Esophageal Motility Research Articles

Integrative effects of transcutaneous auricular vagus nerve stimulation on esophageal motility and pharyngeal symptoms via vagal mechanisms in patients with laryngopharyngeal reflux disease.

Laryngopharyngeal reflux disease (LPRD) is primarily characterized by discomfort in the pharynx and has limited treatment options. This research aimed to assess the efficacy of transcutaneous auricular vagus nerve stimulation (tVNS) in patients with LPRD and delve into the potential underlying mechanisms. A total of 44 participants, diagnosed with LPRD were divided into two groups randomly. Twice-daily stimulation was delivered for 2 weeks for patients in experimental group, with stimulation ranging from 1.0 mA to 1.5 mA (n = 22), while the control group underwent sham tVNS (n = 22) with the same stimulation parameters and different anatomical location. The severity of symptoms and levels of anxiety and depression were monitored using questionnaires. High-resolution esophageal manometry data were collected, and the patients' autonomic function was assessed through heart rate variability analysis. There was a positive correlation between reflux symptom index (RSI) scores and low frequency/high frequency (LF/HF) ratio (r = 0.619; p < 0.001), Hamilton anxiety scale (HAMA) scores (r = 0.623; p < 0.001), and Hamilton depression scale (HAMD) scores (r = 0.593; p < 0.001). Compared to the pre-tVNS phase, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores were significantly reduced after 2 weeks of treatment. Additionally, the resting pressure of the upper esophageal sphincter (UESP; p < 0.05) and lower esophageal sphincter (LESP; p < 0.05) showed significant enhancement. Notably, tVNS led to an increase in root mean square of successive differences (RMSSD; p < 0.05) and high frequency (HF; p < 0.05) within heart rate variability compared to the pre-treatment baseline. Compared to the control group, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores in tVNS group were significantly lower at the end of treatment. Similarly, the resting pressure of UESP (p < 0.05) and LESP (p < 0.05) in tVNS group were significantly higher than that of control group. Notably, RMSSD (p < 0.05) and HF (p < 0.05) in tVNS group were significantly higher than that of control group. This study demonstrated that tVNS as a therapeutic approach is effective in alleviating LPRD symptoms. Furthermore, it suggests that improvements in esophageal motility could be associated with vagus nerve-dependent mechanisms.

Prediction, prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy: An update.

Achalasia cardia, the most prevalent primary esophageal motility disorder, is predominantly characterized by symptoms of dysphagia and regurgitation. The principal therapeutic approaches for achalasia encompass pneumatic dilatation (PD), Heller's myotomy, and the more recent per-oral endoscopic myotomy (POEM). POEM has been substantiated as a safe and efficacious modality for the management of achalasia. Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy, the incidence of gastroesophageal reflux disease (GERD) following POEM is notably higher than with the aforementioned techniques. While symptomatic reflux post-POEM is relatively infrequent, the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications. Contemporary advancements in the field have enhanced our comprehension of the risk factors, diagnostic methodologies, preventative strategies, and therapeutic management of GERD subsequent to POEM. This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux, potential modifications in the POEM technique to mitigate GERD risk, and the strategies for managing reflux following POEM.

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

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. 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. 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. 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.

Esophageal motility disorders

Esophageal motility disorders

Short-term results of laparoscopic anti-reflux surgery with the RefluxStop device in patients with gastro-esophageal reflux disease and ineffective esophageal motility

PurposeIn gastro-esophageal reflux disease (GERD) requiring surgical treatment, concomitant ineffective esophageal motility (IEM) is a decisive factor in surgical planning, due to concern regarding dysphagia. Anti-reflux surgery with the RefluxStop device is a promising technique. We assessed initial feasibility and clinical outcomes of RefluxStop surgery in patients with GERD and IEM.MethodsRetrospective analysis of patients with GERD, hiatal hernia (HH), and IEM, who underwent surgery with RefluxStop at our institution and achieved 12-month follow-up. Technique feasibility was assessed, in addition to symptom resolution (GERD-HRQL questionnaire), adverse events, HH recurrence, dysphagia, and patient satisfaction. Placement of the device was confirmed by video fluoroscopy on postoperative day 1, and at 3 and 12 months.ResultsBetween June 2020 and November 2022, 20 patients with IEM underwent surgery with RefluxStop and completed 12-month follow-up. All patients reported typical symptoms of GERD, and 12 had preoperative dysphagia. The median HH length was 4.5 cm (IQR, 3.75–5). The median operating time was 59.5 min (IQR, 50.25–64) with no implant-related intra- or postoperative complications. No HH recurrence was observed. One patient reported persistent left-sided thoracic pain at 11 months post-surgery, which required diagnostic laparoscopy and adhesiolysis. Three patients reported severe postoperative dysphagia: balloon dilatation was performed towards resolution. The mean GERD-HRQL scores improved (from 40.7 at baseline to 4.8 at 3 months and 5.7 at 12 months (p <0.001)).ConclusionRefluxStop surgery was feasible and offered effective treatment for this group of patients with GERD and IEM. All patients had complete resolution or significant improvement of GERD symptoms, and 90% of them were satisfied with their quality of life 1 year after surgery.

Autonomic Nervous System Dysfunction in Achalasia.

Achalasia is an esophageal motility disorder characterized by dysphagia and noncardiac chest pain. Impairment of vagal function has been reported in achalasia. This study evaluated autonomic nervous system (ANS) dysfunctions in patients with achalasia to establish a correlation between an ANS dysfunction and the clinical symptoms of achalasia. Nineteen patients with achalasia (six males/13 females; mean age, 47.1±16.3 years) and 10 healthy controls (four males/six females; 34.8±10.7 years) were enrolled prospectively at Gangnam Severance Hospital between June 2013 and June 2014. All patients completed a questionnaire on ANS dysfunction symptoms and underwent a heart rate variability (HRV) test. ANS dysfunction symptoms were present in 13 patients with achalasia (69%) and three controls (30%). The ANS dysfunction score was significantly higher in patients with achalasia than in the controls (p=0.035). There were no significant differences in the standard deviation of all normal R-R intervals, high frequency (HF), low frequency (LF), and LF/HF ratio in the HRV test. In subgroup analysis comparing female achalasia patients with controls, the cardiac activity was significantly higher in the female achalasia patients than in the controls (p=0.036). The cardiac activity (p=0.004) and endurance to stress (p=0.004) were significantly higher in the achalasia patients with ANS dysfunction symptoms than the achalasia patients without ANS dysfunction symptoms. ANS dysfunction symptoms are common in patients with achalasia. Female achalasia patients and those with ANS dysfunction symptoms showed increased cardiac activity. Hence, more attention should be paid to cardiac overload in achalasia patients who are female or have ANS dysfunction symptoms.

A212 SYMPTOMS IN PATIENTS WITH NORMAL ESOPHAGEAL MOTILITY MAY DIFFER BASED ON AGE AND SEX

Abstract Background High resolution esophageal manometry (HREM) is used to diagnose esophageal motility disorders. While esophageal symptoms including dysphagia are common and seen in up to 20% of adults, a minority of symptomatic patients have esophageal dysmotility, when defined by the Chicago Classification v4 (CCv4). The generation of esophageal symptoms in a patient with normal esophageal motor function is complex, but may relate to visceral hypersensitivity, inappropriate pain perception or unidentified contraction abnormalities. The Esophageal Symptom Questionnaire (ESQ-30) is a validated tool in the assessment of esophageal symptoms and measures the frequency and severity of dysphagia, reflux and globus through three separate sub-scales (ESQ-D, ESQ-R, ESQ-G respectively). Aims To determine age and sex in esophageal symptoms (as measured by ESQ-30 sub-scales) in a population of symptomatic patients with normal esophageal motility. Methods Retrospective analysis of consecutive reports from HRM studies performed between October 2021 – March 2023 who provided consent for inclusion in the motility databank and completed ESQ-30 questionnaires. All values expressed as median (IQR: 25-75-centile). Spearman’s bivariate correlations were performed between ESQ-D, ESQ-R, ESQ-G and manometric variables (IRP, DCI, % failed, and % weak) as well as demographic variables (age). Group means were compared with the non-parametric Mann-Whitney U test. Results Within the study period, 681 patients underwent HREM and had complete ESQ-30 questionnaires. Of these patients, 151 female and 73 male participants (mean age 51.8 +/- 15.2 years) had normal esophageal motility by CCv4. ESQ-D and ESQ-R scores were significantly higher in women in comparison to men. ESQ-D was 10 in women and 5 in men (p=.021), and ESQ-R was 28 in women and 19 in men (p=.029). There was a weak negative correlation between age and reflux symptoms (R2 -.139, p = 0.038). There was no significant difference in manometric parameters between males and females (p ampersand:003E .05 for all comparisons). Dysphagia and globus weakly negatively correlated with median IRP (R2 -.156, p = .019 and R2 -.139, p = .038 for dysphagia and globus respectively). Conclusions In a population of symptomatic patients with normal esophageal motility, symptom profile differed based on age and sex. Women had higher dysphagia and reflux symptoms compared to men, while older patients had lower reflux symptoms. These findings suggest that esophageal sensitivity may vary with age and sex in patients with normal esophageal motility. The finding of higher dysphagia and globus symptoms in patients with lower median IRP (integrated relaxation pressure) is an unexpected finding and may reflect reflux effect. Further studies to assess for the impact of GERD (using 24h pH-metry/MII) on patients with normal esophageal motor function are warranted. Funding Agencies None

A202 A CASE OF MYCOBACTERIUM WOLINSKYI PULMONARY INFECTION SECONDARY TO LONG-STANDING ACHALASIA IN AN IMMUNOCOMPETENT PATIENT

Abstract Background Achalasia is an esophageal motility disorder resulting in chronic esophageal obstruction and stasis. Rapidly growing mycobacterium (RGM) pulmonary infections have been previously observed in individuals with underlying gastro-esophageal motility disorders. To date, pulmonary Mycobacterium wolinskyi infection (MWI) in the setting of achalasia has not previously been reported. Aims Our aim is to present a novel case of M. wolinskyi pneumonia in a patient with achalasia. We also searched the medical literature to identify previously reported associations between achalasia, chronic regurgitation symptoms and MWI. M. wolinskyi is an emerging clinical concern among RGMs. While primarily associated with post-operative, prosthetic joint and skin and soft tissue infections, M. wolinskyi pulmonary infections have not been documented to date in an immunocompetent patient. Methods We present a retrospective clinical case description of our case. We carried out a literature review from 1999 to Oct 2023, with the keywords "M. wolinskyi and infection. Results A 34-year-old male presented with a several-month history of productive cough, exertional dyspnea, fatigue, and unintentional weight loss of 17 kg over the past 6 months. Despite multiple courses of oral and intravenous antibiotics, there was no clinical improvement. His medical history included long-standing achalasia requiring previous pneumatic dilations. On admission, his chest X-ray revealed bilateral interstitial and alveolar infiltrates with consolidation. Routine microbiology and viral panels were negative. CT scan showed widespread bilateral consolidation and a dilated and fluid-filled esophagus. A timed barium swallow demonstrated dilated esophagus with irregular tertiary contractions and limited GE-J opening. Sputum cultures were positive for MWI on day 8 of admission (BACTEC MGIT). This was confirmed with lung biopsy demonstrating MWI with necrotizing granulomatous inflammation. The patient was prescribed a 12-month course of doxycycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Inpatient pneumatic dilation to 35 mm was performed. At discharge, his swallowing was subjectively improved, and a follow-up swallowing study noted improvement with no evidence of regurgitation. Conclusions Chronic esophageal obstruction provides an ideal lipid-rich environment for RGM infections. Related mycobacterial species have been isolated in pulmonary infections have been linked to chronic esophageal obstruction. To date, no cases of M. wolinskyi pulmonary infection with achalasia have been reported. We present a unique case of M. wolinskyi pulmonary infection in an immunocompetent patient with chronic achalasia, adding to our understanding of this emerging clinical concern. Funding Agencies None

A214 AGE, SEX AND POSITION INFLUENCE UPPER ESOPHAGEAL SPHINCTER PRESSURES

Abstract Background Upper esophageal sphincter (UES) function may be evaluated using high resolution manometry (HRM) to measure manometric parameters specific to the UES. The UES parameters are not well established however there is evidence suggesting a relationship between the UES parameters and esophageal motility disorders as well as UES parameters and symptoms including dysphagia, globus sensation and reflux. The Esophageal Symptom Questionnaire (ESQ-30) is a validated tool in the assessment of esophageal symptoms and measures the frequency and severity of dysphagia, reflux and globus through three separate sub-scales (ESQ-D, ESQ-R, ESQ-G respectively). Aims We aimed to identify the relationship between UES manometric variables and patient demographic variables (age, sex) as well as patient symptoms including broad categories of globus sensation, dysphagia and reflux. Methods Retrospective analysis of consecutive reports from HRM studies performed between October 2021 – March 2023 who provided consent for inclusion in the motility databank and completed ESQ-30 questionnaires. All values expressed as median (IQR: 25-75-centile). Values were compared with the non-parametric Mann-Whitney U test. Relationships between manometric diagnosis, UES pressures and symptomatology were explored. Results 681 patients underwent esophageal manometry and completed the ESQ-30 questionnaire. These patients were 442 (65%) female (mean age 54.6 +/- 14.8 years). Over the study period, 318 patients underwent esophageal HRM in the upright position and were diagnosed according to CCv3 and 361 patients underwent HRM in the supine position and were diagnosed by CCv4 manometric criteria. UES mean basal pressure was significantly higher in females than males (64.6 [42.3-89.1] vs 68.4 [48.4-96.1], p = .015) as well as in the supine position (77.5 [55.9-101.0] vs. 56.0 [38.7-80.3]. UES mean basal pressure was negatively correlated with age (R2 -.28 p ampersand:003C .001). In terms of esophageal symptomatology, dysphagia scores (ESQ-D) were negatively correlated with UES mean basal pressure (R2 -.15, p ampersand:003C .001). Conclusions Age, sex and position may influence UES manometric pressures. The finding of higher UES pressures in the supine position may reflect a mechanism for decreasing proximal reflux. The decreased UES basal pressure with age is possibly related to changes in the integrity of the neuromuscular system. Having a better understanding of the poorly understood normal UES dynamics and how this changes in motility disorders may allow us to more specifically target areas for treatment. Funding Agencies None

Unraveling the Dynamics of Esophageal Motility, Esophagitis Severity, and Age in GERD Patients: A Cross-Sectional Exploration.

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. 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. 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. 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. 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.

Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease.

The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs). To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function. This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means. Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study. CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.

Mental Health and Quality of Life among Egyptian Patients with Esophageal Motility Disorders: A Psychiatric Assessment

Mental Health and Quality of Life among Egyptian Patients with Esophageal Motility Disorders: A Psychiatric Assessment

When less is more: lower esophageal sphincter-preserving peroral endoscopic myotomy is effective for non-achalasia esophageal motility disorders.

Non-achalasia esophageal motility disorders (NAEMDs), encompassing distal esophageal spasm (DES) and hypercontractile esophagus (HCE), are rare conditions. Peroral endoscopic myotomy (POEM) is a promising treatment option. In NAEMDs, unlike with achalasia, the lower esophageal sphincter (LES) functions normally, suggesting the potential of LES preservation during POEM. This retrospective two-center observational study focused on patients undergoing LES-preserving POEM (LES-POEM) for NAEMD. Eckardt scores were assessed pre-POEM and at 6, 12, and 24 months post-POEM, with follow-up endoscopy at 6 months to evaluate for reflux esophagitis. Clinical success, defined as an Eckardt score ≤3, served as the primary outcome. 227 patients were recruited over 84 months until May 2021. Of these, 16 underwent LES-POEM for an NAEMD (9 with HCE and 7 with DES). The median pre-POEM Eckardt score was 6.0 (interquartile range [IQR] 5.0-7.0), which decreased to 1.0 (IQR 0.0-1.8; P<0.001) 6 months post-POEM. This was sustained at 24 months, with an Eckardt score of 1.0 (IQR 0.0-1.8; P<0.001). Two patients (12.5%) developed Los Angeles grade A or B esophagitis. LES-POEM for NAEMD demonstrates favorable clinical outcomes, with infrequent esophagitis and reintervention for LES dysfunction rarely required.

Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.

Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Characterization of Laryngopharyngeal Reflux in the Elderly Population

Laryngopharyngeal reflux (LPR) often is not diagnosed due to its presentation without heartburn. The aim of this study was to analyze the signs and symptoms of elderly patients undergoing treatment for LPR using subjective as well as objective measures including strobovideolaryngoscopies, 24-hour pH studies, and manometry to highlight appropriate considerations for diagnosis and treatment. This was a retrospective review of patients with laryngopharyngeal reflux who were seen from January 2010 to February 2021 in the practice of the senior author (Robert T. Sataloff) who had undergone 24-hour pH testing, and for whom all data were available. Patients aged 60 years and older were considered elderly and compared to patients younger than 40 and between the ages of 40 and 59. However, patients in their 60s, 70s, and 80s were evaluated and compared separately. Objective reflux findings, 24-hour pH studies, and manometry were compared between groups. Two hundred and eighty-eight patients being treated for LPR were included, 100 of whom were over the age of 60. While 94.1% of patients younger than 40 had a chief complaint of hoarseness, 71% percent of those aged 60 and older complained of hoarseness. Patients aged 60 and older were more likely to present with no voice complaint as their age increased (P = 0.001). Lower esophageal sphincter residual pressure was 12.15 ± 6.28 in elderly patients compared to 4.90 ± 3.38 in patients younger than 40 (P < 0.001). Upper esophageal sphincter (UES) basal pressure was decreased in elderly patients at 83.84 ± 50.53 compared to 105.92 ± 51.49 in patients younger than 60 or younger (P = 0.029). Older patients in their 70s and 80s also had lower UES basal pressures at 75.79 ± 47.66 and 63.45 ± 14.50 (P = 0.003). Additionally, while 71.4% of patients younger than 40 had normal esophageal motility (Chicago classification v4), only 40% of elderly patients had normal esophageal motility (P < 0.001). More severe ventricular obliteration also was present in elderly patients compared to non-elderly patients (P = 0.032), and thick endolaryngeal mucus was less likely to be present in elderly patients (P = 0.007). Reflux finding score differed between age groups with patients aged less than 40 scoring 14.78 ± 2.5, 40-59 year olds scoring 15.83 ± 2.13 and patients 60 and older scoring 15.48 ± 2.43 (P = 0.018). Elderly patients diagnosed with LPR have different presentations of the disease compared with younger patients.

Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility: Studies Using High-resolution Manometry.

This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. Codeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Interpretation of Impedance Data on High-resolution Impedance Manometry Studies-A Worldwide Survey.

Esophageal manometry is the gold standard for esophageal motility evaluation. High-resolution esophageal manometry with impedance (HRIM) allows concurrent assessment of bolus transit and manometry. Inconsistencies between concomitant impedance and manometry data pose a clinical dilemma and has not yet been addressed. We aim to assess interpretation trends of HRIM data among gastroenterologists worldwide. A cross-sectional study using an anonymous survey was conducted among gastroenterologists worldwide. Statistical analysis was performed to compare responses between providers. We received responses from 107 gastroenterologists (26 countries). Most were adult providers (69, 64.5%), and most (77, 72.0%) had > 5 years of experience. Impedance was found to be helpful by 83 (77.6%) participants, but over 30% reported inconsistencies between impedance and manometry data. With incomplete bolus clearance and normal manometry 41 (38.7%) recommended observation, 41 (38.7%) recommended 24-hours pH-impedance, and 16 (15.1%) recommended prokinetics. With abnormal manometry and complete bolus clearance, 60 (57.1%) recommended observation while 18 (17.1%) recommended 24-hours pH impedance and 15 (14.3%) recommended prokinetics. A significant difference was found between providers from different continents in treating cases with discrepancy between impedance and manometry findings (P < 0.001). No significant differences were seen in responses between adult versus pediatric providers and between providers with different years of experience. There is no consensus on interpreting HRIM data. Providers' approaches to studies with inconsistencies between manometry and impedance data vary. There is an unmet need for guidelines on interpreting impedance data in HRIM studies.

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.

Fifteen-year symptomatic outcome of patients with nonactionable motor findings on high-resolution manometry.

High-resolution manometry (HRM) is performed for evaluation of esophageal symptoms, but patient outcome is unclear when no actionable motor disorder is identified. We evaluated long-term symptomatic outcome of patients with nonactionable HRM findings. Patients who underwent (HRM) studies in 2006-2008 were tracked. Patients with achalasia spectrum disorders, foregut surgery before or after HRM, and incomplete symptom documentation were excluded. Symptom questionnaires assessing dominant symptom intensity (DSI, product of symptom severity and frequency recorded on 5-point Likert scales) and global symptom severity (GSS, from 10 cm visual analog scale) were repeated. Change in symptom burden was compared against HRM motor findings using Chicago Classification 4.0 (CCv4.0), applied retroactively to 2006-2008 data. Overall, 134 patients (median age 68 years, 64.5% female) could be contacted. The majority (73.1%) had normal motility; others had ineffective esophageal motility (8.2%), esophagogastric junction outflow obstruction (13.4%), hypercontractile esophagus (3.0%), or absent contractility (2.2%), none managed invasively. Over 15 years of follow-up, DSI decreased from 8.0 (4.0-16.0) to 1.0 (0.0-6.0) (p < 0.001) and GSS improved from 5.5 (3.3-7.7) to 2.0 (0.0-4.0) (p < 0.001); improvement was consistent across CCv4.0 diagnoses and subgroups. The majority (82.8%) reported improvement over time, and antisecretory medication was the most effective intervention (83.0% improvement). There was no difference in medication efficacy (p = 0.75) or improvement in symptoms (p = 0.20) based on CCv4 diagnosis. Esophageal symptoms improve with conservative symptomatic management over long-term follow-up when no conclusive obstructive motor disorders or achalasia spectrum disorders are found on HRM.

A Comparison between Chicago Classification Versions 3.0 and 4.0 and Their Impact on Manometric Diagnoses in Esophageal High-Resolution Manometry Cases

High-resolution manometry (HRM) facilitates the detailed evaluation of esophageal motility. In December 2020, Chicago classification (CC) version 4.0 introduced modifications to improve consistency and accuracy. We conducted this study to compare the differences in the interpretations of HRM examinations between CC 3.0 and 4.0. Consecutive HRM records at a Taiwan tertiary medical center, including wet swallows and MRS performed in both supine and sitting positions from October 2019 to May 2021, were retrospectively reviewed and analyzed using both CC versions 3.0 and 4.0. A total of 105 patients were enrolled, and 102 patients completed the exam, while three could not tolerate HRM sitting up. Refractory gastroesophageal reflux disease (GERD) symptoms (n = 65, 63.7%) and dysphagia (n = 37, 36.3%) were the main indications. A total of 18 patients (17.6%) were reclassified to new diagnoses using CC 4.0. Of the 11 patients initially diagnosed with absent contractility, 3 (27.3%) were reclassified as having Type 1 achalasia. Of the 18 patients initially diagnosed with IEM, 6 (33.3%) were reclassified as normal. The incidence of diagnosis changes was similar in both the dysphagia and refractory GERD symptoms groups (21.6% versus 15.3%, p = 0.43). The use of CC 4.0 led to changes in the diagnoses of esophageal motility disease, irrespective of examination indications. Early adoption improves the accuracy of diagnoses and affects patient management.