Lower Esophageal Sphincter Tone Research Articles

The Impact of Chronic Cannabis Use on Esophageal Motility in Patients Referred for Esophageal Manometry.

Tetrahydrocannabinol, the main psychoactive compound in cannabis, binds with high affinity to the cannabinoid 1 receptor. Small randomized controlled studies using conventional manometry have shown that the cannabinoid 1 receptor can modulate esophageal function, namely transient lower esophageal sphincter relaxation frequency and lower esophageal sphincter tone. The effect of cannabinoids on esophageal motility in patients referred for esophageal manometry has not been fully elucidated using high-resolution esophageal manometry (HREM). We aimed to characterize the clinical effect of chronic cannabis use on esophageal motility utilizing HREM. Patients who underwent HREM from 2009 to 2019 were identified at 4 academic medical centers. The study group consisted of patients with a noted history of chronic cannabis use, a diagnosis of cannabis-related disorder, or a positive urine toxicology screen. Age and gender-matched patients with no history of cannabis use were selected to form the control group. Data on HREM metrics based on the Chicago classification V3, and the prevalence of esophageal motility disorders were compared. Confounding effects of BMI and medications on esophageal motility were adjusted for. Chronic cannabis use was found to be an independent negative predictor of weak swallows (β=-8.02, P =0.0109), but not a predictor of failed swallows ( P =0.6890). The prevalence of ineffective esophageal motility was significantly lower in chronic cannabis users compared with nonusers (OR=0.44, 95% CI 0.19-0.93, P =0.0384). There was no significant difference in the prevalence of other esophageal motility disorders between the 2 cohorts. In patients with dysphagia as their primary indication for HREM, chronic cannabis use was found to be independently associated with increased median integrated relaxation pressure (β=6.638, P =0.0153) and increased mean lower esophageal sphincter resting pressure (β=10.38, P =0.0084). Chronic cannabis use is associated with decreased weak swallows and reduced prevalence of ineffective esophageal motility in patients referred for esophageal manometry. In patients referred for dysphagia, chronic cannabis use is associated with increased integrated relaxation pressure and lower esophageal sphincter resting pressure, though not to levels above the normal range.

Protocol for an international multicenter randomized controlled trial assessing treatment success and safety of peroral endoscopic myotomy vs endoscopic balloon dilation for the treatment of achalasia in children.

Achalasia is a rare neurodegenerative esophageal motility disorder characterized by incomplete lower esophageal sphincter (LES) relaxation, increased LES tone and absence of esophageal peristalsis. Achalasia requires invasive treatment in all patients. Conventional treatment options include endoscopic balloon dilation (EBD) and laparoscopic Heller's myotomy (LHM). Recently, a less invasive endoscopic therapy has been developed; Peroral Endoscopic Myotomy (POEM). POEM integrates the theoretical advantages of both EBD and LHM (no skin incisions, less pain, short hospital stay, less blood loss and a durable myotomy). Our aim is to compare efficacy and safety of POEM vs. EBD as primary treatment for achalasia in children. This multi-center, and center-stratified block-randomized controlled trial will assess safety and efficacy of POEM vs EBD. Primary outcome measure is the need for retreatment due to treatment failure (i.e. persisting symptoms (Eckardt score > 3) with evidence of recurrence on barium swallow and/or HRM within 12 months follow-up) as assed by a blinded end-point committee (PROBE design). This RCT will be the first one to evaluate which endoscopic therapy is most effective and safe for treatment of naïve pediatric patients with achalasia.

Vasoactive intestinal polypeptide level in gastroesophageal reflux disease before and after surgical treatment

From year to year, wide spread of gastroesophageal reflux disease (GERD) is attracting greater attention of specialists in the field of this pathology diagnosis and treatment. In-depth studies on etiological and pathogenetic factors in the GERD development are being conducted. Of particular interest is the role of humoral factors, one of which is vasoactive intestinal peptide (VIP). There are currently no data on the dynamics of this hormone during surgical treatment of GERD. The aim of the study was to examine the dynamics of plasma VIP during surgical treatment of GERD and its influence on the lower esophageal sphincter (LES) function. Materials and methods. Surgical treatment in the Nissen modification was performed for 35 patients with GERD. There were 26 women (74.3 %), men – 9 (25.7 %). mean age – 55.3 ± 11.3 years. Comparison group – 20 apparently healthy individuals: women – 14 (70.0 %); men – 6 (30.0 %), mean age – 56.7 ± 10.6 years. VIP was measured in venous blood plasma by an enzyme immunoassay (Vasoactive intestinal peptide ELISA, S-1201, BCM Diagnostics) using an immunoenzyme complex ImmunoChem-2100 (USA). The sampling of the studied samples in the main group was carried out before the operation and 2–3 months post-surgery. Results. In the main group before the surgery, the level of VIP was 3.1 ± 1.1 ng/ml, after the surgery – 2.2 ± 1.0 ng/ml. In the comparison group, VIP was determined at the level of 2.1 ± 1.1 ng/ml. In GERD before the surgery, the VIP level was statistically different from the indicators in the comparison group and from postoperative values. After surgical treatment, VIP values were decreased to the level of apparently healthy individuals. There was a positive correlation between the VIP level and acid exposure time (AET), the total number of refluxes, the number of reflux events longer than 5 minutes, the maximum duration of refluxes and the degree of esophageal inflammation. Conclusions. In the surgical treatment of GERD, the statistically significant decrease in the VIP level to that of apparently healthy individuals is determined. The moderate positive correlation between the levels of VIP, AET, the average number of refluxes, the number of reflux events longer than 5 minutes, and the maximum duration of refluxes confirms the inhibitory effect of VIP on LES tone. The relationship between the degree of esophageal inflammation and the VIP level confirms the indirect, through the action of VIP, inhibitory effect of the esophagitis severity on the LES tone.

Efficacy of metoclopramide for prevention of gastric regurgitation during endotracheal intubation in the emergency department: A randomized controlled trial.

Gastric content regurgitation and aspiration are the dreaded complications of securing the airway. Cricoid pressure hinders intubation and causes lower esophageal sphincter (LES) relaxation. A recent study suggests no added benefit of cricoid pressure in preventing pulmonary aspiration of gastric contents. Metoclopramide increases LES tone, prevents gastroesophageal reflux, and increases antral contractions. Hence, we wanted to study the efficacy of metoclopramide for preventing gastric regurgitation during endotracheal intubation (ETI) in patients presenting to the emergency department (ED). This study was a randomized controlled trial in patients requiring ETI in the ED. The study participants were randomized to receive either metoclopramide (intervention) 10 mg/2 ml intravenous (IV) bolus or a placebo of normal saline (placebo) 2 ml IV bolus 5 min before rapid sequence induction and intubation. The outcome of the study was the visualization of gastric regurgitation at the glottic opening during direct laryngoscopy at the time of intubation. Seventy-four study participants were randomized and allocated to the metoclopramide group (n = 37) or placebo group (n = 37). Gastric regurgitation at the glottis was noted in three study participants (8%) in the metoclopramide group, and six (16%) in the placebo group (odds ratio [OR] - 0.456; 95% confidence interval [CI] of 0.105-1.981; P = 0.295). The study participants who were intubated in the first attempt had less gastric regurgitation compared to ≥2 attempts (OR 0.031; 95% CI of 0.002-0.511; P = 0.015). There was no decrease in regurgitation with metoclopramide as compared to placebo during ETI in study participants presenting to the ED.

595. LAPAROSCOPIC HELLER’S MYOTOMY WITHOUT FUNDOPLICATION. CURRENT EVIDENCE

Abstract Achalasia is a rare esophageal motility disorder which affects the esophageal smooth muscle layer, causing absent or spastic peristalsis, and absent or partial lower esophageal sphincter (LES) relaxation with an increased LES tone. Laparoscopic Heller’s myotomy is the gold standard surgical therapy of esophageal achalasia. The role of fundoplication to minimize GERD after myotomy is debatable. We studied our experience with Laparoscopic Heller Myotomy Without Fundoplication (LHM) for the treatment of esophageal achalasia. A retrospective analysis of prospectively collected data regarding consecutive patients that underwent LHM without fundoplication for the treatment of esophageal achalasia was conducted. All patients were operated between September 1st 2018 and January 1st 2022. Patients included in this study were adults (>18 years old) without upper age limit. All participants completed a subjective dysphagia score questionnaire, received an Eckardt Score preoperatively, as well as at 6 and 12 months following the myotomy procedure. Patients that were treated with endoscopic dilation POEM or esophagectomy were excluded from the study. Twenty-five patients underwent LHM myotomy without fundoplication during the study period. Median age was 42 years (Range: 25-90 years). Median operative time was 70 min (Range: 60-80 min). There was no conversion. Median length of stay was 2 days (Range: 1-15 days). There was one (n=1) mucosal perforation, in a 28-year-old male patient due to overeating, 4 days post LHM. He was treated with laparoscopic primary suturing. There was n=1 (4%) pathologic GERD noted post-operatively. The Eckardt score decreased from 6.5 ± 1.7 to 0.9 ± 1.4 at 1 month and to a 0.8 ± 1.1 at 12 months. Therapy of esophageal achalasia focuses on decreasing the outflow resistance of the GEJ caused by the dysfunctional LES. LHM is considered as the gold-standard therapy for most achalasia patients. LHM is considered safe and effective, while it has been associated with excellent results regarding the relief of dysphagia. There is a reportedly low incidence of new gastroesophageal reflux symptoms. There is no need for fundoplication following LHM since the incidence of GERD is relatively low.

Ca2+ signalling in interstitial cells of Cajal contributes to generation and maintenance of tone in mouse and monkey lower oesophageal sphincters.

The lower oesophageal sphincter (LES) generates tone and prevents reflux of gastric contents. LES smooth muscle cells (SMCs) are relatively depolarised, facilitating activation of Cav 1.2 channels to sustain contractile tone. We hypothesised that intramuscular interstitial cells of Cajal (ICC-IM), through activation of Ca2+ -activated Cl- channels (ANO1), set membrane potentials of SMCs favourable for activation of Cav 1.2 channels. In some gastrointestinal muscles, ANO1 channels in ICC-IM are activated by Ca2+ transients, but no studies have examined Ca2+ dynamics in ICC-IM within the LES. Immunohistochemistry and qPCR were used to determine expression of key proteins and genes in ICC-IM and SMCs. These studies revealed that Ano1 and its gene product, ANO1, are expressed in c-Kit+ cells (ICC-IM) in mouse and monkey LES clasp muscles. Ca2+ signalling was imaged in situ, using mice expressing GCaMP6f specifically in ICC (Kit-KI-GCaMP6f). ICC-IM exhibited spontaneous Ca2+ transients from multiple firing sites. Ca2+ transients were abolished by cyclopiazonic acid or caffeine but were unaffected by tetracaine or nifedipine. Maintenance of Ca2+ transients depended on Ca2+ influx and store reloading, as Ca2+ transient frequency was reduced in Ca2+ free solution or by Orai antagonist. Spontaneous tone of LES muscles from mouse and monkey was reduced ∼80% either by Ani9, an ANO1 antagonist or by the Cav 1.2 channel antagonist nifedipine. Membrane hyperpolarisation occurred in the presence of Ani9. These data suggest that intracellular Ca2+ activates ANO1 channels in ICC-IM in the LES. Coupling of ICC-IM to SMCs drives depolarisation, activation of Cav 1.2 channels, Ca2+ entry and contractile tone. KEY POINTS: The lower oesophageal sphincter (LES) generates contractile tone preventing reflux of gastric contents into the oesophagus. LES smooth muscle cells (SMCs) display depolarised membrane potentials facilitating activation of L-type Ca2+ channels. Interstitial cells of Cajal (ICC) express Ca2+ -activated Cl- channels encoded by Ano1 in mouse and monkey LES. Ca2+ signalling in ICC activates ANO1 currents in ICC. ICC displayed spontaneous Ca2+ transients in mice from multiple firing sites in each cell and no entrainment of Ca2+ firing between sites or between cells. Inhibition of ANO1 channels with a specific antagonist caused hyperpolarisation of mouse LES and inhibition of tone in monkey and mouse LES muscles. Our data suggest a novel mechanism for LES tone in which Ca2+ transient activation of ANO1 channels in ICC generates depolarising inward currents that conduct to SMCs to activate L-type Ca2+ currents, Ca2+ entry and contractile tone.

Effects of standardized [6]-gingerol extracts and [6]-gingerol on isolated ileum and lower esophageal sphincter contractions in mice

Standardized [6]-gingerol extracts were prepared by microwave-assisted extraction using 20% v/v glycerin in ethanol and 20% v/v eutectic mixture of sucrose and citric acid in ethanol as alternative green solvents. The extracts obtained from 20% v/v glycerin in ethanol (GEE) and 20% v/v eutectic mixture of sucrose and citric acid in ethanol (EMSCEE) were standardized by HPLC to contain 17.0 mg/g of [6]-gingerol. The effects of the extracts on mouse ileal contractions via M3 and 5-HT3 receptors as well as lower esophageal sphincter (LES) contraction were determined in vitro relative to the marker compound, [6]-gingerol. [6]-Gingerol, GEE and EMSCEE demonstrated significant and concentration-dependent inhibitory effects on ileal contraction in mice via M3 and 5-HT3 receptors in a noncompetitive manner. In addition, [6]-gingerol and EMSCEE tend to increase the LES tone. These results indicated the potential of GEE and EMSCEE to attenuate nausea and vomiting and might be used as nutraceuticals.

Arecae pericarpium extract induces porcine lower-esophageal-sphincter contraction via muscarinic receptors

BackgroundGastroesophageal reflux disease (GERD) is associated with lower esophageal sphincter (LES) incompetence. In some patients, GERD is refractory to acid reduction therapy which is the main treatment for GERD. So far, medications that can increase LES tone are few. Arecae pericarpium (A. pericarpium) is a medication in Traditional Chinese Medicine known to promote intestinal motility.MethodsWe investigated the effect of A. pericarpium extracts on porcine LES motility. In addition, we used tetrodotoxin (TTX) and atropine to study the underlying mechanism of A. pericarpium extracts-induced contractions of LES.ResultsThe results of this study showed that A. pericarpium extracts and their main active ingredient, arecoline, can induce the contractions of porcine LES sling and clasp muscles in a dose-response manner. TTX did not have an inhibitory effect on the contractions induced by A. pericarpium extracts and arecoline in LES. However, atropine significantly inhibited A. pericarpium extracts- and arecoline-induced contractions of LES.ConclusionA. pericarpium extracts can induce the contractions of porcine LES in a dose dependent manner, possibly through muscarinic receptors, and hence, may be worth developing as an alternative therapy for GERD.

Impact of Feeding Strategies With Acid Suppression on Esophageal Reflexes in Human Neonates With Gastroesophageal Reflux Disease: A Single-Blinded Randomized Clinical Trial.

INTRODUCTION:Aims were to test hypothesis that esophageal provocation-induced reflexes are superior with acid suppression plus feeding modifications vs acid suppression alone among infants treated for gastroesophageal reflux disease (GERD).METHODS:Infants (N = 49, 41.3 ± 2.6 of postmenstrual age) with acid reflux index >3% underwent longitudinal motility testing (weeks 0 and 5) with graded midesophageal provocation to test randomly allocated therapies (4 weeks' proton pump inhibitor [PPI] ± feeding modifications) on sensory-motor aerodigestive reflexes. Feeding modification included restricted fluid volume <140 mL/kg per day, fed over 30 minutes in right lateral position and supine postprandial position. Primary motility outcome was frequency-occurrence of peristaltic reflex. Secondary outcomes included upper esophageal sphincter contractile reflex, lower esophageal sphincter (LES) relaxation reflex, respiratory change, and symptom characteristics.RESULTS:Treatment groups did not differ for primary outcome (odds ratio = 0.8, 95% confidence interval 0.4–1.6, P = 0.99) or secondary outcomes (all P > 0.05). For both treatment groups at follow-up, distal esophageal contraction and LES tone decreased, and LES relaxation reflex occurrence is less frequent (all P < 0.05). In a subgroup analysis, comparing infants with PPI washout (N = 40) vs with continued (N = 9) PPI therapy, no differences were noted for aerodigestive reflex response frequency-occurrence (all P > 0.05).DISCUSSION:In infants with GERD, feeding modification with acid suppression is not superior to acid suppression alone in modifying aerodigestive reflexes (frequency, sensation, or magnitude). Contiguous areas targeted by GER, i.e., LES and distal esophageal functions, worsened at follow-up for both groups despite PPI therapy. Maturation is likely the key factor for GERD resolution in infants, justifying the use of placebo in clinical trials for objectively determined GERD.

Effect of adipocytokines disbalance on the function of the lower esofhageal sphincter in patients with type 2 diabetes mellitus against the background of obesity

The review presents the recent data on the pathogenesis of gastroesophageal reflux disease (GERD) against the background of type 2 diabetes mellitus (DM 2). An analysis of studies of the comorbidity of these nosologies has been carried out, diagnostic significance of the distribution of fat deposits has been examined. It has been revealed that perivascular and visceral adipose tissue against the background of DM 2 undergo considerable functional changes, that results in the formation of peripheral insulin resistance. The changes in eating behaviors based on the levels of adipocytokines (ghrelin, leptin) have been analyzed. Ghrelin concentration was significantly reduced in patients with an overweight and empty stomach. According to the recent data, normal body weight promotes reducing postprandial ghrelin level, which does not normally take place in people with obesity. High leptin levels and the onset of leptin resistance are associated with the trigger of insulin resistance. It is believed that increased GERD morbidity may be explained by the increasing number of overweight people. Insulin resistance, dyslipidemia, hyperglycemia play an important role in the chronic systemic inflammation of esophageal mucosa. Pathogenetic GERD mechanisms can also include the leptin resistance against the background of obesity and decreasing of the ghrelin concentration. Low ghrelin level is associated with slow-up the motility process of the upper parts of the digestive tract and increase the risk of pathological reflux. New data proving the correlation between adipocytokines with lower esophageal sphincter tone in patients with DM 2 and obesity have been presented. The perspective investigations in this area should be purposed on the study of possible risk factors, pathogenesis processes and peculiarities of the GERD course in patients with DM 2 against the background of obesity with the aim of optimization of the diagnosis, prophylaxis and treatment of these pathologies, and prevention of their negative effects on the quality of life and health of this group of patients.

380 High Resolution Manometry Findings in Patients With Absent Contractility

INTRODUCTION: High resolution manometry (HRM) is a widely utilized diagnostic tool for identifying esophageal motility disorders. The Chicago Classification V3.0 (CC3) applies a hierarchical stepwise approach to the analysis of HRM parameters, allowing for characterization and diagnosis of different disorders. While upper esophageal sphincter (UES) parameters are not utilized in CC3, studies have shown that these values could potentially help in differentiating between different disorders. The aim of this study was to evaluate for trends in esophageal sphincter parameters in patients with absent contractility (AC). METHODS: Reports for esophageal HRM performed at a single referral-based motility center between 2013 and 2018 were retrospectively analyzed. We selected patients diagnosed with either AC (study group) or no CC3 abnormality (control group), and divided them by age group. The primary outcome included differences in parameters related to both the lower esophageal sphincter (LES) and UES. Multivariate regression analysis was used to adjust for age group and sex. RESULTS: A total of 455 patients were included in the study (Figure 1), 52 with AC (mean age 51.4, 50.0% female) and 403 without CC3 abnormality (mean age 52.8, 69.5% female). The primary indication for HRM was more likely to be dysphagia in AC patients (73.1% vs 30.5%, P &lt; 0.01), whereas GERD was more likely to be reported in controls (67.2% vs 25.0%, P &lt; 0.01). AC diagnosis was associated with a lower LES mean basal pressure (14.9 vs 27.0 mmHg, P &lt; 0.01) and LES mean residual pressure (5.9 vs 7.9 mmHg, P &lt; 0.01). However, UES mean residual pressure (2.1 vs 0.1 mmHg, P = 0.02) and UES mean relaxation time to nadir (296.4 vs 228.5 ms, P = 0.04) were significantly higher compared to control. No significant difference in UES mean basal pressure was identified between the study group and control. CONCLUSION: AC affects both the LES and UES, causing decreased LES basal and residual pressures, along with increased UES residual pressures and UES relaxation time to nadir. Our data suggest that AC affects smooth muscle in both the esophageal body and LES, where it causes decreased LES tone. The increased UES residual pressures and relaxation time to nadir might be compensatory adaptation to poor esophageal bolus clearance to prevent esophago-pharyngeal reflux. Utilization of UES parameters in future versions of the Chicago Classification may help users better diagnose and manage AC and related disorders.

Omentopexy in Sleeve Gastrectomy Reduces Early Gastroesophageal Reflux Symptoms.

Laparoscopic sleeve gastrectomy (LSG) is one of the surgical procedures indicated in the treatment of obesity. The occurrence of gastroesophageal reflux (GER) in the postoperative period of this surgery is related to a reduction in the lower esophageal sphincter (LES) tone and the presence of gastric residual fundus (RF) associated with increased gastric intraluminal pressure. Fixation of the remaining gastric reservoir to the gastrosplenic and gastrocolic ligaments (omentopexy) has emerged as a technical option to avoid or decrease GER in the postoperative period of LSG. To evaluate the presence of GER symptoms, alterations in LES tone, and the presence of RF in obese subjects submitted to LSG with omentopexy. Twenty obese patients were submitted to LSG with omentopexy from July 2016 to July 2017 at the Hospital Unimed de Teresina, Brazil and was studied prospectively. Clinical evaluations, including a specific questionnaire (clinical score), upper digestive endoscopy and esophageal manometry, were performed preoperatively and on the 90th postoperative day. Contrast x-ray of the esophagus, stomach, and duodenum were performed after the 90th postoperative day. The Fischer exact test was used to evaluate the correlation between GER symptoms and changes in LES tone or the presence of RF. Analysis of variance was used to evaluate the correlation of GER symptoms with the 2 variables together. All analyses adopted a level of significance for α errors >5% (P-value <0.05). The mean clinical score of GER reduced from 6.7 in the preoperative period to 2.7 in the postoperative period. By manometry, there were no significant changes in the LES tone with mean values of 26.04 and 27.07 mm Hg before and after the procedure. RF was identified in 3 cases by contrast radiology. There was no statistical correlation between the changes in the LES tone or the presence of RF with the increase in the clinical score of GER (in cases where this occurred), even when the variables were evaluated together. LSG with omentopexy improved the clinical score of GER in most cases and did not cause significant changes in the LES tone. The presence of RF did not exacerbate the clinical score of GER.

Laryngeal Mask or Endotracheal Intubation in Patients with Laryngeal Carcinoma

Theoretical basis: The presence of laryngeal carcinoma requires precise assessment of the feasibility of endotracheal intubation. Difficult intubation requires preparation of a preliminary plan for ventilation if intubation proves impossible. Some authors report successful use of supraglottic devices when difficult intubation is expected. On the other hand, improper use of the above mentioned may lead to serious complications. The Aim of the study is to determine the advantages and describe the problems of ensuring upper airway patency by the use of laryngeal mask or endotracheal tube. Results: Airway dead space is higher in patients ventilated by laryngeal mask compared to patients ventilated by endotracheal tube. Airway resistance is increased in patients ventilated by endotracheal tube due to reduced airway diameter and reflective airway constriction. Airway resistance is lower in patients ventilated by laryngeal mask because of the larger tube diameter of the device and lack of direct irritation of the trachea. The increase in arterial pressure and heart rate after positioning the laryngeal mask is less than in endotracheal intubation. Intraocular pressure is increased to a lesser extent with the use of laryngeal mask compared to endotracheal intubation. The lower esophageal sphincter tone can be reduced when using laryngeal mask compared to endotracheal tube. There is no consensus on the use of the laryngeal mask in patients with carcinoma of the larynx and the neck. Conclusion: The technique of ventilation of patients with different degree of laryngeal obstruction is still under discussion.

Current status of achalasia management: a review on diagnosis and treatment.

Achalasia is a rare esophageal motility disorder that is characterized by loss of peristalsis and failure of relaxation of the lower esophageal sphincter (LES), particularly during swallowing. This review focuses on the diagnosis of esophageal motility disorders as defined by the Chicago Classification ver 3.0, and presents management options with regard to per-oral endoscopic myotomy (POEM) as the treatment of choice. A concise review of literature was performed for articles related to the management of achalasia, and this was contrasted with our institution's current practice. Achalasia is still incompletely understood, and management is focused on establishing a proper diagnosis, and relieving the obstructive symptoms. Achalasia should be considered when dysphagia is present, and not otherwise caused by an obstruction or inflammation, and when criteria is met as per the Chicago Classification ver 3.0. Lowering LES tone and disruption of LES can be accomplished by various methods, most notably pneumatic balloon dilatation and surgical myotomy. POEM has been gaining momentum as a first line therapy for achalasia symptoms, and can be considered an important tool for motility disorders of the esophagus.

Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaoesophagus: a randomised controlled trial

We evaluated the efficacy of oral sildenafil citrate in dogs with congenital idiopathic megaoesophagus (CIM). Twenty-one puppies were randomly assigned to two groups (treatment and control). The dogs were given...

In vitro effect of nicorandil on the carbachol-induced contraction of the lower esophageal sphincter of the rat

The lower esophageal sphincter (LES) is a specialized region of the esophageal smooth muscle that allows the passage of a swallowed bolus into the stomach. Nitric oxide (NO) plays a major role in LES relaxation. Nicorandil possesses dual properties of a NO donor and an ATP-sensitive potassium channel (KATP channel) agonist, and is expected to reduce LES tone. This study investigated the mechanisms underlying the effects of nicorandil on the LES. Rat LES tissues were placed in an organ bath, and activities were recorded using an isometric force transducer. Carbachol-induced LES contraction was significantly inhibited by KATP channel agonists in a concentration-dependent manner; pinacidil >> nicorandil ≈ diazoxide. Nicorandil-induced relaxation of the LES was prevented by pretreatment with glibenclamide, whereas NG-nitro-l-arginine methyl ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin were ineffective at preventing nicorandil-induced LES relaxation. Furthermore, nicorandil did not affect high K+-induced LES contraction. Reverse-transcription polymerase chain reaction analysis and immunohistochemistry revealed expression of KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1) and ABCC9 (SUR2) subunits of the KATP channel in the rat lower esophagus. These findings indicate that nicorandil causes LES relaxation chiefly by activating the KATP channel, and that it may provide an additional pharmacological tool for the treatment of spastic esophageal motility disorders.

A comparative prospective study to assess the clinical efficacy and safety of pantoprazole monotherapy versus pantoprazole and itopride dual therapy in patients with gastroesophageal reflux disease in a tertiary care hospital

Background: Gastroesophageal reflux disease (GERD) is a common chronic, relapsing condition that carries a risk of significant morbidity and potential mortality from resultant complications. Proton pump inhibitors (PPIs) remained as the main stay in the therapy of GERD but they do not have any role in increasing the tone of lower esophageal sphincter which is the main pathophysiology of GERD. In this regard addition of prokinetic agent like Itopride may be beneficial in improving the symptoms associated with GERD. So the present study has been taken to compare the healing rates of esophagitis and reduction in symptom scores associated with GERD between Pantoprazole monotherapy and Pantoprazole plus Itopride combination. Methods: 100 patients diagnosed with GERD were randomly assigned into two groups, Group A and Group B. Group A received tablet Pantoprazole 40 mg twice daily alone and group B received tablet Pantoprazole 40 mg twice daily and tablet Itopride 50 mg thrice daily 30 minutes before food for 4 weeks. The patients were followed up at the end of 4 weeks and were given the questionnaire to assess the FSSG scores. Endoscopy and FSSG scores were recorded and then the percentage of responders in both groups was compared. Results: Endoscopic evidence of healing of esophagitis was similar in both the groups, 72% in Group A and 74% in Group B. The symptom relief was significantly more in Pantaprozole plus Itopride group 74.5% (4.2±1.6) than Pantaprozole alone 62.5% (6.4±1.1) after 4 weeks (p < 0.001).The occurrence of side effects was less in group B compared to group A (22% vs 30%, p= 0.172). Conclusions: Pantoprazole and combination of Pantoprazole plus Itopride provide more effective endoscopic healing of esophagitis. Pantoprazole and Itopride combination is more efficacious in ameliorating the symptoms of GERD than Pantoprazole alone.

Myotomy of Distal Esophagus Influences Proximal Esophageal Contraction and Upper Esophageal Sphincter Relaxation in Patients with Achalasia After Peroral Endoscopic Myotomy.

Background/AimsThe motility change after peroral endoscopic myotomy (POEM) in achalasia is currently focused on lower esophageal sphincter (LES). This study aims to investigate the correlation of motility response between distal and proximal esophagus after POEM.MethodsA total of 32 achalasia patients who received POEM and high-resolution manometry (HRM) were included for analysis. Eckardt score was used to assess symptom improvement. HRM was applied for studying motility. Main parameters analyzed were (1) LES: resting pressure (restP), 4-second integrated relaxation pressure; (2) esophageal body (EB): contractile integral of distal segment with myotomy (CI-DM) and proximal segment without myotomy (CI-PNM); and (3) upper esophageal sphincter (UES): relaxation pressure (UES-RP).ResultsThere were 6 type I, 17 type II, and 9 type III achalasia patients included for analysis. (1) Eckardt score, LES tone, CI-DM, CI-PNM and UES-RP were reduced remarkably after POEM (P < 0.001). (2) no significant correlation was noted between LES tone and contractile intergral of EB. (3) a positive linear correlation of CI-DM and CI-PNM changes was detected (P < 0.001). (4) the change of UES-RP was positively correlated with the change of contractile integral of EB (P < 0.001).ConclusionsMyotomy of the distal esophagus would attenuate proximal EB contraction and assist UES relaxation in achalasia patients after POEM.

Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter

The lower esophageal sphincter (LES) plays an important role in coordinated esophageal motility. The present study aimed to elucidate how trypsin affects LES contractility. Porcine LES circular smooth muscle strips were prepared. Contractile responses to trypsin were assessed. Trypsin (300nM) induced a transient contraction. At concentrations of 1μM or higher, trypsin induced biphasic responses, consisting of a transient contraction followed by a transient relaxation. Pretreatment with either 1μM tetrodotoxin or carbenoxolone had no effect on these responses. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor. Pretreatment with 10μM FSLLRY-NH2, a PAR2 antagonist, significantly inhibited trypsin-induced biphasic responses. Trypsin (1μM)-induced contractions were partially inhibited by pretreatment with 10μM Y-27632. In addition, trypsin (10μM)-induced relaxation was partially inhibited by pretreatment with 10μM Y-27632, 10μM PD98059 or 10μM SB203580. Trypsin-induced relaxation was abolished by increasing the extracellular K+ concentration to 40mM, but not by pretreatment with l-arginine methyl ester. Furthermore, trypsin-induced relaxation was partially inhibited by pretreatment with 10μM glibenclamide or 1μM 4-aminopyridine. Trypsin causes biphasic regulation of LES tone by directly acting on smooth muscle. Rho-associated protein kinase (ROK) is involved in trypsin-induced contraction, whereas ROK, ERK1/2, p38MAPK, and membrane hyperpolarization are involved in relaxation. The regulation of LES tone by trypsin may play a role in esophageal motility.

Ayurvedic management of achalasia.

Achalasia is an esophageal motor disorder characterized by sustained lower esophageal sphincter contraction and reduced esophageal peristalsis. This pathology eventually results in symptoms like dysphagia, regurgitation and occasional chest pain related to food intake. This is an uncommon disorder of unexplained etiology; however viral, autoimmune and neurodegenerative causes are often afflicted to its manifestation. As per the current state of knowledge, achalasia is considered to be a chronic incurable condition. The treatment options offered here primarily aim at reducing the tone of lower esophageal sphincter by pharmacologic, endoscopic or surgical means. We are presenting here a case of achalasia with two years of symptomatic history of food regurgitation, dysphagia and heart burn without any noticeable response from allopathic medicines. The patient was subsequently kept under ayurvedic therapy considering the symptoms caused by vata impairment and hence requiring vatanulomana and reduction in esophageal muscle tone as the primary management. The patient was kept under suggested Ayurvedic therapy and followed-up for 3 months. A symptom-free follow-up in this case was noticed after completion of 1 month of Ayurvedic therapy.