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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: Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD., Methods: Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively., Results: Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003)., Discussion: The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux-a prerequisite of aspiration), and pulmonary function in patients with IPF., Methods: We prospectively recruited 35 patients with IPF (aged 53-75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment., Results: Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux (P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = -0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = -0.478; P = 0.098) and number of proximal events (r = -0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = -0.520; P = 0.039) and inspiratory LESP (r = -0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008)., Discussion: We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs., (Copyright © 2021 by The American College of Gastroenterology.)

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.)

Introduction: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO., Methods: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated., Results: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02)., Discussion: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol., (Copyright © 2020 by The American College of Gastroenterology.)

Introduction: Ineffective esophageal motility (IEM) is a minor motor disorder with potential reflux implications. Contraction reserve, manifested as augmentation of esophageal body contraction after multiple rapid swallows (MRS), may affect esophageal acid exposure time (AET) in IEM., Methods: Esophageal high-resolution manometry (HRM) and ambulatory reflux monitoring studies were reviewed over 2 years to identify patients with normal HRM, IEM (≥50% ineffective swallows), and absent contractility (100% failed swallows). Single swallows and MRS were analyzed using HRM software tools (distal contractile integral, DCI) to determine contraction reserve (mean MRS DCI to mean single swallow DCI ratio >1). Univariate analysis and multivariable regression analyses were performed to determine motor predictors of abnormal AET in the context of contraction reserve., Results: Of 191 eligible patients, 57.1% had normal HRM, 37.2% had IEM, and 5.8% had absent contractility. Contraction reserve had no affect on AET in normal HRM. Nonsevere IEM (5-7 ineffective swallows) demonstrated significantly lower proportions with abnormal AET in the presence of contraction reserve (30.4%) compared with severe IEM (8-10 ineffective swallows) (75.0%, P = 0.03). Abnormal AET proportions in nonsevere IEM with contraction reserve (32.7%) resembled normal HRM (33.0%, P = 0.96), whereas that in severe IEM with (46.2%) or without contraction reserve (50.0%) resembled absent contractility (54.5%, P ≥ 0.6). Multivariable analysis demonstrated contraction reserve to be an independent predictor of lower upright AET in nonsevere (odds ratio 0.44, 95% confidence interval 0.23-0.88) but not severe IEM., Discussion: Contraction reserve affects esophageal reflux burden in nonsevere IEM. Segregating IEM into severe and nonsevere cohorts has clinical value.

The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.

Introduction: Esophageal dysmotility including features of achalasia may develop because of bariatric surgery. However, the prevalence of these complications is unknown. We sought to define the prevalence of dysphagia and major esophageal motility disorders including achalasia after bariatric surgery through a large retrospective database review., Methods: Patients with a history of laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass who underwent a diagnostic high-resolution impedance manometry (HRIM) either before or after bariatric surgery across 3 large tertiary referral sites from June 2012 through February 2019 were identified from a procedural database. HRIM studies were interpreted per the Chicago classification v3.0 by a blinded investigator (K.R.). Demographic/clinical features were collected. In addition, patients who underwent bariatric surgery from January 2014 to April 2015 were contacted and administered a validated symptom assessment survey to gauge the overall prevalence of dysphagia in a postbariatric population., Results: A total of 137 patients were identified, including 97 who underwent HRIM after bariatric surgery (laparoscopic sleeve gastrectomy [n = 39, 40.1%]; Roux-en-Y gastric bypass [n = 58, 59.8%]) at a median of 5.84 years (interquartile range 2.1-12.5) postoperatively and 40 preoperative bariatric surgery candidates with medically complicated obesity. A manometric pattern consistent with achalasia was identified in 7 (7.2%) postsurgical patients compared with none in the preoperative group (P = 0.08). We further identified a separate achalasia-like pattern defined by aperistalsis and increased intragastric pressure (postobesity surgery esophageal dysfunction [POSED]) in 5 (5.2%) postsurgical patients vs none found preoperatively (P = 0.14). Achalasia or POSED was associated with postbariatric surgery (12.4% vs 0%, P = 0.02). Increasing time since surgery was independently associated with the development of achalasia (median 12.5 vs 5.8 years, P = 0.02), POSED (median 15.0 vs 5.8 years, P = 0.02) and major motility disorders (6.6 vs 4.9 years, P = 0.01). Furthermore, among 271 postbariatric surgery patients contacted for symptom assessment via survey, the prevalence of dysphagia was 13.7% at a mean 3.9 years after surgery., Discussion: Postoperative dysphagia is a common long-term complication of bariatric surgery. This is potentially the consequence of a time-dependent association with the development of postoperative esophageal dysmotility, particularly achalasia and POSED. Consequently, esophageal dysmotility may be an important under-recognized complication of bariatric surgery.

Introduction: Competency-based medical education (CBME) for interpretation of esophageal manometry is lacking; therefore, motility experts and instructional designers developed the esophageal manometry competency (EMC) program: a personalized, adaptive learning program for interpretation of esophageal manometry. The aim of this study was to implement EMC among Gastroenterology (GI) trainees and assess the impact of EMC on competency in manometry interpretation., Methods: GI fellows across 14 fellowship programs were invited to complete EMC from February 2018 to October 2018. EMC includes an introductory video, baseline assessment of manometry interpretation, individualized learning pathways, and final assessment of manometry interpretation. The primary outcome was competency for interpretation in 7 individual skill sets., Results: Forty-four GI trainees completed EMC. Participants completed 30 cases, each including 7 skill sets. At baseline, 4 (9%) participants achieved competency for all 7 skills compared with 24 (55%) at final assessment (P < 0.001). Competency in individual skills increased from a median of 4 skills at baseline to 7 at final assessment (P < 0.001). The greatest increase in skill competency was for diagnosis (Baseline: 11% vs Final: 68%; P < 0.001). Accuracy improved for distinguishing between 5 diagnostic groups and was highest for the Outflow obstructive motility disorder (Baseline: 49% vs Final: 76%; P < 0.001) and Normal motor function (50% vs 80%; P < 0.001)., Discussion: This prospective multicenter implementation study highlights that an adaptive web-based training platform is an effective tool to promote CBME. EMC completion was associated with significant improvement in identifying clinically relevant diagnoses, providing a model for integrating CBME into subspecialized areas of training.

Objectives: High-resolution manometry (HRM) is the preferred method for the evaluation of motility disorders. Recently, an update of the diagnostic criteria (Chicago 3.0) has been published. The aim of this study was to compare the performance criteria of Chicago version 2.0 (CC2.0) vs. 3.0 (CC3.0) in a cohort of healthy volunteers and symptomatic patients., Methods: HRM studies of asymptomatic and symptomatic individuals from several centers of Spain and Latin America were analyzed using both CC2.0 and CC3.0. The final diagnosis was grouped into hierarchical categories: obstruction (achalasia and gastro-esophageal junction obstruction), major disorders (distal esophageal spasm, absent peristalsis, and jackhammer), minor disorders (failed frequent peristalsis, weak peristalsis with small or large defects, ineffective esophageal motility, fragmented peristalsis, rapid contractile with normal latency and hypertensive peristalsis) and normal. The results were compared using McNemar's and Kappa tests., Results: HRM was analyzed in 107 healthy volunteers (53.3% female; 18-69 years) and 400 symptomatic patients (58.5% female; 18-90 years). In healthy volunteers, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 7.5% and 5.6%, respectively, major disorders in 1% and 2.8%, respectively, minor disorders in 25.2% and 15%, respectively, and normal in 66.4% and 76.6%, respectively. In symptomatic individuals, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 11% and 11.3%, respectively, major disorders in 14% and 14%, respectively, minor disorders in 33.3% and 24.5%, respectively, and normal in 41.8% and 50.3%, respectively. In both groups of individuals, only an increase in normal and a decrease in minor findings using CC3.0 were statistically significant using McNemar's test., Discussions: CC3.0 increases the number of normal studies when compared with CC2.0, essentially at the expense of fewer minor disorders, with no significant differences in major or obstructive disorders. As the relevance of minor disorders is questionable, our data suggest that CC3.0 increases the relevance of abnormal results.

Objectives: Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia., Methods: In all, 145 patients (aged 18-85 years, 54% female) with dysphagia that completed upper endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered "abnormal". FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered "abnormal" if EGJ-DI was <2.8 mm 2 /mm Hg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions., Results: HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, and 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was "normal" in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. In all, 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI., Conclusions: FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia.

The development of intraluminal esophageal impedance monitoring has improved our ability to detect and measure gastroesophageal reflux without dependence on acid content. This ability to detect previously unrecognized weak or nonacid reflux episodes has had important clinical implications in the diagnosis and management of gastroesophageal reflux disease (GERD). In addition, with the ability to assess bolus transit within the esophageal lumen, impedance monitoring has enhanced the recognition and characterization of esophageal motility disorders in patients with nonobstructive dysphagia. The assessment of the intraluminal movement of gas and liquid has also been proven to be of diagnostic value in conditions such as rumination syndrome and excessive belching. Further, alternative applications of impedance monitoring, such as the measurement of mucosal impedance, have provided novel insights into assessing esophageal mucosal integrity changes as a consequence of inflammatory change. Future applications for esophageal impedance monitoring also hold promise in esophageal conditions other than GERD. However, despite all of the clinical benefits afforded by esophageal impedance monitoring, important clinical and technical shortcomings limit its diagnostic value and must be considered when interpreting study results. Overinterpretation of studies or application of impedance monitoring in patients can have deleterious clinical implications. This review will highlight the clinical benefits and limitations of esophageal impedance monitoring and provide clinical pearls and pitfalls associated with this technology.

Objectives: Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT., Methods: Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder., Results: The total group agreement was moderate (κ=0.57; 95% CI: 0.56-0.59) for EPT and fair (κ=0.32; 0.30-0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65-0.71) for EPT and moderate (κ=0.46; 0.43-0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45-0.50) for EPT and poor to fair (κ=0.20; 0.17-0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4-4.5; P<0.0001), and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than with EPT (OR: 3.4; 2.4-5.0; P<0.0001)., Conclusions: Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses were demonstrated with analysis using EPT over CLT among our selected raters. On the basis of these findings, EPT may be the preferred assessment modality of esophageal motility.

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.

Objectives: Although esophageal motor disorders are associated with chest pain and dysphagia, minimal data support a direct relationship between abnormal motor function and symptoms. This study investigated whether high-resolution manometry (HRM) metrics correlate with symptoms., Methods: Consecutive HRM patients without previous surgery were enrolled. HRM studies included 10 supine liquid, 5 upright liquid, 2 upright viscous, and 2 upright solid swallows. All patients evaluated their esophageal symptom for each upright swallow. Symptoms were graded on a 4-point likert score (0, none; 1, mild; 2, moderate; 3, severe). The individual liquid, viscous or solid upright swallow with the maximal symptom score was selected for analysis in each patient. HRM metrics were compared between groups with and without symptoms during the upright liquid protocol and the provocative protocols separately., Results: A total of 269 patients recorded symptoms during the upright liquid swallows and 72 patients had a swallow symptom score of 1 or greater. Of the 269 patients, 116 recorded symptoms during viscous or solid swallows. HRM metrics were similar between swallows with and without associated symptoms in the upright, viscous, and solid swallows. No correlation was noted between HRM metrics and symptom scores among swallow types., Conclusions: Esophageal symptoms are not related to abnormal motor function defined by HRM during liquid, viscous or solid bolus swallows in the upright position. Other factors beyond circular muscle contraction patterns should be explored as possible causes of symptom generation.

Objectives: There are currently no criteria for ineffective esophageal motility (IEM) and ineffective swallow (IES) in esophageal pressure topography (EPT). Our aims were to use high-resolution manometry metrics to define IEM within the Chicago Classification and to determine the distal contractile integral (DCI) threshold for IES., Methods: The EPT of 150 patients with either dysphagia or reflux symptoms were reviewed. Peristaltic function in EPT was defined by the Chicago Classification; the corresponding conventional line tracing (CLT) were reviewed separately. Generalized linear mixed models were used to find thresholds for DCI corresponding to traditionally determined IES and failed swallows. An external validation sample was used to confirm these thresholds., Results: In terms of swallow subtypes, IES in CLT were a mixture of normal, weak, and failed peristalsis in EPT. A DCI of 450 mm Hg-s-cm was determined to be optimal in predicting IES. In the validation sample, the threshold of 450 mm Hg-s-cm showed strong agreement with CLT determination of IES (positive percent agreement 83%, negative percent agreement 90%). The patient diagnostic level agreement between CLT and EPT was good (78.6% positive percent agreement and 63.9% negative percent agreement), with negative agreement increasing to 92.0% if proximal breaks were excluded., Conclusions: The manometric correlate of IEM in EPT is a mixture of failed swallows and weak swallows with breaks in the middle/distal troughs. A DCI value <450 mm Hg-s-cm can be used to predict IES previously defined in CLT. IEM can be defined by >5 swallows with weak/failed peristalsis or with a DCI <450 mm Hg-s-cm.

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.

Objectives: Esophageal high-resolution manometry (EHRM) has evolved rapidly from a research tool to a routine investigation in adult clinical practice. This study proposes and evaluates a standardized EHRM protocol for use in pediatric clinical practice., Methods: Thirty pediatric patients underwent unsedated EHRM. Indications for EHRM were dysphagia, feeding difficulty, or pre-fundoplication assessment. Two 20-channel customized water-perfused silicone catheters, with an outside diameter of 3.8 mm (MuiScientific, Ontario, CA), were used. The catheters had one distal gastric channel, five channels 0.5 cm apart for the e-sleeve, and 14 proximal channels either 1 cm (for children <5 years) or 2 cm apart (for children >5 years). Single wet swallows, multiple rapid swallows (MRS), and solid swallows were systematically studied., Results: The median age was 10 years (range 6 months-15 years). The esophageal motor findings were normal peristalsis (n=15), peristaltic dysfunction (n=12), achalasia (n=3), and spasm on consumption of solid food (n=2). The distal contractile integral adjusted for esophageal length (DCIa) of patients with peristaltic dysfunction was significantly lower than that of patients without peristaltic dysfunction (P<0.001). On MRS, aperistalsis with lack of esophagogastric junction (EGJ) relaxation was observed in patients with achalasia, and aperistalsis with complete EGJ relaxation was observed in patients with severe peristaltic dysfunction. On consumption of solid food, esophageal spasm associated with bolus impaction was observed in two patients., Conclusions: This study provides objective information with regard to topography pressure parameters in esophageal motility disorders of childhood while using a standardized EHRM protocol. The new DCIa variable may be useful for the assessment of patients with peristaltic dysfunction.

Objectives: The pathophysiology of dysphagia in patients with eosinophilic esophagitis (EoE) is unknown but may be related to abnormal esophageal motor function. Symptoms rarely occur during stationary esophageal manometry, so it has been difficult to establish an association between symptoms and motor events. Our aim was to evaluate esophageal motor function in children with EoE with the use of stationary manometry and ambulatory prolonged esophageal manometry and pH-metry (PEMP)., Methods: PEMP was performed in children with EoE and compared with controls and children with gastroesophageal reflux disease (GERD). Peristalsis was considered effective when the esophageal contractions had a normal amplitude and propagation. Results are expressed as mean+/-s.e., Results: Seventeen patients with EoE, 13 with GERD, and 11 controls were studied. Values are expressed as mean+/-s.e. Stationary manometry identified abnormal peristalsis in 41% of children with EoE. During PEMP, children with EoE had an increased number of isolated (16.7+/-3.8 vs. 9.5+/-1.6 vs. 6.5+/-1.1; P<0.03) and high-amplitude contractions (4.1+/-1.2 vs. 1.8+/-0.8 vs. 0.1+/-0.1; P<0.03), and higher percentage ineffective peristalsis both during fasting (70.5%+/-2.5 vs. 57.8%+/-3.0 vs. 53.8%+/-1.9; P<0.05) and during meals (68.4+/-3.4 vs. 55.3+/-2.8 vs. 48.1+/-2.8; P<0.05) when compared with children with GERD and controls. Thirteen patients with EoE experienced 21 episodes of dysphagia, and all correlated with simultaneous abnormal motor function., Conclusions: PEMP allowed the detection of ineffective peristalsis in children with EoE. Symptoms observed in children with EoE may be related to esophageal motor dysfunction.

Background: Esophageal bolus clearance requires a preferential esophagogastric pressure gradient sustained for a sufficient period. We aimed to validate a high-resolution manometry (HRM) paradigm for predicting bolus clearance., Methods: Twenty volunteers and 30 patients were studied with HRM during barium swallows with concurrent fluoroscopy. Simultaneous bolus domain pressure and esophagogastric junction (EGJ) obstruction pressure were plotted and flow permissive time was tallied during which the bolus domain pressure exceeded the EGJ obstruction pressure. Distal peristaltic integrity was assessed at incrementally increasing pressure isobaric contour thresholds from 15-40 mmHg. ROC analysis was performed to assess the sensitivity and specificity of cutoff values for flow permissive time and peristaltic amplitude for predicting incomplete clearance as verified fluoroscopically., Results: Flow permissive time < or =2.5 s had a sensitivity of 86% and specificity of 92% for predicting incomplete clearance. In contrast, a 30-mmHg peristaltic amplitude had a sensitivity of only 48% and specificity of 88%. Incomplete clearance was variably attributable to functional EGJ obstruction, hiatus hernia, or impaired peristalsis., Conclusions: A detailed analysis of intraluminal pressure gradients in the distal esophagus and across the EGJ in the postdeglutitive period predicts esophageal bolus clearance with far greater accuracy than any threshold value of peristaltic amplitude.

Background: Ineffective esophageal motility (IEM) has been defined by the presence of > or = 30% liquid swallows with contraction amplitude < 30 mmHg (ineffective swallows) in the distal esophagus ("old" IEM). A recent study with combined multichannel intraluminal impedance and manometry (MII-EM) raised the question whether the manometric diagnosis of IEM should be based on a new definition: > or = 50% ineffective liquid swallows ("new" IEM). The aim of this study was to evaluate the association between the number of ineffective liquid swallows and symptoms and bolus transit in patients with "new" or "old" IEM who underwent MII-EM studies using 10 liquid and 10 viscous swallows., Materials and Methods: There were 150 patients with "old" IEM included in the study. The patients diagnosed with "old" IEM (N = 150) (group A) were compared with those who retained a manometric diagnosis of IEM by the new definition (N = 101) (group B). The patients who did not retain their manometric diagnosis of IEM by the new definition (N = 49) (group C) were compared with group B. IEM was characterized as mild (normal bolus transit for both liquid and viscous swallows), moderate (abnormal bolus transit either for liquid or viscous swallows), or severe (abnormal bolus transit for both liquid and viscous swallows)., Results: There was no statistical difference in frequency of mild, moderate, or severe IEM and frequency of symptoms between group A and B. Group C had a significantly higher frequency of mild IEM and significantly lower frequency of severe IEM than group B. Heartburn (25.7%vs 10.2%, P= 0.03) and dysphagia (24.8%vs 12.3%, P= 0.08) showed a trend towards a greater frequency in group B than in group C., Conclusion: Our study indicates that IEM with > or = 50% ineffective liquid swallows is frequently associated with bolus transit abnormalities and esophageal symptoms. Our results underscore the rationale for using the new definition of IEM.

Intraluminal impedance monitoring is a new technique that can be used to detect the flow of liquids and gas through hollow viscera. In combination with manometry, it is used for esophageal function testing and while manometry provides information on contractile activity, impedance provides information on esophageal bolus transit. This is especially useful in patients with nonobstructive dysphagia. However, impedance monitoring appears to be less suitable for the evaluation of patients with achalasia. When used in combination with esophageal pH monitoring, impedance monitoring makes gastroesophageal reflux monitoring more complete because it allows recognition of both acidic and weakly acidic reflux episodes. The results of several studies suggest that impedance-pH monitoring is useful in the evaluation of patients with PPI-resistant typical reflux symptoms, chronic unexplained cough, excessive belching, and rumination.

Background: Patients with achalasia, diffuse esophageal spasm (DES), and nutcracker esophagus have a thicker muscularis propria than normal subjects. The goal of our study was to determine the prevalence of increased muscle thickness in a group of unselected patients referred to the esophageal function laboratory for evaluation of the symptoms., Methods: We studied 40 normal subjects and 94 consecutive patients. Manometry and ultrasound images were recorded concurrently, using a special custom-built catheter. Esophageal muscle thickness and muscle cross-sectional area were measured at 2 and 10 cm above the lower esophageal sphincter (LES). Patients were assigned manometric diagnosis and determination was made if they had increased muscle thickness and muscle cross-sectional area., Results: Nearly all patients with well-defined spastic motor disorders, i.e., achalasia, DES, and nutcracker esophagus, revealed (a) an increase in the muscle thickness/cross-sectional area, (b) increase in esophageal muscle thickness/cross-sectional area was also seen, albeit at a lower prevalence rate, in patients with less well-characterized manometric abnormalities, i.e., hypertensive LES, impaired LES relaxation, and ineffective esophageal motility, and (c) 24% of patients with esophageal symptoms but normal manometry were also found to have an increase in muscle thickness/cross-sectional area. Dysphagia was more likely, and heartburn less likely in patients with increased muscle thickness, but there were no differences in chest pain and regurgitation symptoms between the groups., Conclusion: We describe, for the first time, increased muscle thickness in patients with esophageal symptoms and normal manometry. We suggest that increased esophageal muscle thickness is likely to be an important marker of esophageal motor dysfunction.

Objective: Patients with iron deficiency may have reduced power of the pharyngeal muscle for bolus propulsion into the esophagus. We hypothesized that esophageal muscle is similarly impaired., Methods: We studied the oropharyngeal and esophageal transits and esophageal motility of 12 patients (11 women) aged 31-50 yr (median 36 yr) with iron deficiency anemia (serum iron less than 40 microg/dl) and 17 normal volunteers (16 women) aged 26-52 yr (median 37 yr) with serum iron greater than 60 microg/dl. The esophageal motility was studied by the manometric method, with continuous perfusion and 10 swallows of a 2-ml bolus of water alternated with 10 swallows of a 7-ml bolus; and the oropharyngeal and esophageal transits were studied by scintigraphy, with swallows of a 10-ml bolus for the study of oropharyngeal transit and of a 10-ml bolus for the study of esophageal transit. Motility and transit were studied in the supine position., Results: The amplitude, duration and area under the curve of contractions were lower in patients than in volunteers. There were no differences in peristaltic contraction velocity, lower esophageal sphincter pressure, and lower esophageal sphincter relaxation duration. There was no difference in oropharyngeal transit. In the esophagus the transit was slower in patients than in volunteers. The time needed by the scintigraphic activity to reach a peak in the proximal esophagus was longer in patients than in volunteers., Conclusions: Iron deficiency may decrease esophageal contractions and impair esophageal transit.

Objective: Previous studies have suggested that ineffective esophageal motility (IEM) may be a marker for gastroesophageal reflux disease (GERD), particularly supraesophageal reflux disease. We evaluated the relationship between esophageal acid exposure and esophageal body motility in patients undergoing both esophageal manometry and 24-h pH metry in the absence of antisecretory therapy., Methods: We conducted a retrospective database review of 84 patients (mean age 47 yr, 46% male) evaluated in our GI physiology laboratory. The indication for testing was recorded and characterized as esophageal or supraesophageal. Abnormal esophageal acid exposure was defined as a distal esophageal pH <4 for more than 4.2% of the total monitoring time (>6.3% upright, >1.2% supine) or a proximal esophageal acid exposure time of greater than 1.1% total (>1.3% upright, 0% supine). IEM was defined as more than two of 10 ineffective peristaltic waves., Results: Seventy-two patients had esophageal-presenting symptoms, and 12 had supraesophageal symptoms. The prevalence of abnormal esophageal acid exposure was similar in patients with esophageal and supraesophageal symptoms (69% vs 92%, p = 0.17). Abnormal motility was identified in 26 patients (31%). IEM was the most common motility disturbance (77%, 20 patients). The frequency of motility disorders was similar in patients with and without abnormal esophageal acid exposure (30% vs 35%, p = 0.79), in patients with esophageal or supraesophageal symptoms (32% vs 25%, p = 0.75, for all patients; 30% vs 27%, p = 1.00, for patients with abnormal esophageal acid exposure), and among upright, supine, and combined refluxers (33%, 9%, and 35%, p = 0.26)., Conclusions: IEM does not stand alone as a significant marker for the presence of GERD in general or supraesophageal reflux disease in particular.

Objective: Nutcracker esophagus (NE) is defined as the presence of peristaltic contractions in which the average distal esophageal amplitude is greater than 180 mm Hg. The underlying mechanism responsible for these abnormalities is not known. The aim of this study was to test the hypothesis that NE might be caused by a defect in the inhibitory pathway controlling esophageal peristalsis., Methods: Eight patients with NE (seven women, 1 man, mean age 50 yr) and eight age- and sex-matched normal volunteers (seven women, 1 man, mean age 48 yr) underwent a special protocol using three-channel (3, 8, and 16 cm above the lower esophageal sphincter) solid state esophageal manometry to evaluate deglutitive inhibition. Ten pairs of 5 ml of wet swallows were given at each of five different time intervals (30, 20, 15, 10, and 5 s). Pairs of swallows were spaced by 30 s, and different time intervals were spaced by 1 min. Tracings were recorded using a computer program and blindly automatically analyzed for both amplitude and duration of the contraction separately for the first and second swallow of each pair. Presence of deglutitive inhibition or muscle refractoriness was assessed according to interactions between the first and second swallow of the pair. Results were found abnormal when larger than the mean percent variation of the second and first swallow calculated for the 30-s interval, considered as baseline for each participant. Statistics included paired and nonpaired nonparametrical comparisons as appropriate., Results: The median amplitude for the NE was 202 mm Hg (range 186-376) and for the controls was 118 mm Hg (range 64-167) (p = 0.0002). The median duration in the NE group was 5.1 s (range 4-9.3) versus 4.1 (range 3.3-5.0) for the controls (p = 0.02). The percent variation in duration (p = 0.31), amplitude (p = 0.42), and propagation velocity of the peristaltic waves (p = 0.69) did not differ between the control and NE groups. Peristalsis frequency dropped at the 5-s interval for both studied groups (p = 0.84)., Conclusion: Central and local inhibitory mechanisms induced by closely timed swallows are preserved in the NE and do not explain the mechanism of the high amplitude and long duration contractions.

Objective: Many patients with functional (noncardiac) chest pain exhibit both hypersensitivity and motor dysfunction of the esophageal wall. We aimed to determine whether the sensory or motor dysfunction plays an important role in the pathogenesis of chest pain., Methods: We performed graded balloon distentions of the esophagus using impedance planimetry in 16 consecutive patients with chest pain and otherwise normal cardiac and esophageal evaluations and in 13 healthy controls. In those patients who experienced chest pain with balloon distention, the test was repeated after atropine was given. Sensory and biomechanical parameters were measured., Results: Balloon distention reproduced typical chest pain in 13/16 patients (81%) and at lower (p < 0.01) sensory thresholds than controls. Pain was reproduced in all 13 patients and at lower (p < 0.05) sensory thresholds after atropine. Also, after atropine, the esophageal cross-sectional area and wall tension increased (p < 0.05), the tension/strain association shifted to the right (p < 0.05), and reactivity decreased (p < 0.002) relative to results before atropine or in healthy controls (i.e., the esophageal wall relaxed and became more deformable)., Conclusions: Even after relaxing the esophageal wall, most patients experienced chest pain and at lower sensory thresholds. Hence, hyperalgesia rather than motor dysfunction appears to be the predominant mechanism for functional chest pain of esophageal origin.

Objective: Few studies have compared esophageal dysfunction with diabetic neuropathy, and their relationship is not yet clear. The aim of this study was to investigate the relationship between esophageal function and diabetic neuropathy., Methods: A total of 59 patients with type 2 diabetes were studied. Long-term ambulatory esophageal pH and motility monitoring were performed. The motor nerve conduction velocity (MCV) and coefficient of variation of R-R intervals (CVRR) were also examined., Results: The 59 patients were classified into four groups: group 1 consisted of patients with both diabetic autonomic neuropathy (DAN) and diabetic motor neuropathy (DMN), group 2 had DMN alone, group 3 had DAN alone, and group 4 had neither DAN nor DMN. In pH monitoring, differences were observed among the four groups in DeMeester score, total number of acid reflux episodes, and % time pH < 4 (p < 0.05). A correlation was observed between % time pH < 4 and MCV; however, no correlation with CVRR was observed. In motility monitoring, differences were observed among the four groups in amplitude of peristaltic waves (p < 0.001), rising velocity of peristaltic waves (p < 0.01), and percentage of effective peristalsis (p < 0.01). A correlation was observed between esophageal motility and MCV; however, no correlation with CVRR was observed., Conclusions: Esophageal motility disorder and abnormal acid reflux were related to DMN in diabetic patients. A significant correlation was found between esophageal dysfunction and MCV. However, no significant correlation was found between esophageal dysfunction and CVRR.

Objectives: Nutcracker esophagus is a manometric pattern that is commonly seen in patients with functional (noncardiac) chest pain. However, this pattern is often unassociated with pain. Consequently, the pathophysiology of chest pain in these patients is unclear., Methods: We prospectively examined the sensory perception and biomechanical properties of the esophagus in 10 patients with chest pain and a nutcracker esophagus, along with those properties in 12 healthy controls using impedance planimetry., Results: Stepwise balloon distentions reproduced typical chest pain in 9/10 (90%) patients. The threshold for chest pain was lower (p < 0.05) in patients than in controls (mean +/- SD 43+/-5 vs 62+/-4 cm H2O) but only 2/12 controls experienced pain. The thresholds for first perception and moderate discomfort were also lower (18+/-8 vs 30+/-11 cm H2O, p < 0.01 and 28+/-9 vs 62+/-5 cm H2O, p < 0.001) in patients than in controls, but only 3/12 controls experienced moderate discomfort. The esophageal reactivity to balloon distention was higher in patients than in controls (p < 0.001). The tension-strain curve shifted to the left in the patient group when compared to that in the controls (p < 0.05)., Conclusions: Patients with a nutcracker esophagus demonstrate a hypersensitive and stiff esophagus. Because balloon distention reproduced their chest pain, visceral hyperalgesia of the esophagus may be relevant to the pathogenesis of their pain. Balloon distention test may be more useful in the evaluation of patients with functional chest pain and a nutcracker esophagus.

Objective: Topographical manometric methods have improved the understanding of esophageal peristalsis in research applications but require a large number of recording sensors. Commonly used methods limited to four sensors were compared to topographical methods to determine whether the latter also had significant clinical utility., Methods: Two hundred twelve patients referred for esophageal manometry were studied with a data acquisition system having 21 intraluminal recording sites, and the findings were analyzed independently using both limited (pull-through plus four recording sites) and topographical approaches (all sites). Discrepant results were clarified using supportive clinical data., Results: The two methods were in diagnostic agreement in 187 cases (88.2%). Topographical methods correctly identified all 26 patients with achalasia within the group with aperistalsis (n = 36). The limited methods could not confidently identify six achalasia patients and were significantly less effective in segregating aperistaltic disorders (p < 0.05 across methods). Topographical methods alone detected evidence of incomplete lower esophageal sphincter relaxation in 12 additional patients, eight of whom had clinical data supporting the findings. Topographical methods identified the upper margin of the lower sphincter in all but three subjects (1.4%); limited methods could not identify this location in these and five additional subjects (3.8%) and differed from the topographical measurement by > or = 2 cm in 11.9% of cases., Conclusions: Topographical methods are more accurate than commonly used methods in diagnosing the type of severe motor dysfunction and provide additional information important in the clinical practice of esophageal manometry.

Objective: The aim of this study was to investigate the relationship between esophageal dysfunction and pulmonary involvement in patients with systemic sclerosis (SSc)., Methods: Pulmonary function parameters were compared between groups of patients with and without manometric evidence for SSc-induced esophageal dysmotility., Results: Twenty-six of 43 patients (60.5%) exhibited a marked hypo- or aperistalsis of the smooth muscle portion of the esophagus. Total lung capacity, inspiratory vital capacity, and forced vital capacity were significantly lower in patients with esophageal dysfunction compared with those with normal esophageal peristalsis (p < 0.001). Patients with the diffuse form of SSc (n = 20) had significantly lower values for total lung capacity and inspiratory vital capacity compared with patients with the limited type of SSc (n = 23; p < 0.05)., Conclusion: There is a significant association of esophageal dysmotility with reduced lung volumes in SSc. Possible explanations for these findings are pulmonary damage due to increased gastroesophageal reflux and, more likely, simultaneous involvement of the lungs and the esophagus in the disease process.

Esophageal motility abnormalities in patients treated endoscopically for variceal hemorrhage are rarely studied and usually are not addressed in the clinical setting. However, a review of the literature revealed that esophageal varices reduce the mean amplitude and increase the mean duration of peristaltic waves but have little effect on lower esophageal sphincter function. Transit time is delayed and gastroesophageal reflux disease is common in up to 64% of the patients. Whereas band ligation appears to have little impact on esophageal motility, data are limited and are hampered by lack of standardization, rendering conclusions about safety rather premature. Injection sclerotherapy spares the lower esophageal sphincter, as well, but it significantly reduces mean amplitude contractions, mainly in the lower one-third to one-half of the esophagus. In addition, normal peristalsis may be occasionally or completely replaced by nonpropagating simultaneous contractions that may result in chest pain and/or dysphagia in the absence of stricture. Transient prolongation of acid clearance usually resolves within a week, except in patients who have developed stricture. Pathogenesis of the abnormal motility remains poorly understood, and treatment has been empirical. However, a short course of anti-reflux treatment after each therapeutic session is justified, as well as long-term treatment for patients with stricture. The choice of treatment for esophageal motility abnormalities is less clear and requires future studies.

Objectives: Occult panic disorder (PD) may underlie 10-43% of chest pain syndromes in patients with normal coronary arteries. A variety of agents, such as intravenous lactate, oral caffeine, and inhaled CO2, has been identified that may provoke panic attacks in susceptible patients. The aims of this study were (1) to better define the relationship between noncardiac chest pain syndromes and panic disorder; and (2) to assess the diagnostic utility of PD provocative testing with inhaled CO2 in eliciting chest pain and/or esophageal manometric disturbances., Methods: Fourteen patients with chest pain syndromes and negative coronary angiograms or stress thallium tests were evaluated for PD and underwent (1) standard esophageal manometry followed by continuous manometric recording; (2) inhalation by face mask of room air or 35% CO2, single blinded, in random order; (3) a previously validated Acute Panic Inventory questionnaire administered before and immediately after each inhalation; and (4) Tensilon 10 mg i.v. administration., Results: Of 14 patients, 8 met DSM-IIIR criteria for panic disorder. Mean Acute Panic Inventory scores (reflecting panic symptoms) increased significantly after CO2 inhalation relative to room air in all patients. Of 14 patients, 8 (4 PD, 4 non-PD) experienced chest pain after CO2 inhalation, whereas no patient had chest pain after room air inhalation. Of 14 patients, 5 had pain with Tensilon (4 of 5 whom responded to CO2). No specific manometric abnormalities occurred during any chest pain episode., Conclusion: CO2 inhalation is as effective as Tensilon in provoking chest pain in patients with noncardiac chest pain. The high prevalence of PD in such patients suggests that CO2 inhalation, a known panicogen, may be useful in evaluating such patients. The mechanism of CO2 induced chest pain remains unknown, but does not appear to be attributable to demonstrable esophageal motility abnormalities.

Gastroesophageal reflux disease (GERD) is a complex, multifactorial disease for which the initiating factors are unknown. Acid in contact with the esophageal epithelium, however, is a central event in the development of the disease--the disease developing when acid overwhelms the intrinsic esophageal epithelial defenses. Acid breakdown of the tissue defenses is what ultimately leads to symptom production, ulceration, and other complications of GERD. Patients with GERD generally, although not always, have more episodes of reflux than healthy subjects; this is due to more frequent transient lower esophageal sphincter relaxations in the disease group. GERD patients may also have some impairment in peristaltic frequency on swallowing and/or weakness in the strength of peristaltic contractility. Contributions from other components of the acid clearance and tissue-defensive mechanisms are possible but remain to be adequately established as contributing to GERD. It is likely that one reason for the wide clinical spectrum observed with GERD results from differences in types and degrees of defects within the tripartite esophageal defensive system against damage from the phenomenon of gastroesophageal reflux.

Objectives: Hyperventilation is known to cause esophageal spasm, but the importance of this interaction in clinical practice is unknown. In the present study, we report the effects of hyperventilation provocation on esophageal motility in a consecutive series of patients with noncardiac chest pain., Methods: In a prospective observational study design, 46 consecutive patients with normal coronary angiograms were studied. Esophageal motility was recorded at rest and after voluntary over-breathing at 40 breaths/min for 3 min., Results: Hyperventilation was associated with a significant fall in mean distal peristaltic amplitude [66 (SD 28) to 55 (SD 24) mm Hg, p <0.001] and mean duration [2.9 (SD 0.7) to 2.6 (SD 0.9) s,p = 0.02]. It induced diffuse spasm in two (4%) patients, and nonspecific motility disorders in 10 (22%). Chest pain was reproduced in seven (15%) patients, but in none did this coincide with an important change in peristaltic amplitude, duration, or frequency., Conclusion: Hyperventilation has important effects on esophageal motility, and manometrists should be aware of these before recommending that anxious patients overbreathe to help relaxation during clinical studies. Although overbreathing is a common source of dysmotility, it rarely produces chest pain via its effects on the esophagus.

Objective: To determine the importance of acid reflux-induced dysmotility in the genesis of noncardiac chest pain in children., Method: We performed esophageal manometries during intraesophageal perfusion with 0.9% NaCl or 0.1 N HCl in 19 children (age, 14.5 +/- 0.5 yr) with gastroesophageal reflux, biopsy-proven esophagitis, and complaints of at least one episode of chest pain per day., Results: Baseline esophageal motilities were normal in all patients. Eight of 19 children (42%) complained of chest pain during intraesophageal acid perfusion. In three of these eight patients, complaints of chest pain during acid perfusion were temporally associated with "conversion" of previously normal motility patterns to manometric tracings, indicating esophageal dysmotility. Compared with findings during saline perfusion, esophageal acid exposure in these three children resulted in significant increases in both the duration (13.6 +/- 4.0 vs 3.2 +/- 0.2 s, p < 0.05) and amplitude (105.2 +/- 7.8 vs 61.2 +/- 2.1 mm Hg, p < 0.05) of esophageal contractions during wet swallows. Symptoms of chest pain resolved in all patients after therapy with H2-receptor antagonists., Conclusions: These data represent the first demonstration of acid-induced esophageal dysmotility in children with chest pain and suggest that reflux-induced motor abnormalities contribute to the onset and/or exacerbation of chest pain in pediatric patients with gastroesophageal reflux and esophagitis.

Objectives: In patients with AIDS, esophageal symptoms are commonly due to opportunistic esophageal infection with Candida, cytomegalovirus (CMV), herpes simplex virus (HSV), and HIV. Despite apparently appropriate therapy against these pathogens, some patients continue to complain of dysphagia or odynophagia. This study was designed to determine whether such complaints were associated with a motility disorder of the esophagus., Methods: Sixteen patients underwent esophagoscopy and biopsy followed by esophageal manometry, performed using a 5-channel water perfused system (Synectics Medical, Inc., Irving, Texas). All patients had odynophagia, and eight had dysphagia., Results: Identified infections included: Candida (11), HSV and Candida (1), CMV (3), and a giant ulcer presumably caused by HIV (1); one patient also had lymphoma. Seven patients had normal esophageal motility, and in nine patients, a nonspecific motility disorder was found. After therapy, one of 10 patients had persistent odynophagia and dysphagia, and two had odynophagia only. At follow-up endoscopy, complete healing was demonstrated in six of eight patients with Candida. One of two patients with CMV and the patient with HSV also showed complete healing of the esophagus. Repeat esophageal motility studies were performed after therapy in 10 patients. Five had a persisting abnormality despite eradication of the pathogen (three Candida, one HSV, one CMV); in four, the previously identified motor abnormalities resolved after eradication of the infection (three Candida, one CMV)., Conclusions: These findings suggest that a nonspecific motility disorder exists in AIDS patients with esophageal symptoms and may contribute to the persistence of symptoms despite appropriate therapy of esophageal opportunistic infections.

The most common esophageal motility abnormality in patients with noncardiac chest pain is nutcracker esophagus. Most investigators regard nutcracker esophagus as a diffuse process involving the distal esophagus. Others consider it a segmental disturbance affecting isolated regions of the distal esophageal smooth muscle. This study compared the prevalence, clinical features, consistency, and manometric course of patients with either segmental high-amplitude peristaltic contractions (SHAPC) or those with the traditional diffuse contraction abnormalities termed nutcracker esophagus (NE). We particularly sought to determine whether patients with SHAPC represent an early spectrum evolving into a more diffuse contraction disorder--NE. The prevalence and clinical features of patients with either motility disturbance were similar. Thirty-nine percent of our patients had abnormally high peristaltic amplitude in locations of the proximal esophagus not previously described. Follow-up manometric studies demonstrated that only 53% of patients in the NE and 20% with SHAPC retained the same manometric diagnosis. In addition, 33% of patients in the NE group and 40% of the SHAPC group permutated into each other. These findings indicate that patients with SHAPC do not represent an early process subsequently evolving into a more diffuse contraction abnormality. Rather, the motility pattern of high-amplitude peristaltic contractions--segmental or diffuse--constitutes a labile marker associated with noncardiac chest pain.

A review of our 402 motility records of patients undergoing evaluation of noncardiac chest pain identified 40 patients with the diagnosis of nutcracker esophagus. Gastroesophageal reflux was found in 13 of 20 patients (65%) who underwent pH studies, and endoscopy detected one patient with erosive esophagitis. Thus, at least 14 (35%) of our nutcracker esophagus patients had evidence of reflux. Twelve of these subjects agreed to enter an open-label therapeutic trial. After 8 wk of intensive antireflux treatment with high doses of ranitidine or omeprazole, repeat 24-h pH studies and endoscopy demonstrated normalization of pH parameters and healing of esophagitis in all patients. Ten (83%) patients obtained significant symptomatic improvement in frequency of pain episodes, number of days with pain, and pain severity. However, repeat manometry showed normalization of motor findings in only two (18%) patients. These observations warrant further placebo-controlled trials. Until more information is available, the results of this study suggest that gastroesophageal reflux should be excluded in patients with noncardiac chest pain and nutcracker esophagus before initiation of smooth muscle relaxant therapy.

In the manometric evaluation of patients complaining of chest pain, a nonspecific esophageal motor disorder is commonly identified. Yet, the clinical characteristics of these patients and stability of the manometric pattern with time have not been previously described. This study reports a 3.2-yr clinical and manometric follow-up of 23 patients with nonspecific esophageal motor disorder. These subjects were most commonly middle-aged women with long-standing, persistent, and debilitating clinical symptoms. Ninety-six percent (22/23) of our patients complained of chest pain; 65% (15/23) had dysphagia. In addition, 15 (65%) had evidence of reflux during ambulatory pH studies. Symptoms caused such concern that the patients frequently sought medical assistance to exclude serious diseases. Although the symptoms tended to persist, the motility patterns changed in some patients. Follow-up manometric studies were normal in 29%, and nonspecific esophageal motor disorder persisted in 57% of the patients. In three patients (14%), the pattern evolved into diffuse esophageal spasm. When symptoms were compared with these changes in follow-up manometric patterns, the correlation was poor. This observation suggests that additional mechanism(s) other than disturbed esophageal motility may be responsible for the symptoms seen in these individuals.

Unlabelled: A randomized double-blind, cross-over prospective trial in 22 patients was designed to evaluate possible effect of an oral calcium channel blocker, diltiazem, on symptoms of chest pain and/or dysphagia in patients with nutcracker esophagus. We studied 22 consecutive patients referred to an esophageal diagnostic center for evaluation of noncardiac chest pain or dysphagia having high amplitude esophageal contractions, 14 of whom completed the study. Diltiazem (60-90 mg qid) was compared with placebo, each being administered for 8 wk. Patients were evaluated with esophageal motility pre- and posttreatment periods and with regular symptom assessment throughout each 8-wk treatment. Active diltiazem therapy resulted in significantly lower (p less than 0.05) mean distal esophageal peristaltic pressure (128 +/- 20 mm Hg; +/- SE) than placebo (158 +/- 16 mm Hg). Mean chest pains scores were significantly (p less than 0.05) lower with diltiazem therapy than with placebo. Only nine of the 14 patients fulfilled presently acceptable criteria for diagnosing nutcracker esophagus, and the diltiazem effect was similar, although not significant, because of the smaller sample., Conclusions: In this preliminary study involving 14 patients, the oral calcium channel blocker, diltiazem, appeared to improve noncardiac chest pain associated with strong esophageal contraction, the nutcracker esophagus. These improved symptoms were associated with significant decreases in contraction pressure.

To assess prospectively the effects of endoscopic intravariceal sclerosis (EIS) on esophageal function, we performed esophageal manometry on 13 cirrhotic patients before EIS, 24 h after the second session and 4 wk after the fourth session. EIS had no impact on lower esophageal sphincter pressure. However, a significant decrease in the amplitude of peristaltic waves was observed immediately post-EIS in the lower two-thirds of the esophagus. There was no modification of duration or velocity of progression of peristaltic waves. A four-fold increase in simultaneous contractions was observed early after EIS. These changes were reversible, as assessed by late esophageal testing after EIS. No correlations were demonstrated between esophageal motor parameters and doses of sclerosant. We conclude that sclerosant injection into the esophageal wall acutely impairs esophageal motility, but motor function is partially restored 4 wk after completion of EIS, suggesting that dysmotility is reversible.

There is conflicting evidence regarding whether lower esophageal sphincter and esophageal contractile pressures are affected by changes in the severity of gastroesophageal reflux disease. We compared the manometric and endoscopic findings from 30 patients before and after treatment for esophagitis. Before treatment, the grade of esophagitis (I-III) was significantly correlated (r = -0.37; p less than 0.05) with lower esophageal sphincter pressure, but not with esophageal contractile pressure. After treatment, the grade of esophagitis did not change or became worse in 15 patients, and became better in 15 patients. Of these, seven healed. The group that showed no endoscopic improvement demonstrated no change in lower esophageal sphincter or esophageal contractile pressures. The group that did show endoscopic improvement also demonstrated no increase in lower esophageal sphincter or esophageal contractile pressures, and this was particularly evident in those whose esophagitis healed. These data suggest that healing of esophagitis does not result in improvement of esophageal motor function.