Peroral endoscopic myotomy in pediatric jackhammer esophagus.

The jackhammer esophagus is a rare hypercontractile disorder and diagnosis is based on high-resolution manometry. Peroral endoscopic myotomy (POEM) of the spastic esophagus segments has been described. We report a pediatric patient with jackhammer esophagus that was treated endoscopically.

The effect of platelet-rich plasma on motility changes in experimental caustic esophageal burn.

BACKGROUND: Besides stricture formation, diminished esophageal motility after caustic esophageal burns also plays a role in the deterioration of the clinical course. In this study, we aimed to investigate the effect of caustic burn on the esophageal contractions and the effect of platelet-rich plasma (PRP) on these changes. METHODS: Twenty-one Wistar albino rats were divided into three groups [Sham operation (n = 8), caustic esophageal burn with NaOH (n = 6), PRP treatment after caustic burn (n = 7)]. After 3 weeks, esophagectomy was performed and contractions and EFS responses were evaluated in the organ bath. RESULTS: KCl- and acetylcholine-induced responses were reduced in the Burn group, but increased in Sham and PRP groups (p < 0.05). EFS responses were higher in Burn group compared to the other groups. Response with L-arginine was increased in Burn group, but decreased in PRP group. There was more decrease in the contraction in Sham and PRP groups compared to the Burn group after SNP (sodium nitroprusside) incubation (p < 0.05). L-NAME (Nω-Nitro-L-arginine methyl ester) did not change the EFS responses in the Burn group, but EFS responses were decreased significantly in Sham and PRP groups (p < 0.05). EFS responses were decreased in all groups, but more in the Sham and PRP groups after Y-27632 (Rho-kinase inhibitor) incubation (p < 0.05). CONCLUSIONS: For the first time, we demonstrated that both cholinergic and non-adrenergic non-cholinergic mechanisms are responsible for the altered motility in corrosive esophageal injury. Our results suggest that PRP treatment may be helpful in regulating the esophageal motility and decreasing altered contractions in corrosive burns. This effect may also contribute to the reduction of stricture formation, especially by reducing inappropriate contractions of the esophageal wall during the post-burn healing phase.

Complications of botulinum toxin injections for treatment of esophageal motility disorders†.

In achalasia and spastic esophageal motility disorders, botulinum toxin (botox) injection is considered an effective and low-risk procedure for short-term symptom relief. It is mainly offered to medically high-risk patients. However, no analysis of risks of botox injections has been performed. To determine the incidence and risk factors of procedure-related complications after esophageal botox injections, we analyzed the records of all patients undergoing botox injection therapy for esophageal motility disorders at four university hospitals in Europe and North America between 2008 and 2014. Complications were assigned grades according to the Clavien-Dindo classification. In 386 patients, 661 botox treatments were performed. Main indications were achalasia (51%) and distal esophageal spasm (DES) (30%). In total, 52 (7.9%) mild complications (Clavien-Dindo grade I) were reported by 48 patients, the majority consisting of chest pain or heartburn (29 procedures) or epigastric pain (5 procedures). No ulceration, perforation, pneumothorax, or abscess were reported. One patient died after developing acute mediastinitis (Clavien-Dindo grade V) following injections in the body of the esophagus. In univariate logistic regression, younger age was associated with an increased risk of complications (OR 1.43, 95%CI 1.03-1.96). Treatment for DES, injections into the esophageal body, more injections per procedure, more previous treatments and larger amount of injected botulinum toxin were no risk factors for complications. Esophageal botox injection seems particularly appropriate for high-risk patients due to low complication rate. However, it should not be considered completely safe, as it is associated with rare side effects that cannot be predicted.

Effects of Acotiamide on the Esophageal Motility Function in Patients with Esophageal Motility Disorders: A Pilot Study.

BACKGROUND AND AIM: Acotiamide is a newly developed prokinetic drug that is clinically used to treat functional dyspepsia (FD). The objective of this study was to assess the therapeutic effects of acotiamide in patients with esophageal motility disorders (EMDs). METHODS: Twenty-nine patients with both symptoms of FD and symptoms suspicious of EMDs were enrolled. Esophageal motility function was evaluated by high-resolution manometry before and after 2 weeks administration of acotiamide (100 mg) 3 times per day. RESULTS: Twenty-nine patients were diagnosed with achalasia (n = 4), esophagogastric junction outflow obstruction (EGJOO) (n = 6), absent peristalsis (n = 2), distal esophageal spasm (n = 4), frequently failed peristalsis (n = 7), weak peristalsis (n = 2) and 4 of them were found to be normal. An analysis in all 29 patients showed that acotiamide had no effects on based on distal contractile integral (DCI), basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP). Subgroup analysis, however, showed that acotiamide dramatically reduced IRP, from 19.5 (15.1-30.8) to 12.1 (5.6-16.4) mm Hg, and DCI, from 2,517.9 (1,451.0-8,385.0) to 1,872.5 (812.3-5,225.3) mm Hg·cm·s, in the 6 patients with EGJOO. CONCLUSIONS: Acotiamide potentially normalized impaired LES relaxation in patients with EGJOO, while having no effects on normal esophageal motility patterns. Acotiamide may be a promising treatment for EGJOO.

Gastroesophageal dysmotility is associated with the impairment of cough-specific quality of life in patients with cough variant asthma.

BACKGROUND: Gastroesophageal reflux disease (GERD) is known as a common comorbidity of asthma and chronic cough. The impact of GERD symptoms on cough-specific quality of life (QoL) in patients with asthmatic cough is poorly understood. The aim of this study is to determine the association of GERD symptoms with cough-specific quality of life in patients with cough variant asthma (CVA) using the Leicester Cough Questionnaire (LCQ). METHODS: A total of 172 consecutive patients (121 females) with mean cough duration of 45.1 months (range 2-480 months) completed the Japanese version of the LCQ. The Frequency Scale for the Symptoms of Gastroesophageal reflux was administered to assess symptoms of acid-reflux and dysmotility. A range of clinical variables that may determine cough-specific QoL (LCQ) were estimated. RESULTS: The mean LCQ scores was 12.9 (SD 3.5), consistent with severe impairment in QoL. Female gender, symptoms of gastroesophageal dysmotility, sensitization to allergens (house dust and Japanese cedar pollen) and the number of sensitized allergens were associated with lower LCQ scores (i.e. impaired cough-specific QoL) in univariate regression analysis. Acid-reflux symptoms, airway hyperresponsiveness, fractional exhaled nitric oxide, and sensitization to molds were unrelated to the LCQ score. After adjustment for gender, symptoms of gastroesophageal dysmotility was the only significant determinant of impaired cough-specific QoL accounting for 23% of the variance. CONCLUSIONS: Cough-specific QoL is severely impaired in patients with CVA. Symptoms of gastroesophageal dysmotility are an independent predictor of cough-specific QoL of patients with CVA.

Botulinum toxin injection for hypercontractile or spastic esophageal motility disorders: may high-resolution manometry help to select cases?

Endoscopic injections of botulinum toxin in the cardia or distal esophagus have been advocated to treat achalasia and spastic esophageal motility disorders. We conducted a retrospective study to evaluate whether manometric diagnosis using the Chicago classification in high-resolution manometry (HRM) would be predictive of the clinical response. Charts of patients with spastic and hypertensive motility disorders diagnosed with HRM and treated with botulinum toxin were retrospectively reviewed at two centers. HRM recordings were systematically reanalyzed, and a patient's phone survey was conducted. Forty-five patients treated between 2008 and 2013 were included. Most patients had achalasia type 3 (22 cases). Other diagnoses were jackhammer esophagus (8 cases), distal esophageal spasm (7 cases), esophagogastric junction outflow obstruction (5 cases), nutcracker esophagus (1 case), and 2 unclassified cases. Botulinum toxin injections were performed into the cardia only in 9 cases, into the wall of the distal esophagus in 19 cases, and in both locations (cardia and distal esophagus) in 17 cases. No complication occurred in 31 cases. Chest pain was noticed for less than 7 days in 13 cases. One death related to mediastinitis occurred 3 weeks after botulinum toxin injection. Efficacy was assessed in 42 patients: 71% were significantly improved 2 months after botulinum toxin, and 57% remained satisfied for more than 6 months. No clear difference was observed in terms of response according to manometric diagnosis; however, type 3 achalasia previously dilated and with normal integrated relaxation pressure (4s-integrated relaxation pressure < 15 mmHg) had the worst outcome: none of these patients responded to the endoscopic injection of botulinum toxin. Endoscopic injections of botulinum toxin may be effective in some patients with spastic or hypercontractile esophageal motility disorders. The manometric Chicago classification diagnosis does not seem to predict the results. Prospective randomized trials are required to identify patients most likely to benefit from esophageal botulinum toxin treatment.

Effects of mosapride on secondary peristalsis in patients with ineffective esophageal motility.

OBJECTIVE. Ineffective esophageal motility is frequently found in patients with gastroesophageal reflux diseases. Secondary peristalsis contributes to esophageal acid clearance. Mosapride improves gastrointestinal (GI) motility by acting on 5-hydroxytrypatamine4 receptors. The authors aimed to evaluate the effect of mosapride on secondary peristalsis in patients with ineffective esophageal motility. MATERIAL AND METHODS. After recording primary peristalsis baseline, secondary peristalsis was stimulated by slowly and rapidly injecting mid-esophageal air in 18 patients. Two separate experiments were randomly performed with 40 mg oral mosapride or placebo. RESULTS. Mosapride had no effect on the threshold volume of secondary peristalsis during slow air distension (9.8 ± 0.97 vs. 10.2 ± 1.0 mL; p = 0.84), but decreased the threshold volume during rapid air distension (4.1 ± 0.2 vs. 4.6 ± 0.3 mL; p = 0.001). The efficiency of secondary peristalsis during rapid air distension increased with mosapride (70% [40-95%]) compared with placebo (60% [10-85%]; p = 0.0003). Mosapride had no effect on the amplitudes of distal pressure wave of secondary peristalsis during slow (94.3 ± 9 vs. 101.9 ± 9.1 mmHg; p = 0.63) or rapid air distension (89.3 ± 9 vs. 95.2 ± 8.3 mmHg; p = 0.24). CONCLUSIONS. Mosapride improves esophageal sensitivity of secondary peristalsis by abrupt air distension but has limited effect on the motor properties of secondary peristalsis in ineffective esophageal motility patients. Despite its well-known prokinetic effect, mosapride enhances the efficiency of secondary peristalsis in patients with ineffective esophageal motility through augmenting esophageal sensitivity instead of motility.

Topical bethanechol for the improvement of esophageal dysmotility: a pilot study.

OBJECTIVES: We studied a case series to evaluate the effect of topical bethanechol chloride on esophageal function in individuals with ineffective esophageal motility. METHODS: Five subjects with ineffective esophageal motility underwent high resolution esophageal manometry. Ten 5 mL liquid swallows were performed to establish a baseline. Five milligrams of topical bethanechol was then administered. After 10 minutes, the subjects completed 10 additional liquid swallows. This procedure was repeated with 10 mg of bethanechol in 4 subjects. RESULTS: After administration of 5 mg of topical bethanechol, the mean (+/- SD) distal contractile integral, an index of esophageal contractility, increased from 178.3 +/- 83.1 mm Hg x s x cm to 272.3 +/- 216.9 mm Hg x s x cm (p = 0.69). The percentage of failed swallows decreased from 52.8% +/- 33.2% to 29.4% +/- 18.3% (p = 0.14). The percentage of peristaltic swallows increased from 28.0% +/- 26.8% to 67.2% +/- 15.3% (p = 0.04). The contractile front velocity was essentially unchanged. After administration of 10 mg of bethanechol,the distal contractile integral decreased from 349.3 +/- 371.0 mm Hg x s x cm to 261.8 +/- 293.5 mm Hg x s x cm (p = 0.72). The percentage of failed swallows increased from 57.5% +/- 37.7% to 66.8% +/- 24.9% (p = 0.46). The percentage of peristaltic swallows increased from 17.5% +/- 23.6% to 28.3% +/- 19.1% (p = 0.29). The contractile front velocity decreased from 11.6 +/- 5.2 cm/s to 4.9 +/- 3.0 cm/s (p = 0.32). No adverse side effects occurred. CONCLUSIONS: The results of this pilot study support the need for further investigation with larger sample sizes and dose escalation.

Evolving pharmacological approaches in gastroesophageal reflux disease.

INTRODUCTION: Proton pump inhibitors (PPIs) have considerably improved quality of life in patients with gastroesophageal reflux disease (GERD). However, many patients remain symptomatic despite standard PPI therapy. AREAS COVERED: This review focuses on evolving therapeutic strategies related to the pathophysiological processes of GERD and insufficient response to PPIs. Several clinical trials evaluated new PPI formulations and newer types of acid-suppressive drugs. These studies have evaluated traditional end points in GERD, but have not shown clinical superiority to current PPIs. Novel therapeutic strategies targeting underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxations (TLESRs) and esophageal hypersensitivity, are being developed for add-on therapy to PPIs. Prokinetic drugs may also have some potential in the add-on treatment of GERD with insufficient response to PPIs. Add-on studies are hampered by insufficient information on optimal patient selection and lack of established end points. EXPERT OPINION: Newer drugs for symptomatic control in GERD have largely focused on improved acid suppression, without evidence of clinical superiority. Drugs targeting esophageal motility and sensitivity to be used as add-onc therapy in PPI insufficient responders have not reached Phase III trials to date, due to difficulties with patient selection, tolerability and end points.

Tolerance to enteral nutrition therapy in traumatic brain injury patients.

OBJECTIVE: To evaluate the tolerance to enteral nutrition (EN) and the effects of pro-kinetic drugs in critical traumatic brain injury (TBI) patients. METHODS: Transversal observational study. A total of 32 out of 45 TBI patients of both genders receiving EN were evaluated in a trauma referral hospital intensive care unit (ICU). Data from each patient were collected for a period of 10 consecutive days after initiation of enteral feeding: gastric residue, presence of vomiting, abdominal distension, Glasgow coma scale and the use of pro-kinetic agents. RESULTS: In 20 of the 32 patients high levels of gastric residue were found. Of these 20 patients, half could not tolerate the diet within the first 72 hours following infusion. However, no association was found between disease severity and occurrence of gastrointestinal complications (p > 0.05). Feeding intolerance was observed in 75.0% (n = 24) of patients, even with the systematic use of metaclopramide from the outset of nutritional therapy. All patients with feeding intolerance who used erythromycin by nasogastric tube showed improvement. CONCLUSIONS: The high level of gastric residue was the most common feeding intolerance and the delivery of erythromycin by nasogastric tube seems to control gastrointestinal disorders in TBI patients.

[Pharmacological Treatments of Esophageal Dysphagia].

Patients with esophageal dysphagia need a step-by-step approach for diagnosis and treatment. Endoscopic with biopsy and barium esophagogram are the essential tests evaluating anatomical abnormality and esophageal bolus stasis. Further imaging or esophageal function tests such as high-resolution esophageal manometry, functional endoluminal imaging probe, CT or endoscopic ultrasound are required. In the case of dysphagia due to esophageal motility disorder, whether it is the major motility disorder or minor motility disorder should be identified in high resolution manometry. Major motility disorders show esophagogastric junction obstruction or major peristaltic defects. In this case, the severity of the symptoms should be assessed and patients who need endoscopic or surgical treatment targeting lower esophageal sphincter should be screened. Impaired lower esophageal sphincter relaxation (achalasia, esophagogastric junction outflow obstruction, esophageal spasm or abnormal hypercontraction (jackhammer esophagus), hypotensive contraction (ineffective esophageal motility, failed peristalsis), esophageal hypersensitivity (noncardiac chest pain), gastroesophageal reflux disease and esophageal bolus stasis are the possible mechanisms causing dysphagia symptoms. The proper medical treatment depends on underlying mechanisms.

Esophageal hypercontractility is abolished by cholinergic blockade.

BACKGROUND: Esophageal hypercontractility (EHC) is considered a major esophageal motor disorder of unclear etiology. Different mechanisms have been proposed, including an imbalance in inhibitory and excitatory esophageal innervation. We hypothesized that patients with EHC suffer from cholinergic hyperactivity. AIM: To interrogate the excitatory and inhibitory neurotransmission in EHC by assessing the esophageal motor response to atropine (ATR) and cholecystokinin (CCK), respectively, in EHC patients. METHOD: We retrospectively reviewed patients who underwent high-resolution manometry (HRM) with pharmacologic challenge in a tertiary referral center between 2007 and 2017. We identified 49 EHC patients who were categorized based on frequency of hypercontractile peristaltic sequence into "frequent" and "infrequent" and motility diagnosis groups. Deglutitive pressure metrics and esophageal motor responses to ATR (12 mcg/kg iv) and CCK (40 ng/kg iv) were analyzed across groups. RESULTS: Atropine abolished hypercontractility across all groups studied, converting nearly half of patients to a motor pattern of ineffective esophageal motility. Abnormal CCK responses primarily occurred in the patient groups with concomitant outflow obstruction. CONCLUSIONS: Hypercontractility is cholinergically mediated in all esophageal motor disorders. Most patients with isolated EHC appear to have excessive cholinergic drive, rather than loss of inhibitory innervation, and might be candidates for treatment with anticholinergic agents.

Observational comparative trial of the efficacy of proton pump inhibitors versus histamine-2 receptor antagonists for uninvestigated dyspepsia.

BACKGROUND AND AIMS: It is still controversial which drugs, proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA), are more effective for dyspepsia in the Japanese population. METHODS: Patients with uninvestigated dyspepsia (n = 104; male/female 41/63) were treated with either rabeprazole 10 mg o.d. (n = 62) or lafutidine 10 mg b.i.d. (n = 42) for 4 weeks. Questionnaires (modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease [mFSSG] and quality of life [QOL], SF-8) were administered before and after therapy. The mFSSG was classified into a total score (Q-T), reflux score (Q-R), dyspepsia score (Q-D) and pain score (Q-P). The SF-8 had a physical component summary (PCS) and mental component summary (MCS). The predominant type of symptom was reflux (R-S), pain (P-S) or dysmotility (D-S). RESULTS: R-S was 19.2%, P-S 48.1%, D-S 24.0% and overlap 8.7%. In the R-S, Q-T and Q-R significantly improved with rabeprazole, but neither scale improved with lafutidine. MCS significantly improved with rabeprazole. In P-S, Q-T, Q-R, Q-D and Q-P significantly improved with both drugs. PCS significantly improved with both, whereas the MCS significant improved with rabeprazole. In D-S, Q-R and Q-D significant improved with rabeprazole, but neither improved with lafutidine. QOL did not improve with either. With overlap, neither scale nor the QOL reached a significant difference. CONCLUSION: Both PPI and H2RA have a positive effect on P-S, but H(2)RA therapy is limited for R-S and D-S, whereas PPI therapy is generally effective. Therefore, careful prescription based on symptoms is important.

Markedly Effective Steroid Treatment of Three Patients with Allergy-related Jackhammer Esophagus.

We experienced marked efficacy with steroid treatment of three patients with jackhammer esophagus (JHE). An esophageal biopsy revealed eosinophilic esophagitis (EoE) in two patients. One of the patients without EoE had eosinophilia and an increased serum immunoglobulin E level, and endoscopic ultrasonography revealed thickening of the esophageal muscularis propria. Esophageal manometry was used to diagnose all cases of JHE. Treatment consisted of steroid administration, which improved the symptoms and resolved the esophageal muscularis propria thickening in all patients. The esophageal manometry findings also normalized following treatment. Allergic diseases, including EoE, were assumed to have caused JHE.

The effect of oral buspirone, pyridostigmine, and bethanechol on esophageal function evaluated with combined multichannel esophageal impedance-manometry in healthy volunteers.

BACKGROUND: There is limited information on medications with promotility effects on the esophagus. Studies in healthy volunteers have shown the potential role of the direct cholinergic agonist bethanechol and the serotonin receptor agonist buspirone in improving esophageal motility. It has been also shown that an acetylcholinesterase inhibitor, the short-acting drug edrophonium administered intravenously caused a greater increase in the esophageal contraction amplitude and duration than bethanechol. Edrophonium cannot be used as a promotility therapy owing to short duration of action and lack of oral administration. The use of another acetylcholinesterase inhibitor pyridostygmine with longer duration of action has not been studied. The aim of the study was to evaluate the effect of oral pyridostygmine (60 mg), buspirone (20 mg), and bethanechol (25 mg) on esophageal function assessed by combined multichannel intraluminal impedance-esophageal manometry. MATERIALS AND METHODS: Ten healthy volunteers were enrolled in a double blind randomized 3-period crossover study. Multichannel intraluminal impedance-esophageal manometry recorded esophageal pressures and bolus transit data during 6 liquid and 6 viscous swallows at baseline and 20, 40, and 60 minutes after the randomized oral administration of each drug. RESULTS: Blinded analysis found significant increases in mean distal esophageal amplitude for liquid swallows from baseline to 60 minutes postdosing after pyridostygmine (87.6 vs. 118.0 mm Hg, P<0.001), buspirone (85.1 vs. 101.9 mm Hg, P<0.05), and bethanechol (87.6 vs. 118.8 mm Hg, P<0.01). Only pyridostygmine showed a significant decrease in mean distal onset velocity for liquid swallows at 60 minutes postdosing (3.4 vs. 2.3 cm/s, P<0.01) and increase in total bolus transit time at 60 minutes postdosing (7.9 vs. 9.3 s, P<0.05). All 3 agents significantly increased mean lower esophageal sphincter residual pressure for liquid swallows at 20, 40, and 60 minutes postdosing. Increased lower esophageal sphincter resting pressure was not significant. Similar results were found with viscous swallows. CONCLUSIONS: Oral pyridostygmine, buspirone, and bethanechol enhance esophageal motility with pyridostygmine appearing to have the greatest effect. A potential effect on improving esophageal function and symptoms in patients requires further study.

Botulinum toxin for the treatment of hypercontractile esophagus: Results of a double-blind randomized sham-controlled study.

INTRODUCTION: Botulinum toxin injection is known to be efficient to treat achalasia. We conducted a randomized trial in order to evaluate its efficacy to treat symptomatic hypercontractile esophageal disorders as characterized by esophageal high-resolution manometry. METHODS: Patients with significant dysphagia and/or thoracic pain related to an hypercontractile esophageal motility disorder as defined by the Chicago Classification were randomized to receive an injection of botulinum toxin (100 U in 10 points in the distal part of the esophageal wall) or a sham procedure. Symptoms were assessed at 3 months with the Eckardt score. Patients could receive a first or second botulinum toxin injection 1 month later if symptoms persisted. RESULTS: Twenty-three patients (13 women, mean age 60 years) were included: 13 received botulinum toxin injection, and 10 a sham procedure. The improvement of symptoms at 3 months was significant compared to baseline, but similar in the active treatment and sham procedure arms. However, there was no change in quality of life scores. Seventeen patients received a second injection at 4 months. There was a significant trend toward improvement of symptoms up to the end of follow-up at 12 months, without a significant relationship with the administration of botulinum toxin. DISCUSSION: Botulinum toxin injection is not superior to a sham procedure to improve symptoms related to hypercontractile esophageal disorders, suggesting an important placebo effect in for this type of disease. This observation must be taken into account when evaluating more aggressive therapies such as endoscopic myotomy (clinicaltrials.gov: NCT01955174).

[Ineffective esophageal motility]. / Le syndrome de motricité œsophagienne inefficace.

Ineffective esophageal motility is the most frequent esophageal motility disorder. It is currently defined by 50% or more ineffective esophageal contractions and a normal lower esophageal sphincter relaxation on high-resolution esophageal manometry. Although reported in patients without symptoms, it is typically associated with gastro-esophageal reflux disease, and might be a consequence of the reflux. Ineffective esophageal motility can account for a certain degree of dysphagia, and is associated with a more severe gastroesophageal reflux. Todate, no specific endoscopic or pharmacologic treatment is available, and proton pump inhibitor are advisable when gastro-esophageal reflux is associated.