Treatment Of Esophageal Motility Disorders Research Articles

Effective treatment improves the body composition of patients with esophageal motility disorders.

Although treatment for esophageal motility disorder improves dysphagia and increases body weight, the effect of the treatment on body composition is unclear. This study aimed to assess the change in body composition between before and after treatment, the preoperative predictors of muscle increase, and the association between muscle increase and quality of life. Sixty-one patients (achalasia, n=55; spastic esophageal disorder n=6) who underwent per-oral endoscopic myotomy were analyzed in a single-arm prospective observational study. Appendicular skeletal muscle mass was measured with dual X-ray absorptiometry before and 3 months after per-oral endoscopic myotomy. For subgroup analysis, patients with postoperative appendicular skeletal muscle mass increase were defined as the muscle-increase group and the rest as the non-muscle-increase group. Preoperative factors related to the muscle-increase group were clarified via multivariate analysis. Further, the improvement after per-oral endoscopic myotomy in health-related quality-of-life score (Short Form-36) was compared between the muscle-increase and non-muscle-increase groups. Appendicular skeletal muscle mass increased significantly 3 months after per-oral endoscopic myotomy (P=0.0002). The patients who underwent effective treatment (postoperative Eckardt score<3) showed a significant improvement in appendicular skeletal muscle mass compared to those who did not (P=0.04). In the stepwise logistic regression analysis, the preoperative Eckardt score (odds ratio: 1.95, 95% confidence interval 1.30-3.26, P=0.0005) and preoperative serum prealbumin (odds ratio: 0.83, 95% confidence interval 0.70-0.97, P=0.02) were identified as independent factors related to postoperative muscle increase. The improvements in the Short Form-36 domains of General Health (P=0.0007) and Vitality (P=0.003) were significantly higher in the muscle-increase group. The findings show that effective treatment improved the body composition of patients with esophageal motility disorder and that the Eckardt score and serum prealbumin may aid the prediction of increased appendicular skeletal muscle mass after treatment, resulting in a better quality of life.

Na+ /Ca2+ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons.

Our earlier studies showed that mechanical stretch activates inhibitory motor neurons of the oesophagus; however, the underlying molecular mechanisms are unclear. Here, we sought to examine if Na+ /Ca2+ exchanger 1 (NCX1) is responsible for the mechanosensitivity in the esophageal myenteric neurons (EMN) of rats and humans. The function of NCX1 in primary culture of neurons was determined using calcium imaging, and mechanosensitivity was tested using osmotic stretch and direct mechanical stretch. Axial stretch-induced relaxation of the lower esophageal sphincter (LES) was also studied in vivo in rats. The expression and co-localization of NCX1 with nNOS were identified in the EMN from both rats and humans. The extracellular Ca2+ entry caused by ATP through purinergic signalling in the rat EMN was significantly inhibited by selective NCX blockers. Removal of extracellular Na+ to activate the Ca2+ entry mode of NCX1 induced an increase in the cytoplasmic calcium ([Ca2+ ]cyt ), which was attenuated by NCX blockers. Osmotic stretch and mechanical stretch-induced [Ca2+ ]cyt signalling in the rat and human EMN were attenuated by NCX blockers as well as specific NCX1 knockdown. Osmotic stretch and mechanical stretch also induced [Ca2+ ]cyt signalling in the Chinese hamster ovary (CHO) cells with NCX1 over-expression, which was attenuated by NCX blockers. Finally, NCX blockade inhibited axial stretch-activated LES relaxation in vivo experiments in the rats. We demonstrate a novel NCX1/Ca2+ pathway in the mechanosensitive neurons of rat and human oesophagus, which may provide a potential therapeutic target for the treatment of oesophageal motility disorders.

Upper Esophageal Sphincter (UES) Abnormalities Are a Frequent Finding on High Resolution Manometry (HREM) and Associated With Esophageal Motility Disorders (EMD)

Introduction: While there has been an increased frequency of UES abnormalities noted among patients with esophageal motility disorders (EMD), the Chicago Classification for manometric disorders does not comment on UES findings. Here, we assess the frequency and type of UES abnormalities among patients referred for HREM; the frequency of UES abnormalities among patients with EMD (achalasia and esophagogastric junction outflow obstruction (EGJOO)); bolus clearance, lower esophageal sphincter (LES) and UES residual pressures to determine the severity of disease in patients with both EMD and a UES abnormality and; if presence of UES abnormalities in patients with EMD is associated with poor treatment response. Methods: This retrospective study at 3 tertiary care hospitals identified 136 consecutive patients referred for HREM to assess for a suspected motility disorder from 10/2016-10/2017. UES pressures were measured before 10 wet swallows. HREM reports were analyzed for UES, LES and bolus transit abnormalities. Medical records were reviewed for demographic data. Results: UES abnormalities were present in 38% (n=51) of all patients referred for HREM (n=136) and in 43% of 54 patients with EMD. Of those with UES abnormalities present, 45% (n=23) had an EMD. Of these individuals, 61% (n=14) were diagnosed with EGJOO and 39% (n=9) with achalasia (predominantly Type II (n=7/9)). There was a significant correlation between impaired LES residual pressure and UES residual pressure (r=0.238, P=0.005) in patients with EMD. Incomplete bolus clearance was not significantly associated with UES pressure abnormalities (p=0.48, CI: 0.5699 to 3.3019). Data on treatment response was captured in 35 patients with EMD (57% had pharmacological treatment, 1 had fundoplication, and 46% had combined pharmacological and procedural treatment). There was a trend towards presence of UES abnormalities in EMD with poorer outcomes but was not statistically significant (p=0.37). Botox therapy was performed more commonly in the treatment of EMD with normal UES (62%) compared to those with abnormal UES (24%). Conclusion: There appears to be a significant correlation between impairment in UES and LES relaxation, suggesting a shared pathophysiological mechanism. A stratification scheme, based on pathophysiological defect, and inclusion of UES findings while evaluating EMD patients may help in understanding this increasingly common but undoubtedly heterogeneous syndrome and facilitate the development of targeted therapies.

Ten Initial Cases of Peroral Endoscopic Myotomy for Treatment of Esophageal Motility Disorders at Okayama University Hospital.

Peroral endoscopic myotomy (POEM) for treatment of esophageal motility disorders has recently been reported to be highly effective and less invasive than other treatment. POEM was recently introduced in Okayama University Hospital under the supervision of a physician from a high-volume center. To verify the safety and efficacy of POEM during its introduction in our institution. We examined 10 cases in whom POEM was performed between January 2016 and April 2017. The patients included 7 men and 3 women, with a median age (range) of 49 years (17-74) and median symptom duration of 6 years (1-21). Seven patients had a straight esophagus, and the remaining 3 had a sigmoid esophagus. According to the Chicago classification, 6 patients were diagnosed with type I achalasia, 2 with type II achalasia, and 2 with distal esophagus spasm. Treatment outcomes and adverse events were evaluated. Treatment success was defined as a > 3 decrease in Eckardt score or a score of <3 at the time of discharge. The treatment success rate was 90%, with the average Eckardt score decreasing significantly, from 4.7 to 0.9 (p<0.05). No mucosal perforation, severe infection, mediastinitis, severe bleeding, or gastroesophageal reflux occurred intraoperatively or postoperatively. POEM was introduced to Okayama University Hospital, and the first 10 cases were accomplished safely and effectively under the supervision of an expert physician from a high-volume center.

Esophageal motility disorders: new perspectives from high-resolution manometry and histopathology.

High-resolution manometry (HRM) and peroral endoscopic myotomy (POEM) have contributed significantly to the field of esophageal motility disorders in recent years. The development of HRM has categorized various esophageal motility disorders with a focus on a diverse range of manometric anomalies. Additionally, the Chicago classification criteria is widely used for manometric diagnosis. Moreover, POEM was introduced as a minimally invasive radical therapy for achalasia and shows promise for other spastic esophageal motility disorders as well. POEM has also enabled a transluminal endoscopic approach for determining the histology of the esophageal muscle layer, which is expected to assist in elucidating the etiology of disorders associated with esophageal motility. The purpose of this review is to update the diagnosis, pathology, and treatment of esophageal motility disorders, with a focus on the recent advances in this field.

Clinical Utility of Imaging Following Peroral Endoscopic Myotomy

Introduction: Per-oral endoscopic myotomy (POEM) is a safe and effective endoscopic procedure primarily for treatment of esophageal motility disorders. In recent studies, it has been shown to have similar efficacy when compared to Heller myotomy, and is associated with fewer complications and shorter recovery times. Post-POEM imaging protocols vary from hospital to hospital but are all designed to detect complications of the procedure. At our center, post procedure protocol included a CXR, performed immediately following POEM, as well as gastrograffin swallow study, performed 1 day after POEM. We evaluate the clinical utility of post-POEM imaging with CXR and/or gastrograffin swallow study. Methods: This was a retrospective study performed at a tertiary care university-setting hospital over a period of 3 years from December 2013-April 2017. POEM procedures were performed under general anesthesia using the previously described technique (Figure 1). Indications for POEM included achalasia, esophagogastric junction outlet obstruction, nutcracker esophagus, and epiphrenic diverticulum with or without previous unsuccessful pneumatic dilation, botulinum toxin, and/or Heller myotomy. CXR was performed immediately following POEM and gastrograffin swallow study was performed on post-operative day 1 well as 3-4 weeks following the procedure.Figure: (a) Mucosal incision after submucosal injection, (b) creation of submucosal tunnel via endoscopic submucosal dissection, (c) completed submucosal tunnel (d) circular muscle myotomy, (e) completed myotomy and, (f) closure of mucosal entry with clips.Results: POEM was performed on 79 patients with mean age of 55 years and a total of 46 males (58%). Details of indication for POEM and prior treatment are summarized in Table 1. Of the 79 patients, 65 patients underwent CXR immediately post-op with 36 patients having a normal CXR (46%). None of the patients required intervention based on CXR findings, summarized in Table 2. 68 of the 79 patients underwent gastrograffin swallow study 24 hours after POEM. Findings concerning for contrast leak were identified in 2 patients (Figure 2), both of whom were asymptomatic. The second patient underwent repeat EGD with fluoroscopy within 24 hours of the initial POEM, with no active contrast leak. All patients were discharged w/in 24-48 hours after POEM and were followed up in 4-6 weeks. No early (24-48 hours) or delayed (4-6 weeks) post-op events were noted.Figure: (a) Patient one post-op gastrograffin study with small contained submocosal leak at the site of the surgical clips (b) Patient two post-op gastrograffin study showing a linear tract of contrast coursing towards the right mediastinum.Table: Table. Indication for POEM and Prior TreatmentsTable: Table. Summary of CXR Findings and Interventions Based off of CXR FindingsConclusion: Our findings suggest that CXR as well as gastrograffin swallow study within 24 hours of POEM are of low clinically yield and should only be considered in patients who are symptomatic. Based on our findings, we suggest that if a patient is clinically stable, they can be discharged without any imaging.

Tu1421 Complications of Botulinum Toxin Injections for Treatment of Esophageal Motility Disorders

Tu1421 Complications of Botulinum Toxin Injections for Treatment of Esophageal Motility Disorders

High-resolution manometry in diagnosis and treatment of achalasia: help or hype.

High-resolution manometry (HRM) with 36 pressure transducers spanning the esophagus has revolutionized the diagnosis and treatment of esophageal motility disorders, especially with respect to achalasia. The three major contributions of HRM are as follows: (a) Integrated relaxation pressure (IRP) at the esophagus gastric junction (EGJ) >15 mmHg has a sensitivity of 97 % for the diagnosis of achalasia; (b) there are three distinct subtypes of achalasia - type 1 (no distal pressurization), type II (panesophageal pressurization), and type III (spastic contractions); and (c) subtypes predict the success of treatment with type II patients doing the best and type III being the most difficult to treat. Recent studies also suggest that HRM is superior to conventional manometry for diagnosis of achalasia. Other useful observation from HRM is the recognition of EGJ outflow obstruction (type IV achalasia) with normal peristalsis which may be due to mechanical or functional impairment at the EGJ. Finally, after successful treatment of achalasia, the IRP falls to less than 15 mmHg and the achalasia pressurization pattern resolves sometimes with the return of weak peristalsis. This complements well with the information obtained by the timed barium esophagram.

Treatment of esophageal motility disorders based on the chicago classification.

The Chicago Classification divides esophageal motor disorders based on the recorded value of the integrated relaxation pressure (IRP). The first group includes those with an elevated mean IRP that is associated with peristaltic abnormalities such as achalasia and esophagogastric junction outflow obstruction. The second group includes those with a normal mean IRP that is associated with esophageal hypermotility disorders such as distal esophageal spasm, hypercontractile esophagus (jackhammer esophagus), and hypertensive peristalsis (nutcracker esophagus). The third group includes those with a normal mean IRP that is associated with esophageal hypomotility peristaltic abnormalities such as absent peristalsis, weak peristalsis with small or large breaks, and frequent failed peristalsis. The therapeutic options vary greatly between the different groups of esophageal motor disorders. In achalasia patients, potential treatment strategies comprise medical therapy (calcium channel blockers, nitrates, and phosphodiesterase 5 inhibitors), endoscopic procedures (botulinum toxin A injection, pneumatic dilation, or peroral endoscopic myotomy) or surgery (Heller myotomy). Patients with a normal IRP and esophageal hypermotility disorder are candidates for medical therapy (nitrates, calcium channel blockers, phosphodiesterase 5 inhibitors, cimetropium/ipratropium bromide, proton pump inhibitors, benzodiazepines, tricyclic antidepressants, trazodone, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors), endoscopic procedures (botulinum toxin A injection and peroral endoscopic myotomy), or surgery (Heller myotomy). Lastly, in patients with a normal IRP and esophageal hypomotility disorder, treatment is primarily focused on controlling the presence of gastroesophageal reflux with proton pump inhibitors and lifestyle modifications (soft and liquid diet and eating in the upright position) to address patient's dysphagia.

723 Per Oral Endoscopic Myotomy (P.O.E.M.) for Treatment of Esophageal Motility Disorders - From Bench to Bedside

723 Per Oral Endoscopic Myotomy (P.O.E.M.) for Treatment of Esophageal Motility Disorders - From Bench to Bedside

Motility disorders in childhood: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Motility disorders in childhood: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Esophagoscopy and endoscopic esophageal ultrasound in the assessment of esophageal function.

Esophagoscopy is an ideal method to detect mucosal or structural abnormalities of the esophagus and proximal stomach. The exclusion of malignant dysphagia is the prime role of esophagoscopy in assessment of esophageal function. Esophagoscopy and biopsy are mandatory for mucosal assessment of patients with gastroesophageal reflux disease (GERD). Indirect and sometimes subtle evidence of abnormal esophageal motility is a valuable and underused aspect of esophagoscopy in the evaluation of swallowing disorders. Esophagoscopy has multiple roles in the appraisal and treatment of esophageal motility disorders, including the detection of secondary or pseudoachalasia, placement of manometry catheters, and dilation of peptic strictures caused by GERD associated with disorders such as scleroderma.

Diagnosis and treatment of esophageal motility disorders

Apart from gastroesophageal reflux disease, achalasia, non-cardiac chest pain and functional dysphagia are the most important manifestations of disturbed esophageal motility. Achalasia is characterized by esophageal aperistalsis and impaired deglutitive relaxation of the lower esophageal sphincter. The morphological correlate is a degeneration of nitrergic neurons in the myenteric plexus. Diagnosis is based on barium esophagram or esophageal manometry with the latter setting the gold standard. Endoscopic exclusion of a tumor at the gastroesophageal junction is mandatory. Appropriate therapeutic interventions are pneumatic dilatation or (laparoscopic myotomy) of lower esophageal sphincter. In patients unfit for these procedures endoscopic injection of botulinum toxin into the lower esophageal sphincter is appropriate. Non-cardiac chest pain may be of esophageal origin. Gastroesophageal reflux, spastic motility disorders and visceral hypersensitivity are arguable underlying mechanisms. The most important diagnostic procedure is 24 h esophageal pH metry correlating symptoms and reflux episodes. Proton pump inhibitors and tricyclic antidepressants serving as visceral analgesics are appropriate therapeutic approaches. Functional dysphagia defines the sensation of impaired passage without mechanical obstruction or a neuromuscular disease with known pathology, e.g. scleroderma. Impaired transit is proven by esophageal scintigraphy or radiogram both using solid boluses. Manometry assesses the underlying mechanisms.

Esophageal pharmacology and treatment of primary motility disorders.

Swallowing is a complex mechanism based on the coordinated collaboration of tongue, pharynx and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain or regurgitation. The major primary esophageal motility disorders--achalasia, diffuse esophageal spasm, hypercontractile esophagus ('nutcracker esophagus') and non-specific motility disorder--are of unknown etiology. Other esophageal diseases, such as cervical diverticula or gastroesophageal reflux disease, might also be caused by a primary esophageal motility disorder. Medical treatment of esophageal disorders with esophageal hyper- or dysmotility requires agents that reduce esophageal contractile force (anticholinergic agents, nitrates, calcium antagonists). Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment of esophageal motility disorders is rather disappointing. Calcium channel antagonist, alone or in combination with anticholinergics or nitrates, can be used as a medical trial, especially in mild achalasia. However, medical therapy is clearly inferior to pneumatic balloon dilation therapy. Recently, botulinum toxin injection was suggested as a therapeutic option in achalasia patients with good results on lower esophageal sphincter pressure (LESP) and symptom scores that were similar to the results achieved by pneumatic balloon dilation. Hypercontractile esophagus shows a good manometric response to calcium channel antagonists, but only little clinical effect in terms of improvement of symptoms. Diffuse esophageal spasm is a relatively rare disease and few clinical studies are available. The use of calcium channel antagonists can be beneficial, at least in some patients with diffuse esophageal spasm. From clinical and epidemiological studies, there is some evidence of a 'psychological' component in the pathogenesis or perception of esophageal symptoms. There is some clinical benefit from centrally acting drugs such as benzodiazepines or antidepressants. With the exception of botulinum toxin for achalasia, medical therapy of primary esophageal motility disorders is rather limited and the clinical results are poor. Further understanding of esophageal pathophysiology as well as development of new receptor-selective drugs might increase our chances of a successful treatment of primary esophageal motility disorders.

Medical treatment of esophageal motility disorders.

Swallowing is a complex mechanism that is based on the coordinated interplay of tongue, pharynx, and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain, or regurgitation. The major esophageal motility disorders include achalasia, diffuse esophageal spasm, hypercontractile esophagus ("nutcracker esophagus"), and hypocontractile esophagus ("scleroderma esophagus"). Other esophageal diseases such as hypopharyngeal (Zenker's) diverticula or gastroesophageal reflux disease also may be sequelae of primary esophageal motility disorder. Finally, a substantial group of patients referred for evaluation of possible esophageal motor disorders have milder degrees of dysmotility--referred to as nonspecific esophageal motor disorder--that are of unclear clinical significance. Medical treatment of esophageal motility disorders involves the uses of agents that either reduce (anti-cholinergic agents, nitrates, calcium antagonists) or enhance (prokinetic agents) esophageal contractility. Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment is often disappointing. From clinical and epidemiological studies there is some evidence for a "psychological" component in the pathogenesis or perception of esophageal symptoms. Further understanding of esophageal pathophysiology, as well as development of new receptor selective drugs, might increase our chances of successful treatment of esophageal motility disorders.

Therapeutic progress--review XXXIII. Are we making progress in the drug treatment of oesophageal disease?

Oesophageal problems are common. There are three areas where drug treatment can be helpful, namely in the control of gastro-oesophageal reflux and its symptoms, the treatment of oesophageal motility disorders and when oesophageal infection occurs. In this review the management of these three disorders is considered.

Verapamil—A Potent Inhibitor of Esophageal Contractions in the Baboon

Verapamil, a calcium channel blocking agent, has been shown to be a potent inhibitor of smooth muscle contraction. We studied the effects of verapamil on lower esophageal sphincter pressure and esophageal peristalsis in 5 awake baboons. An infusion of verapamil (80 micrograms/kg . min) decreased amplitude of peristalsis by 63% in the smooth muscle segments of the esophagus but had no effect on striated muscle. Duration of peristaltic waves in the smooth muscle portion of the esophagus was also shortened, but there was no effect on velocity of the contraction wave. Lower esophageal sphincter pressure decreased by 74% during verapamil infusion. These studies suggest that verapamil or other calcium channel blocking agents may be of potential use in the treatment of esophageal motility disorders associated with increased pressure.