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Our prior study reveals that the distension-contraction profiles using high-resolution manometry impedance recordings can distinguish patients with dysphagia symptom but normal esophageal function testing ("functional dysphagia") from control subjects. The aim of this study was to determine the diagnostic value of the recording protocol used in our prior studies (10-mL swallows with subjects in the Trendelenburg position) against the standard clinical protocol (5-mL swallows with subjects in the supine position). We used advanced machine learning techniques and robust metrics for classification purposes. Studies were performed on 30 healthy subjects and 30 patients with functional dysphagia. A custom-built software was used to extract the relevant distension-contraction features of esophageal peristalsis. Ensemble methods, i.e., gradient boost, support vector machines (SVMs), and logit boost, were used as the primary machine learning algorithms. Although the individual contraction features were marginally different between the two groups, the distension features of peristalsis were significantly different. The receiver operating characteristic (ROC) curve values for the standard recording protocol and the distension features ranged from 0.74 to 0.82; they were significantly better for the protocol used in our prior studies, ranging from 0.81 to 0.91. The ROC curve values using three machine learning algorithms were far superior for the distension than the contraction features of esophageal peristalsis, revealing a value of 0.95 for the SVM algorithm. Current patient classification for esophageal motility disorders, based on the contraction phase of peristalsis, ignores a large number of patients who have an abnormality in the distension phase of peristalsis. Distension-contraction plots should be the standard for assessing esophageal peristalsis in clinical practice. NEW & NOTEWORTHY Our findings underscore the superiority of distension features over contraction metrics in diagnosing esophageal dysfunctions. By leveraging state-of-the-art machine learning techniques, our study highlights the diagnostic potential of distension-contraction plots of peristalsis. Implementation of these plots could significantly enhance the accuracy of identifying patients with esophageal motor disorders, advocating for their adoption as the standard in clinical practice.

Background and Aims: This study aimed to systematically evaluate a classification scheme of secondary peristalsis using functional luminal imaging probe (FLIP) panometry through comparison with primary peristalsis on high-resolution manometry (HRM)., Methods: 706 adult patients that completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers ("controls") were included. Secondary peristalsis, that is, contractile responses (CRs), was classified on FLIP panometry by the presence and pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), absent (ACR), or spastic-reactive (SRCR). Primary peristalsis on HRM was assessed according to the Chicago Classification., Results: All 35 of the controls had antegrade contractions on FLIP panometry with either NCR (89%) or BCR (11%). The average percentages of normal swallows on HRM varied across contractile response patterns from 84% in NCR, 68% in BCR, 39% in IDCR, to 11% in ACR, as did the percentage of failed swallows on HRM: 4% in NCR, 12% in BCR, 36% in IDCR, and 79% in ACR. SRCR on FLIP panometry was observed in 18/57 (32%) patients with type III achalasia, 4/15 (27%) with distal esophageal spasm, and 7/15 (47%) with hypercontractile esophagus on HRM., Conclusions: The FLIP panometry contractile response patterns reflect a pathophysiologic transition from normal to abnormal esophageal peristaltic function with shared features with primary peristaltic function/dysfunction on HRM. Thus, these patterns of the contractile response to distension can facilitate the evaluation of esophageal motility using FLIP panometry., (© 2021 John Wiley & Sons Ltd.)

Introduction: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0)., Methods: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0., Results: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0., Discussion: Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction: High amplitude peristaltic esophageal contractions, that is, nutcracker esophagus, were originally described in association with "angina-like pain" of esophageal origin. However, significant number of nutcracker patients also suffer from dysphagia. High-resolution esophageal manometry (HRM) assesses only the contraction phase of peristalsis. The degree of esophageal distension during peristalsis is a surrogate of relaxation and can be measured from the intraluminal esophageal impedance measurements., Aims: Determine the amplitude of distension and temporal relationship between distension and contraction during swallow-induced peristalsis in nutcracker patients., Methods: HRM impedance (HRMZ) studies were performed and analyzed in 24 nutcracker and 30 normal subjects in the Trendelenburg position. A custom-built software calculated the numerical data of the amplitudes of distension and contraction, the area under the curve (AUC) of distension and contraction, and the temporal relationship between distension and contraction., Results: In normal subjects, the distension peaks similar to contraction traverse sequentially the esophagus. The amplitude of contraction is greater in the nutcracker esophagus but the amplitude of distension and area under the curve of distension are smaller in patients compared to controls. Distension peaks are aligned closely with contraction in normal subjects, but in patients, the bolus travels faster to the distal esophagus, resulting in a smaller time interval between the onset of swallow and distension peak. Receiver operative characteristics (ROC) curve reveals high sensitivity and specificity of the above parameters in patients., Conclusion: Abnormalities in the distension phase of peristalsis are a possible mechanism of dysphagia in patients with nutcracker esophagus., (© 2021 John Wiley & Sons Ltd.)

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., (© 2020 John Wiley & Sons Ltd.)

Background/aim: The aim was to investigate whether there is a difference in secondary peristalsis on high-resolution manometry (HRM) among gastroesophageal reflux disease (GERD) patients with and without ineffective esophageal motility (IEM), and healthy individuals., Methods: Twenty-eight GERD patients and seventeen healthy controls were included. Secondary peristalsis was stimulated by a rapid injection of 20 ml air in mid-esophagus. We compared HRM metrics and the response and effective rate of triggering secondary peristalsis between patients with and without IEM and healthy controls., Results: Sixteen patients had IEM, and the remaining 12 had normal manometry. By triggering of secondary peristalsis, patients without IEM and healthy controls had significantly higher distal contractile integral (DCI) values than IEM patients (p = 0.006). A successful secondary peristalsis was triggered more frequently in healthy controls than in GERD patients with normal peristalsis or IEM (56.9% vs. 20.2% vs. 9.1%, all p < 0.001). The effective rate which determined as DCI > 450 mm Hg.cm.s was higher in healthy controls compared to patients with normal peristalsis (36.5% vs. 19.4%, p < 0.001) and IEM (36.5% vs. 6.3%, p < 0.001). Patients with IEM had lower successful triggering response (9.1% vs. 20.2%) and effective secondary peristalsis (6.3% vs. 19.4%) compared with patients without IEM (p < 0.001)., Conclusions: Our work has demonstrated that GERD patients, in particular those with IEM, have significant defects in the triggering of secondary peristalsis on HRM. HRM helps characterize esophageal secondary peristalsis which exhibits differently in patients with and without IEM., (© 2020 John Wiley & Sons Ltd.)

Hypercontractile esophagus (HE) is a heterogeneous major motility disorder diagnosed when ≥20% hypercontractile peristaltic sequences (distal contractile integral >8,000 mm Hg*s*cm) are present within the context of normal lower esophageal sphincter (LES) relaxation (integrated relaxation pressure < upper limit of normal) on esophageal high-resolution manometry (HRM). HE can manifest with dysphagia and chest pain, with unclear mechanisms of symptom generation. The pathophysiology of HE may entail an excessive cholinergic drive with temporal asynchrony of circular and longitudinal muscle contractions; provocative testing during HRM has also demonstrated abnormal inhibition. Hypercontractility can be limited to the esophageal body or can include the LES; rarely, the process is limited to the LES. Hypercontractility can sometimes be associated with esophagogastric junction (EGJ) outflow obstruction and increased muscle thickness. Provocative tests during HRM can increase detection of HE, reproduce symptoms, and predict delayed esophageal emptying. Regarding therapy, an empiric trial of a proton pump inhibitor, should be first considered, given the overlap with gastroesophageal reflux disease. Calcium channel blockers, nitrates, and phosphodiesterase inhibitors have been used to reduce contraction vigor but with suboptimal symptomatic response. Endoscopic treatment with botulinum toxin injection or pneumatic dilation is associated with variable response. Per-oral endoscopic myotomy may be superior to laparoscopic Heller myotomy in relieving dysphagia, but available data are scant. The presence of EGJ outflow obstruction in HE discriminates a subset of patients who may benefit from endoscopic treatment targeting the EGJ., (Copyright © 2020 by The American College of Gastroenterology.)

Background: The definition and relevance of ineffective esophageal motility (IEM) remains debated. Our aim was to determine motility patterns and symptoms associated with IEM defined as impaired bolus clearance., Methods: To define altered bolus clearance, normal range of swallows with complete bolus transit (CBT) on high-resolution impedance manometry (HRIM) was determined in 44 asymptomatic controls. The results were then applied to a cohort of 81 patients with esophageal symptoms to determine the motility patterns which best predicted altered bolus clearance. Subsequently, in a cohort of 281 consecutive patients the identified motility patterns were compared with patients' customary symptoms., Key Results: In asymptomatic controls, the normal range of swallows with CBT was 50%-100%. In patients, altered bolus transit (<50% CBT) was only associated with 30% or more failed contractions (P < .001). Neither weak peristalsis nor absence of contraction reserve (CR) was associated with altered bolus clearance. The patterns which best predicted altered bolus clearance were failed contractions ≥30% (specificity 88.2% and sensitivity of 84.6%), and ≥70% ineffective (failed + weak) contractions (sensitivity 84.6% and specificity 80.9%). No motility pattern was correlated to symptom scores., Conclusions and Inferences: Based on bolus clearance assessed by HRIM, ≥30% failed contractions and ≥70% ineffective contractions have the best sensitivity and specificity to predict altered bolus clearance. Weak contractions and absence of CR are not relevant with respect to bolus clearance., (© 2020 John Wiley & Sons Ltd.)

Background: The contractile activity of Jackhammer esophagus(JE) is heterogeneous and abnormalities in the balance of pre- and post-peak contractile activity has been reported. We observed that the progression of the peak contraction is disordered in JE patients, which reflect underlying abnormalities in the inhibitory and excitatory influence in esophageal contraction. In order to better define this abnormality, we developed novel time metrics to define trajectory of the pressure wave peak and assessed it in healthy controls and JE patients., Methods: 38 patients with JE (ages 43-70, 19 females) and 71 asymptomatic controls (ages 19-48; 33 females) were retrospectively evaluated. High resolution manometry was performed in all subjects with 10 supine liquid swallows. The first 5 intact supine swallows and supine swallow with the greatest DCI were analyzed using ManoView™ software and customized MATLAB program. The time distance, negative time distance sum and chaotic ratio were calculated. JE patients were subcategorized by the Brief Esophageal Dysphagia Questionnaire (BEDQ) with cut-off of 6., Key Results: Jackhammer patients had longer time distance, longer negative time distance, and higher chaotic ratio than controls( p < 0.001). The distribution of the number of negative time distances differed between JE patients with BEDQ>6 and BEDQ≤6., Conclusions & Inferences: The trajectory of the pressure wave peak propagation commonly occurred in an unordered fashion in JE, but rarely in controls. Additionally, differences in pressure propagation trajectory was associated with higher symptom scores thus trajectory of the pressure wave peak may be an important marker of abnormal esophageal motor function., (© 2019 John Wiley & Sons Ltd.)

Background: Hypercontractile motility of the esophagus is occasionally noted on high-resolution manometry (HRM), but its clinical correlations are unclear. We compared symptom severity and clinical presentation of patients with hypercontractile motility of the esophagus., Methods: This was a retrospective cohort study. We queried a prospectively maintained database for patients who underwent esophageal function testing from October 1, 2016, to October 30, 2018. We included patients with jackhammer esophagus (JE; ≥2 swallows with distal contractile integral [DCI] ≥8,000 mm Hg∙cm∙s), nutcracker esophagus (NE; mean DCI 5,000-8,000 mm Hg∙cm∙s without meeting JE criteria), or esophagogastric junction outflow obstruction ([EGJOO]: abnormal median integrated relaxation pressure (>15 mm Hg) without meeting achalasia criteria, with JE [EGJOO-h], or normal motility [EGJOO-n]). HRM, endoscopy, barium esophagram, ambulatory pH studies, and symptom questionnaires were reevaluated for further analysis. Clinical parameters were analyzed using Spearman Rho correlation. Categorical variables were assessed with Fisher exact or chi-square test., Results: Altogether, 85 patients met inclusion criteria. They were divided into 4 subgroups: 28 with JE, 18 with NE, 15 with EGJOO-h, and 24 with EGJOO-n. Patients with EGJOO-h were the most symptomatic overall. No correlation was seen between symptoms and mean DCI (p ≥ 0.05 all groups) or number of hypercontractile swallows (≥8,000 mm Hg∙cm∙s, p ≥ 0.05). A significant correlation was noted between dysphagia and lower esophageal sphincter pressure (LESP) and LESP integral (p ≤ 0.05)., Conclusion: The number of hypercontractile swallows and mean DCI were not associated with patient-reported symptoms. Elevated LESP may be a more relevant contributor to dysphagia., (© 2020 S. Karger AG, Basel.)

Purpose of Review: Esophageal peristalsis is a highly sophisticated function that involves the coordinated contraction and relaxation of striated and smooth muscles in a cephalocaudal fashion, under the control of central and peripheral neuronal mechanisms and a number of neurotransmitters. Esophageal peristalsis is determined by the balance of the intrinsic excitatory cholinergic, inhibitory nitrergic and post-inhibitory rebound excitatory output to the esophageal musculature., Recent Findings: Dissociation of the longitudinal and circular muscle contractions characterizes different major esophageal disorders and leads to esophageal symptoms. Provocative testing during esophageal high-resolution manometry is commonly employed to assess esophageal body peristaltic reserve and underpin clinical diagnosis. Herein, we summarize the main factors that determine esophageal peristalsis and examine their role in major and minor esophageal motility disorders and eosinophilic esophagitis.

The purpose of the review is to determine the relationship between the clinical symptoms of diseases and disorders of the motor function of the esophagus, stomach and duodenal bulb, to present modern methods of their diagnosis and pathogenetic principles of treatment of diseases. Depending on the pathogenesis, it is possible to distinguish secondary motility disorders resulting from organic lesions, and primary (functional) changes. The emergence of clinical symptoms is associated with impaired motor - evacuation function of the digestive tract, which can be divided into two large groups: changes in the peristaltic activity of the organ wall and the work of the sphincter apparatus. The basis of the regulation of motility of the esophagus, stomach and duodenum is the interaction of nervous and humoral factors, the central processing of impulses is carried out in the cerebral cortex. In case of violation of the coordinated action of inhibitory and excitatory regulation systems, pathological contractile activity occurs, which manifests itself as hypo - or hyper - motor dyskinesia. X-ray, ultrasound, high resolution manometry of the esophagus, pH-meter, scintigraphy, computed tomography, antroduodenal manometry and a number of others are used to diagnose disorders of the motor function of the digestive tract, which can determine the mechanism of the development of symptoms and prescribe pathogenetic treatment to the patient. Thus, the occurrence of clinical symptoms is associated with changes in the motor - evacuation function of the digestive tract due to a violation of the coordinating action of inhibitory and excitatory factors. The use of modern diagnostic methods for the study of motor function makes it possible to determine the mechanism for the development of clinical symptoms, which allows the patient to prescribe an effective pathogenetic treatment.

Background and Aim: Acute esophageal acid infusion promotes distension-induced secondary peristalsis. The gamma-aminobutyric acid receptor type B (GABA-B) receptors activation inhibits secondary peristalsis. This study aimed to test the hypothesis whether acid excitation of secondary peristalsis can be influenced by baclofen., Methods: Secondary peristalsis was performed with intra-esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1 N HCl following pretreatment with placebo or baclofen was randomly performed at least 1 week apart. Symptom intensity, distension thresholds, and peristaltic parameters were determined and compared between each study protocol., Results: The intensity of heartburn symptom in response to esophageal acid infusion was significantly greater with baclofen than the placebo (P = 0.002). The threshold volume of secondary peristalsis during slow air injections in response to acid infusion was significantly greater with baclofen than the placebo (P = 0.001). Baclofen significantly increased the threshold volume of secondary peristalsis during rapid air injections in response to acid infusion (P = 0.001). The frequency of secondary peristalsis in response to acid infusion was significantly decreased by baclofen as compared with the placebo (P = 0.001). Baclofen significantly decreased peristaltic amplitudes in response to acid infusion during rapid air injections (P = 0.007)., Conclusions: Gamma-aminobutyric acid receptor type B agonist baclofen inhibits acid excitation of secondary peristalsis in human esophagus, which is probably mediated by both muscular and mucosal mechanoreceptors. This work supports the evidence of potential involvement of GABA-B receptors in negative modulation of acid excitation of esophageal perception as well as secondary peristalsis., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: This study assessed whether high-resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression., Methods: This prospective, longitudinal cohort study recruited 68 consecutive SSc patients (group #1: 32 established disease (ACR, American College of Rheumatology /EULAR, The European League against Rheumatism 2013 and ACR 1980 criteria fulfilled); group #2: 24 early disease (only ACR/EULAR 2013 fulfilled); group #3: 12 very early disease (clinical expert diagnosis of SSc) and 72 healthy controls. HRM evaluated esophageal motility for water swallows and a solid test meal., Results: Systemic sclerosis patients had less frequent effective esophageal contractions during the test meal compared to healthy controls even in very early disease (0.15, 1.0, 2.1 per minute for groups #1, #2, and #3, vs 2.5 per minute in health; P < 0.001, P < 0.001, and P < 0.0085, respectively). Ineffective motility at HRM was associated with a higher modified Rodnan skin score at baseline. Moreover, at mean 18 (10-31) months of follow-up, the presence of ineffective motility at baseline was associated with progression of skin disease (P = 0.01). Cox proportional hazard regression analysis identified hypotensive peristalsis in the test meal (<15% effective solid swallows) and low distal contractile integral (DCI; <400 mm Hg·cm·s) as predictors for skin aggravation, but not for new organ involvement., Conclusion: Ineffective motility during a test meal is present already in patients with very early SSc. Findings on HRM studies are associated with disease severity at baseline, and low percentage of effective swallows in test meal and low mean DCI are both predictors of skin progression during follow-up., (© 2018 John Wiley & Sons Ltd.)

The Chicago Classification version 3.0 (CC v 3.0) defines hypercontractile peristalsis as Jackhammer esophagus (JE); Nutcracker esophagus (NE) is no longer recognized. Data regarding patient characteristics and treatment response for JE versus NE are limited. We aimed to compare demographic characteristics, high resolution manometry (HRM) features, clinical presentation, management strategies, and treatment outcomes in patients with JE versus NE. We performed a retrospective analysis of adult patients diagnosed with NE (CC v 2.0) or JE (CC v 3.0) by HRM from January 2012 to August 2015. Demographics, symptoms, treatments, and response to therapy (none or partial/complete) were ascertained by chart review, for statistical comparisons. In 45 patients with JE and 29 with NE, there was no significant difference in rate of dysphagia (73% and 59%) or chest pain (44% and 59%). Treatment data were available in 29 JE (smooth muscle relaxants in 4, pain modulators in 3, botulinum toxin injection (BTX) in 10, endoscopic dilation in 5, multimodal treatment in 7), and 20 NE patients (smooth muscle relaxants in 2, pain modulators in 2, (BTX) in 6, endoscopic dilation in 3, multimodal treatment in 7). Follow-up data on 26/29 JE and 20/20 NE patients showed similar treatment response (96.4% vs. 82.1%, p= 0.08) after mean follow-up of 11.2 and 11 months, respectively. There were no major differences for JE versus NE in demographics, symptoms, or type of and response to therapy. Larger prospective, controlled trials are needed to clarify the clinical significance and response to treatment in JE and NE., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A manometric diagnosis of esophagogastric junction outflow obstruction (EGJOO) without a mechanical cause creates a therapeutic conundrum. The aim of this study was to assess esophageal bolus clearance in EGJOO and assess manometric factors associated with clearance in EGJOO., Methods: Bolus clearance was assessed using line-tracing method and contour method to determine Complete Bolus Transit (CBT) and Functional Clearance (FC), respectively, on combined High-Resolution Impedance Manometry (HRIM). HRIM studies of EGJOO patients, as well as a sample of achalasia types I-III and asymptomatic controls, were retrospectively analyzed. In EGJOO, associations between Integrated Relaxation Pressure (IRP) or Distal Contractile Integral (DCI) and clearance were assessed using receiver-operating-characteristic (ROC) curves., Key Results: Seventy-five EGJOO, 28 achalasia, and 11 normal subjects were included. Agreement between CBT and FC was good (Kappa=0.75). CBT across swallows in each group was as follows: type I achalasia: 14%, type II achalasia: 8%, type III achalasia: 61%, EGJOO: 86%, and normal: 98% (p values .023, .006, and <.0001 for EGJOO vs normals, type III achalasia, and all achalasia, respectively). In idiopathic EGJOO, CBT ≥60% of swallows was seen in 96.4% of patients when mean DCI>610 mmHg-s-cm (accuracy 87.7%, P=.004). Complete Bolus Transit( CBT) across individual swallows was 97.8% when DCI>884 mmHg-s-cm (accuracy 81.9%, P<.0001). IRP was poorly associated with bolus clearance., Conclusions & Inferences: Bolus clearance in EGJOO is impaired compared to normal, but not as severely as in achalasia. In idiopathic EGJOO, weak peristalsis is associated with poor bolus clearance. Bolus transit appears to be unimpaired when DCI>900 mmHg-s-cm., (© 2017 John Wiley & Sons Ltd.)

Objectives: Bowel dysfunction has been recognized as a predominant side effect of opioid use. Even though the effects of opioids on the stomach and small and large intestines have been well studied, there are limited data on opioid effects on esophageal function. The aim of this study was to compare esophageal pressure topography (EPT) of patients taking opioids at the time of the EPT (≤24 h) with chronic opioid users who were studied off opioid medications for at least 24 h using the Chicago classification v3.0., Methods: A retrospective review identified 121 chronic opioid users who completed EPT between March 2010 and August 2012. Demographic and manometric data were compared between the two groups using general linear models or χ(2)., Results: Of the 121 chronic opioid users, 66 were studied on opioid medications (≤24 h) and 55 were studied off opioid medications for at least 24 h. Esophagogastric junction (EGJ) outflow obstruction was significantly more prevalent in patients using opioids within 24 h compared with those who did not (27% vs. 7%, P=0.004). Mean 4 s integrated relaxation pressure was also significantly higher in patients studied on opioids (10.71 vs. 6.6 mm Hg, P=0.025). Resting lower esophageal sphincter pressures tended to be higher on opioids (31.61 vs. 26.98 mm Hg, P=0.25). Distal latency was significantly lower in patients studied on opioids (6.15 vs. 6.74 s, P=0.044)., Conclusions: Opioid use within 24 h of EPT is associated with more frequent EGJ outflow obstruction and spastic peristalsis compared with when opioid use is stopped for at least 24 h before the study.

Objective: To perform pressure-flow analysis (PFA) in a cohort of pediatric patients who were referred for diagnostic manometric investigation., Study Design: PFA was performed using purpose designed Matlab-based software. The pressure-flow index (PFI), a composite measure of bolus pressurization relative to flow and the impedance ratio, a measure of the extent of bolus clearance failure were calculated., Results: Tracings of 76 pediatric patients (32 males; 9.1 ± 0.7 years) and 25 healthy adult controls (7 males; 36.1 ± 2.2 years) were analyzed. Patients mostly had normal motility (50%) or a category 4 disorder and usually weak peristalsis (31.5%) according to the Chicago Classification. PFA of healthy controls defined reference ranges for PFI ≤142 and impedance ratio ≤0.49. Pediatric patients with pressure-flow (PF) characteristics within these limits had normal motility (62%), most patients with PF characteristics outside these limits also had an abnormal Chicago Classification (61%). Patients with high PFI and disordered motor patterns all had esophagogastric junction outflow obstruction., Conclusions: Disordered PF characteristics are associated with disordered esophageal motor patterns. By defining the degree of over-pressurization and/or extent of clearance failure, PFA may be a useful adjunct to esophageal pressure topography-based classification., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Backgrounds: It is generally thought that esophageal motility decreases with age; however, a decrease in esophageal motility may also be caused by esophagitis. The aim of this study is to investigate the effects of aging and acid reflux on esophageal motility., Methods: 40 young (under 45) healthy subjects (HS), 40 elderly (over 65) HS, and 40 elderly (over 65) patients with mild reflux esophagitis (RE), underwent esophageal high-resolution manometry (HRM). Lower esophageal sphincter pressure (LESP), primary peristalsis (PP), and secondary peristalsis (SP) were evaluated., Results: There was no difference in the LESP and also in the success rate of PP between young and elderly HS or between elderly HS and RE. There was no difference in the distal contractile integral (DCI) of PP and SP between the young and elderly HS, but in the elderly RE, it was significantly lower than in the elderly HS. There was no difference in the success rate of SP between elderly HS and RE, but in elderly HS it was significantly lower than in young HS., Conclusions: Aging may cause a decrease in the success rate of SP, and acid reflux itself may cause a decrease of the DCI in PP and SP., (© 2015 S. Karger AG, Basel.)

The function of the esophagus is transporting nutrients from the oropharyngeal cavity to the stomach. This is achieved by coordinated contractions and relaxation of the tubular esophagus and the upper and lower esophageal sphincter. Multichannel intraluminal impedance monitoring offers quantification of esophageal bolus transit and/or retention without the use of ionizing radiation. Combined with conventional or high-resolution manometry, impedance measurements complement the quantification of esophageal body contraction and sphincter relaxation, offering a more comprehensive evaluation of esophageal function. Further studies evaluating the utility of quantifying bolus transit will help clarify the role and position of impedance measurements., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that proximal aerodigestive clearance mechanisms mediated by pharyngoesophageal motility during spontaneous respiratory events (SREs) are distinct in infants with apparent life threatening events (ALTEs)., Study Design: Twenty infants (10 with proven ALTE, 10 healthy controls) had pharyngoesophageal manometry to investigate motility changes concurrent with respiratory events detected by respiratory inductance plethysmography and nasal thermistor methods. We measured changes in resting upper esophageal and lower esophageal sphincter pressures, esophageal peristalsis characteristics, and gastroesophageal reflux. Statistical analysis included mixed models; data presented as mean±SD, median (range), or percentage., Results: Infants with ALTE (vs controls) had: (1) delays in restoring aerodigestive normalcy as indicated by more frequent (P=.03) and prolonged SREs (P<.01); (2) a lower magnitude of protective upper esophageal sphincter contractile reflexes (P=.01); (3) swallowing as the most frequent esophageal event associated with SREs (84%), with primary peristalsis as the most prominent aerodigestive clearance mechanism (64% vs 38%, P<.01); (4) a higher proportion of failed esophageal propagation (10% vs 0%, P=.02); and (5) more frequent mixed apneic mechanisms (P<.01) and more gasping breaths (P=.04)., Conclusions: In infants with ALTE, prolonged SREs are associated with ineffective esophageal motility characterized by frequent primary peristalsis and significant propagation failure, thus suggestive of dysfunctional regulation of swallow-respiratory junction interactions. Hence, treatment should not target gastroesophageal reflux, but rather the proximal aerodigestive tract., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Functional dysphagia (FD) is characterized by the presence of dysphagia without evidence of mechanical esophageal obstruction, GERD, and histopathology-based esophageal motor disorders. Dysphagia is common in older patients; however, there is a paucity of information regarding the type and frequency of peristaltic abnormalities compared to younger patients. Based on recently validated criteria for classification of weak peristalsis using high-resolution manometry (HRM), we hypothesized that older patients with FD would have more peristaltic defects detected by HRM compared to younger FD patients. A retrospective review of our motility database yielded 65 patients that met inclusion criteria. Patients were divided into two groups based on age (younger: <70 years; older: ≥70 years). Patients were interviewed, completed a quality-of-life questionnaire, and underwent solid-state HRM. The two groups differed in age but in no other demographic characteristics, severity of dysphagia, or quality of life. Dyspeptic symptoms, including nausea (p < 0.001), early satiety (p = 0.01), bloating (p = 0.02), and belching (p = 0.01), were also more prevalent in younger FD patients. Older age was associated with weak peristalsis involving frequent failed peristalsis, small proximal peristaltic defects (2-5 cm), and large proximal peristaltic defects (>5 cm) (p < 0.001). The mean contraction amplitude was also lower in the older group (p < 0.05). These data support the hypothesis that older patients with FD have a higher frequency of peristaltic abnormalities on HRM compared to younger patients. Older age was associated with increased frequency of weak peristalsis with small and large peristaltic defects.

Purposes: The purpose of this study was to evaluate the feasibility and safety of esophageal functional magnetic resonance imaging (fMRI) for the diagnosis of achalasia., Methods: Eleven patients with suspected achalasia and three normal subjects underwent fMRI while swallowing clear liquid with original sequences; "T2-weighed single-shot fast spin-echo" and "Fast Imaging Employing Steady-state Acquisition". The fMRI-based diagnosis was compared with that based on manometry. The luminal fluctuation index (LFI) and Dd/Ds ratio were used for the objective evaluation of the esophageal peristalsis and relaxation of the lower esophageal sphincter (LES)., Results: Functional MRI showed a dilated tortuous esophagus with no tumor, poor clearance, simultaneous waves, aperistalsis, and impaired LES relaxation in all but one case, allowing the diagnosis of achalasia with accuracy similar to that of manometry. The LFI (median 0.08, range 0.03-0.25) and Dd/Ds ratio (1.40, 1.0-2.3) of the patient group were significantly lower than those of the normal subjects [1.50, 2.32-4.05, and 2.59 (2.32-4.05)]. No severe adverse events directly related to fMRI were noted., Conclusions: Using our protocol, fMRI was considered to be safe and feasible for the diagnosis of achalasia. Given the widespread use of MRI, esophageal fMRI, which does not require exposure to radiation, could be a potentially useful diagnostic tool for patients with esophageal motility disorders.

Background and Aims: The study aimed to investigate the hypothesis whether the presence of Ineffective esophageal motility would affect physiological characteristics of secondary peristalsis., Methods: Secondary peristalsis was performed with slow and rapid air injections into mid-esophagus of 18 ineffective esophageal motility patients and 15 age-matched controls. Severity of ineffective esophageal motility was defined by the application of combined multichannel intraluminal impedance and manometry., Results: Ineffective esophageal motility patients included 11 patients without impedance abnormality and seven patients with impedance abnormality during liquid and/or viscous swallowing. The prevalence of failed secondary peristaltic response during slow air injection was significantly greater in ineffective esophageal motility patients without impedance abnormality (3/11 [27%], P < 0.001) and with impedance abnormality (4/7 [57%], P = 0.04) than healthy subjects. The threshold volume for inducing secondary peristalsis during rapid air injection was significantly greater in ineffective esophageal motility patients with impedance abnormality (6.1 ± 0.3 mL) than healthy subjects (4.6 ± 0.3 mL, P < 0.05) and ineffective esophageal motility patients without impedance abnormality (4.1 ± 0.4 mL, P < 0.05). The frequency of peristaltic response during rapid air injection was significantly lower in ineffective esophageal motility patients with impedance abnormality (40% [20-50%] than healthy subjects (90% [90-100%], P < 0.05)., Conclusions: Defective activation of secondary peristalsis is present in ineffective esophageal motility patients with impedance abnormality. Our study indicates that increased ineffective esophageal motility severity associated with defective triggering of secondary peristalsis may contribute to impaired esophageal clearance in patients with gastroesophageal reflux disease., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Aim: To investigate dysfunctions in esophageal peristalsis and sensation in patients with Barrett's esophagus following acid infusion using endoscopy-based testing., Methods: First, physiological saline was infused into the esophagus of five healthy subjects, at a rate of 10 mL/min for 10 min, followed by infusion of HCl. Esophageal contractions were analyzed to determine whether the contractions observed by endoscopy and ultrasonography corresponded to the esophageal peristaltic waves diagnosed by manometry. Next, using nasal endoscopy, esophageal sensations and contractions were investigated in patients with, as well as controls without, Barrett's esophagus using the same infusion protocol., Results: All except one of the propulsive contractions identified endoscopically were recorded as secondary peristaltic waves by manometry. Patients with long segment Barrett's esophagus (LSBE) tended to have a shorter lag time than the control group, although the difference did not reach statistical significance (88 ± 54 s vs 162 ± 150 s respectively, P = 0.14). Furthermore, patients with LSBE had significantly fewer secondary contractions following the infusion of both saline and HCl than did either the control group or patients with short segment Barrett's esophagus (4.1 ± 1.2 vs 8.0 ± 2.8, P < 0.001 and 7.3 ± 3.2, P < 0.01, respectively, following saline infusion; 5.3 ± 1.2 vs 8.4 ± 2.4 and 8.1 ± 2.9 respectively, P < 0.01 for both, following infusion of HCl)., Conclusion: Using nasal endoscopy and a simple acid-perfusion study, we were able to demonstrate disorders in secondary peristalsis in patients with LSBE.

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.

Background: High-resolution manometry and esophageal pressure topography have enhanced our ability to analyze esophageal motor disturbances by improving the detail and accuracy of measurements of peristaltic activity.This has been extremely helpful in the evaluation of disorders of rapid propagation as the technique is able to define important time points and physiologic landmarks that are crucial in defining peristaltic velocity and latency intervals., Purpose: The goal of the current review will be to assess how esophageal pressure topography has impacted our ability to define important phenotypes of rapid propagation. Additionally, this review will also be utilized to complement the description of the Chicago Classification of Esophageal Motor Disorders, which is presented in this supplement issue., (© 2012 Blackwell Publishing Ltd.)

Background: Systemic sclerosis (SS) patients with severe esophageal affection have impaired peristalsis. However, motor function evaluated in vivo by manometry and fluoroscopy does not provide detailed information about the individual contraction cycles., Aims: To apply, for the first time in gastrointestinal (GI) patients, a method and principles modified from cardiac research to study esophageal muscle behavior in SS patients., Methods: Muscle contraction cycles were analyzed using pressure-cross-sectional area (P-CSA) loops during distension pressure up to 5 kPa. The probe with bag and electrodes for CSA measurements was positioned 7 and 15 cm above the lower esophageal sphincter (LES) in eleven healthy volunteers and eleven SS patients. The P-CSA, the wall tension, Δtension (afterload tension - preload tension), contraction velocity, work output (area of the tension-CSA loops), and power output (preload tension × CSA rate) were analyzed., Results: The P-CSA loops consisted of phases with relaxation and contraction behavior. The tension-stretch ratio loops in patients were shifted to the left at both distension sites, indicative of a stiffer wall in patients. Lower contraction amplitudes and smaller P-CSA loops were observed for the SS patients. The work output, power output, Δtension, and contraction velocity were lower in patients (P < 0.001). Association was found between disease duration and the work output, Δtension, and velocity at pressure steps higher than 3 kPa (P < 0.05)., Conclusions: Distension-evoked esophageal contraction can be studied in vivo and analyzed with advanced methods. Increased esophageal stiffness and impaired muscle function that depended on disease duration were observed for SS patients. The analysis may be useful for characterization of other diseases affecting GI function.

Background: Non-specific esophageal dysmotility with impaired clearance is often present in patients with gastro-esophageal reflux disease (GERD), especially those with erosive disease; however the physio-mechanic basis of esophageal dysfunction is not well defined., Methods: Retrospective assessment of patients with erosive reflux disease (ERD; n=20) and endoscopy negative reflux disease (ENRD; n=20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n=20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3cm break in 30 mmHg isocontour)., Key Results: Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P<0.023 vs controls, P=0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18%vs 33%, P=0.082) and ENRD (22%vs 54%, P=0.046) but not ERD (62%vs 76%, P=0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P<0.017 vs controls and P<0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r=0.52 vs 0.27)., Conclusions & Inferences: Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate., (© 2011 Blackwell Publishing Ltd.)

Esophageal motor abnormalities are frequently found in patients with gastroesophageal reflux disease. The role of bile in reflux-induced dysmotility is still elusive. Furthermore, it is questionable weather mucosal or muscular stimulation leads to motor dysfunction. The aims of this study were to analyze (i) the effect of bile in the amplitude of esophageal contractions; and (ii) the effect of mucosal versus muscular stimulation. Eighteen guinea pig esophagi were isolated, and its contractility assessed with force transducers. Three groups were studied. In group A (n= 6), the entire esophagus was incubated in 100 µmL ursodeoxycholic acid for 1 hour; in group B (n= 6) the mucosal layer was removed and the muscular layer incubated in 100 µmL ursodeoxycholic acid for 1 hour; and in group C (n= 6) (control group) the entire esophagus was incubated in saline solution. In all groups, five sequential contractions induced by 40 mm KCl spaced by 5 minutes were measured before and after incubation. Contractions amplitudes before incubation were 1.319 g, 0.306 g, and 1.795 g, for groups A, B, and C, respectively. There were no differences between groups A and C (P= 0.633), but there were differences between groups A and B (P= 0.039), and B and C (P= 0.048). After incubation amplitude of contraction were 0.709 g, 0.278 g, and 1.353 g for groups A, B, and C, respectively. Only group A showed difference when pre and post-stimulation amplitudes were compared (P= 0.030). Our results show that (i) bile exposure decreases esophageal contraction amplitude; and (ii) the esophageal mucosa seems to play an important role in esophageal motility., (© 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background: Multichannel Intraluminal Impedance (MII) Monitoring is a method of examining oesophageal bolus transit without the need for radiation. In combination with oesophageal manometry it allows correlation of bolus transit with peristaltic activity. The clinical application of impedance manometry is still being refined. This audit looked to examine whether impedance manometry had advantages over standard manometry in assessment of patients with dysphagia., Methods: 41 patients with the presenting symptom of dysphagia were assessed by combined MII and oesophageal manometry at a Wellington Hospital between February 2008 and December 2009. Each underwent manometry and MII using standardised techniques., Findings: Achalasia was diagnosed in 23 patients (56.1%), Ineffective oesophageal motility (IEM) in 5 patients (12.2%), Diffuse oesophageal Spasm (DES) in 7 patients (17.1%), and Nutcracker oesophagus in 2 patients (4.9%). 4 patients had normal manometry studies (9.8%). All patients with achalasia, IEM, and DES had abnormal bolus transit. All patients with normal manometry had abnormal bolus transit. Both patients with nutcracker oesophagus had normal bolus transit. 4 patients with achalasia had undergone previous Hellers myotomy. Two of these patients (50.0%) now had normal LES relaxation pressures, but all four still had abnormal oesophageal peristalsis and abnormal bolus transit., Interpretation: Multichannel Intraluminal Impedance manometry has advantages over standard manometry in characterising the physiological abnormalities associated with dysphagia. Patients in this study had severe defects including achalasia where bolus transit was invariably poor meaning little further information was gained. Extension of this study to include a wider group of patients with dysphagia may yield different results., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Objectives: Esophageal manometry is frequently used to assess for weak peristalsis. Although commonly used clinically, there are currently no validated metrics of weak peristalsis in high-resolution esophageal pressure topography (EPT). This study aimed to develop a classification of weak peristalsis in EPT based on a comparative analysis of control subjects and patients with unexplained non-obstructive dysphagia., Methods: High-resolution esophageal pressure topography (high-resolution impedance manometry) studies were carried out in 16 control subjects to verify EPT features associated with incomplete bolus transit (IBT). The technique of superimposing EPT plots in a computer simulation was used to derive normal limits of peristaltic integrity in EPT in another 75 control subjects. The occurrence of critical EPT defects was then compared between control subjects and 113 patients with non-obstructive dysphagia identified from a large clinical series., Results: IBT occurred with failed peristalsis or with breaks in the 20 mm Hg isobaric contour occurring at the proximal or distal pressure troughs in EPT plots. The normal range for isobaric contour breaks was 0-20% for large (>5 cm) and 0-30% for small (2-5 cm) breaks, with both occurring significantly more frequently in dysphagic patients. Failed peristalsis was not more frequent in dysphagic patients., Conclusions: A classification of weak peristalsis adapted to EPT is proposed based on the occurrence of breaks in the 20 mm Hg isobaric contour wherein weak peristalsis with large breaks is defined by those occurring with >20% of swallows and weak peristalsis with small breaks defined by those occurring with >30% of swallows.

Most studies on the effect of aging on esophageal motor function have shown that peristaltic function deteriorates with age. Esophageal motor function is traditionally studied by means of manometry and radiography. Distension of the esophagus with evaluation of active and passive mechanical parameters have become available during recent years. In this study, we did a manometric swallow analysis and used the distension method to study esophageal properties and function during aging. An impedance planimetric probe with a bag for distension was placed in the distal esophagus of 25 healthy volunteers with a median age of 35 (range 23-86) years. Distensions were done at an infusion rate of 25 ml min(-1) with and without relaxation of neuromuscular activity with butylscopolamine. The infusion was reversed when moderate pain was experienced by the subjects. Swallow-induced contraction amplitudes decreased as function of age for persons older than 40 years (P < 0.05). The total and passive tension showed an exponential increase as function of the change in radius, whereas the active tension increased until it reached a local maximum point. The maximum active tension deteriorated as a function of age after the age of 40 years (P < 0.05). Furthermore, esophagus became stiffer with age. In conclusion, age-related changes of increased stiffness and reduced primary and secondary peristalsis were found in the human esophagus with a deterioration of esophageal function after the age of 40 years. Such changes may contribute to the high prevalence of reflux disease in elderly.

This study analysed the association between oesophageal transition zone (TZ) defects [characterized by a delay and/or spatial gap between the terminus of the proximal oesophageal (striated muscle) contraction and the initiation of the distal oesophageal (smooth muscle) contraction] and dysphagia in a large patient cohort. Four hundred consecutive patients (178 with dysphagia) and 75 controls were studied with 36-channel high-resolution manometry (HRM). The resultant pressure topography plots were first analysed for impaired oesophagogastric junction (OGJ) relaxation, distal segment contractile abnormalities, and proximal contractile abnormalities using normal values from the 75 controls. If these aspects of oesophageal motility were deemed normal, the TZ was characterized by length and duration between the proximal and distal contractions using a 20 mmHg isobaric contour to establish the segment boundaries. Patients were then classified according to whether or not they exhibited TZ defects (spatial separation or delay) and the occurrence of unexplained dysphagia. Of the 400 patients, 267 were suitable for TZ analysis and of these 55 had a spatial or temporal TZ measurement exceeding the 95th percentile of the controls (2 cm, 1 s). Exactly 34.6% of the patients (n = 19) with spatial and/or temporal TZ defects had unexplained dysphagia, which was significantly more than seen with normal TZ dimensions (19.8%). Although far less common than distal peristaltic or OGJ abnormailites, TZ defects may be related to dysphagia in a minority of patients (<4% in this series) and should be considered a distinct oesophageal motility disorder.

The pathogenesis of nutcracker oesophagus (NE) and ineffective oesophageal motility (IEM) is unclear. Damage to the enteric nervous system or smooth muscle can cause oesophageal dysmotility. We tested the hypothesis that NE and IEM are associated with abnormal muscular or neural constituents of the oesophageal wall. Oesophageal manometry was performed in patients prior to total gastrectomy for gastric cancer. The oesophageal manometries were categorized as normal (n = 7), NE (n = 13), or IEM (n = 5). Histologic examination of oesophageal tissue obtained during surgery was performed after haematoxylin and eosin (H&E) and trichrome staining. Oesophageal innervation was examined after immunostaining for protein gene product-9.5 (PGP-9.5), choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS). There were no significant differences in inner circular smooth muscle thickness or degree of fibrosis among the three groups. Severe muscle fibre loss was found in four of five patients with IEM. The density of PGP-9.5-reactive neural structures was not different among the three groups. The density of ChAT immunostaining in the myenteric plexus (MP) was significantly greater in patients with NE (P < 0.05) and the density of nNOS immunostaining in the circular muscle (CM) was significantly greater in IEM patients (P < 0.05). The ChAT/nNOS ratio in both MP and CM was significantly greater in NE patients. NE may result from an imbalance between the excitatory and inhibitory innervation of the oesophagus, because more than normal numbers of ChAT-positive myenteric neurones are seen in NE. Myopathy and/or increased number of nNOS neurones may contribute to the hypocontractile motor activity of IEM.

Background: We determined any difference in oesophageal function between reflux patients with and without erosive esophagitis by the application of concurrent manometry and impedance., Methods: Twenty patients with erosive esophagitis, 20 patients with non-erosive reflux disease, and 15 controls were included in this study. All subjects underwent studies with a catheter containing four impedance-measuring segments and five solid-state pressure transducers. Each subject received 10 liquid and 10 viscous boluses to be swallowed., Results: Healthy controls had greater distal oesophageal peristaltic amplitude than both patient groups (p < 0.05). Normal oesophageal peristalsis was found more frequently in healthy controls than either of the patient groups (p < 0.05). Patients with erosive esophagitis exhibited a lower percentage of complete bolus transit compared to healthy controls and non-erosive reflux disease patients (both p < 0.05). Patients with erosive esophagitis had a longer total bolus transit time compared to healthy controls and non-erosive reflux disease patients (both p < 0.05)., Conclusions: Erosive esophagitis is characterized by longer oesophageal bolus transit and fewer complete bolus transit than non-erosive reflux disease. The noted differences in oesophageal bolus transit may reflect a continuum of dysfunction secondary to increasing oesophageal mucosal damage.

Two recent advances have revolutionized the performance of clinical esophageal manometry; the introduction of practical high resolution manometry (HRM) systems and the development of sophisticated algorithms to display the expanded manometric dataset as pressure topography plots. We utilized a large clinical experience of 400 consecutive patients and 75 control subjects to develop a systematic approach to analyzing esophageal motility using HRM and pressure topography plots. The resultant classification scheme has been named as the Chicago Classification of esophageal motility. Two strengths of pressure topography plots compared with conventional manometric recordings were the ability to (1) delineate the spatial limits, vigor, and integrity of individual contractile segments along the esophagus and (2) to distinguish between loci of compartmentalized intraesophageal pressurization and rapidly propagated contractions. Making these distinctions objectified the identification of distal esophageal spasm, vigorous achalasia, functional obstruction, and nutcracker esophagus subtypes. Applying these distinctions made the diagnosis of spastic disorders quite rare: spasm in 1.5% of patients, vigorous achalasia in 1.5%, and a newly defined entity, spastic nutcracker, in 1.5%. Ultimately, further clinical experience will be the judge, but it is our expectation that pressure topography analysis of HRM data, along with its well-defined functional implications, will prove valuable in the clinical management of esophageal motility disorders.

Background: The aim of this study was to assess the relationship between the duration of diabetes and esophageal dysfunction., Methods: We examined 66 patients with type 2 diabetes. Duration of diabetes was determined by asking patients and from their medical records. The patients were divided into three groups according to the duration of their diabetes: group A, 1-4 years, n=26; group B, 5-9 years, n=20; and group C, 10+ years, n=20. Ambulatory esophageal 24-h pH and motility were monitored, and gastroesophageal reflux and esophageal motility disorders were estimated in detail., Results: When the duration of diabetes was long, the percentage of time with pH<4 tended to increase. The amplitude of esophageal peristaltic waves and the frequency of effective peristalsis were reduced when the duration of diabetes was long. A significant correlation was observed between the duration of diabetes and the frequency of effective peristalsis. The number of esophageal peristaltic waves per minute and the percentage of multipeaked peristaltic waves increased significantly in group B, and decreased when the duration of diabetes became longer., Conclusions: Gastroesophageal reflux and esophageal motility disorders worsened with long duration of diabetes. These esophageal dysfunctions should be considered in patients with long-standing diabetes.

Background & Aims: High-resolution manometry demonstrates a chain of 3 sequential pressure segments that represent esophageal peristalsis in children and adults. We performed high-resolution manometry in preterm and term neonates to determine the ontogenesis of esophageal motility with regard to this segmental architecture., Methods: Sixteen preterm (gestational age 32.9 +/- 2.6 weeks at examination) and 14 term neonates (38.9 +/- 1.6 weeks) underwent manometry with a 9-lumen perfused catheter having recording side holes spaced at 1-cm intervals. Pressure responses to swallows were evaluated for the presence of peristaltic segments on isobaric contour maps by an investigator who was blinded to gestational age., Results: The second segment was well developed in > or =50% of swallows in all preterm and term neonates. In contrast, the first segment was present in > or =50% of swallows in only 2 preterm neonates (12.5%) and 8 term neonates (57.1%; P < .05 for each compared with second segment) with identical findings for the third segment (12.5% preterm and 57.1% term neonates; P < .05 for each). Completed peristalses with intact segmental contraction sequences throughout the esophageal body were present in 26% +/- 6% of swallows in preterm neonates vs 55% +/- 9% in term neonates (P = .01)., Conclusions: The second pressure segment in the midesophagus (proximal smooth-muscle region) is well developed before term. Presence of other segments significantly improves at term, but peristalsis remains incomplete in nearly half of swallows. Control mechanisms for both striated- and smooth-muscle esophageal regions are incompletely developed in neonates, the outcome of which could participate in infant reflux disease.

Reflux esophagitis (RE) is characterized by excessive esophageal acid exposure. The number of acid reflux episodes, the way acid comes up after reflux and the delay of acid bolus clearance cause excessive esophageal acid exposure. Transient lower esophageal sphincter relaxation(TLESR) is the major mechanism of acid reflux in both healthy subjects (HS) and in patients with acid reflux disease, but there is no difference in the rate of TLESRs or in the rate of acid reflux during TLESRs above the LES between HS and patients with severe RE. In patients with severe RE, refluxed acid above the LES rises more easily to the proximal esophagus but it does not clear easily from the esophagus when compared with HS. The pathophysiology of non-erosive reflux disease (NERD) is poorly understood, however with regard to esophageal motility in patients with NERD, the LES pressure, the pressure wave amplitude and the rates of successful primary peristalsis were similar to that of HS but the triggering of secondary peristalsis was defective. This may lead to prolonged contact time between refluxed gastric acid and esophageal mucosa thereby leading to symptoms.

Background: Aperistalsis with complete lower esophageal sphincter (LES) relaxation, characterized by the complete relaxation of the LES and aperistalsis of the esophageal body on manometry, has been considered by some authors to be an early manifestation of classic achalasia, which is defined as incomplete relaxation of the LES and aperistalsis of the esophageal body. The aim of the present study was to compare the clinical features of patients with aperistalsis with complete LES relaxation, with those of patients with classic achalasia., Methods: Eighteen patients with aperistalsis with complete LES relaxation and 53 patients with classic achalasia were analyzed with regard to clinical history, the maximal diameter of the esophageal body on barium esophagogram, LES resting pressure and the duration of LES relaxation on manometric recordings, and the selected treatment and its efficacy., Results: The aperistalsis with complete LES relaxation group had distinctly different features compared to those of the classic achalasia group including older age, more frequent association with non-cardiac chest pain, less frequent association with dysphagia and weight loss, lower LES resting pressures, and longer duration of LES relaxation. However, the two groups were similar in terms of maximal diameter of the esophageal body, and efficacy associated with pneumatic dilation., Conclusions: Aperistalsis with complete LES relaxation on manometry is not necessarily an early manifestation of classic achalasia. However, this condition does not preclude a diagnosis of achalasia or a good response to achalasia therapy.

We summarize from previous works the functions of circular vs. longitudinal muscle in esophageal peristaltic bolus transport using a mix of experimental data, the conservation laws of mechanics and mathematical modeling. Whereas circular muscle tone generates radial closure pressure to create a local peristaltic closure wave, longitudinal muscle tone has two functions, one physiological with mechanical implications, and one purely mechanical. Each of these functions independently reduces the tension of individual circular muscle fibers to maintain closure as a consequence of shortening of longitudinal muscle locally coordinated with increasing circular muscle tone. The physiological function is deduced by combining basic laws of mechanics with concurrent measurements of intraluminal pressure from manometry, and changes in cross sectional muscle area from endoluminal ultrasound from which local longitudinal shortening (LLS) can be accurately obtained. The purely mechanical function of LLS was discovered from mathematical modeling of peristaltic esophageal transport with the axial wall motion generated by LLS. Physiologically, LLS concentrates circular muscle fibers where closure pressure is highest. However, the mechanical function of LLS is to reduce the level of pressure required to maintain closure. The combined physiological and mechanical consequences of LLS are to reduce circular muscle fiber tension and power by as much as 1/10 what would be required for peristalsis without the longitudinal muscle layer, a tremendous benefit that may explain the existence of longitudinal muscle fiber in the gut. We also review what is understood of the role of longitudinal muscle in esophageal emptying, reflux and pathology.

Background: First- and second-order esophageal contractions are important factors responsible for esophageal clearance of refluxed gastric content. The aim of this study was to estimate the influence of acid reflux on second-order esophageal peristalsis., Material/methods: Simultaneous 24-h esophageal pH-metry and 24-h motility monitoring was performed in 213 patients with non-cardiac chest pain. Pathological gastroesophageal acid reflux (pGER) was defined as pH <4 for more than 4.5% of the total monitoring time., Results: The group of pGER patients (n=65, 31%) had a lower percentage of complete and effective peristalsis, a higher percentage of incomplete peristalsis, and a lower mean contraction amplitude than the group of patients with normal esophageal acid exposure (nGER). Analysis of motility parameters in three periods, i.e. during acid reflux and 2 min before and 10 min after episodes (second-order peristalsis), showed that the pGER group had a lower percentage of effective peristalsis (20.6 +/- 13.3 vs. 29.6 +/- 16.2%, p = 0.002) and a higher percentage of ineffective peristalsis both during and after acid reflux, a lower mean contraction amplitude (56.5 +/- 30.3 vs. 70.0 +/- 32.8 mmHg, p=0.025), and a lower contraction frequency during acid reflux (1.6 +/- 0.7 vs. 2.6 +/- 3.1/min, p=0.001) and 10 min after (1.9 +/- 1.9 vs. 20.6 +/- 30.2/min, p=0.002), which indicated a lack of esophageal peristalsis acceleration after acid reflux in the pGER group., Conclusions: (1) pGER patients had ineffective esophageal peristalsis more frequently than nGER patients. (2) Impaired second-order peristalsis in pGER patients may be an important factor determining prolonged exposure of the esophageal mucosa to gastric content in addition to lower esophageal sphincter function.

Objective: Artificial neural networks (ANNs) can rapidly analyse large data sets and exploit complex mathematical relationships between variables. We investigated the feasibility of utilizing ANNs in the recognition and objective classification of primary oesophageal motor disorders, based on stationary oesophageal manometry recordings., Material and Methods: One hundred swallow sequences, including 80 that were representative of various oesophageal motor disorders and 20 of normal motility, were identified from 54 patients (34 F; median age 59 years). Two different ANN techniques were trained to recognize normal and abnormal swallow sequences using mathematical features of pressure wave patterns both with (ANN(+)) and without (ANN(-)) the inclusion of standard manometric criteria. The ANNs were cross-validated and their performances were compared to the diagnoses obtained by standard visual evaluation of the manometric data., Results: Interestingly, ANN(-), rather than ANN(+), programs gave the best overall performance, correctly classifying >80% of swallow sequences (achalasia 100%, nutcracker oesophagus 100%, ineffective oesophageal motility 80%, diffuse oesophageal spasm 60%, normal motility 80%). The standard deviation of the distal oesophageal pressure and propagated pressure wave activity were the most influential variables in the ANN(-) and ANN(+) programs, respectively., Conclusions: ANNs represent a potentially important tool that can be used to improve the classification and diagnosis of primary oesophageal motility disorders.

Background & Aims: The increases in intraluminal pressure and muscle cross-sectional area (CSA) during esophageal contraction are markers of circular and longitudinal muscle contractions. The goal of our study was to determine temporal synchrony between circular and longitudinal muscle contraction in healthy subjects and patients with nutcracker esophagus., Methods: Pressure and high-frequency intraluminal ultrasound (HFIUS) images were recorded simultaneously in healthy subjects and patients with nutcracker esophagus at 2 and 10 cm above the lower esophageal sphincter during wet swallow. HFIUS images were digitized and analyzed for the muscle CSA. The time interval (delta-t) between the peak muscle CSA and the peak pressure was determined., Results: In healthy subjects, a close temporal correlation existed between the peak contraction pressure and the peak muscle CSA with a maximum delta-t of 0.5 seconds at the 2- and 10-cm levels (0-0.5 seconds). On the other hand, the patient group had a median delta-t of 1.25 seconds (0.75-3.5 seconds) at the 2-cm level and 0.75 seconds (0-2.0 seconds) at the 10-cm level. Ninety-eight of 103 contractions in patients showed a delta-t >0.5 seconds. There was a significant correlation between delta-t and the amplitude of pressure wave, the duration of pressure wave, and the peak muscle CSA. The duration of pressure wave but not the duration of CSA wave was longer in patients with nutcracker esophagus as compared with healthy subjects., Conclusions: Patients with nutcracker esophagus show temporal asynchrony between the contractions of circular and longitudinal muscle layers.

The 5-HT1 agonist sumatriptan (SUM) elicits an increase in amplitude of oesophageal motor waves and of lower oesophageal sphincter (LOS) tone in healthy subjects. The aim of the study was to evaluate whether such an effect occurs also in patients with ineffective oesophageal motility (IOM). 16 patients (nine males and seven females, age range 34-55 years) with chest pain and mild to moderate dysphagia were studied; all had undergone previous cardiologic, radiologic and upper gastrointestinal endoscopic exams that were normal. An oesophageal manometry was performed using an electronic probe to record swallows, oesophageal, LOS and gastric motility. The patients whose motor pattern were compatible with IOM (>30% of motor waves with amplitude <30 mmHg and/or non-transmitted) received SUM or placebo 6 mg s.c., injected in the morning and in the afternoon in a random order. The data analysis was limited to 1 h before and 1 h after the drug injections. Ten out of the 16 patients showed an IOM motor pattern. The administration of SUM caused a significant increase in the number of swallows (SUM 99.5 +/- 15.4 vs 78.6 +/- 16.1 basal, P = 0.03) and of primary oesophageal motor waves (SUM 89.6 +/- 13.4 vs 67.2 +/- 12.9 basal, P = 0.04) with no significant changes in the percentage of swallows associated with propagation. Placebo was not associated with increase in the number of swallows (80.3 +/- 14.6, P = 0.9) or of primary oesophageal motor waves (70.1 +/- 12.3, P = 0.7). The amplitude and the percentage of propagated oesophageal motor waves as well as the mean basal LOS tone were unaltered by SUM. There was no change in the symptoms reported after SUM. Although effective in healthy subjects, SUM 6 mg s.c. improves only the numbers but not the amplitude or propagation of oesophageal motility of patients with IOM. The 5-HT1 pathway and its acute stimulation seem to play only a minor role in the pathogenesis of such a disease.

The aim of the present study was to correlate the severity of oesophageal motor dysfunction with the severity of cutaneous disease in systemic sclerosis (SS). Patients were divided into three groups based on the degree of skin involvement: type I, acrosclerosis distal to the wrist; type II, scleroderma extending above the wrist in proximal direction; type III, diffuse cutaneous systemic sclerosis. Impedance planimetry employing distensions with pressures up to 5 kPa with the concomitant measurement of oesophageal cross-sectional area (CSA) was used in combination with standard oesophageal manometry. Measurements were made at 7 and 15 cm above the lower oesophageal sphincter (LOS). Thirty patients (16 type I, six type II and eight type III patients) and 23 normal controls were included. LOS pressure was lower in SS patients than in normal patients, with the lowest values in type III. The CSAs were higher in SS patients than in controls at both sites (P < 0.001). The CSAs at the distal site were highest in type III, as compared to type I and II (P < 0.03). The CSA at the highest induced pressure (5.0 kPa) was 613 +/- 45, 719 +/- 79, and 808 +/- 115 mm2 in types I, II and III, respectively. No differences in CSA were found at the proximal site between the three types of SS. The distensibility did not differ between SS and normal patients at the distal site. The distensibility was lowest in SS patients (P < 0.001) at the proximal distension site. The distensibility did not vary with the type of SS at either site. Significant differences in contraction frequency of the secondary peristalsis as function of wall tension were demonstrated between the SS patients and controls at the distal site (P < 0.05). No differences were found at the proximal site. The contraction frequency and amplitude at the distal and proximal sites did not differ among the three types. In conclusion for most parameters studied, SS patients differed from normal patients. Among SS types, the most pronounced changes were found in type III.

Background: Gastrosophageal reflux disease (GERD) of long duration is frequently associated with impaired esophageal body motility. This condition has been considered unsuitable for antireflux surgery., Methods: In order to investigate the outcome of antireflux surgery in the presence of impaired esophageal peristalsis, we studied 67 consecutive GERD patients with poor esophageal body function who underwent laparoscopic partial posterior fundoplication. A standardized questionnaire, upper GI endoscopy, esophageal manometry and 24-hour pH monitoring were performed preoperatively and at a median of 28 months (range, 6-54 months) postoperatively. Esophageal motility was analyzed for contraction amplitudes in the distal two thirds of the esophagus (level 3, 4, and 5), frequency of peristaltic, simultaneous and interrupted waves and total number of defective propagations. In addition, parameters defining the function of the lower esophageal sphincter (LES) were-evaluated., Results: Following antireflux surgery 65 patients (97%) were free of heartburn and regurgitation and had no esophagitis on endoscopy, confirmed by histology. The rate of dysphagia was reduced from 49% preoperatively to 9% postoperatively (p < 0.001). There was significant improvement in esophageal peristalsis after the antireflux procedure. The median DeMeester reflux score was reduced from 33.3 to 1.1 (p < 0.001). Lower esophageal sphincter pressure and intra-abdominal length were normal after surgery., Conclusions: Partial posterior fundoplication provides an effective antireflux barrier in patients with impaired esophageal body motility in the long term. Postoperative dysphagia is avoided by improving esophageal body function.