BACKGROUND: Long-term outcome data are limited for non-achalasia esophageal motility disorders treated by peroral endoscopy myotomy (POEM) as a separate group. We investigated a subset of symptomatic patients with hypercontractile esophagus (Jackhammer esophagus).
METHODS: Forty two patients (mean age 60.9 years; 57% female, mean Eckardt score 6.2 ± 2.1) treated by primary peroral myotomy for symptomatic Jackhammer esophagus 2012-2018 in seven European centers were retrospectively analyzed; myotomy included the lower esophageal sphincter but did not extend more than 1 cm into the cardia in contrast to POEM for achalasia. Manometry data were re-reviewed by an independent expert. The main outcome was the failure rate defined by retreatment or an Eckardt score >3 after at least two years following POEM.
RESULTS: Despite 100% technical success (mean intervention time 107 ± 48.9 min, mean myotomy length 16.2 ± 3.7 cm), the 2-year success rate was 64.3% in the entire group. In a subgroup analysis, POEM failure rates were significantly different between Jackhammer-patients without (n = 22), and with esophagogastric junction outflow obstruction (EGJOO, n = 20) (13.6% % vs. 60%, p = 0.003) at a follow-up of 46.5 ± 19.0 months. Adverse events occurred in nine cases (21.4%). 14 (33.3%) patients were retreated, two with surgical fundoplication due to reflux. Including retreatments, an improvement in symptom severity was found in 33 (78.6%) at the end of follow-up (Eckardt score ≤3, mean Eckardt change 4.34, p < 0.001). EGJOO (p = 0.01) and frequency of hypercontractile swallows (p = 0.02) were predictors of POEM failure. The development of a pseudodiverticulum was observed in four cases within the subgroup of EGJOO.
CONCLUSIONS: Patients with symptomatic Jackhammer without EGJOO benefit from POEM in long-term follow-up. Treatment of Jackhammer with EGJOO, however, remains challenging and probably requires full sphincter myotomy and future studies which should address the pathogenesis of this variant and alternative strategies.

Background and objective Achalasia cardia is a primary esophageal motility disorder, and the etiopathology of this disease\'s progression is not known. Moreover, autonomic dysfunction has not been studied in different types of achalasia. In light of this, we aimed to address this lack of data in this study. Methods The diagnosis of achalasia was done using high-resolution esophageal manometry (HRM)-based Chicago classification v4.0. Autonomic function tests (AFT) such as the head-up tilt test, deep breathing test (DBT), Valsalva maneuver (VM), handgrip test (HGT), and cold pressor test (CPT), as well as the heart rate variability (HRV) test, were performed among the cohort and the results were compared with those of 39 age- and sex-matched healthy controls. Results AFT and HRV tests were done on 62 patients (30 achalasia type I, 28 type II, and 4 type III) and compared with 39 age- and sex-matched healthy controls. The mean duration of symptoms, high Eckardt score, and dysphagia were most common in type I achalasia, followed by type II and III. The results of AFT showed a generalized loss of parasympathetic and baroreflex-independent sympathetic reactivity in all types of achalasia. However, baroreflex-dependent cardiovascular adrenergic reactivity was normal. Regarding cardiac autonomic tone, there was a loss of parasympathetic and sympathetic influence, but sympathovagal balance was maintained. The severity of the loss of autonomic functions was higher in type I, followed by type II. Conclusions In all types of achalasia, parasympathetic reactivity, baroreflex-independent sympathetic reactivity, and cardiac autonomic tone were lower compared to healthy controls, and the severity of dysfunction increased during the progression of the disease from type II to type I.

BACKGROUND: Improvement in lower esophageal sphincter (LES) competency after laparoscopic Nissen fundoplication (LNF) is well established, yet esophageal body physiology data are limited. We aimed to describe the impact of LNF on whole esophagus physiology using standard and novel manometric characteristics.
METHODS: A cohort of patients with an intact fundoplication without herniation and no postoperative dysphagia were selected and underwent esophageal manometry at one-year after surgery. Pre- and post-operative manometry files were reanalyzed using standard and novel manometric characteristics and compared.
RESULTS: A total of 95 patients were included in this study. At 16.1 (8.7) months LNF increased LES overall and abdominal length and resting pressure (p < 0.0001). Outflow resistance (IRP) increased [5.8 (3-11) to 11.1 (9-15), p < 0.0001] with a 95th percentile of 20 mmHg in this cohort of dysphagia-free patients. Distal contractile integral (DCI) also increased [1177.0 (667-2139) to 1321.1 (783-2895), p = 0.002], yet contractile amplitude was unchanged (p = 0.158). There were direct correlations between pre- and post-operative DCI [R: 0.727 (0.62-0.81), p < 0.0001] and postoperative DCI and postoperative IRP [R: 0.347 (0.16-0.51), p = 0.0006]. Contractile front velocity [3.5 (3-4) to 3.2 (3-4), p = 0.0013] was slower, while distal latency [6.7 (6-8) to 7.4 (7-9), p < 0.0001], the interval from swallow onset to proximal smooth muscle initiation [4.0 (4-5) to 4.4 (4-5), p = 0.0002], and the interval from swallow onset to point when the peristaltic wave meets the LES [9.4 (8-10) to 10.3 (9-12), p < 0.0001] were longer. Esophageal length [21.9 (19-24) to 23.2 (21-25), p < 0.0001] and transition zone (TZ) length [2.2 (1-3) to 2.5 (1-4), p = 0.004] were longer. Bolus clearance was inversely correlated with TZ length (p = 0.0002) and time from swallow onset to proximal smooth muscle initiation (p < 0.0001). Bolus clearance and UES characteristics were unchanged (p > 0.05).
CONCLUSIONS: Increased outflow resistance after LNF required an increased DCI. However, this increased contractile vigor was achieved through sustained, not stronger, peristaltic contractions. Increased esophageal length was associated with increased TZ and delayed initiation of smooth muscle contractions.

Esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation with preserved peristalsis. Studies have shown that Heller myotomy with Dor fundoplication (HMD) and per oral endoscopic myotomy (POEM) are effective treatments for EGJOO. However, there is paucity of data comparing the efficacy and impact of these two procedures. Therefore, the aim of this study was to compare outcomes and impact on esophageal physiology in patients undergoing HMD or POEM for primary EGJOO.
This was a retrospective review of patients who underwent either HMD or POEM for primary EGJOO at our institution between 2013 and 2021. Favorable outcome was defined as an Eckardt score ≤ 3 at 1 year after surgery. GERD-HRQL questionnaire, endoscopy, pH monitoring, and high-resolution manometry (HRM) results at baseline and 1 year after surgery were compared pre- and post-surgery and between groups. Objective GERD was defined as DeMeester score > 14.7 or LA grade C/D esophagitis.
The final study population consisted of 52 patients who underwent HMD (n = 35) or POEM (n = 17) for EGJOO. At a mean (SD) follow-up of 24.6 (15.3) months, favorable outcome was achieved by 30 (85.7%) patients after HMD and 14 (82.4%) after POEM (p = 0.753). After HMD, there was a decrease GERD-HRQL total score (31 (22-45) to 4 (0-19); p < 0.001), and objective reflux (54.2 to 25.9%; p = 0.033). On manometry, there was a decrease in LES resting pressure (48 (34-59) to 13 (8-17); p < 0.001) and IRP (22 (17-28) to 8 (3-11); p < 0.001), but esophageal body characteristics did not change (p > 0.05). Incomplete bolus clearance improved (70% (10-90) to 10% (0-40); p = 0.010). After POEM, there was no change in the GERD-HRQL total score (p = 0.854), but objective reflux significantly increased (0 to 62%; p < 0.001). On manometry, there was a decrease in LES resting pressure (43 (30-68) to 31 (5-34); p = 0.042) and IRP (23 (18-33) to 12 (10-32); p = 0.048), DCI (1920 (1600-5500) to 0 (0-814); p = 0.035), with increased failed swallows (0% (0-30) to 100% (10-100); p = 0.032). Bolus clearance did not improve (p = 0.539). Compared to HMD, POEM had a longer esophageal myotomy length (11 (7-15)-vs-5 (5-6); p = 0.001), more objective reflux (p = 0.041), lower DCI (0 (0-814)-vs-1695 (929-3101); p = 0.004), and intact swallows (90 (70-100)-vs-0 (0-40); p = 0.006), but more failed swallows (100 (10-100); p = 0.018) and incomplete bolus clearance (90 (90-100)-vs-10 (0-40); p = 0.004).
Peroral endoscopic myotomy and Heller myotomy with Dor fundoplication are equally effective at relieving EGJOO symptoms. However, POEM causes worse reflux and near complete loss of esophageal body function.

BACKGROUND: This study was performed to evaluate the orientation of lower esophageal sphincter (LES) pressure in patients with untreated achalasia using three-dimensional high-resolution manometry (3D-HRM).
METHODS: The study involved 20 patients with untreated achalasia (10 men, 60 [47-74] years of age). The 3D-HRM assembly had 32 standard channels and 12 3D channels. During basal LES pressure measurements, the orientations of the LES high- and low-pressure zones were evaluated at end-expiration. The directional relationships between the orientation of the LES high- and low-pressure zones were also evaluated.
RESULTS: The LES high-pressure zones were located on the greater curvature side in nine (45%) patients, from the greater curvature to posterior wall side in six (30%), and from the greater curvature to anterior wall side in five (25%). The LES high-pressure zones were located mainly on the greater curvature side, but there were some variations of the orientation among the patients. The LES low-pressure zones were most frequently located from the lesser curvature to the posterior wall side in 11 (55%) patients, from the lesser curvature to anterior wall side in 6 (30%), on the posterior wall side in 2 (10%), and on the anterior wall side in 1 (5%). Significant differences were found in the directional relationships between the orientation of the LES high- and low-pressure zones (P = 0.0053).
CONCLUSIONS: This is the first report from Japan focusing on the LES pressure orientation using 3D-HRM. Such evaluation may be useful for clarifying the pathophysiology of achalasia.

Magnetic sphincter augmentation (MSA)was introduced as an alternative to laparoscopic Nissen fundoplication (LNF). This reproducible, outpatient procedure addresses the etiology of gastroesophageal reflux disease by implanting a ring of magnetic beads across the esophagogastric junction (EGJ). MSA is designed to resist effacement of the lower esophageal sphincter (LES) and, similar to LNF, results in restoration of anti-reflux barrier competency by increasing overall length, intraabdominal length and resting pressure of the sphincter. However, the novel use of magnets to augment the physiology of the LES poses unique challenges to the physiology of the EGJ and esophagus. These impacts are best revealed through manometry. The degree of restrictive forces at the EGJ, as measured by intrabolus pressure and integrated relaxation pressure, is higher after MSA compared with LNF. In addition, contrary to the LNF, which retains neurohormonal relaxation capability during deglutition, the magnetic forces remain constant until forcibly opened. Therefore, the burden of overcoming EJG resistance is placed solely on the esophageal body contractile force, as measured by distal contractile integral and distal esophageal amplitude. The main utility of preoperative manometry is in determining whether a patient\'s esophagus has sufficient contractility or peristaltic reserve to adapt to the challenge of an MSA. Manometric thresholds predictive of MSA outcomes deviate from those used to define named Chicago Classification motility disorders. Therefore, individual preoperative manometric characteristics should be analyzed to aid in risk stratification and patient selection prior to MSA.

BACKGROUND: The surgical treatment of achalasia by both laparoscopic and endoscopic approaches has been recognized as the definitive management in children. Despite reported low volumes in many centers, there has been an increasing worldwide experience with endoscopic approaches to pediatric achalasia. The aim of this study is to report our institutional experience with per oral endoscopic myotomy (POEM) as first-line or revisional therapy for achalasia.
METHODS: An IRB approved retrospective review of all patients who underwent operative procedures for achalasia, specifically with the POEM technique, from July 2015 to September 2021. Data including demographics, intra-operative details, pre and post operative Eckardt scores, complications, outcomes, and follow-up were obtained.
RESULTS: During the study period, a total of 43 children underwent 46 operations for achalasia including POEM and laparoscopic Heller myotomy (LHM). Operations included 37 POEMS (33 primary POEMS; 3 POEMS after failed LHM; and 1 POEM after failed POEM). Additionally, 9 LHM operations including, 4 primary LHM; 3 attempted POEMS converted to LHM; 1 attempted POEM after failed LHM converted to redo LHM; and 1 LHM after failed POEM. In the POEM group (n = 37), based on the high resolution esophageal manometry findings Chicago Classification types at diagnosis were as follows: 9 patients were type I (24.3%); 25 patients were type II (67.6%); 2 patients were type III (5.9%) and 1 patient was unknown type (2.7%). Sixteen children (43.2%) had prior endoscopic treatment of achalasia prior to POEM [Pneumatic Balloon Dilatation (PBD), and/or Botox injection (BTI)],), while prior operative intervention occurred in 4 patients (10.8%), 3 LHM and 1 POEM. Age at operation was 2-18 years (mean ± SD age: 11.6 ± 4.5 years). Weight at operation 11.8-100.7 kg (mean ± SD kg; 39 ± 19.9 kg). Range of baseline Eckardt score was 4-10 (mean ± SD: 6.73 ± 1.5). Operative time was 64-359 min (mean ± SD minutes: 138.1 ± 62.2 min). Intraoperative complications occurred in 16 patients (43.2%) but did not require reoperation during index admission including: 4 mucosotomy (11.8%); 9 pneumothoraces (24.3%); 2 pneumomediastinum (5.4%); 10 pneumoperitoneum (27%); 0 sub-mucosal tunnel bleeding (0%); 0 open conversion/death (0%). Post operative complications included: 5 recurrent dysphagia (13.5%); 0 esophageal leak (0%); 3 GERD (8.1%); 1 failed POEM (2.7%). Median length of stay was 2 days (mean ± SD days: 2.4 ± 0.9 day). Follow-up ranged from 1 to 74 months (median 15 months), mean follow-up 22.6 months ± 20 months. Post POEM Eckardt score was 0.6 ± 0.9. Five patients required a single PBD post POEM (13.5%) and 1 patient required a repeat myotomy (LHM) after POEM (2.7%) for a 16.2% reintervention rate. Subsequent normalization of Eckardt scores (≤ 3) and symptomatic relief was achieved in all patients (100%).
CONCLUSIONS: POEM as first-line therapy for pediatric achalasia, or as a secondary procedure after failed prior myotomy or POEM, in our experience is safe and effective. We have shown equivalent results to our own prior experience with LHM. Long-term follow-up will be performed to monitor for recurrent symptoms, adequate physical growth, and general development.
METHODS: II.

UNASSIGNED: Pathophysiology of gastroesophageal reflux disease (GERD) shows a multifactorial background. Different anatomical and functional alterations can be determined such as weakness of the lower esophageal sphincter (LES), changes in anatomy by a hiatal hernia (HH), an impaired esophageal motility (IEM), and/or an associated gastric motility problem with either duodeno-gastro-esophageal reflux (DGER) or delayed gastric emptying (DGE). The purpose of this study is to assess a large GERD-patient population to quantitatively determine different pathophysiologic factors contributing to the disease.
UNASSIGNED: For this analysis only patients with documented GERD (pathologic esophageal acid exposure) were selected from a prospectively maintained databank. Investigations: history and physical, body mass index, endoscopy, esophageal manometry, 24 h-pH-monitoring, 24 h-bilirbine-monitoring, radiographic-gastric-emptying or scintigraphy, gastrointestinal quality of life index (GIQLI).
UNASSIGNED: In total, 728 patients (420 males; 308 females) were selected for this analysis. Mean age: 49.9 years; mean BMI: 27.2 kg/m2 (range, 20-45 kg/m2); mean GIQLI of 91 (range: 43-138; normal level: 121); no esophagitis: 30.6%; minor esophagitis (Savary-Miller type 1 or Los Angeles Grade A): 22.4%; esophagitis [2-4]/B-D: 36.2%; Barrett\'s esophagus 10%. Presence of pathophysiologic factors: HH 95.4%; LES-incompetence 88%, DGER 55%, obesity 25.6%, IEM 8.8%, DGE 6.8%.
UNASSIGNED: In our evaluation of GERD patients, the most important pathophysiologic components are anatomical alterations (HH), LES-incompetence and DGER.

BACKGROUND: Vasoactive intestinal peptide (VIP) is an important neurotransmitter involved in the modulation of gastrointestinal function through the stimulation of VIP receptors. However, the expression of VPAC1R, VPAC2R and PAC1R in the human Lower esophageal sphincter (LES) has not been fully clarified. Therefore, the purpose of this study is to explore the expression of these receptors in the human Lower esophageal sphincter, the responses of the Lower esophageal sphincter to Vasoactive intestinal peptide, and the role of Vasoactive intestinal peptide receptors in the responses.
METHODS: Sling and clasp fiber samples of LES were acquired from patients undergoing subtotal esophagectomy, while circular muscle bundles from the esophagus and gastric fundus were used as control groups. Western blotting and RT-PCR technology were performed to determine the expression of the three VIP receptor subtypes. The isometric tension responses of the muscle sample strips to Ro25-1553 and PG99-465, and the effect of electrical field stimulation (EFS) on the sling and clasp fibers were studied.
RESULTS: We found that VPAC2R messenger RNA (mRNA) and protein were expressed in the sling and clasp fibers of human LES. However, no VPAC1R or PAC1R mRNA and protein expressions were found in the LES samples. The sling and clasp fibers of the LES produced significant concentration-dependent relaxation following exposure to Ro25-1553 and EFS could induce them to produce frequency-dependent relaxation. Furthermore, the relaxation responses of the LES were inhibited by PG99-465 and induced by EFS and Ro25-1553.
CONCLUSIONS: VPAC2R, but not VPAC1R or PAC1R, is expressed by the human LES. The relaxation responses of the LES generated by the VIP receptor agonist Ro25-1553 and EFS could be inhibited by the selective VPAC2 receptor antagonist PG99-465. VPAC2R may be important for the generation of relaxation and functional regulation of the LES.

BACKGROUND: Globus pharyngeus is common and has a low cure rate. Its etiology is complex and reported to be associated with laryngopharyngeal reflux (LPR). However, some patients with globus do not exhibit any reflux symptoms or respond to proton pump inhibitors (PPIs) treatments. The purpose of this study was to clarify the related risk factors of these patients with a final objective of improving the curative effect.
METHODS: Forty two patients afflicted with globus pharyngeus (G group) and 38 patients without globus pharyngeus (NG group) were included in this study. According to the laryngopharyngeal Reflux Symptom Index and the response to PPIs treatments, the patients were further divided into reflux groups (G-R, NG-R) and non-reflux groups (G-NR, NG-NR). High Resolution Manometry (HRM) was performed to assess esophageal motility. Questionnaires, including categories such as life exposure factors, were conducted.
RESULTS: a) The average resting and residual pressures of the upper esophageal sphincter (UES) in the G-NR group was higher than in the NG-NR and NG-R groups (P < 0.05). b) The average resting and residual pressures of the lower esophageal sphincter showed no differences between the G-NR group and the NG-NR group (P > 0.05). c) The esophageal distal contractile integral score of the G-NR group was not different from the NG-NR group (P > 0.05). d) Compared to the NG-NR group, the G-NR group showed higher incidence of stress, smoking, drinking, high salt and anxiety (P < 0.05).
CONCLUSIONS: Globus pharyngeus without LPR may occur due to high UES pressure. Stress, smoking, alcoholic drinking, high salt and anxiety may be its risk factors.