Achalasia Type Research Articles

Single-session endoscopic fundoplication after peroral endoscopic myotomy (POEM+F) for prevention of post gastroesophageal reflux - 1-year follow-up study.

Peroral endoscopic myotomy (POEM) is an established treatment for achalasia cardia; however, post-POEM gastroesophageal reflux (GER) remains a significant problem. Concomitant endoscopic fundoplication following POEM (POEM + F) was recently described to reduce post-POEM GER. This single-center study reports short-term outcomes of POEM + F. This was a retrospective analysis of a prospectively maintained database of patients undergoing POEM + F. Abstracted data included demographics, achalasia type, pre-POEM Eckardt score, prior therapy, follow-up. Follow-up assessment was 3-monthly for 1 year and included post-POEM Eckardt score, GerdQ score, wrap integrity and esophagitis on esophagogastroduodenoscopy, and pH studies. GER was defined according to Lyon Consensus. 25 patients underwent POEM + F (mean age 40.1 years [standard deviation (SD) 13.7]; 12 females). POEM + F was technically successful in 23/25 (92.0 %). Significant dysphagia improvement was seen in all 25 patients (mean pre- and post-POEM Eckardt scores 8.21 [SD 1.08] and 0.1 [SD 0.3], respectively; P = 0.001). Mean total procedure and fundoplication times were 115.6 (SD 27.2) minutes and 46.7 (SD 12.4) minutes, respectively; times reduced significantly after the initial five cases. Median follow-up was 12 months (interquartile range [IQR] 9-13). Intact wrap was seen in 19/23 (82.6 %). GER (abnormal esophageal acid exposure time [EAET]) was seen in 2/18 (11.1 %) and there was one reported GerdQ > 8. Borderline GER (asymptomatic grade A esophagitis, normal EAET) was identified in 4/22 (18.2 %). Three (12.0 %) minor delayed adverse events occurred but required no intervention. CONCLUSIONS : POEM + F was safe and reproducible. At 12 months' follow-up, incidence of post-POEM + F GER was low and acceptable.

Retrograde Myotomy as an Alternative to Antegrade Myotomy in Peroral Endoscopic Myotomy (POEM) for Achalasia Cardia - Is It Better?

Antegrade approach myotomy is usually performed in peroral endoscopic myotomy (POEM) for achalasia cardia. This study assessed the feasibility of retrograde approach as an alternative. This is a retrospective review of a prospectively maintained database of patients undergoing POEM, comparing the 2 techniques of antegrade myotomy (AM) and retrograde myotomy (RM). AM was performed by the conventional technique of proximal to distal myotomy while RM was from the distal end to proximal. The time required for myotomy, complications, and technical nuances were compared. Of the 24 cases of POEM, 6 were done by RM and 18 by AM approach. The baseline characteristics, symptomatology, type of achalasia, and preprocedure Eckardt score were similar between the 2 technique arms. The median myotomy time for AM was 21 minute while for RM was 25 minute (P=0.07). Complication rates were similar.Technical issues during RM included: (1) difficulty in visualizing the depth of myotomy; (2) incomplete myotomy requiring back and forth scope adjustment; (3) need for antegrade movement for completion of myotomy; (4) difficulty visualizing the axis of myotomy; (5) added arm strain during posterior myotomy. Our study did not find any additional benefit of RM compared with AM approach for POEM.

Endoscopic treatment for persistent dysphagia after heller myotomy in a patient with spastic type of achalasia with the use of the intraoperative high-resolution manometry

A Peroral Endoscopic Myotomy was performed on the patient with the persistent dysphagia despite preceding Heller myotomy combined with partial fundoplication, relaparotomy, fundoplication wrap reconstruction, gastrostomy and left-sided thoracoscopy with the drainage of the thoracic abscess. The use of intraoperative High-Resolution Manometry during Endoscopic Peroral Myotomy helped to reveal the reasons for the failure of previous treatment and to address the dysphagia.

Achalasia: physiology and diagnosis.

Achalasia is a rare motility disorder with incomplete relaxation of the lower esophageal sphincter and ineffective contractions of the esophageal body. It has been hypothesized that achalasia does not result from only one pathway but rather involves a combination of infectious, autoimmune, and familial etiological components. On the basis of other observations, a novel hypothesis suggests that a muscular form of eosinophilic esophagitis is involved in the pathophysiology of achalasia in some patients. This appears to progressively diminish the myenteric plexus at stage III, gradually destroy it at stage II, and finally eliminate it at stage I, the most advanced and final stage of achalasia. Although high-resolution manometry has identified these three different types of achalasia, another subset of patients with a normal-appearing sphincter relaxation has been proposed. Provocative maneuvers, such as the rapid drinking challenge, have recently been demonstrated to improve diagnosis in certain borderline patients, but have to be studied in more detail. However, whether the different types of achalasia will have a long-term impact on tailored therapies is still a matter of debate. Additionally, novel aspects of the standard timed barium swallow appear to be an important adjunct of diagnosis, as it has been shown to have a diagnostic as well as a predictive value.

Hirschsprung disease and other gastrointestinal motility disorders in patients with CCHS.

Congenital central hypoventilation syndrome (CCHS) is an autonomic nervous system dysfunction due to PHOX2B gene mutation. Little is known about gastrointestinal motility disorders in CCHS patients. This study aims to describe the spectrum of gastrointestinal motility disorders in CCHS and provide PHOX2B genotype-phenotype correlation with Hirschsprung Disease (HD). We reviewed the records of 72 CCHS patients seen at Children's Hospital Los Angeles from 1999 to 2019. Data collected included demographics, PHOX2B genotype, ventilator dependence, medical and surgical history, and gastrointestinal motility studies. Of the 72 patients, 31% had HD, 50% females, and 60% had 20/27 PARM. Rectosigmoid HD formed 73% of the cases whereas long segment (up to splenic flexure involvement) forms represented 23%. Four patients had total colonic aganglionosis, including one patient with 20/25 PARM genotype. One HD patient was identified with colonic myopathy in the residual segment. One patient was found to have achalasia type 1.Conclusion: Nearly one third of our CCHS patients had HD. Although most had 20/27 PARM, 2 patients had 20/25 PARM. Thus, CCHS patients with constipation are at risk for HD regardless of genotype. Colonic myopathy may coexist in treated HD with refractory constipation. Achalasia may occur in patients with CCHS. What is Known: • Patients with CCHS have motility disorders and present with esophageal dysmotility and constipation as a manifestation of their autonomic nervous system dysfunction. • About 20% of patients with CCHS have Hirschsprung disease and previously described to be associated with NPARM and 20/27 PARM genotype. What is New: • Thirty-one percent of CCHS patients in our series have Hirschsprung disease (HD). •HD, including the more severe total colonic aganglionosis was found in a patient with 20/25 PARM genotype suggesting that CCHS patients withconstipation should be screened for HD regardless of genotype.

S0449 A Genetic “Mototype” of LES Muscle Distinguishes Among Manometric Phenotypes in Patients With Achalasia Associated With Mast Cell Degranulation

INTRODUCTION: Noting that the activated eosinophils and mast cells (MCs) that accumulate in the esophagus of eosinophilic esophagitis (EoE) patients secrete myoactive, pro-inflammatory, and cytotoxic products capable of causing the motor abnormalities and neuronal degeneration of achalasia, we proposed that an allergy-mediated, esophageal muscle-predominant form of EoE might cause achalasia. In earlier studies exploring that proposal, we found that LES muscle of achalasia patients exhibits striking MC degranulation. Although the hypercontraction and poor relaxation that characterize achalasic LES muscle have been attributed solely to its loss of inhibitory neurons, we hypothesized that abnormalities intrinsic to LES muscle cells themselves might contribute to motor disturbances in achalasia associated with MC degranulation. This study aimed to explore genetic factors that might underlie such intrinsic abnormalities. METHODS: We performed qPCR for a panel of genes known to mediate smooth muscle contraction and Ca2+ handling on LES muscle specimens obtained from 7 achalasia patients (2 type I, 4 type II, 1 type III) and 3 EGJ outflow obstruction (EGJOO) patients during Heller myotomy; control LES muscle was taken from 2 organ donors. RESULTS: Hierarchical clustering analysis revealed two discrete clusters that we call “mototype” gene patterns; one control subject grouped within each cluster (Figure 1). Mototype Cluster 1, comprised of the 2 type I and 1 type III achalasia patients as well as 2 EGJOO patients, exhibited upregulation of genes involved in smooth muscle contraction and Ca2+ handling (gene expression relative to corresponding control, Figure 2). In contrast, Mototype Cluster 2, comprised of all 4 achalasia type II patients and 1 EGJOO patient, exhibited downregulation of those same genes. Principal component analysis recapitulated this clustering of mototypes that separated achalasia types I and III from type II (Figure 3), and Rand Index calculations demonstrated that this clustering was not due to chance. CONCLUSION: We show that the genetic mototype of LES muscle can distinguish the manometric phenotypes of achalasia that are associated with MC degranulation. These findings support our proposal that there is an allergy-mediated form of achalasia, and suggest that when patients acquire this form of achalasia, their underlying genetic mototype might contribute to the resulting manometric phenotype.Figure 1.: Heat-map and hierarchical clustering with dendrogram generated from qPCR gene expression data of LES muscle for 2 control subjects, 7 achalasia patients (2 type I, 4 type II, 1 type III) and 3 EGJ outflow obstruction (EGJOO) patients reveals clustering of achalasia types I and III in mototype 1, and achalasia type II into mototype 2. Red color corresponds to high relative expression and blue color corresponds to low relative expression.Figure 2.: Heat-map and hierarchical clustering with dendrogram generated from qPCR gene expression data of LES muscle from 7 achalasia patients and 3 EGJOO patients relative to their corresponding control highlights differences between the two mototype clusters. Note the relative upregulation of the calcium handling genes PLN, RYR3, IP3R1 and the smooth muscle contraction and contractility genes RHOA, COL1A2, MYLK, and ACTA2 in mototype 2 patients and the relative downregulation of these same genes in mototype 1 patients. Red/blue colors indicate up/down-regulation with respect to corresponding control in each mototype.Figure 3.: Principal component (PC) analysis of gene expression data confirms mototype clustering of achalasia types 1 and III distinct from achalasia type II.

339 OPTIMAL CUTOFF VALUE OF INTEGRATED LOWER ESOPHAGEAL SPHINCTER RELAXATION PRESSURE FOR ACHALASIA USING STARLET HIGH-RESOLUTION MANOMETRY SYSTEM

Abstract The Starlet high-resolution manometry (HRM) system is currently used in Japan. HRM provides integrated relaxation pressure (IRP) of which value represents adequacy of lower esophageal sphincter (LES) relaxation. The upper limit of normal IRP for the Starlet was proposed as 26 mmHg using healthy subjects. However, few studies have addressed whether this cutoff may well-distinguish patients diagnosed with/without achalasia. We propose the optimal cutoff of IRP for detecting achalasia using the Starlet. Methods Patients who underwent HRM test using the Starlet system at our institution between July 2018 and December 2019 were included. Of these, we excluded patients who had a history of achalasia surgery and/or endoscopic intervention, or whose HRM testing of poor quality. Achalasia was diagnosed if impaired esophageal emptying was evident based on timed barium esophagogram, upper endoscopy, and/or computed tomography. The optimal cutoff value of IRP was estimated using the receiver operating characteristic curve analysis. We further investigate difference in IRP values between achalasia subtypes to identify characteristics of patients who are more likely to be misdiagnosed. Results In total, 145 patients met study criteria. The mean age in our cohort was 52.5 ± 15.5 years, 89 patients (61.4%) were men. Of these, 42 patients (29.0%) were diagnosed with achalasia. In achalasia patients, IRP values extended to a wide-range from minimal 18.7 to maximal 63.9 mmHg. The optimal cutoff value of IRP was 24.7 mmHg with sensitivity 90.5% and specificity 90.3% (AUC 0.96 [95% CI; 0.92¬ to 0.99]). Patients with achalasia type I based on Chicago classification were most likely to have IRP value below the threshold of 25 mmHg (4/19 patients [21.1%]). Conclusion The optimal cutoff value of IRP to distinguish achalasia was ≥25 mmHg using the Starlet HRM system. This value was nearly close to the upper limit of normal IRP value of 26 mmHg in healthy volunteers. Achalasia type I was more likely to have normal IRP value indicating that comprehensive foregut assessment (eg, timed barium esophagogram, upper endoscopy, and computed tomography) is still valuable for management of achalasia.

Assessment of esophageal motility disorders by real-time MRI

PurposeTo investigate imaging findings of esophageal motility disorders on dynamic real-time. Material and methods102 patients with GERD-like symptoms were included in this retrospective study between 2015−2018. Dynamic real-time MRI visualized the transit of a 10 mL pineapple juice bolus through the esophagus and EGJ with a temporal resolution of 40 ms. Dynamic and anatomic parameters were measured by consensus reading. Imaging findings were compared to HRM utilizing the Chicago classification of esophageal motility disorders, v3.0. ResultsAll 102 patients completed real-time MRI in a median examination time of 15 min. On HRM, 14 patients presented with disorders with EGJ outlet obstruction (EGJOO) (13.7 %), 7 patients with major disorders of peristalsis (6.9 %), and 32 patients with minor disorders of peristalsis (31.4 %). HRM was normal in 49 patients (48.0 %). Incomplete bolus clearance was significantly more frequent in patients with esophageal motility disorders on HRM than in patients with normal HRM (p = 0.0002). In patients with motility disorders with EGJOO and major disorders of peristalsis, the esophageal diameter tended to be wider (23.6 ± 8.0 vs. 21.2 ± 3.5 mm, p = 0.089) and the sphincter length longer (19.7 ± 7.3 vs. 16.7 ± 3.0 mm, p = 0.091) compared to patients with normal HRM. 3/7 patients with achalasia type II were correctly identified by real-time MRI and one further achalasia type II patient was diagnosed with a motility disorder on MRI films. The other 3/7 patients presented no specific imaging features. ConclusionReal-time MRI is an auxiliary diagnostic tool for the assessment of swallowing events. Imaging parameters may assist in the detection of esophageal motility disorders.

A Case of Achalasia Presenting with Cardiac Arrest due to Left Atrial Compression

Achalasia is a rare primary esophageal motility disorder characterized by the loss of enteric neurons leading to an absence of peristalsis and impaired relaxation of the lower esophageal sphincter. The subsequent stasis of ingested food not only leads to symptoms of dysphagia, regurgitation, chest pain, and weight loss, but also results in an increased risk of esophageal carcinoma. Structural or functional pulmonary abnormalities occur in more than half of patients and may be due to recurrent aspiration or tracheal compression from a dilated esophagus. Delayed diagnosis or ineffective intervention may lead to progressive dilation of the esophagus and the development of a megaesophagus. Respiratory distress and cardiopulmonary arrest from tracheal or left atrial compression secondary to a megaesophagus are rare complications of achalasia. There is only limited evidence that pneumatic dilation may be used as a first-line therapy for a megaesophagus. The choice of definitive treatment will depend on many factors including achalasia type, patient wishes, performance status, and surgical expertise.

Continue to strengthen the study on diagnosis and surgical treatment of primary esophageal motility disorders and gastroesophageal reflux diseases

The advent of high-resolution esophageal manometry in this century produced manometric types of esophageal achalasia, which was very important for the selection of treatment methods and the assessment of prognosis. The application of 24-hour esophageal pH monitoring combined with impedance played a decisive role in determination of gastroesophageal reflux and refluxant. Advanced technologies such as laparoscopic Heller myotomy and per-oral endoscopic myotomy were used for surgical treatment of achalasia, laparoscopic anti-reflux procedures and magnetic sphincter augmentation were applied to the treatment of gastroesophageal reflux diseases (GERD). These advanced procedures implied that the treatment of primary esophageal motility disorders (PEMD) and GERD came into the minimally invasive era. However, the diagnosis and treatment of PEMD and GERD are not popular enough in our country, the studies and high-level clinical evidences are insufficient on uncommon PEMD and complex GERD, which are the further directions of efforts.

Sa1262 A LARGE SINGLE-CENTER STUDY ON THE CLINICAL OUTCOMES OF PER-ORAL ENDOSCOPIC MYOTOMY FOR SIGMOID TYPE 2 ACHALASIA

Per-oral endoscopic myotomy (POEM) has been recognized as a safe and effective minimally-invasive endoscopic treatment for achalasia. Good clinical outcomes have been reported on the application of POEM in straight type achalasia. On the other hand, results of POEM in sigmoid type achalasia, especially sigmoid type 2, are limited. This study aims to report the clinical outcomes of POEM for sigmoid type 2 achalasia. A single-center retrospective study was conducted. A prospectively collected database of 2000 patients who underwent POEM in Showa University between September 2008 to June 2019 has been reviewed. Patients who were diagnosed as sigmoid type 2 achalasia and underwent POEM were included in this study. Sigmoid type 2 achalasia was defined as an enormously dilated and tortuous esophagus in barium esophagram and double esophageal lumen in some CT slices. The primary outcome was the success rate, defined as an Eckardt Symptom Score(ESS) of less than 3 without additional treatments such as balloon dilation or redo POEM. The secondary outcomes were integrated relaxation pressure(IRP), mean lower esophageal sphincter(LES) pressure, and GERD after POEM. Patient’s characteristics: A total of 108 patients (age: 58.4±14.7 y/o, 51 females(47%), BMI: 21.7±4.6kg/m2) were included. Based on Chicago Classification, the type of achalasia seen were as follows: Type I/II/III= 28/8/1, and there were 71 unidentified cases due to the difficulty of inserting catheters. Diameter of esophagus was 48.1±17.5mm. Duration of symptoms was 17.4(7.7-29)years. ESS was 5(3-7). As pre-treatment, 49 patients had balloon dilation, Hellor-Dor in 8 patients, and Heller myotomy in 2 patients. Procedure-related parameters: Operation time was 95.9±32.1min. Myotomy length was 7(5-9)cm at the esophageal side, and 3(2-3)cm at the gastric side. Post-operative hospital stay was 4(4-5) days. The following complications were noted: mucosal perforation in 3 patients, submucosal hematoma or bleeding in 3 patients. Treatment outcomes: Success rate after 2 months was 89.1%(82/92). Pre- and 2-months post-POEM ESS were 5.0±2.5 and 1.1±1.0 (p<0.0001), respectively. Pre- and 2-months post-POEM IRP were 15.7±9.9 and 8.6±5.5 mmHg (p=0.0012), respectively. Pre- and 2-months post-POEM mean LES pressure were 19.9±13.9 and 14.6±7.7 mmHg (p=0.066), respectively. GERD 2-months post-POEM were as follows: Grade(N/A/B/C/D=37/29/13/7/1). Patients with GERD symptoms were 11.3%(10/88). PPI usage rate was 16.1%(13/81). Success rate after 1 year was 87.8%(43/49). Since good results of the short- and mid-term success rate and significant improvement of ESS and IRP value were achieved, POEM shows to be an effective procedure for sigmoid type 2 achalasia. Long-term results are expected in future studies.CT slice showing double esophageal lumenView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Sa1289 OBESITY POST-PER ORAL ENDOSCOPIC MYOTOMY: HOW BIG A PROBLEM IS IT?

Per oral endoscopy myotomy (POEM) has revolutionized the minimally-invasive treatment of achalasia. Weight gain after successful achalasia treatment is expected but little data exists on the extent of this following POEM. We speculate that in some patients, weight gain is excessive. An analysis was performed on a prospectively maintained database of all patients undergoing POEM by a single experienced operator at Kingston Health Sciences Centre, Kingston, Canada from March 2016 to August 2019. Data examined included pre- and post-POEM body mass index (BMI), procedural characteristics and Eckardt scores. 81 patients underwent POEM during the study period. 66 patients (35 male, age range 16 to 82 years) had pre- and post- POEM BMI data available (Table 1). Prior to POEM, 6 patients had a BMI < 18.5 (underweight), 20 patients had a BMI 18.5-24.9 (normal), 21 patients had a BMI 25-29.9 (overweight) and 19 patients had a BMI ≥ 30 (obese). The mean follow-up time was 19 months (range 2 to 41 months). There was no difference in the change in pre- and post-POEM Eckardt scores, myotomy length or change in pre- and post-POEM BMI between the 4 BMI categories. However, 2 patients (33%) in the underweight category were overweight at follow-up. 7 patients (35%) in the normal category were overweight and 1 (5%) was obese after POEM. Of the patients in the overweight category, 8 out of 21 (38%) were obese at follow-up. Similarly, of those obese prior to POEM, 7 out of 19 (37%) developed Class III (morbid) obesity (BMI ≥ 40) after POEM. No patients in the overweight or obese category attained a normal BMI at follow-up. There was no association between achalasia type, procedural characteristics or change in Eckardt score and weight gain after POEM. Patients may experience a marked increase in BMI following POEM, with over a third of patients becoming overweight, obese or morbidly obese from their pre-procedure BMI category. Consideration should be given to identifying predictors of weight gain after POEM and to offer weight management interventions in these patients pre- and post-procedure.

Sa1302 OUTCOMES OF EUS-DIRECTED UNDERWATER PERORAL ENDOSCOPIC MYOTOMY (UPOEM) FOR ACHALASIA USING A STANDARDIZED PROTOCOL

We have previously reported the feasibility of underwater peroral endoscopic myotomy (UPOEM) for achalasia, substituting conventional gas insufflation with water submersion [GIE 2016; 83; 454]. Potential advantages of UPOEM include avoidance of pneumomediastinum, heat-sink effect, and optical enhancements. This study aimed to evaluate the clinical outcomes of UPOEM for achalasia using a standardized protocol. A prospectively collected database on patients treated with UPOEM for achalasia using a standardized protocol over a 12-month period was retrospectively reviewed. All subjects had high resolution manometry, endoluminal functional lumen imaging (Endoflip) and radial scanning endoscopic ultrasound (EUS) prior to POEM. The proximal extent of the esophageal myotomy was EUS-directed, determined by circular muscularis propria (MP) thickness (>2mm). The distal extent was 3 cm below the crus muscle as measured by EUS. Tunnel opening was 4 cm proximal to the myotomy. After posterior entry into the submucosal space, submucosal dissection as well as myotomy were performed under saline submersion with gas insufflation turned off. The longitudinal MP was preserved. Tunneling distal to the cardia was confirmed by double scope transillumination technique. Endoflip was repeated immediately after myotomy. The tunnel opening was closed with 5-7 clips. All patients underwent a swallow study on day 1 post-UPOEM to confirm absence of leak and discharged if pain-free. Clinical success was defined as Eckdardt score ≤3 after POEM. 26 consecutive patients (58.7±2.8yrs, 18M:8F) with achalasia (type 1=2, type 2=16, type 3=8) were treated with UPOEM. Five (18%) patients had previous surgical myotomy with fundoplication, 1 had prior botox injection. All had a thickened circular MP on EUS. Procedural time was 134±9min with 100% technical success, no serious intra-procedural adverse events, and all bleeding successfully controlled. After a mean myotomy length of 120±7mm, there was an immediate improvement in distensibility (1.1±0.2 to 4.3±0.2, P<0.001). No leaks, pneumo-mediastinum/peritoneum or pleural effusions were observed on post-UPOEM swallow study. Only 2(8%) patients reported self-limited chest pain managed conservatively. The remaining patients had no chest pain. After a follow-up of 5.8±0.8 months, clinical success was achieved in 22/24 (92%) patients, with Eckardt score substantially reduced from 7.6±0.5 to 1.2±0.3 (P<0.01). Two patients were lost follow up. None had worsening of reflux symptoms or need to start proton pump inhibitor therapy. UPOEM using a standardized EUS-directed protocol resulted in high clinical success rates with no serious adverse effects and low incident of post-procedural chest pain. Validation of our EUS-guided protocol to determine optimal myotomy length is warranted.

Opioid-induced esophageal dysfunction.

Chronic opioid use is common and can cause opioid-induced esophageal dysfunction (OIED). We will discuss the pathophysiology, diagnosis, and management of OIED. OIED is diagnosed based on symptoms, opioid use, and manometric evidence of distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or jackhammer esophagus. Chronic opioid use appears to interfere with inhibitory signals involved in control of esophageal motility, allowing for unchecked excitatory stimuli, and leading to spastic contractility and impaired esophagogastric junction relaxation. Patients may present with dysphagia and chest pain. OIED is significantly more prevalent in patients taking the stronger opioids oxycodone and hydrocodone compared with the weaker opioid tramadol. Based on 24-h morphine equivalent doses, patients with OIED take higher opioid doses than those without OIED. Impaired inhibitory signaling was recently demonstrated in a study showing reduced deglutitive inhibition during multiple rapid swallows in patients taking opioids. OIED is frequent in chronic opioid users undergoing manometry for esophageal symptoms, especially at higher doses or with stronger opioids. OIED appears to be due to impaired inhibitory signals in the esophagus. Opioid cessation or dose reduction is recommended, but studies examining management of OIED are lacking.

Long-term outcomes of per-oral endoscopic myotomy in achalasia patients with a minimum follow-up of 4 years: a multicenter study.

Background and study aims Per-oral endoscopic myotomy (POEM) is associated with a short-term clinical response of 82 % to 100 % in treatment of patients with achalasia. Data are limited on the long-term durability of the clinical response in these patients. The aim of this study was to determine the long-term outcomes of patients undergoing POEM for management of achalasia. Methods This was a retrospective multicenter cohort study of consecutive patients who underwent POEM for management of achalasia. Patients had a minimum of 4 years follow-up. Clinical response was defined by an Eckardt score ≤ 3. Results A total of 146 patients were included from 11 academic medical centers. Mean (± SD) age was 49.8 (± 16) years and 79 (54 %) were female. The most common type of achalasia was type II, seen in 70 (47.9 %) patients, followed by type I seen in 41 (28.1 %) patients. Prior treatments included: pneumatic dilation in 29 (19.9 %), botulinum toxin injection in 13 (8.9 %) and Heller myotomy in seven patients (4.8 %). Eight adverse events occurred (6 mucosotomies, 2 pneumothorax) in eight patients (5.5 %). Median follow-up duration was 55 months (IQR 49.9–60.6). Clinical response was observed in 139 (95.2 %) patients at follow-up of ≥ 48 months. Symptomatic reflux after POEM was seen in 45 (32.1 %) patients, while 35.3 % of patients were using daily PPI at 48 months post POEM. Reflux esophagitis was noted in 16.8 % of patients who underwent endoscopy. Conclusion POEM is a durable and safe procedure with an acceptably low adverse event rate and an excellent long-term clinical response.

Distal esophageal spasm: Update on diagnosis and management in the era of high-resolution manometry.

Distal esophageal spasm (DES) is a rare major motility disorder in the Chicago classification of esophageal motility disorders (CC). DES is diagnosed by finding of ≥ 20% premature contractions, with normal lower esophageal sphincter (LES) relaxation on high-resolution manometry (HRM) in the latest version of CCv3.0. This feature differentiates it from achalasia type 3, which has an elevated LES relaxation pressure. Like other spastic esophageal disorders, DES has been linked to conditions such as gastroesophageal reflux disease, psychiatric conditions, and narcotic use. In addition to HRM, ancillary tests such as endoscopy and barium esophagram can provide supplemental information to differentiate DES from other conditions. Functional lumen imaging probe (FLIP), a new cutting-edge diagnostic tool, is able to recognize abnormal LES dysfunction that can be missed by HRM and can further guide LES targeted treatment when esophagogastric junction outflow obstruction is diagnosed on FLIP. Medical treatment in DES mostly targets symptomatic relief and often fails. Botulinum toxin injection during endoscopy may provide a temporary therapy that wears off over time. Myotomy through peroral endoscopic myotomy or via surgical Heller myotomy can provide long term relief in cases with persistent symptoms.

Gastroesophageal reflux disease after peroral endoscopic myotomy is unpredictable, but responsive to proton pump inhibitor therapy: a large, single-center study.

Gastroesophageal reflux disease (GERD) is an important concern after peroral endoscopic myotomy (POEM). However, there are limited data on the risk factors for post-POEM GERD and its responsiveness to proton pump inhibitors (PPIs). In this study, we aimed to analyze the variables affecting the occurrence of GERD and its response to PPI therapy. Consecutive patients with idiopathic achalasia who underwent POEM (December 2016 to January 2018) were evaluated for GERD using 24-hour pH impedance, esophagogastroduodenoscopy (EGD), and symptoms. Multivariate analysis was performed to identify the variables affecting the incidence of post-POEM GERD. A total of 209 patients with esophageal motility disorders, including 194 patients with non-sigmoid achalasia, underwent POEM during the study period. Comprehensive evaluation of GERD was completed on 167 patients (86.1 %): 47.3 % women with a mean (standard deviation) age of 41 (14.42) years and body mass index of 22.2 (3.89) kg/m2; the majority (70.7 %) were treatment naïve. A high DeMeester score (> 14.72), reflux esophagitis, and symptomatic GERD were identified in 47.9 %, 41.9 %, and 29.3 % of patients, respectively. On logistic regression analysis, type of achalasia, technique of POEM (anterior vs. posterior), pre- or post-POEM esophageal manometry variables, and patient characteristics were not associated with post-POEM GERD. Erosive esophagitis responded to PPI therapy in the majority of patients (81.4 %). The incidence of GERD is high after POEM. Most of the reflux esophagitis is mild and responsive to PPI therapy. There are no procedural or patient-related variables that appear to affect the incidence of post-POEM GERD.

Effects of peroral endoscopic myotomy on esophageal motility in patients with achalasia

Objective To evaluate the effects of peroral endoscopic myotomy (POEM) on esophageal motility in patients with achalasia(AC) after POEM. Methods Demographics, clinical and manometric data, and outcomes were collected from the medical records of patients who received POEM as the primary therapy for AC in Beijing Friendship Hospital from January 2012 to June 2016. The rate of treatment success and change in esophageal dynamics before and after treatment were compared in different types of AC. Results At 6 months′ follow-up of POEM, the symptom remission rate of AC patients with type Ⅰ, type Ⅱ, and type Ⅲ was 100.0% (13/13), 95.5% (42/44) and 90.1% (10/11), respectively. Within 6 months after POEM, lower esophageal sphincter resting pressure [10.5 (6.9, 15.8) mmHg VS 24.6 (18.3, 35.1) mmHg, 1 mmHg=0.133 kPa], 4 s integrated relaxation pressure [6.0 (3.7, 8.8) mmHg VS 21.8 (15.3, 28.0) mmHg], upper esophageal sphincter (UES)resting pressure [43.4 (33.7, 57.3) mmHg VS 45.3 (33.2, 71.1) mmHg] and UES residual pressure [1.5 (0.0, 4.6) mmHg VS 3.9 (1.1, 6.9) mmHg] were significantly improved compared with those of pre-operation (all P<0.05). At 6 months after POEM, esophageal dilatation diameter (3.0±0.7 cm VS 3.9±1.1 cm) and Eckardt scores [1 (0, 2) VS 6 (5, 8)] were also significantly improved compared with those of pre-operation (all P<0.001). After POEM, the esophageal body peristalsis did not recover in type Ⅰ AC patients. Four patients (9.1%, 4/44) of type Ⅱ AC recovered weak peristalsis or premature contraction, and 10 patients (90.9%, 10/11) of type Ⅲ AC recovered with more normal peristaltic wave, and the rate of pre-systolic contraction or weak peristalsis increased. Conclusion POEM can improve the esophagogastric junction outflow tract obstruction and change the esophageal body motility.After POEM, part patients have recovery of esophageal body motility, which is most obvious in type Ⅲ AC, followed by type Ⅱ, and type Ⅰ AC patients have no significant change. Key words: Esophageal achalasia; Peroral endoscopic myotomy; Esophageal motility

Per-oral endoscopic myotomy (POEM) for a sigmoid type of achalasia: short-term outcomes and changes in the esophageal angle.

Per-oral endoscopic myotomy (POEM) is an endoscopic procedure whereby the esophageal muscle is incised in order to lower the lower esophageal sphincter (LES) pressure. Since the time it was first performed in 2008 and subsequently reported on in 2010 by Inoue et al., POEM has been shown to be safe and effective for straight type of achalasia. On the other hand, the efficacy of POEM had been controversial for patients with achalasia of the sigmoid type, in which a high LES pressure is accompanied by morphological changes, including dilation, acute angulation, and rotation. The aim of this study is to evaluate the safety and efficacy of POEM in patients with sigmoid type of achalasia. Between May 2015 and December 2017, 16 patients with a sigmoid type of achalasia underwent POEM in our institute. The POEM procedure was the same as that for the straight type of achalasia. The double-scope technique was used to check the distal end of the submucosal tunnel from the gastric side. The primary endpoint was improvement of Eckardt score at 2months after POEM. The secondary endpoints comprised operating time, change in the esophageal angulation, and adverse events. All patients underwent POEM without severe adverse events. The respective parameters before and after POEM significantly differed in terms of mean (SD) Eckardt score [4.9 (2.0) vs. 0.4 (0.6), p < 0.01], LES pressure [19.4 (10.2) vs. 9.2 (6.4), p < 0.01], and integrated relaxation pressure [17.6 (9.2) vs. 7.9 (5.5), p < 0.01]. The average operation time was 94.7 ± 31.4min. The average esophageal angulation was 88.4° ± 23.1° before POEM and 109.5° ± 16.7° after POEM (p < 0.01). Four patients had postoperative complications that were treated conservatively. POEM can improve both LES pressure and esophageal angulation in patients with sigmoid achalasia.

390 Opioids Interfere With Deglutitive Inhibition Assessed by Response to Multiple Rapid Swallows During High Resolution Esophageal Manometry

INTRODUCTION: We previously showed an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and Jackhammer esophagus. Assessment of response to multiple rapid swallows (MRS) during high-resolution esophageal manometry (HRM) enables detection of impaired inhibition during MRS. Healthy subjects respond to MRS by deglutitive inhibition during MRS followed by an augmented contraction with higher vigor than single swallows. Hypothesis: during MRS, opioids may interfere with deglutitive inhibition and may enhance post MRS contraction. Aim: compare response to MRS in opioid users, non-users and healthy controls. METHODS: Response to MRS was evaluated in 200 patients with esophageal symptoms (100 chronic opioid users on oxycodone, hydrocodone, or tramadol for ≥3 months, 100 not on opioids), and 19 asymptomatic healthy controls that underwent HRM. Patients with prior gastroesophageal surgery, pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, esophageal stricture, achalasia type I or II, and scleroderma were excluded. Demographic and symptom data were extracted from a prospectively maintained motility database. Response to MRS was evaluated for complete versus incomplete inhibition (contractility with DCI &gt;100 mmHg-sec-cm during MRS), and presence of post MRS contraction augmentation (DCI post MRS greater than mean DCI for single swallows). Categorical variables were analyzed by chi square. RESULTS: Patients were older than controls (Table 1). HRM indications are shown in Table 2. Incomplete inhibition during MRS was significantly more frequent in chronic opioid users compared to patients not on opioids and healthy controls (26% vs 11% vs 0% P = 0.002; Figure 1). There was a significant difference in the rate of incomplete MRS inhibition for patients on oxycodone, hydrocodone, and tramadol (27% vs 34% vs 22% P = 0.002). The proportion of patients with augmentation post MRS was similar for opioid users, non-opioid users and healthy controls (P = 0.05). CONCLUSION: Impaired deglutitive inhibition during MRS was significantly more frequent among opioid users compared to non-opioid users and healthy controls. This was more common with stronger opioids (oxycodone and hydrocodone) compared to tramadol. These findings support our hypothesis that opioids interfere with inhibitory signals in the esophagus.