Methods: HRM was performed in healthy volunteers (HV) with the following protocol of swallows: liquids 10 × 5 mL, 5 × 10 mL, and 3 × 10 mL multiple rapid swallows; applesauce 5 × 5 mL and 5 × 10 mL; and bread 5 × 2 × 2 cm and 5 × 4 × 4cm. HV rated difficulty of each swallow on a 5-point Likert scale. All HVs performed the protocol in supine position first and then in "semi-upright" (sitting 70 degrees in a bed) and "upright" (sitting in a chair) in a randomized order., Key Results: Thirty-seven HVs, median age 27 years, 64% female completed this study. Median distal contractile integral (DCI) and integrated relaxation pressure 4 s (IRP4) of 5 mL liquid swallows significantly differed (all p < 0.01) between position performed. Large volume swallows resulted in higher DCI and lower IRP4. IRP4 results were significantly increased for 2 × 2 cm pieces of bread compared to 5 mL water swallows. DCI results were higher for 2 × 2 cm pieces of bread compared to 5 mL water swallows. Distal latency was shorter in more upright positions. Among this cohort of HV, perceived difficulty of bolus passage was more likely to occur with solid boluses., Conclusions and Inferences: The volume and consistency of a swallow and the position it is performed in, significantly alter HRM metrics. Interpretation of HRM studies should incorporate different normative values which are specific to the position and bolus type., (© 2023 John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder characterized by a lack of relaxation of the esophagogastric junction (EGJ), with preserved esophageal body peristalsis. We propose new terminology for the coexistence of EGJOO with hypercontractile esophagus and distal esophageal spasm as a major mixed motility disorder (MMMD), and normal peristalsis or a minor disorder of peristalsis such as ineffective esophageal motility with EGJOO as isolated or ineffective EGJOO (IEGJOO)., Methods: We reviewed prior diagnoses of EGJOO, stratified diagnoses as IEGJOO or MMMD, and compared their symptomatic presentations, high-resolution manometry (HRM) and endoluminal functional lumen imaging probe (EndoFLIP) metrics, and treatment responses at 2-6 months of follow-up., Results: Out of a total of 821 patients, 142 met CCv3 criteria for EGJOO. Twenty-two were confirmed by CCv4 and EndoFLIP as having EGJOO and were clinically managed. Thirteen had MMMD, and nine had IEGJOO. Groups had no difference in demographic data or presenting symptoms by Eckardt score (ES). HRM showed MMMD had greater distal contractile integral, frequency of hypercontractile swallows, and frequency of spastic swallows, and greater DI by EndoFLIP. Patients with MMMD showed greater reduction in symptoms after LES-directed intervention when measured by ES compared with IEGJOO (7.2 vs. 4.0)., Conclusion: Patients with MMMD and IEGJOO present similarly. Detectable differences in HRM portend different responses to endoscopic therapy. Because patients with MMMD have greater short-term prognosis, they should be considered a different diagnostic classification to guide therapy., (© 2023 John Wiley & Sons Ltd.)

Hypercontractile esophagus with concomitant esophagogastric junction outflow obstruction (EGJOO) is a rare entity that is characterized by both esophageal hypercontractility and lack of relaxation of the EGJ. The clinical characteristics of these patients are not well-described and there is no strict recommendation regarding the treatment of this condition. We report four cases of patients with hypercontractile esophagus and concomitant to EGJOO. All patients underwent upper gastrointestinal (GI) endoscopy, high-resolution esophageal manometry (HRM) and barium swallow and met the criteria of Chicago Classification for both EGJOO and hypercontractile esophagus. Patients were followed up to four years from diagnosis and clinical symptoms were recorded. Four patients, who underwent evaluation for dysphagia, were found to have both EGJOO and hypercontractile esophagus on HRM. Two of them had mild symptoms and did not undergo treatment with no progression of symptoms on follow-up. Of the two patients who underwent treatment, one had botulinum toxin injection to the EGJ via upper GI endoscopy and one underwent per-oral endoscopic myotomy. Symptoms in both patients improved. Patients with concomitant hypercontractile esophagus and EGJOO present with varying degrees of symptoms and the treatment approach should be personalized according to the degree of symptoms and general clinical condition., (© 2022. Indian Society of Gastroenterology.)