Multicentric short term and safety study of ineffective esophageal motility patients treated with RefluxStop device.

Gastroesophageal reflux disease (GERD) presents a general health problem with a variety of symptoms and an impairment of life quality. Conservative therapies do not offer sufficient symptom relief in up to 30% of patients. Patients who suffer from ineffective esophageal motility (IEM) and also GERD may exhibit symptoms ranging from mild to severe. In cases where surgical intervention becomes necessary for this diverse group of patients, it is important to consider the potential occurrence of postoperative dysphagia. RefluxStop is a new alternative anti-reflux surgery potentially reducing postoperative dysphagia rates. In this bicentric tertiary hospital observational study consecutive patients diagnosed with PPI refractory GERD and IEM that received RefluxStop implantation were included. A first safety and efficacy evaluation including clinical examination and GERD-HRQL questionnaire was conducted. 40 patients (25 male and 15 female) were included. 31 patients (77.5%) were on PPI at time of surgery, with mean acid exposure time of 8.14% ± 2.53. The median hospital stay was 3 days. Postoperative QoL improved significantly measured by GERD HRQL total score from 32.83 ± 5.08 to 6.6 ± 3.71 (p < 0.001). A 84% reduction of PPI usage (p < 0.001) was noted. 36 patients (90%) showed gone or improved symptoms and were satisfied at first follow-up. Two severe adverse events need mentioning: one postoperative slipping of the RefluxStop with need of immediate revisional operation on the first postoperative day (Clavien-Dindo Score 3b) and one device migration with no necessary further intervention. RefluxStop device implantation is safe and efficient in the short term follow up in patients with GERD and IEM. Further studies and longer follow-up are necessary to prove long-lasting positive effects.

INFLUENCE OF ESOPHAGEAL MOTILITY IMPAIRMENT ON UPPER AND LOWER ESOPHAGEAL SPHINCTER PRESSURE IN CHAGAS DISEASE.

BACKGROUND: Chagas disease causes digestive anatomic and functional changes, including the loss of the myenteric plexus and abnormal esophageal radiologic and manometric findings. OBJECTIVE: To evaluate the association of abnormal esophageal radiologic findings, cardiac changes, distal esophageal contractions, and complaints of dysphagia and constipation in upper (UES) and lower (LES) esophageal sphincter basal pressure in Chagas disease patients. METHODS: The study evaluated 99 patients with Chagas disease and 40 asymptomatic normal volunteers. The patients had normal esophageal radiologic examination (n=61) or esophageal retention without an increase in esophageal diameter (n=38). UES and LES pressure was measured with the rapid pull-through method in a 4-channel water-perfused round catheter. Before manometry, the patients were asked about dysphagia and constipation and submitted to electrocardiography and chest radiography. RESULTS: The amplitude of esophageal distal contraction decreased from controls to chagasic patients with esophageal retention. The proportion of failed and simultaneous contractions increased in patients with abnormal radiologic examination (P<0.01). There were no significant differences in UES and LES pressure between the groups. UES pressure was similar between Chagas disease patients with cardiomegaly (n=27, 126.5±62.7 mmHg) and those without it (n=72, 144.2±51.6 mmHg, P=0.26). Patients with constipation had lower LES pressure (n=23, 34.7±20.3 mmHg) than those without it (n=76, 42.9±20.5 mmHg, P<0.03). CONCLUSION: Chagas disease patients with absent or mild esophageal radiologic involvement had no significant changes in UES and LES basal pressure. Constipation complaints are associated with decreased LES basal pressure.

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

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

Inability to belch syndrome: what the gastroenterologist needs to know.

PURPOSE OF REVIEW: To review recent publications on the inability to belch syndrome. RECENT FINDINGS: Five recent retrospective case series indicate that the inability to belch syndrome usually starts in early childhood and is often accompanied by gurgling noises in the chest, pain in the chest or upper abdomen, bloating, and excessive flatulence. Currently, the vast majority of patients who have been identified with inability to belch have self-diagnosed the syndrome on the basis of information available on the internet. A favorable response to injection of botulinum toxin in the cricopharyngeus muscle is regarded as confirmation of the diagnosis. In a mechanistic study in eight patients, absence of reflexogenic relaxation of the upper esophageal sphincter upon rapid gaseous esophageal distension was confirmed to play a pivotal role in the pathogenesis of the syndrome. SUMMARY: The inability to belch syndrome, caused by failure of the upper esophageal sphincter to relax when the esophageal body is distended, clearly exists and may not be as rare as thought hitherto. However, overdiagnosis is also likely to occur because the diagnosis is usually made on the basis of symptoms only. The efficacy of botulinum toxin injection in the upper sphincter needs to be assessed in double-blind placebo-controlled studies.

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

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

Personalized anti-reflux surgery: connecting GERD phenotypes in 690 patients to outcomes.

BACKGROUND: Anti-reflux operations are effective treatments for GERD. Despite standardized surgical techniques, variability in post-operative outcomes persists. Most patients with GERD possess one or more characteristics that augment their disease and may affect post-operative outcomes-a GERD "phenotype". We sought to define these phenotypes and to compare their post-operative outcomes. METHODS: We performed a retrospective review of a prospective gastroesophageal database at our institution, selecting all patients who underwent an anti-reflux procedure for GERD. Patients were grouped into different phenotypes based on the presence of four characteristics known to play a role in GERD: hiatal or paraesophageal hernia (PEH), hypotensive LES, esophageal dysmotility, delayed gastric emptying (DGE), and obesity. Patient-reported outcomes (GERD-HRQL, dysphagia, and reflux symptom index (RSI) scores) were compared across phenotypes using the Wilcoxon rank-sum test. RESULTS: 690 patients underwent an anti-reflux procedure between 2008 and 2022. Most patients underwent a Nissen fundoplication (302, 54%), followed by a Toupet or Dor fundoplication (205, 37%). Twelve distinct phenotypes emerged. Non-obese patients with normal esophageal motility, normotensive LES, no DGE, with a PEH represented the most common phenotype (134, 24%). The phenotype with the best post-operative GERD-HRQL scores at one year was defined by obesity, hypotensive LES, and PEH, while the phenotype with the worst scores was defined by obesity, ineffective motility, and PEH (1.5 ± 2.4 vs 9.8 ± 11.4, p = 0.010). There was no statistically significant difference in GERD-HRQL, dysphagia, or RSI scores between phenotypes after five years. CONCLUSIONS: We have identified distinct phenotypes based on common GERD-associated patient characteristics. With further study these phenotypes may aid surgeons in prognosticating outcomes to individual patients considering an anti-reflux procedure.

Peroral endoscopic myotomy: a two-center retrospective study of practice and adverse events.

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.

Implementation and Analysis of a 5-Year Online Esophageal Motility Curriculum for Gastroenterology Fellows.

BACKGROUND: Motility disorders are frequently encountered in gastroenterology (GI) practice, yet a national structured training curriculum for GI fellows in motility disorders is lacking. Since GI fellowships vary considerably in opportunities for specialized esophageal motility (EM) training, novel educational technology may be leveraged to provide standardized EM curriculum to train GI fellows in esophageal manometry. METHODS: GI fellows participated in an online EM learning program at a single academic center from 2017 to 2022. Fellows answered case-based questions and were provided with evidence-based, corrective feedback related to core EM learning objectives. The primary outcome was change in knowledge and comfort in interpretation and clinical application of EM studies. RESULTS: Sixty-nine fellows actively participated in the online EM curriculum. 65 fellows completed a pre-curriculum test, and 54 fellows completed a post-curriculum test. There was a cumulative improvement between pre-curriculum test and post-curriculum test scores from 70 to 87%, respectively (p < 0.001). Fellows had a mean improvement of 19% in questions as they progressed through the curriculum. Prior to enrolling in the EM course, 26% of fellows felt comfortable in interpreting EM studies compared to 54% of fellows after completion of the program (p < 0.001). CONCLUSION: An online, technology-based curriculum was effective in educating GI fellows on core competencies of EM. Fellows demonstrated improvement in proficiency of clinically important EM studies and increased comfort in interpreting EM studies. Further studies are needed to evaluate the use of technology-based learning to widely disseminate a structured training curriculum in EM, particularly in training programs without a motility presence.

Pediatric retrograde cricopharyngeal dysfunction diagnosed by high-resolution impedance manometry.

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.

The impact of lung transplantation on esophageal motility and inter-relationships with reflux and lung mechanics in patients with restrictive and obstructive respiratory disease.

BACKGROUND: For many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed. METHODS: We prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33-75 years; 42 men) who underwent high resolution impedance manometry and 24-h pH-impedance before and after LTx. KEY RESULTS: RLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post-LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre-LTx (p < 0.001), reducing only in OLD patients' post-LTx (p = 0.02). Reduced EL post-LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco-abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05). CONCLUSIONS AND INFERENCES: RLD patients are more likely to show improvement in esophageal motility than OLD patients post-LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration.

Peroral endoscopic myotomy and its use in non-achalasia disorders.

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.

Does the presence of an esophageal motor disorder influence the response to anti-reflux mucosectomy (ARMS) for refractory GERD?

INTRODUCTION: The prevalence of esophageal motor disorders (EMD) in PPI-refractory gastroesophageal reflux disease (GERD) is substantial. However, limited data exist on their impact on the efficacy of endoscopic treatments like anti-reflux mucosectomy (ARMS). This study aimed to evaluate the influence of EMD on ARMS efficacy in patients with PPI-refractory GERD. METHOD: This single-center retrospective study enrolled patients with refractory GERD treated with ARMS-b (anti-reflux mucosectomy band-ligation). High-resolution esophageal manometry (HREM) was conducted before the procedure to identify EMD presence. The primary endpoint was treatment efficacy, defined as >50% improvement in GERD-HRQL score at 1 year. Secondary endpoints included PPI intake, symptom control, ARMS complications, and overall patient satisfaction at 12 months. RESULTS: The study included 65 patients, with 41 (63.1%) showing EMD on HREM. Treatment efficacy was achieved by 33.8% (22) of patients, with 8 without EMD, 11 having isolated LES hypotonia, and 3 with both LES hypotonia and esophageal body motor disorder. No significant differences were observed between patients with and without EMD regarding the primary endpoint, PPI use, symptom control, or complications. Dysphagia developed in 52.3% (34) within 6 months, leading to esophageal dilatation in 15.3% (10). Two patients experienced acute hemorrhage, and one had perforation. CONCLUSION: The presence of esophageal motor disorders does not seem to impact ARMS response, suggesting the technique's consideration in this population. Larger studies are essential for confirming these results and exploring treatment response and post-operative predictors.

Artificial Intelligence Tools for Improving Manometric Diagnosis of Esophageal Dysmotility.

PURPOSE OF REVIEW: Artificial intelligence (AI) is a broad term that pertains to a computer's ability to mimic and sometimes surpass human intelligence in interpretation of large datasets. The adoption of AI in gastrointestinal motility has been slower compared to other areas such as polyp detection and interpretation of histopathology. RECENT FINDINGS: Within esophageal physiologic testing, AI can automate interpretation of image-based tests, especially high resolution manometry (HRM) and functional luminal imaging probe (FLIP) studies. Basic tasks such as identification of landmarks, determining adequacy of the HRM study and identification from achalasia from non-achalasia patterns are achieved with good accuracy. However, existing AI systems compare AI interpretation to expert analysis rather than to clinical outcome from management based on AI diagnosis. The use of AI methods is much less advanced within the field of ambulatory reflux monitoring, where challenges exist in assimilation of data from multiple impedance and pH channels. There remains potential for replication of the AI successes within esophageal physiologic testing to HRM of the anorectum, and to innovative and novel methods of evaluating gastric electrical activity and motor function. The use of AI has tremendous potential to improve detection of dysmotility within the esophagus using esophageal physiologic testing, as well as in other regions of the gastrointestinal tract. Eventually, integration of patient presentation, demographics and alternate test results to individual motility test interpretation will improve diagnostic precision and prognostication using AI tools.

Surgical and per-oral endoscopic myotomy (POEM) for the treatment of primary esophageal motility disorders: A systematic analysis of current trends in Germany between 2011 and 2019.

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.

Achalasia alters physiological networks depending on sex.

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.

Role of mechanoregulation in mast cell-mediated immune inflammation of the smooth muscle in the pathophysiology of esophageal motility disorders.

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.