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Esophageal high resolution manometry (HRM) is the gold standard for assessment of esophageal motor disorders, but motor responses to the standard 5 mL water swallow protocol may not provide precision in defining minor motor disorders. Provocative maneuvers, particularly multiple rapid swallows (MRS), have been used to assess deglutitive inhibition during the repetitive swallows, and the contractile response following the final swallow of the sequence. The augmentation of esophageal smooth muscle contraction following MRS is termed contraction reserve. This is determined as the ratio between esophageal body contraction vigor (distal contractile integral, DCI) following MRS to the mean DCI after single swallows, which is ≥1 in the presence of contraction reserve. Reliable assessment of contraction reserve requires the performance of 3 MRS maneuvers during HRM. Absence of contraction reserve is associated with a higher likelihood of late postfundoplication dysphagia and may correlate with higher esophageal reflux burden on ambulatory reflux monitoring. Esophageal motor responses to abdominal compression, functional lumen imaging probe (FLIP) balloon distension, and pharmacologic testing (using edrophonium and cisapride) may correlate with contraction reserve. Other provocative tests useful during HRM include rapid drink challenge, solid and viscous swallows, and standardized test meals, which are more useful in evaluation of esophageal outflow obstruction and dysphagia syndromes than in identification of contraction reserve. Provocative maneuvers have been recommended as part of routine HRM protocols, and while useful clinical information can be gleaned from these maneuvers, further research is necessary to determine the precise role of provocative testing in clinical esophagology.

Background: Videoesophagram (VEG) and esophageal manometry (EM) are components of the preoperative evaluation for foregut surgery. EM is able to identify motility disorders and diminished contractility that may alter surgical planning. However, there are no clearly defined criteria to guide this. Reliable manometry is not always easily obtained, and therefore its necessity in routine preoperative evaluation is unclear. We hypothesized that if a patient has normal videoesophagram, manometry does not reveal clinically significant esophageal dysfunction., Methods: We reviewed patients who underwent protocolized videoesophagram and manometry at our institution. Measures of esophageal motility including the mean distal contractile integral (DCI), mean wave amplitude (MWA), and percent of peristaltic swallows (PPS) were analyzed. The Chicago Classification was used for diagnostic criteria of motility disorders. Normal VEG was defined as stasis of liquid barium on less than three of five swallows., Results: There were 418 patients included. 231 patients (55%) had a normal VEG, and 187 patients (45%) had an abnormal VEG. In the normal VEG group, only 2/231 (0.9%) patients had both abnormal DCI and PPS, 1/231 (0.4%) patients had both abnormal DCI and MWA and no patients had both abnormal MWA and PPS. There were no patients with achalasia or absent contractility and 1 patient with ineffective esophageal motility (IEM) in the normal VEG group. This was significantly different from the abnormal VEG group which included 4 patients with achalasia, 1 with absent contractility and 22 with IEM (p < 0.0001). The negative predictive value of VEG was 99.6% and the sensitivity was 96.4%., Conclusions: A normal videoesophagram reliably excluded the presence of clinically significant esophageal dysmotility that would alter surgical planning. Routine manometry is not warranted in patients with normal videoesophagram, and should be reserved for patients with abnormal VEG.

Background: Upper esophageal sphincter (UES) metrics on high-resolution manometry (HRM), particularly nadir UES residual pressure (UES-RP), are abnormal in achalasia and may help characterize the underlying mechanism or predict management outcome in esophagogastric junction outflow obstruction (EGJOO)., Methods: A database of consecutive patients undergoing esophageal HRM from 2008 to 2013 yielded 134 patients (59.8 ± 1.4 years, 68% F) with EGJOO. Final clinical diagnoses and treatment response were extracted from chart review. Esophageal body, UES, and lower esophageal sphincter (LES) metrics were compared between EGJOO and asymptomatic healthy controls (n = 16, 27.7 ± 0.7 years, 56% F). Logistic regression evaluated differences between HRM metrics amongst etiologies of EGJOO grouped into motor versus mechanical disorders., Key Results: Distal contractile integral, distal latency, and nadir UES-RP were significantly different between EGJOO subgroups (P ≤ 0.01 for each comparison), but only nadir UES-RP remained independently predictive of subgroups (adjusted odds ratio 1.15, 95% confidence intervals 1.05-1.27, P < 0.01). Nadir UES-RP was highest in achalasia variants, and lowest in mechanical EGJOO and controls (P < 0.001). Of 19 patients who underwent LES myotomy, durable benefit was reported by 68.4% over mean 3.6 years of follow-up. Significantly higher nadir UES-RP was noted with symptom relief (3.4 vs -0.7 mm Hg with symptom recurrence, 95% confidence intervals of difference = 1.35-6.83). A threshold UES-RP of ≥2.0 mm Hg yielded a sensitivity of 84.6% and specificity of 83.3% in predicting symptom resolution following myotomy., Conclusions and Inferences: Nadir UES-RP offers clues to differentiation of subtypes within EGJOO and may predict symptom outcome from myotomy., (© 2019 John Wiley & Sons Ltd.)

Goals: The aim of our study was to characterize jackhammer esophagus symptoms and their relationship with the distal contractile integral (DCI) and bolus transit., Background: Jackhammer esophagus is defined by the Chicago Classification version 3.0. This diagnosis is relatively new, with the most current definition being established in 2014. The forerunners of this diagnosis, nutcracker (or hypercontractile) esophagus, have been associated with noncardiac chest pain (NCCP)., Study: A retrospective chart review was performed of motility studies from 2011 to 2016. Studies with a diagnosis of jackhammer esophagus, hypercontractile esophagus, nutcracker, esophagogastric junction outflow obstruction, or hypertensive lower esophageal sphincter were reread using Chicago Classification version 3.0, and were included if they met criteria for jackhammer esophagus. Unpaired t-tests were used for analysis (P≤0.05)., Results: In total, 142 studies were identified with the above diagnoses. After excluding 84 studies, 58 remained for analysis and 17 were found to have jackhammer esophagus (29%). The mean age was 54 (28 to 75), 5 (29%) were males and 12 (71%) were females. The primary indications were NCCP (5), dysphagia (8), and other causes (4) (cough, heartburn, or regurgitation). The mean DCIs were 17,245 mm Hg×s×cm (NCCP), 14,669 mm Hg×s×cm (dysphagia), and 11,264 mm Hg×s×cm (other causes). The mean DCIs were compared: NCCP versus dysphagia (P=0.41), and NCCP versus other causes (P=0.05). Fifteen (88%) had normal bolus transit for both liquid and viscous swallows., Conclusions: In our small sample size, dysphagia was frequently the presenting symptom followed by NCCP. Those with NCCP have a trend toward a higher DCI. Bolus transit appeared to be normal in this patient population. More data are needed to further elucidate the genesis of symptoms and how they relate to the degree of contractility.

Background: The present study aimed to evaluate whether the detailed observation of pH/MII waveforms and the analysis of baseline impedance (BI) values could detect esophageal dysmotility in pediatric patients with esophageal disorders., Patients and Methods: Eleven patients with congenital esophageal disorder in whom pH/MII was conducted from April 2011 to June 2015, were enrolled in this study. The diagnoses of the patients were as follows: postoperative esophageal atresia (EA), n = 6; esophageal achalasia (EAch), n = 4; and congenital esophageal stenosis (CES), n = 1. The characteristics of the pH/MII waveform, pathological GERD, BI value, and the average BI value of the 2 distal channels (distal BI; DBI) were analyzed in each disorder., Results: Two EA (33%) patients and one EAch (25%) patient were diagnosed with GERD. The mean DBI values of the EA, EAch and CES patients was 912 ± 550, 2153 ± 915 and 1392 Ω, respectively. The EA patients showed consistently low DBI values. One CES patient and two infantile EAch patients showed postprandial prolonged low DBI values. Whereas, the pH/MII waveforms of the adolescent EAch patients were difficult to interpret due to their extremely low BI values., Conclusions: The present study demonstrated that the detailed observation of the pH/MII waveforms in all channels and the analysis of BI were useful for evaluating esophageal motility in children with congenital esophageal disorders. In particular, infantile patients with EAch showed DBI findings that were distinct from those of adult EAch patients. Considering the difficulty of performing esophageal manometry in young children, the detailed observation of the pH/MII waveform may help in the diagnosis of esophageal dysmotility in children.

Goals: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD)., Background: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure., Study: Patients post-LTx (n=48, 24 female; aged 20 to 73 y) completed high-resolution impedance manometry and 24-hour pH/impedance., Results: Patients who had undergone unilateral LTx were more likely to exhibit esophagogastric junction outflow obstruction (47% vs. 18%; P=0.046) and less likely to exhibit hypocontractility (0% vs. 21%; P=0.058) than those who had undergone bilateral LTx. Although the proportion of patients exhibiting gastroesophageal reflux was no different between groups (33% vs. 39%; P=0.505), those undergoing bilateral LTx were more likely to exhibit proximal reflux (8% vs. 37%; P=0.067). Univariate Cox proportion hazards regression analysis did not show a difference between unilateral versus bilateral LTx in the development of o-CLAD (hazard ratio=1.17; 95% confidence interval, 0.48-2.85; P=0.723)., Conclusion: The type of LTx performed seems to lead to different risk factors for the development of o-CLAD. Physicians should be aware of these differences, as they may need to be taken into account when managing patient's post-LTx.

Background: Jackhammer esophagus is a hypercontractile esophageal disorder recently brought to light with the advent of high resolution manometry (HRM). As little is known about its clinical presentation, the aim of this study was to identify the clinical characteristics associated with this new gastrointestinal motility disorder., Methods: A retrospective study was conducted on patients visiting the CHUM's Gastro-Intestinal Motility Center from January 2015 to December 2017. The HRM diagnoses were collated in a database along with age and sex of every individual. The latest Chicago classification (version 3.0) was used. Among all the patients subjected to HRM, those diagnosed with Jackhammer esophagus were included in the study. Patient charts were reviewed to collect relevant demographic and clinical data., Key Results: A total of 36 patients with Jackhammer esophagus were included (62 ± 13 years age, 89% females). Their main symptoms were dysphagia (72%), pyrosis (42%), retrosternal chest pain (36%), and epigastralgia (33%). Other manometric findings were hypertonia (22%) and/or inadequate relaxation (19%) of the lower esophageal sphincter. Among the 26 patients who had esogastroduodenoscopy, hiatal hernia was seen in 3 patients. Pathological gastroesophageal reflux was found in 4 of the 10 patients investigated by pH-monitoring., Conclusions and Inferences: Jackhammer esophagus represents 3% of the HRM diagnoses in this study, with a significant female preponderance. In more than two-thirds of cases, the clinical presentation of Jackhammer esophagus is dysphagia.

Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink challenge (RDC) are complementary tests used during high-resolution manometry (HRM) that evaluate inhibitory and excitatory neuromuscular function and latent obstruction, respectively. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 men; median age: 63 yr; IQR: 54-70 yr). Twenty-one healthy subjects (11 men; median age: 28 yr; range: 26-30 yr) were used as a control group. All patients underwent solid-state HRM with ten 5-ml single swallows (SS) and one to three 10-ml MRS; 34 patients also underwent RDC. Data are shown as median (interquartile range). Abnormal motor inhibition was noted during at least one MRS test in 48% of JE patients compared with 29% of controls ( P = 0.29). Mean distal contractile integral (DCI) after MRS was significantly lower than after SS [6,028 (3,678-9,267) mmHg·cm·s vs. 7,514 (6,238-9,197) mmHg·cm·s, P = 0.02], as was highest DCI ( P < 0.0001). Consequently, 66% of JE patients had no contraction reserve. At least one variable of obstruction during RDC (performed in 34 patients) was outside the normal range in 25 (74%) of JE patients. Both highest DCI after SS and pressure gradient across the esophagogastric junction (EGJ) during RDC were higher in patients with dysphagia versus those without ( P = 0.04 and 0.01, respectively). Our data suggest altered neural control in JE patients with heterogeneity in inhibitory function. Furthermore, some patients had latent EGJ obstruction during RDC, which correlated with the presence of dysphagia. NEW & NOTEWORTHY Presence of abnormal inhibition was observed during multiple rapid swallows (MRS) in some but not all patients with jackhammer esophagus (JE). Unlike healthy subjects, JE patients were more strongly stimulated after single swallows than after MRS. An obstructive pattern was frequently observed during rapid drink challenge (RDC) and was related to presence of dysphagia. MRS and RDC during high-resolution manometry are useful to show individual pathophysiological patterns in JE and may guide optimal therapeutic strategies.

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.)

Background: High-resolution impedance manometry (HRIM) allows evaluation of esophageal bolus retention, flow, and pressurization. We explored novel HRIM measures and assessed their temporal relationship to dysphagia symptoms for boluses of different volume and consistency in non-obstructive dysphagia (NOD) patients., Methods: Thirty-three NOD patients (n = 19 minor or no disorder of peristalsis ("Normal") and n = 14 esophagogastric junction outflow obstruction ("EGJOO")) were evaluated with HRIM. Patients were administered 5 and 10 mL liquid, semisolid, and 2 and 4 cm solid boluses and indicated bolus perception during individual swallows using a 5-point Likert scale. HRIM was analyzed to assess Chicago Classification and pressure flow metrics, esophageal impedance integral (EII) ratio, and bolus flow time (BFT)., Key Results: Overall, bolus perception increased with increasing bolus consistency (P < 0.001), but did not differ significantly between EGJOO and Normal patients. EGJOO patients had higher IRP4, higher levels of bolus residual (ie, EII ratio and IR), and restricted esophageal emptying. The results for linking semisolid bolus perception to semisolid-derived measures revealed more biomechanically plausible and consistent patterns when compared to those derived for liquid boluses. In Normal patients, perception of boluses of heavier viscosity was related to higher bolus flow resistance during transport, whilst in EGJOO, perception was related to restriction of esophageal emptying., Conclusion & Inferences: These novel pressure-impedance measures may aid in the evaluation of NOD patients by revealing abnormal motor patterns, which may explain symptom generation. Future studies are needed to evaluate which of these measures are worthy of calculation and to establish protocol settings that allow for their meaningful interpretation., (© 2018 John Wiley & Sons 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.)

Objectives: We investigated the diagnostic utility of distal contractile integral (DCI) to esophageal impedance integral (EII) ratio (DCIIR) in high-resolution impedance manometry (HRIM) of ineffective esophageal motility (IEM) in children., Methods: We performed HRIM in 31 children with dysphagia, odynophagia, chronic vomiting, chest pain, or heartburn sensation. Based on the Chicago classification version 3.0, 20 subjects were diagnosed with IEM, and 11 subjects were normal. We analyzed the EII and DCIIR using MATLAB software., Results: The DCIIR calculated at the impedance cutoff at 1500 Ω (DCIIR1500) were significantly lower in IEM group than patients with normal motility (P = 0.007). Receiver operating characteristic (ROC) curve analysis showed that a DCIIR1500 < 0.009 mmHg/Ω best predicted IEM in children (P < 0.001). A DCIIR1500 < 0.008 mmHg/Ω is associated with significant body weight loss > 10% within 6 months in children. (P < 0.001)., Conclusions: The calculation of DCIIR1500 may assist the automatic analysis of bolus transit in HRIM study to diagnose IEM in children. An DCIIR1500 < 0.009 mmHg/Ω may assist in the diagnosis of IEM in children, and DCIIR1500 < 0.008 mmHg/Ω correlated with significant body weight loss. The calculation of DCIIR may serve as possible parameters for HRIM.

Background: Gastric and esophageal dysmotility syndromes are some of the most common motility diagnoses, but little is known about their interrelationship., Aims: The aim of our study was to determine if a correlation exists between gastric and esophageal dysmotility syndromes., Methods: We reviewed the records of all patients who underwent both solid gastric emptying scintigraphy (GES) and high-resolution esophageal manometry (HRM) within a 2 year period, with both done between August 2012 and August 2017. All GESs were classified as either rapid, normal, or delayed. All HRMs were classified according to the Chicago Classification 3.0. Correlations were assessed using Fisher's exact test and multiple logistic regression., Results: In total, 482 patients met inclusion criteria. Of patients with a normal, delayed, and rapid GES, 53.1, 64.5, and 77.3% had an abnormal HRM, respectively (p < 0.05 vs. normal GES). Likewise, patients with an abnormal HRM were more likely to have an abnormal GES (54.9 vs. 41.8%, p = 0.005). Multiple logistic regression showed abnormal GES [odds ratio (OR) 2.14], age (OR 1.013), scleroderma (OR 6.29), and dysphagia (OR 2.63) were independent predictors of an abnormal HRM. Likewise, an abnormal HRM (OR 2.11), diabetes (OR 1.85), heart or lung transplantation (OR 2.61), and autonomic dysfunction (OR 2.37) were independent predictors of an abnormal GES., Conclusions: The correlation between an abnormal GES and HRM argues for common pathogenic mechanisms of these motility disorders, and possibly common future treatment options. Clinicians should have a high index of suspicion for another motility disorder if one is present.

Esophageal high-resolution manometry (HRM) has advanced the understanding of esophageal motor function and the ability to diagnose and manage disorders of esophageal motility. In this review, we describe the indications for and the technical performance of HRM. The Chicago classification of esophageal motor function, now in its third iteration, streamlines and standardizes the nomenclature and basic interpretation of HRM data depicted as Clouse topographic plots. In clinical practice, HRM is an important diagnostic test for patients with dysphagia as well as patients with suspected gastroesophageal reflux disease (GERD), particularly in those patients with a suboptimal symptomatic response to antisecretory therapy. HRM can support diagnoses such as achalasia, as well as provide evidence for behavioral disorders such as rumination syndrome or supragastric belching with the assistance of postprandial HRM with impedance. Further, the GERD classification of motor function introduces a three-part hierarchical evaluation of esophageal motor function in GERD, highlighting the value of assessment of esophageal contractile reserve through provocative maneuvers during HRM such as multiple rapid swallows.

Background: High-resolution manometry (HRM), which is breakthrough testing equipment to evaluate esophageal motor function, was developed in Europe and United State and has garnered attention. Moreover, multichannel intraluminal impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux including not only acid but also non-acid reflux. We examined the impact of the presence of reflux esophagitis (RE) on esophageal motor function before and after laparoscopic fundoplication., Materials and Methods: The subjects included 100 patients (male: 63 patients, mean age: 54.1 ± 15.8) among 145 patients who underwent laparoscopic fundoplication for GERD associated diseases during a 4-year period from October 2012 to September 2016, excluding 6 patients who underwent further surgery, 32 patients on whom HRM was not performed, 3 patients who had technical errors during testing, and 4 patients for whom the status of RE was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for the analysis, Mano View version 3.0 from the same company was used, after which data was calculated based on the Chicago Classification advocated by Pandolfino et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill Scientific. Inc. was used and automatic analysis was conducted by a computer. Postoperative assessments were conducted 3 months following surgery for all. Data was described in the median value and inter-quartile range, with a statistically significant difference defined as p < 0.05 by Chi square, Mann-Whitney, and Wilcoxon tests., Results: RE+ group (Los Angeles classification A:B:C:D = 7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE- group (62 vs. 50 years, p = 0.012) and a higher Body Mass Index value (24.0 vs. 22.5, p = 0.045); however, no differences were observed in terms of gender and duration of symptoms. In the preoperative findings on MII-pH, the RE+ group demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p = 0.005), while in the HRM findings, the RE- group demonstrated a significantly longer abdominal esophagus (0 vs. 0.4 cm, p = 0.049) and maintained esophageal body motor function (DCI: 1054 vs. 1407 mmHg s cm, p = 0.021, Intact peristalsis ratio: 90 vs. 100%, p = 0.037). As to the comparison of the treatment effect before and after laparoscopic fundoplication (Toupet fundoplication for all), significant improvements were observed in both groups in various parameters regarding reflux including acid reflux time, total number of liquid reflux episodes and total number of reflux episodes. Moreover, for both groups, the total length of the lower esophageal sphincter (LES) (RE+ group: 2.7 vs. 3.2 cm, p = 0.001, RE- group: 3.0 vs. 3.4 cm, p = 0.003) and the total length of the abdominal esophagus (RE+ group: 0 vs. 1.6 cm, p < 0.001, RE- group: 0 vs. 1.8 cm, p = 0.001) were significantly extended following surgery; however, no change was observed in DCI before and after surgery., Conclusions: Regardless of the presence of RE, cardiac function and LES function were improved following laparoscopic Toupet fundoplication, but no changes were observed in esophageal body motor function.

Background: High-resolution manometry (HRM) is used to assess esophageal motility diseases. Abnormalities in a number of HRM parameters have been reported in patients with dysphagia. However, it is unclear whether some of abnormal HRM parameters are predictive of dysphagia. The aim of this retrospective study was to investigate the roles of HRM parameters in predicting incomplete bolus clearance (IBC) in patients with dysphagia using high-resolution impedance manometry., Methods: A total of 644 wet swallows were reviewed and analyzed in 63 patients with symptoms of dysphagia or reflux who underwent a clinical high-resolution impedance manometry test. IBC was defined based on impedance measurement. The relationship of each of abnormal HRM parameters with IBC was analyzed and their roles in predicting IBC were determined., Results: Patients with symptoms of both dysphagia and reflux showed the highest IBC rate, and patients with symptoms of reflux had the lowest IBC rate. The IBC was more prevalent in the distal esophagus. Premature contractions and peristalsis with large breaks were associated with a higher IBC rate in the proximal esophagus (P<0.05); large breaks, ineffective peristalsis, and abnormalities of the esophageal gastric junction functions were associate with higher IBC rates in the distal esophagus (P<0.05). Abnormalities in a number of motility parameters were able to predict IBC with high specificities and/or high sensitivity, such as pan esophageal pressurization, ineffective peristalsis, and large breaks. Abnormal integrative relaxation pressure of the lower esophageal sphincter with concurrent pan esophageal pressurization, ineffective peristalsis, or large breaks is predictive of IBC with nearly 100% of specificity., Conclusions: Abnormalities in a number of HRM parameters are not only useful in diagnosing esophageal motility diseases, but also valuable in predicting IBC during swallowing.

Nocturnal gastroesophageal reflux has been associated with poor sleep quality. Normal physiological adaptations of the aerodigestive system to sleep prolong and intensify nocturnal reflux events. This occurrence leads to sleep disruption, as well as to esophageal, laryngeal, and laryngopharyngeal reflux. Controversy exists on whether OSA and nocturnal reflux are causally linked or merely associated because of shared risk factors. Advances in diagnostic technology have provided new insights into gastroesophageal reflux and the mechanisms of nocturnal reflux during sleep. This update reviews new data on causal links between sleep and gastroesophageal reflux disease., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Esophagogastric junction outflow obstruction (EGJOO) may be due to anatomical abnormalities, but it is unclear how to evaluate them after high-resolution manometry. We aimed to determine (i) clinical and high-resolution manometry parameters differentiating anatomical EGJOO from functional EGJOO, (ii) investigations chosen and yield for anatomical EGJOO, and (iii) clinical outcomes of functional EGJOO., Methods: Medical records of consecutive patients with symptomatic EGJOO from February 2012 to December 2015 were reviewed. EGJOO was defined as anatomical if investigations identified a macroscopic or microscopic pathology accounting for EGJOO., Results: Forty of 292 (13.7%) had EGJOO, of which 6/40 (15%) had anatomical EGJOO (two PPI-responsive esophageal eosinophilia, two infiltrating cancers, and two external compressions). Anatomical EGJOO was more likely to present with dysphagia (100% vs 29.4%, P = 0.001) and less likely with regurgitation (0% vs 41.2%, P = 0.05). Anatomical EGJOO had higher frequencies of premature contraction (50% vs 5.9%, P = 0.003) and lower mean values of distal latency (5.6 +/- 1.3 vs 6.7 +/- 1.2, P = 0.004). Computed tomography scans revealed 50% (3/6) of etiologies of anatomical EGJOO. Approximately, 73.5% (25/34) of patients with functional EGJOO had spontaneous resolution of their symptoms. One underwent pneumatic dilatation with symptom resolution while remaining eight with persistent symptoms were attributed to gastroesophageal reflux disease., Conclusion: Anatomical causes are present in 15% of EGJOO. Evaluation is warranted especially in patients presenting with dysphagia. Esophageal biopsies, barium swallows, computed tomography scans, and endoscopic ultrasound are complementary in EGJOO evaluation. In patients with non-obstructive symptoms and no anatomical etiologies, monitoring for spontaneous resolution is an option., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

BACKGROUND The esophagus can be affected by a variety of disorders that may be primary or secondary to another pathologic process, but the resulting symptoms are usually not pathognomonic for a specific problem, making diagnosis and further management somewhat challenging. High resolution impedance manometry (HRiM) has established itself as a valuable tool in evaluating esophageal motility disorder. HRiM is superior in comparison with conventional water perfused manometric recordings in delineating and tracking the movement of functionally defined contractile elements of the esophagus and its sphincters, and in distinguishing the luminal pressurization of spastic esophageal contraction from a trapped bolus. Making these distinctions can help to identify achalasia, distal esophageal spasm, functional obstruction, and subtypes according to the latest Chicago Classification of Esophageal Motility Disorders version 3.0. CASE REPORT We report a case series of 4 patients that presented with dysphagia; and with the ancillary help of the HRiM, we are able to diagnose esophageal motility disorder and evaluate its pathogenetic mechanism. This approach aids in tailoring each management individually and avoiding disastrous mismanagement. CONCLUSIONS From the series of case reports, we believe that HRiM has an important role to play in deciding appropriate management for patients presenting with esophageal motility disorders, and HRiM should be performed before deciding on management.

Purpose of Review: This review addresses the similarities and differences between the spastic esophageal disorders, including jackhammer esophagus, distal esophageal spasm (DES), and type III (spastic) achalasia. The pathophysiology, diagnosis, and treatment of each separate disorder are discussed herein, with an emphasis on overlapping and discordant features., Recent Findings: The Chicago Classification is a hierarchical organizational scheme for esophageal motility disorders, currently in its third iteration, with direct impact on the definitions of these three disorders. Complementary diagnostic tools such as impedance planimetry and novel manometric parameters continue to evolve. The suite of potential treatments for these disorders is also expanding, with progressive interest in the role of peroral endoscopic myotomy alongside established pharmacologic and mechanical interventions. Although jackhammer esophagus, distal esophageal spasm, and type III achalasia frequently overlap in terms of their clinical presentation and available management approaches, the divergences in their respective diagnostic criteria suggest that additional study may reveal additional mechanistic distinctions that lead in turn to further refinements in therapeutic decision-making.

Purpose: Pulmonary aspiration of gastric refluxate is one of the indications for anti-reflux surgery. Effectiveness of surgery in preventing pulmonary aspiration post-operatively has not been previously tested. The aim of this project is to assess effectiveness of anti-reflux surgery on preventing pulmonary aspiration of gastric refluxate., Methods: Retrospective analysis of prospectively populated database of patients with confirmed aspiration of gastric refluxate on scintigraphy. Patients that have undergone anti-reflux surgery between 01/01/2014 and 31/12/2015 and had scintigraphy post-operatively were included. Objective data such as resolution of aspiration, degree of proximal aero-digestive contamination, surgical complications and oesophageal dysmotility as well as patient quality of life data were analysed., Results: Inclusion criteria were satisfied by 39 patients (11 male and 28 female). Pulmonary aspiration was prevented in 24 out of 39 patients (61.5%) post-operatively. Significant reduction of isotope contamination of upper oesophagus supine and upright (p = 0.002) and pharynx supine and upright (p = 0.027) was confirmed on scintigraphy post-operatively. Severe oesophageal dysmotility was strongly associated with continued aspiration post-operatively OR 15.3 (95% CI 2.459-95.194; p = 0.02). Majority (24/31, 77%) of patients were satisfied or very satisfied with surgery, whilst 7/31 (23%) were dissatisfied. Pre-operative GIQLI scores were low (mean 89.77, SD 20.5), modest improvements at 6 months (mean 98.4, SD 21.97) and deterioration at 12 months (mean 88.41, SD 28.07) were not significant (p = 0.07)., Conclusion: Surgery is partially effective in reversing pulmonary aspiration of gastric refluxate on short-term follow-up. Severe oesophageal dysmotility is a predictor of inferior control of aspiration with surgery.

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

Purpose of Review: Bariatric surgery is the best therapeutic approach to patients with morbid obesity, but there is mounting evidence that it is associated with esophageal dysfunctions, including gastroesophageal reflux disease (GERD) and motor disorders. In the present review, we summarize the existing information on the complex link between bariatric surgery and esophageal disorders., Recent Findings: Although high-quality studies on these effects are lacking, because of evident methodological flaws and retrospective nature, the review of published investigations show that pure restrictive procedures, such as laparoscopic adjustable gastric banding (LAPG) and laparoscopic sleeve gastrectomy (LSG), are associated with de novo development or worsening of GERD. Moreover, LAGB is the procedure with the greatest frequency of esophageal motor disorders, including impairment of LES relaxation and ineffective esophageal peristalsis associated with esophageal dilation. LSG seems to be less associated with esophageal dysmotility, although evidence derived from studies with objective measurements of esophageal dysfunction is limited. Finally, RYGB seems to be the best procedure for improvement of GERD symptoms and preservation of esophageal function., Summary: Overall, the restrictive-malabsorptive approach represented by RYGB must be preferred to pure restrictive operations in order to avoid the negative consequences of bariatric surgery on esophageal functions.

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

Background: Proximal reflux and incomplete transit of boluses swallowed are risk factors for obstructive chronic lung allograft dysfunction (o-CLAD) post-lung transplantation (LTx). Likewise, so is esophagogastric junction outflow obstruction (EGJOO), but not hypo-contractility, when diagnosed using Chicago Classification (CC) v3.0. Given, peristaltic breaks as defined using CCv2.0 can prolong esophageal clearance, both swallowed and refluxed, but which are deemed within normality using CCv3.0, our aim was to determine whether hypo-contractility as diagnosed using CCv2.0, influences the association with reflux, along with its clearance, and that of boluses swallowed, and thus its association to allograft failure., Methods: Esophageal motility abnormalities were classified using CC v3.0 and v2.0 in 50 patients post-LTx (26 female, 55 years (20-73 years))., Results: Reclassification from CCv3.0 to v2.0 resulted in 7 patients with normal motility being reclassified to hypo-contractility (n = 6) or hyper-contractility (n = 1); 2 patients with hypo-contractility to normal motility; and 3 patients with EGJOO without hyper-contractility to EGJOO with hyper-contractility. The main consequence of reclassification was that the sub-group exhibiting hypo-contractility became more likely to have abnormal numbers of reflux events (P = .025) and incomplete bolus transit (P = .002) than those with normal motility using CCv2.0; associations not seen using CCv3.0. Irrespective of CC used only patients with EGJOO appeared more likely to develop o-CLAD than those with normal motility (P < .05)., Conclusions: Irrespective of CC used, o-CLAD appears linked to EGJOO. CCv2.0 however, accentuates the increased reflux and incomplete bolus transit associated with hypo-contractility post-LTx, suggesting that these motor abnormalities, though considered minor, may be of importance after lung transplant., (© 2018 John Wiley & Sons Ltd.)

Background: Esophago-gastric junction (EGJ) outflow obstruction is of unclear significance. Rapid drink challenge (RDC) test is easy to perform during esophageal high resolution manometry. We aimed to assess the yield of RDC test in patients with EGJ outflow obstruction., Methods: Manometry studies of patients with EGJ outflow obstruction according to the Chicago Classification v3.0 were retrospectively reviewed. Pan-esophageal pressurization (PEP), esophageal shortening, and pressure gradient across the EGJ were analyzed during RDC test (200-mL free drinking in sitting position) and compared according to the causes of EGJ outflow obstruction determined by charts review., Key Results: Seventy-five patients (29 males, mean age 62 years) were included. Causes of EGJ outflow obstruction were previous esophago-gastric surgery (40%), incomplete form of achalasia (7%), mediastinal neoplasia (7%), other associated conditions (21%), and undetermined (25%). Rapid drink challenge test was successfully performed in 70 patients and associated with PEP and shortening in 41% and 13%, respectively. The causes of EGJ outflow obstruction were similarly distributed in patients with and without PEP during RDC test. Esophageal shortening tended to be more likely in patients with definitive findings of obstruction (achalasia, previous surgery, neoplasia) than in the others. Dysphagia was more severe in patients with PEP and/or shortening during RDC test compared to those without., Conclusions & Inferences: Pan-esophageal pressurization and esophageal shortening were associated with symptoms severity but did not predict the cause of this disorder. Further prospective studies are necessary to determine if RDC test could help to select patients who might benefit from treatment., (© 2018 John Wiley & Sons Ltd.)

Background: High-resolution esophageal manometry (HREM) has become a leading tool in the assessment of esophageal motor disorders, replacing conventional manometry. However, there is limited data about the contribution of HREM as compared with conventional manometry to the assessment of esophageal motor disorders in patients with non-cardiac chest pain (NCCP). The aim of the study was to compare the distribution of esophageal motor disorders in patients with NCCP using HREM as compared with conventional manometry and to determine if HREM improved diagnosis of these disorders., Methods: In this study, we included 300 consecutive patients with NCCP who underwent either HREM or conventional manometry over a period of 10 years. A total of 150 patients had conventional manometry and the other 150 patients HREM. The Chicago 3.0 classification and the Castell and Spechler classification were used to determine the esophageal motor disorder of NCCP patients undergoing HREM and conventional manometry, respectively., Key Results: In both HREM and the conventional manometry groups, normal esophageal motility was the most frequent finding (47% and 36%; respectively, P = .054). Hypotensive lower esophageal sphincter was the most common motility disorder identified by conventional manometry (27.3%), while ineffective esophageal motility was the most common esophageal motor disorder identified by HREM (25.3%)., Conclusions & Inferences: There is a discrepancy in the type of esophageal motor disorders identified by HREM as compared with conventional manometry in NCCP patients. Hypotensive motility disorders are the most commonly diagnosed by both manometric techniques., (© 2017 John Wiley & Sons Ltd.)

Background: Esophageal pressure topography (EPT) diagnosis of ineffective esophageal motility (IEM) can be non-specific with unclear clinical significance., Aims: To determine whether peristaltic vigor or lower esophageal sphincter (LES) integrity is associated with poor clearance and acid reflux in IEM., Methods: Bolus clearance on high-resolution impedance manometry (HRIM) and available reflux studies in patients with IEM were retrospectively reviewed. Bolus clearance was assessed using both line tracing and colored contour methods on HRIM. EPT parameters, bolus clearance, and acid reflux variables were explored., Key Results: Eighty-eight patients with IEM were included. Bolus clearance occurred in 71% of all swallows, and 55.7% of patients had complete bolus transit (CBT, bolus clearance in ≥80% of swallows). Bolus clearance was impaired in swallows with distal contractile integral (DCI) <100 mmHg•cm•s compared to DCI 100-450 (0.43 vs 0.79, P < .0001). A cutoff at DCI 100 mmHg•cm•s was associated with clearance with an accuracy of 76% compared to 49% at DCI 450 (P = .0001 for both). A median DCI <100 was associated with a higher Eckardt score (9 vs 3, P = .03), and on reflux testing available in 47 patients, with abnormal acid exposure time (P = .002). Peristaltic reserve (PR) defined as (DCI of multiple rapid swallow/median DCI of wet swallows), integrated relaxation pressure, and resting lower esophageal sphincter pressure were not associated with clearance or acid exposure., Conclusions & Inferences: Failed peristalsis, as defined by DCI <100 mmHg•cm•s, is associated with impaired bolus clearance and more severe dysphagia in IEM, and likely abnormal acid exposure., (© 2018 John Wiley & Sons Ltd.)

Electric stimulation (ES) could induce contraction of intestinal smooth muscle. The aim of this study was to analyze the effects of ES on esophageal motility and the underlying mechanism in vivo. Twenty-eight rabbits were equipped with a pair of subserosa electrodes (connected to an electrical stimulator) in the lower segment of the esophagus. The ES signal consisted of bipolar rectangular pulse trains, lasting for 3 s, with different amplitudes (1 mA, 3 mA, 5 mA and 10 mA), and frequencies (10 Hz, 20 Hz and 50 Hz). The amplitude of the contraction was recognized by high-resolution manometry. The effect of ES was tested under anesthesia and following administration of atropine, phentolamine or L-NAME. ES induced esophageal contraction at the stimulated site. A statistically significant increase in esophageal pressure was observed when the stimulation amplitude was above 3 mA. The increase in esophageal pressure was associated with the amplitude of stimulus as well as the frequency. During stimulation, atropine, phentolamine and L-NAME had no effect on the increase of esophageal pressure induced by ES. These findings implied that ES induced esophageal contraction were not mediated via the NANC, adrenergic or cholinergic pathway. The amplitude of esophageal contraction was current and frequency dependent.

Background: We hypothesized that symptoms in Jackhammer esophagus (JH) are associated with an imbalance between the prepeak and postpeak phases of contraction. Thus, we developed a method to distinguish the contractile integral components of prepeak and postpeak phase contractile activity to determine the contribution of each phase and their association with dysphagia., Methods: Patients diagnosed with JH were enrolled and compared to controls. The first five intact swallows during manometry were analyzed. A single swallow was divided into a prepeak and postpeak phase. The contractile integral of each phase and its corresponding time-controlled integral were computed. All metrics were compared between controls and JH patients subcategorized by the impaction dysphagia question (IDQ) score with cut-off of 6., Key Results: Thirty eight JH patients and 71 controls were included. Twelve JH patients had IDQ ≤ 6 and 26 with IDQ > 6. JH patients had higher contractile integral in both phases, and a higher ratio between postpeak to prepeak contractile integral independent of duration. Similarly, JH patients with an IDQ > 6 had higher contractile metrics than those with IDQ ≤ 6. There was a correlation between the IDQ score and the ratio within the postpeak to prepeak contractile integral (r = .375)., Conclusions: Abnormalities in contractile integral of the postpeak phase are more significant in JH with higher dysphagia scores Although the total postpeak contractile integral was higher in symptomatic patients, this was associated with longer duration of postpeak activity suggesting that dysphagia patients with JH have a defect in the postpeak phase of peristalsis., (© 2017 John Wiley & Sons Ltd.)

Longitudinal esophageal body shortening with swallow-induced peristalsis has been reported in healthy individuals. Esophageal shortening is immediately followed by esophageal re-elongation, and the lower esophageal sphincter (LES) returns to the baseline position. High-resolution manometry (HRM) allows for objective assessment of extent of shortening and duration of shortening. In patients without hiatal hernia at rest, swallow-induced esophageal shortening can lead to transient hiatal hernia (tHH) which at times may persist after the completion of swallow. This manometric finding has not been investigated in the literature, but a question arises whether this swallow-induced transient herniation can effect on the likelihood of gastroesophageal reflux. This study aims to assess the relationship between gastroesophageal reflux and the subtypes of swallow-induced esophageal shortening, i.e. tHH and non-tHH, in patients without hiatal hernia at rest. After Institutional Review Board (IRB) approval, we queried a prospectively maintained database to identify patients who underwent HRM evaluation and 24-hour pH study between January to December 2015. Patients with type-I esophagogastric junction (EGJ) morphology (i.e. no hiatal hernia) according to the Chicago classification v3.0 were included. The patterns of the esophageal shortening with swallows were divided into two subtypes, i.e. tHH and non-tHH. tHH was defined as an EGJ double high-pressure zones (≥1 cm) at the second inspiration after the termination of swallow-induced esophageal body contraction. The number of episodes of tHH was counted per 10 swallows and tHH size was measured for each patient. In total, 41 patients with EGJ morphology Type-I met the inclusion criteria. The mean age was 47.2 years, 35 patients (85.4%) were women, and the mean body mass index was 33.9 kg/m2. The mean number of tHH episodes was 3 out of 10 swallows; mean maximal tHH size was 1.3 cm. Patients who had tHH in ≥3 out of 10 swallows (n = 16; 39.0%) were more likely to have abnormal DeMeester scores than patients with <3 swallows (56% vs. 28%; P = 0.070). Patients with maximal tHH ≥2 cm in at least 1 swallow (n = 17; 41.5%) were more likely to experience pathological reflux than patients with maximal tHH <2 cm (59% vs. 25%; P = 0.029). In conclusion, we showed that, in a subset of patients with Type-I EGJ morphology, swallowing induced transient EGJ double high-pressure zones (≥1 cm) after peristalsis. We have named this new manometric finding the swallow-induced tHH. A high prevalence of pathological reflux disease was observed in patients with maximal tHH ≥2 cm. The degree of swallow-induced tHH could be an early indicator of lower esophageal sphincter dysfunction in patients without manometric hiatal hernia.

This study aims to investigate pre-clinical esophageal involvement in systemic sclerosis (SSc) by high-resolution impedance manometry (HRiM), its associations with disease features including lung involvement, and its predictivity of esophageal symptoms overtime. Charts of 45 asymptomatic (no heartburn/regurgitation/dysphagia) SSc patients (96% females; mean age 46 years) with at least one follow-up (FU) visit and complete clinical, serological, functional, and radiological assessment, including high-resolution computed tomography (HRCT) of the chest and lung function tests, that had undergone esophageal HRiM were retrospectively evaluated. Esophagogastric junction-contractile integral (EGJ-CI) and esophageal body motility, as evaluated by mean distal contractile integral (DCI), were assessed. SSc patients had a normal esophageal motility in 7/45 cases, a defective EGJ-CI in 28, an ineffective esophageal motility (IEM) in 17, and aperistalsis in 12. Defective EGJ-CI was associated with IEM/aperistalsis in 20 cases, while 9 patients had isolated IEM. Defective EGJ-CI and/or IEM/aperistalsis were associated with a diffusing lung capacity for CO < 80% of predicted value (all p < 0.05), while defective EGJ-CI was also associated with interstitial lung disease on HRCT (p = 0.03). Prevalence of any HRiM abnormality was higher in anti-centromere antibody negative patients (all p < 0.05). IEM/aperistalsis independently increased the risk of esophageal symptoms by 2.3-fold (95% CI 1.1-5.7) and was associated with their higher cumulative incidence with respect to patients with other HRiM patterns at FU (χ 2  = 4.63; p = 0.03). SSc patients asymptomatic for esophageal involvement can have HRiM abnormalities in up to 84% of cases. A baseline-impaired motility is a risk factor for symptomatic esophageal disease.

Purpose: Cough Hypersensitivity Syndrome is the urge to cough following minimal stimulation, but its mechanism and method of provocation remain unexplained. 121 patients (44 males, 77 females; age range 18-81 years) were evaluated., Procedures: High resolution manometry was performed on consecutive patients presenting with unexplained respiratory symptoms (Respiratory Group 61). Data were compared with matched controls, i.e. dyspepsia without respiratory symptoms (Dyspepsia Group 60)., Main Findings: Results showed increased inspiratory gastro-oesophageal pressure gradient due to significantly lower intra-oesophageal pressure on inspiration (p = 0.001), and reduced oesophageal motility in the Respiratory Group., Conclusions: Further research in respiratory conditions characterised by decreased intrathoracic pressure during inspiration is needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testing as part of the wait-listing process but guidelines for testing in this population are lacking. The aim of this study is to describe whether symptoms of gastroesophageal reflux correlate with abnormal results on pH-metry and high-resolution manometry and can be used to identify those who require testing. We performed a retrospective cohort study of 226 lung transplant candidates referred for high-resolution manometry and pH-metry over a 12-month period in 2015. Demographic data, results of a standard symptom questionnaire and details of esophageal function testing were obtained. Associations between the presence of symptoms and test results were analyzed using Fisher's exact tests and multivariable logistic regression. The most common lung disease diagnosis was interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%) patients and the presence of symptoms was significantly associated with an abnormal study (p < 0.01). Dysmotility was found in 98 (43%) patients, with major peristaltic or esophageal outflow disorders in 45 (20%) patients. Symptoms were not correlated with findings on esophageal high-resolution manometry. Fifteen of 25 (60%) asymptomatic patients had an abnormal manometry or pH-metry. These results demonstrate that in patients with advanced lung disease, symptoms of gastroesophageal reflux increase the likelihood of elevated acid exposure on pH-metry but were not associated with dysmotility. Given the proportion of asymptomatic patients with abnormal studies and associated post-transplant risks, a practice of universal high-resolution manometry and pH-metry testing in this population is justifiable.

Background: Dysphagia and non-cardiac chest pain are common symptoms associated with a novel hypercontractile disorder, namely Jackhammer esophagus (JE). The aim of this study was to explore these symptoms in patients with JE and to elucidate associations with disease defining metrics, crucial for subsequent therapies., Methods: All consecutive patients, who were referred between January 2014 and December 2016 and fulfilled the criteria for JE were included in this study. Exclusion criteria were opioid intake, previous gastrointestinal surgery, mechanical esophageal obstruction and diseases explaining their symptoms., Key Results: Of 2205 examined subjects, thirty patients (females: n = 17, 56.7%) with a median age of 58 (51.6-64.9) years were finally enrolled. Dysphagia was noted in 53.3% (n = 16), whereas non-cardiac chest pain was specified within 40% (n = 12) with symptom duration of up to 10 years. Perception of dysphagia (P = .03) and presence of both symptoms (P = .008) increased to the end of the study period. Dysphagia was significantly associated with distal contractile integral (DCI) scores of all (P = .023), hypercontractile (P = .011) and maximum DCI swallows (P = .008). Symptoms duration influenced hypercontractile DCI scores (P = .015, r = .438) and significantly correlated with the intensity of perceived dysphagia (P = .01, r = .585). Presence of non-cardiac chest pain was not associated with any of these metrics., Conclusions & Interferences: The DCI mediates dysphagia in patients with JE. Duration of symptoms affected hypercontractile DCI scores and aggravated perception of dysphagia indicating a progressive character of disease., (© 2017 John Wiley & Sons Ltd.)

High-resolution manometry (HRM) and peroral endoscopic myotomy (POEM) have contributed significantly to the field of esophageal motility disorders in recent years. The development of HRM has categorized various esophageal motility disorders with a focus on a diverse range of manometric anomalies. Additionally, the Chicago classification criteria is widely used for manometric diagnosis. Moreover, POEM was introduced as a minimally invasive radical therapy for achalasia and shows promise for other spastic esophageal motility disorders as well. POEM has also enabled a transluminal endoscopic approach for determining the histology of the esophageal muscle layer, which is expected to assist in elucidating the etiology of disorders associated with esophageal motility. The purpose of this review is to update the diagnosis, pathology, and treatment of esophageal motility disorders, with a focus on the recent advances in this field.

Background: Multiple rapid swallows (MRS) is a provocative test for assessment of contraction reserve, however reproducibility on repetitive MRS is incompletely understood. Our aim was to determine the optimal number of MRS sequences for consistent assessment of contraction reserve., Methods: One hundred and fifty-nine consecutive patients (79 IEM and 80 normal motility) who underwent high-resolution manometers were enrolled. Ten single swallows (SS) and 10 MRS were performed. Gold standard for evaluation of the contraction reserve was the ratio between the mean DCI of 10 MRS and the mean DCI of 10 SS (MRS/SS DCI ratio). Rates of false negatives and false positives were calculated for increasing numbers of MRS sequences, using either mean DCI or the MRS with the highest DCI., Key Results: According to the gold standard, 50 IEM and 50 normal motility patients had contraction reserve. With progressively increasing numbers of MRS sequences, contraction reserve was detected using mean MRS DCI within three and four MRS sequences in IEM and normal motility respectively, whereas two and three MRS sequences were needed using the MRS sequence with the highest DCI. False positives were much higher with highest DCI method compared with mean DCI, (22% vs 9% respectively in IEM; 24% vs 9% in normal motility) when three MRS sequences were considered., Conclusions & Inferences: At least three MRS are needed to reliably assess contraction reserve. The mean DCI of the three MRS sequences is the best variable to utilize as evidence of contraction reserve., (© 2017 John Wiley & Sons Ltd.)

Introduction: Swallowing difficulties, the pathophysiology behind which is incompletely understood, have been reported in 47-83% of goiter patients referred for thyroidectomy. We aimed at examining the influence of thyroid surgery on swallowing symptoms and esophageal motility., Methods: Thirty-three patients with benign nodular goiter undergoing thyroid surgery were included. All completed high-resolution esophageal manometry examinations and the goiter symptom scale score, assessed by the thyroid-specific patient-reported outcome measure. The evaluations were performed before and 6 months after surgery., Results: Before surgery, the goiter symptom score was median 39 points (range 2-61), which improved to median five points (range 1-52) after surgery (p < 0.001). The motility parameters were within the limits of normal swallowing physiology, both before and after surgery. Only the upper esophageal sphincter (UES) pressure increased significantly from 70.6 ± 27.7 to 87.7 ± 43.2 mmHg after surgery (p = 0.04). Using regression analyses, there was no significant correlation between change in goiter symptoms and weight of the removed goiter, motility parameters, or motility disturbances. However, patients undergoing total thyroidectomy experienced a larger reduction in pressure in the area of the UES and former thyroid gland after surgery in comparison with patients undergoing less extensive surgery., Conclusions: Goiter symptoms improved significantly after thyroidectomy, but without correlation to esophageal motility disturbances. This information is essential when interpreting dysphagia in patients with nodular goiter, and when balancing patients' expectations to surgical goiter therapy., Registration Number: NCT03100357 ( www.clinicaltrials.org ).

High resolution manometry (HRM) is the gold standard to diagnose esophageal motility disorders but has some limitations. The inclusion of provocative tests might enhance the diagnostic yield of HRM. These tests are easy to perform and to add to the regular manometry protocol. Multiple rapid swallows (MRS; 5 2-mL swallows) is useful to assess the contractile reserve and deglutitive inhibition. The optimal number of MRS to perform might be 3 as suggested by Mauro et al. in this issue of Neurogastroenterology & Motility. The absence of contractile reserve might be associated with gastro-esophageal reflux disease and with an increased risk of post fundoplication dysphagia. Single viscous and solid swallows might enhance the detection of esophageal motility disorders but are not significantly associated with symptom occurrence. Test meal has the advantage to represent a real-life scenario and is promising to depict significant motility findings responsible for esophageal symptoms. Post-prandial recording might also be of interest to diagnose rumination and belching disorders. The best indication of rapid drink challenge test (free drinking of 200 mL) is currently the diagnosis of esophago-gastric junction obstruction. Finally, abdominal compression might be an option to evaluate response of esophageal peristalsis in a context of outflow resistance as proposed by Brink et al. in this issue. These provocative maneuvers appear to provide a complementary role in the evaluation of esophageal motility but require prospective studies to determine the validity of the findings and whether they will lead to changes in clinical practice., (© 2018 John Wiley & Sons Ltd.)

Background: Increased esophagogastric junction (EGJ) distensibility is thought to contribute to gastroesophageal reflux disease (GERD). Using the functional lumen imaging probe (FLIP), we aimed to assess the esophageal response to distension among patients undergoing esophageal pH monitoring., Methods: 25 patients (ages 22-73; 13 females) who underwent ambulatory wireless esophageal pH testing while off proton-pump inhibitors were evaluated with FLIP during sedated upper endoscopy. Esophageal reflux was quantified by total percent acid exposure time (AET; <6% was considered normal). FLIP studies were analyzed using a customized program generate FLIP topography plots to identify esophageal contractility patterns and to calculate the EGJ-distensibility index (DI). Reflux symptoms were assessed with the GERDQ. Values reflect median (interquartile range)., Results: Among all patients, the AET was 7.2% (3.7-11.1) and EGJ-DI was 4.2 (2.5-7.6) mm 2 /mm Hg. Repetitive antegrade contractions (RACs) were induced in 19/25 (76%) of patients; AET was lower among patients with (6.1%, 3-7.8) than without (14.9, 8.5-22.3) RACs (P = .009). Correlation was weak and insignificant between AET and EGJ-DI, GERDQ and AET, and GERDQ and EGJ-DI. Patients with abnormal AET (n = 16) and normal AET (n = 9) had similar EGJ-DI, 4.6 mm 2 /mm Hg (2.9-9.2) vs 3.2 (2.2-5.1), P = .207 and GERDQ, P = .138., Conclusions: Abnormal esophageal acid exposure was associated with an impaired contractile response to volume distention of the esophagus. This supports that acid exposure is dependent on acid clearance mechanisms., (© 2017 John Wiley & Sons Ltd.)

Background: Upper gastrointestinal symptoms in children are common and motility disorders are considered in the differential diagnosis. High resolution esophageal manometry (HRM) has revolutionized the study of esophageal physiology, and the addition of impedance has provided new insights into esophageal function. Antroduodenal motility has provided insight into gastric and small bowel function., Purpose: This review highlights some of the recent advances in pediatric esophageal and antroduodenal motility testing including indications, preparation, performance, and interpretation of the tests. This update is the second part of a two part series on manometry studies in children (first part was on anorectal and colonic manometry [Neurogastroenterol Motil. 2016;29:e12944]), and has been endorsed by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the American Neurogastroenterology and Motility Society (ANMS)., (© 2017 John Wiley & Sons Ltd.)

Background: Chronic intestinal idiopathic pseudo-obstruction (idiopathic CIPO) is a rare heterogeneous condition for which the different phenotypes are difficult to be established. Oesophageal motility has shown to be impaired in patients with idiopathic CIPO at traditional manometry, whereas no studies have assessed it by high resolution manometry (HRM)., Aims: To evaluate oesophageal motility by HRM in patients with idiopathic CIPO., Methods: 14 patients with idiopathic CIPO underwent oesophageal HRM. Multiple rapid swallows (MRS) were performed in order to evaluate contraction reserve. The Chicago Classification 3.0 was used to classify the oesophageal motility disorders., Results: One idiopathic CIPO patient had type-II achalasia, one aperistalsis and 12 had minor disorder of peristalsis (11 ineffective oesophageal motility and one fragmented peristalsis). These minor disorders were not significantly different from those of 50 other consecutive patients who underwent HRM for dysphagia or GERD and received the diagnosis of ineffective oesophageal motility. Three of the 12 idiopathic CIPO patients with minor disorder of peristalsis had no contraction reserve after MRS., Conclusions: HRM is able to identify different grades of oesophageal motor impairment in patients with idiopathic CIPO. Presence of major oesophageal dismotility or absent contraction reserve suggest a more severe and widespread motor disorder., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives Dysphagia is common in total laryngectomees, with some symptoms suggesting esophageal dysmotility. Tracheoesophageal (TE) phonation requires effective esophagopharyngeal air passage. Hence, esophageal dysmotility may affect deglutition or TE phonation. This study aimed to determine (1) the characteristics of esophageal dysmotility in laryngectomees, (2) whether clinical history is sensitive in detecting esophageal dysmotility, and (3) the relationship between esophageal dysmotility and TE prosthesis dysfunction. Study Design Multidisciplinary cross-sectional study. Setting Tertiary academic hospital. Subjects and Methods For 31 participants undergone total laryngectomy 1 to 12 years prior, clinical histories were taken by a gastroenterologist and a speech pathologist experienced in managing dysphagia. Esophageal high-resolution manometry was performed and analyzed using Chicago Classification v3.0. Results Interpretable manometric studies were obtained in 23 (1 normal manometry). Esophageal dysmotility patterns included achalasia, esophagogastric junction outflow obstruction, diffuse esophageal spasm, and other major (30%) and minor (50%) peristaltic disorders. The sensitivity of predicting any esophageal dysmotility was 28%, but it is noteworthy that patients with achalasia and diffuse esophageal spasm (DES) were predicted. Two of 4 participants with TE puncture leakage had poor esophageal clearance. Of 20 TE speakers, 12 had voice problems, no correlation between poor voice, and any dysmotility pattern. Conclusions Peristaltic and lower esophageal sphincter dysfunction are common in laryngectomees. Clinical history, while not predictive of minor motor abnormalities, predicted correctly cases with treatable spastic motor disorders. Dysmotility was not associated with poor phonation, although TE puncture leakage might be linked to poor esophageal clearance. Esophageal dysmotility should be considered in the laryngectomees with persisting dysphagia or leaking TE puncture.

Background and Aim: Although basic research has shown that certain cytokines affect gastrointestinal motility, the clinical evidence is lacking. The objective of this study was to explore the association between mucosally expressed cytokines and the esophageal motility function in humans., Methods: We enrolled a total of 57 patients with suspected esophageal motility disorders (EMDs) who underwent high-resolution manometry., Results: The diagnoses of the patients were as follows: normal esophageal motility (n = 25), ineffective esophageal motility (n = 5), esophagogastric junction outflow obstruction (EGJOO; n = 10), distal esophageal spasm (n = 5), achalasia (n = 10), absent contractility (n = 1), and jackhammer esophagus (n = 1). The expression of tumor necrosis factor (TNF)-α in the esophagogastric junction (EGJ) was significantly higher in EGJOO (14.6, 14.0-15.8, n = 10) than in normal esophageal motility (13.3, 12.8-14.1, n = 25); however, there was no difference in the expression of TNF-α between achalasia (13.4, 13.0-14.1, n = 10) and normal esophageal motility (13.3, 12.8-14.1, n = 25). EGJOO was discriminated from achalasia/normal by a linear discriminant analysis (AUC = 0.917). A multivariable regression analysis revealed that interleukin (IL)-13 and IL-23A were predictive of the distal contractile integral, whereas TNF-α and IL-6 were predictive of the basal EGJ pressure., Conclusions: The esophageal motility was associated with mucosally expressed cytokines in humans; these cytokines could be useful targets for the diagnosis and treatment of EMDs., (© 2018 S. Karger AG, Basel.)

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.)

To determine trends in the diagnostic distribution of esophageal motility disorders after implementation of the Chicago Classification Version 3.0 (CC V3.0) for interpretation of high-resolution manometry (HRM) studies compared to non-Chicago Classification criteria. Retrospective trends analysis of patients with an HRM study conducted at a single center from January 1, 2013 to September 30, 2015. The implementation of the CC V3.0 for manometry interpretation occurred in September 2014. Patient charts were manually reviewed for data collection including demographics and HRM diagnoses. The prevalence and relative risks (RR) of CC V3.0 diagnostic categories (i.e. normal, indeterminate, achalasia, and EGJ outflow obstruction [EJGOO], and major and minor motility disorders) were calculated before and after CC V3.0 implementation. Four hundred sixty-five HRM studies were included in the study including 268 before and 179 after CC V3.0 implementation. The mean ± SD age was 54 ± 15.4 years and 59.8% were female (n = 278). The percentage with indeterminate diagnosis decreased from 35.3% before CC V3.0 implementation to 16.8% after implementation (adjusted RR 0.5, 95%CI 0.30-0.70, p < 0.001). The percentage with a major motility disorders decreased from 13.9% to 7.3% (adjusted RR 0.5, 95%CI 0.2-1.0, p < 0.001). The percentage with EJGOO and minor diagnoses increased from 1.4% to 14.5% and 11.9% to 22.9%, respectively. The percentage with achalasia and normal diagnosis did not change over the study period. Implementation of CCV3.0 was associated with changes in the distribution of esophageal motility diagnoses in clinical practice. The percentage of indeterminate and major diagnosis decreased and EGJOO and minor diagnoses increased. The decrease in the number of indeterminate studies suggests that the CC V3.0 may clarify the criteria for the interpreting physician. The increase in studies with a diagnosis of EGJ outflow obstruction may reflect the heterogeneity of disorders with clinically relevant outflow obstruction., (Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The classic manometric findings in systemic sclerosis are aperistalsis of the esophageal body with hypotensive lower esophageal sphincter. These changes contribute to gastroesophageal reflux disease in these patients. With widespread use of high-resolution esophageal manometry, diverse abnormalities are seen. The aim of this study is to characterize esophageal dysmotility in patients with systemic sclerosis undergoing high-resolution esophageal manometry and compare demographic features and diagnostic test results among patients with varying degrees of esophageal dysmotility. Patients with systemic sclerosis who underwent high-resolution esophageal manometry between January 2008 and October 2014 at our institution were identified. High-resolution esophageal manometry studies were reinterpreted using the Chicago Classification, v3.0 criteria. We also reviewed the patient charts for demographic data, indications for manometry, esophagogastroduodenoscopy findings, pH studies, medication use, and autoantibody panel. The cohort consisted of 122 patients with a mean age of 53.3 ± 15.3 years. High-resolution esophageal manometry was normal in 23, showed ineffective esophageal motility in 22, absent contractility in 73, and one case each of type II achalasia, esophagogastric junction outflow obstruction, hypercontractile esophagus, and distal esophageal spasm. Patients with absent contractility were younger and more likely to have erosive esophagitis, hiatal hernia, and esophageal strictures than patients with ineffective esophageal motility or normal manometry. There were no statistically significant differences in the groups based on autoantibodies or indications for manometry. Diverse esophageal motility abnormalities were noted in systemic sclerosis with ineffective esophageal motility or absent contractility observed in over three-fourth of the patients. Patients with absent contractility were younger and had more severe reflux. The severity of gastroesophageal reflux disease related endoscopic findings correlated with the degree of esophageal dysmotility on high-resolution esophageal manometry., (© 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.)