Search

Background: Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index are novel impedance-based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy-negative GERD partially responsive to PPI therapy., Methods: All patients underwent off-PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII-pH), and bile reflux monitoring. Abnormal esophageal acid exposure time (AET) was required for inclusion. Symptom intensity (using 10-cm visual analog scales), and conventional and novel MII-pH metrics were compared between patients with and without abnormal bile reflux., Key Results: We evaluated 42 NERD patients (29 males, mean age: 53.4 ± 13. years), mean AET 6.1 ± 2%, of which 21 had abnormal bile reflux (Group A, 10.2 ± 4.9%), and 21 had normal bile reflux (Group B, 0.4 ± 0.1%, P < .05 compared with Group A). Heartburn reporting on PPI was higher in Group A (7.2 ± 2.1 vs 5.8 ± 0.9; P = .002), but AET, number of reflux events (acidic and weakly acidic), did not differ between the two groups. However, both PSPW index and MNBI were lower in Group A (P < .001). A strong inverse linear correlation was found between bile reflux and both MNBI (Pearson's test; R = -0.714; P < .001) and PSPW index (R = -0.722; P < .001)., Conclusions and Inferences: Compared to acid reflux alone, the presence of bile in an acidic esophageal environment is associated with more severe heartburn, lesser relief from PPI therapy, higher impairment of esophageal mucosal integrity and less effective chemical clearance., (© 2020 John Wiley & Sons Ltd.)

Esophageal dysphagia is a common symptom in adults. Fluoroscopic contrast studies, endoscopy, and esophageal manometry have been used in the diagnosis of esophageal dysphagia for many years. The diagnostic yield has been improved with new test protocols that highlight abnormal bolus transit in the esophagus and outflow obstruction, as well as new high-definition and high-resolution technical advances in equipment. Functional luminal impedance planimetry and the addition of impedance to high-resolution esophageal manometry have also allowed the assessment of new parameters to better understand esophageal structure and function. In this concise review, we describe the role and utility of various diagnostic modalities in the assessment of patients with esophageal dysphagia., (© 2020 New York Academy of Sciences.)

Impedance has traditionally been employed in esophageal disease as a means to assess bolus flow and reflux episodes. Recent and ongoing research has provided new and novel applications for this technology. Measurement of esophageal mucosal impedance, via either multichannel intraluminal impedance catheters or specially designed endoscopically deployed impedance catheters, provides a marker of mucosal integrity. Mucosal impedance has been shown to segregate gastroesophageal reflux disease (GERD) and eosinophilic esophagitis from non-GERD controls and may play a role in predicting response to reflux intervention. More data are needed with regard to other esophageal subgroups, outcome studies, and functional disease. Our paper reviews the history of impedance in esophageal disease, the means of assessing baseline and mucosal impedance, data with regard to the newly developed mucosal impedance probes, the clinical utility of mucosal impedance in specific clinical conditions, and limitations in our existing knowledge, along with suggestions for future studies., (© 2020 New York Academy of Sciences.)

Gastroesophageal reflux disease (GERD) is a common condition characterized by troublesome symptoms or esophageal mucosal lesions attributed to excessive esophageal acid exposure. Various pathophysiological mechanisms account for GERD, including impaired esophageal peristalsis and anatomical or physiological defects at the esophagogastric junction (EGJ). Endoscopy identifies GERD complications and detects potential alternative diagnoses. However, if symptoms persist despite proton pump inhibitor therapy, functional esophageal tests are useful to characterize reflux burden and define the symptom association profile. Ambulatory pH or pH-impedance monitoring measures the 24-h acid exposure time, which remains the most reproducible reflux metric and predicts response to antireflux therapy. Apart from identifying peristaltic dysfunction, esophageal high-resolution manometry defines the morphology and contractile vigor (EGJ-CI) of the EGJ. Novel metrics obtained from pH-impedance monitoring include the postreflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance, which augment the diagnostic value of pH-impedance testing. Mucosal impedance can also be recorded using a probe inserted through a gastroscope, or a novel balloon catheter with arrays of impedance electrodes inserted following sedated endoscopy. The latest developments in functional esophageal tests define the GERD phenotype based on pathogenesis, reflux exposure, structural or motility disorders, and symptom burden, facilitating appropriate treatment., (© 2020 New York Academy of Sciences.)

Background: Paraesophageal hernias (PEH) can be associated with obstructive symptoms, but high-resolution manometry (HRM) characteristics have not been described in detail., Methods: HRM studies of confirmed PEH patients (n = 60, 66.3 ± 1.5 years, 76.7% F), axial hernias (n = 125, 56.1 ± 1.1 years, 58.4% F), and healthy controls (n = 20, 27.9 ± 0.7 years, 45% F) were analyzed. Axial hernias (type 1) were compared to PEH subtyped as isolated PEH (type 2), PEH with axial hernia (type 3), PEH with herniated abdominal organs (type 4), and unknown. Distal contractile integral (DCI), esophageal length, lower esophageal sphincter pressures (LESP), EGJ contractile integral (EGJ-CI), and integrated relaxation pressure (IRP) were extracted. Intra-luminal pressures were measured proximal (intrabolus pressure, IBP) and distal (intragastric pressure, IGP) to EGJ. Univariate and multivariate analyses were performed to characterize esophageal and EGJ motor physiology in PEH., Key Results: PEH patients had LESP and EGJ-CI similar to controls; axial hernia patients had lower LESP. While IRP was within normal limits, PEH had elevated IBP and IGP, and shorter esophageal length compared to axial hernia and normal controls (P ≤ .0001 across groups). Short esophageal length was consistent across PEH subtypes (P = .06). On multivariate regression analysis, IBP remained an independent predictor of PEH (P < .0001). Within PEH subtypes, gastric pressure was higher when axial HH was also present, in contrast to isolated PEH (P = .03); other metrics did not differ., Conclusions & Inferences: Luminal pressure increase both upstream and downstream of the EGJ on HRM likely represents obstructive phenomena in PEH, identification of which may support suspicion of PEH., (© 2020 John Wiley & Sons Ltd.)

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.

Background & Aims: Wireless pH monitoring measures esophageal acid exposure time (AET) for up to 96 hours. We evaluated competing methods of analysis of wireless pH data., Methods: Adult patients with persisting reflux symptoms despite acid suppression (n = 322, 48.5 ± 0.9 years, 61.7% women) from 2 tertiary centers were evaluated using symptom questionnaires and wireless pH monitoring off therapy, from November 2013 through September 2017; 30 healthy adults (control subjects; 26.9 ± 1.5 years; 60.0% women) were similarly evaluated. Concordance of daily AET (physiologic <4%, borderline 4%-6%, pathologic>6%) for 2 or more days constituted the predominant AET pattern. Each predominant pattern (physiologic, borderline, or pathologic) in relation to data from the first day, and total averaged AET, were compared with other interpretation paradigms (first 2 days, best day, or worst day) and with symptoms., Results: At least 2 days of AET data were available from 96.9% of patients, 3 days from 90.7%, and 4 days from 72.7%. A higher proportion of patients had a predominant pathologic pattern (31.4%) than control subjects (11.1%; P = .03). When 3 or more days of data were available, 90.4% of patients had a predominant AET pattern; when 2 days of data were available, 64.1% had a predominant AET pattern (P < .001). Day 1 AET was discordant with the predominant pattern in 22.4% of patients and was less strongly associated with the predominant pattern compared with 48 hour AET (P = .059) or total averaged AET (P = .02). Baseline symptom burden was higher in patients with a predominant pathologic pattern compared with a predominant physiologic pattern (P = .02)., Conclusions: The predominant AET pattern on prolonged wireless pH monitoring can identify patients at risk for reflux symptoms and provides gains over 24 hours and 48 hours recording, especially when results from the first 2 days are discordant or borderline., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The underlying physiology of post-reflux swallow-induced peristaltic wave (PSPW) is unclear. We aimed to: 1) calculate the probability of a random association between reflux and PSPW; 2) characterize factors that could underlie triggering of PSPW and 3) assess the chemical clearance effect of PSPW in healthy asymptomatic subjects., Methods: A total of 251 impedance-pH tracings from healthy asymptomatic subjects were analysed. Twenty consecutive tracings from this pool with 20-40 reflux episodes/24 h and a PSPW index higher than 50% were separately analyzed to evaluate the probability of a random association between reflux and PSPW. The characteristics of reflux episodes followed by a PSPW were compared with those not associated with PSPW., Results: A mean time interval of 29.3 s between a reflux episode and the first swallow captured 71% of total reflux episodes, and 67% of accompanying swallows were non-random. Compared to reflux without PSPW, reflux episodes with PSPW were more frequently acidic (P = 0.048), mixed with gas (P < 0.0001), of high proximal extent (P < 0.0001), while awake (P < 0.0001), and with shorter chemical clearance time (P = 0.040). High proximal extent, gas presence and occurring while awake were independent factors associated with PSPW (P < 0.0001)., Conclusion: Using a time window between reflux and PSPW of around 30 s, the probability of a chance association is around 30%. Reflux episodes with high proximal extent, containing gas and occurring while awake are important factors associated with PSPW in healthy subjects. Reflux episodes with PSPW have a shorter chemical clearance time.

Diseases of the esophagus, such as gastroesophageal reflux (GER), can result in changes to mucosal integrity, neurological function, and the microbiome. Although poorly understood, both age and GER can lead to changes to the enteric nervous system. In addition, the esophagus has a distinct microbiome that can be altered in GER. Mucosal integrity is also at risk due to persistent damage from acid. Diagnostic tools, such as ambulatory pH/impedance testing and esophageal mucosal impedance, can assess short-term and longitudinal GER burden, which can also assess the risk for mucosal compromise. The quality of the mucosal barrier is determined by its intercellular spaces, tight junctions, and tight junction proteins, which are represented by claudins, occludins, and adhesion molecules. Fortunately, there are protective factors for mucosal integrity that are secreted by the esophageal submucosal mucous glands and within saliva that are augmented by mastication. These protective factors have potential as therapeutic targets for GER. In this article, we aim to review diagnostic tools used to predict mucosal integrity, aging, and microbiome changes to the esophagus and esophageal mucosal defense mechanisms., (© 2020 New York Academy of Sciences.)

Background: Straight leg raise (SLR) is a provocative maneuver that assesses esophagogastric junction (EGJ) barrier function during high-resolution manometry (HRM). We evaluated the value of SLR in symptomatic reflux patients undergoing ambulatory reflux monitoring., Methods: Adult patients being evaluated for reflux symptoms with esophageal physiologic testing off antisecretory therapy over a 12 month period were studied. Demographics, clinical presentation, HRM studies, and reflux monitoring studies were analyzed. Intra-abdominal and intra-esophageal pressures were extracted at baseline and during SLR from HRM studies. Acid exposure time (AET) was derived from reflux monitoring studies, and EGJ morphology and tone from HRM studies. SLR pressure metrics predicting abnormal AET were evaluated., Key Results: Of 122 patients, 70 (57.4%) had ≥50% peak intra-abdominal pressure increase during SLR (58.0 ± 1.4 years, 75.7% female). Peak intra-esophageal pressure gradient between baseline and SLR predicted pathologic AET when ≥100% (AUC 0.78, sensitivity 71%, specificity 75%, P < .001), seen in 60.7% with AET > 6%, but only 23.7% with AET < 4% (P = .01). Peak intra-esophageal pressure gradient ≥100% was most discriminative in identifying abnormal acid burden in type 1 EGJ morphology (P = .005) but trended toward significance in type 2 and type 3 morphology (P = .1). Normal and abnormal EGJ contractile integral did not associate with peak intra-esophageal pressure gradient either collectively or when subdivided by EGJ morphology (P ≥ .2)., Conclusions & Inferences: Analysis of intra-esophageal pressure gradients during SLR, a simple HRM maneuver, may augment evaluation of symptomatic GERD, and provide adjunctive evidence supporting GERD., (© 2020 John Wiley & Sons Ltd.)

Background and Aims: The newest addition in the management of achalasia and esophagogastric junction outflow obstruction (EGJOO) is a 30-mm hydrostatic balloon dilator that uses impedance planimetry technology. It allows for the measurement of the diameter and cross-sectional area to determine effective dilation. We aimed to (1) determine the clinical success (defined as a decrease in Eckardt score to ≤3) in the treatment of esophageal motility disorders and (2) report the safety (rate/severity of adverse events)., Methods: This retrospective multicenter study involved 4 centers. Patients with esophageal motility disorders who underwent hydrostatic balloon dilation between January 2015 and October 2018 were included., Results: Fifty-one patients (mean age, 54.1 years; women, 49%) underwent hydrostatic dilation for achalasia (n = 37) or EGJOO (n = 14) during the study period. Forty-seven patients had a median baseline Eckardt score of 5 (range, 3-8; achalasia, n = 35, 6 [range, 3-8]; EGJOO, n = 12, 4 [range, 3.25-6.5]). Clinical success was achieved in 60% of cases (achalasia vs EGJOO: 68.4% vs 33.3%, P = .18). Dilation resulted in a significant decrease in the median Eckardt score from 5 (range, 3-8) to 1.5 (range, 1-4.75; P < .001). Patients with achalasia had a decrease in Eckardt score from 6 (range, 3-8) to 1 (range, 1-4; P < .001), whereas those with EGJOO experienced no significant change. One patient had mild postprocedure chest pain., Conclusions: The hydrostatic balloon dilator is a new tool in our armamentarium to treat esophageal motility disorders. This is the first multicenter study showing the device to be safe and moderately efficacious., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, encouraging patients to ask questions to facilitate their consultation with their physician., Aim: The aim of this study was to develop a QPL specific to adults with gastroesophageal reflux disease (GERD), created by esophageal experts., Methods: The QPL content (78 questions) was derived through a modified Delphi method consisting of 2 rounds. In round 1, 18 esophageal experts provided 5 answers to the prompt "What you wish your patients would ask" and "What questions do patients often not ask, that I wish they would ask?" In round 2, the experts rated each question on a 5-point Likert scale, and responses rated as "essential" or "important," determined by an a priori threshold of ≥4.0, were accepted for the QPL., Results: Twelve esophageal experts participated. Of 143 questions from round 1, 110 (76.9%) were accepted for inclusion in the QPL, meeting a median value of ≥4.0, and, subsequently, it reduced to 78, minimizing redundancy. Median values ranged between 4.0 and 5.0, with the highest agreement median (5.0) for questions asking dosing and timing of proton pump inhibitor therapy, and surveillance in Barrett's. Questions were categorized into the following categories: "What does this illness mean," "lifestyle modifications," "general treatment," "treatment with proton pump inhibitors," "What I should expect for my future," and "Barrett's." The largest number of questions covered lifestyle modifications (21.8%), with the highest agreement median (5.0) for "How helpful are lifestyle modifications in GERD?", Conclusions: A preliminary GERD-specific QPL, the first of its kind, was developed by esophageal experts. Modification after more patient consultation and feedback is planned in subsequent versions to create a GERD-QPL for eventual use in clinical gastroenterology.

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.

Objective: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects., Design: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI)., Results: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie., Conclusion: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings., Competing Interests: Competing interests: DS receives research grants from Reckitt Benckiser UK, Jinshan Technology China and Alfa Sigma, Italy. SR: consulting Medtronic, research support Diversatek Healthcare, Medtronic; ES: Lecture Fee: Medtronic, Takeda, Janssen, MSD, Abbvie, Malesci; Consulting: Medtronic, Takeda, Janssen, MSD, Reckitt Bencikser, Sofar, Unifarco, SILA, Oftagest. CPG consults for Medtronic, Diversatek, Ironwood, IsoThrive and Quintiles., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The American Neurogastroenterology and Motility Society Task Force recommends that gastrointestinal motility procedures should be performed in motility laboratories adhering to the strict recommendations and personal protective equipment (PPE) measures to protect patients, ancillary staff, and motility allied health professionals. When available and within constraints of institutional guidelines, it is preferable for patients scheduled for motility procedures to complete a coronavirus disease 2019 (COVID-19) test within 48 hours before their procedure, similar to the recommendations before endoscopy made by gastroenterology societies. COVID-19 test results must be documented before performing procedures. If procedures are to be performed without a COVID-19 test, full PPE use is recommended, along with all social distancing and infection control measures. Because patients with suspected motility disorders may require multiple procedures, sequential scheduling of procedures should be considered to minimize need for repeat COVID-19 testing. The strategies for and timing of procedure(s) should be adapted, taking into consideration local institutional standards, with the provision for screening without testing in low prevalence areas. If tested positive for COVID-19, subsequent negative testing may be required before scheduling a motility procedure (timing is variable). Specific recommendations for each motility procedure including triaging, indications, PPE use, and alternatives to motility procedures are detailed in the document. These recommendations may evolve as understanding of virus transmission and prevalence of COVID-19 infection in the community changes over the upcoming months.

Background/aims: Impaired esophageal motility and disrupted esophagogastric junction (EGJ) on high-resolution manometry (HRM) have been associated with increased reflux severity in gastroesophageal reflux disease (GERD) patients. However, there are limited data evaluating HRM parameters in proton pump inhibitors (PPI) non-responders., Methods: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH studies performed of PPI therapy in patients with typical GERD symptoms were reviewed from 3 international centers. Frequency of GERD symptoms was assessed on and off PPI therapy in both non-responders (< 50% symptom improvement on PPI therapy) and responders. Rome IV definitions identified non-erosive reflux disease, reflux hypersensitivity, and functional heartburn. Univariate and multivariate analyses were performed to determine predictors of non-response., Results: Of 204 patients, 105 were PPI non-responders and 99 were responders. Non-responders showed higher EGJ contractile integral values, and a lower frequency of type II and III EGJ morphology ( P ≤ 0.03 for each comparison). Esophageal body diagnoses on HRM (fragmented peristalsis, ineffective esophageal motility, or absent peristalsis) did not predict non-response. On multivariate analysis, non-pathological acid exposure time (OR, 2.5; 95% CI, 1.2-5.0; P < 0.001), normal mean nocturnal baseline impedance values (OR, 2.7-2.4; 95% CI, 1.0-6.1; P < 0.05), normal EGJ contractile integral values (OR, 3; 95% CI, 1.3-7.4; P = 0.012), and presence of type I EGJ morphology (OR, 1.9; 95% CI, 1.0-3.4; P = 0.044) were associated with an unfavorable response to PPIs., Conclusions: Intact EGJ metrics on HRM complement normal reflux burden in predicting non-response to PPI therapy. HRM has value in the evaluation of PPI non-responders.

Background/aims: Esophageal baseline impedance (BI) can be extracted from pH-impedance tracings as mean nocturnal baseline impedance (MNBI), and from high-resolution impedance manometry (HRIM), but it is unknown if values are similar between acquisition methods across HRIM manufacturers. We aim to assess correlations between MNBI and BI from HRIM (BI-HRIM) from 2 HRIM manufacturers in the setting of physiologic acid exposure time (AET)., Methods: HRIM and pH-impedance monitoring demonstrating physiologic AET (< 4%) off proton pump inhibitors were required. BI-HRIM was extracted as the average from 5 cm and 10 cm above the lower esophageal sphincter. Distal BI-HRIM (DBI-HRIM) was also extracted from the most distal channel (Medtronic studies). MNBI was extracted from 6 channels. Concordance between BI-HRIM across manufacturers with MNBI was analyzed., Results: Thirty-six patients met the inclusion criteria (59.6 ± 1.7 years; 22% female; body mass index 30.5 ± 0.7; AET 1.6 ± 0.2%). Although MNBI was similar at all channels ( P ≥ 0.18), Diversatek BI-HRIM was lower than Medtronic BI-HRIM ( P = 0.003). Overall, BI-HRIM correlated with MNBI at corresponding recording sites, 7 cm and 9 cm ( P < 0.05), but not at other sites ( P ≥ 0.19). Pearson's correlations > 0.5 were seen at MNBI at 7 cm for both systems, and at 9 cm for Medtronic. DBI-HRIM correlated with MNBI at 3 cm and 5 cm ( P < 0.03), but not at other locations ( P > 0.1)., Conclusions: While numeric differences exist between manufacturers, BI-HRIM correlates with MNBI from corresponding channels in patients with physiologic AET. Comparison with AET elevation is needed to determine correlations between pathologic MNBI with BI-HRIM across manufacturers. The optimal HRIM channels from which BI values should be extracted also warrants further study.

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.

Globus is a non-painful sensation of a tightness or a lump/foreign body in the throat that is not associated with dysphagia and may actually improve during meals. While several otorhinolaryngologic, thyroid, and esophageal disorders have been linked to globus, cause-and-effect relationships are difficult to establish. Consequently, though part of the evaluation, objective otorhinolaryngologic and esophageal testing is often negative. The presence of alarm symptoms, particularly pain, weight loss, dysphagia, or odynophagia is indications for objective testing. A diagnosis of idiopathic globus requires exclusion of pharyngeal, laryngeal, and esophageal disorders with laryngoscopy, endoscopy, high-resolution manometry, barium radiography, and/or ambulatory reflux monitoring. A trial of acid-suppressive therapy may be reasonable in the absence of alarm symptoms, especially if concurrent reflux symptoms are identified. Ablation of heterotopic gastric mucosa in the proximal esophagus has been reported to improve globus symptoms. Beyond these specific approaches, further management of idiopathic globus consists of reassurance, neuromodulators, and complementary approaches. Globus has a benign course with no long-term consequences, and the overall prognosis is good as the magnitude of symptoms may decline over time., (© 2020 John Wiley & Sons Ltd.)

Esophageal symptoms are common and may indicate the presence of gastroesophageal reflux disease (GERD), structural processes, motor dysfunction, behavioral conditions, or functional disorders. Esophageal physiologic tests are often performed when initial endoscopic evaluation is unrevealing, especially when symptoms persist despite empiric management. Commonly used esophageal physiologic tests include esophageal manometry, ambulatory reflux monitoring, and barium esophagram. Functional lumen imaging probe (FLIP) has recently been approved for the evaluation of esophageal pressure and dimensions using volumetric distension of a catheter-mounted balloon and as an adjunctive test for the evaluation of symptoms suggestive of motor dysfunction. Targeted utilization of esophageal physiologic tests can lead to definitive diagnosis of esophageal disorders but can also help rule out organic disorders while making a diagnosis of functional esophageal disorders. Esophageal physiologic tests can evaluate obstructive symptoms (dysphagia and regurgitation), typical and atypical GERD symptoms, and behavioral symptoms (belching and rumination). Certain parameters from esophageal physiologic tests can help guide the management of GERD and predict outcomes. In this ACG clinical guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to describe performance characteristics and clinical value of esophageal physiologic tests and provide recommendations for their utilization in routine clinical practice.

High-resolution manometry evaluates esophageal motor function using 10 supine water swallows. Superimposing impedance over high-resolution manometry pressure topography assesses the relationship between contraction and bolus propulsion and identifies inadequate clearance. Ancillary techniques and maneuvers augment the standard supine high-resolution manometry evaluation by challenging peristaltic function. Increasing bolus volume (rapid drink challenge) and altering bolus consistency (standardized test meal, solid swallows) enhance identification of esophageal outflow obstruction syndromes. Physiologic maneuvers (multiple rapid swallows, abdominal compression) address the ability of the esophageal smooth muscle to augment contraction vigor. Pharmacologic challenge is less commonly used clinically, and elucidates pathophysiology of esophageal motor disorders., Competing Interests: Disclosure C.P. Gyawali has received honoraria for consulting from Medtronic, Diversatek, Torax, Ironwood, and Quintiles, and is on the speaker’s bureau for Medtronic and Diversatek. B.D. Rogers has no conflicts of interest to disclose. No conflicts of interest exist., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Functional dyspepsia is a common functional gastrointestinal (GI) disorder of gastroduodenal origin, diagnosed clinically in the presence of prototypical symptoms of epigastric pain and meal-related symptoms, and without structural explanation. The most recent diagnostic criteria provide for two functional dyspepsia subtypes, epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS) based on the predominant symptom pattern. The evaluation of dyspepsia should keep laboratory, imaging, and invasive testing to a minimum, as extensive or repetitive investigations are of rather low diagnostic yield in the absence of localizing symptoms or alarm features. Factors with etiopathologic relationships to functional dyspepsia include micro-inflammation, GI infections, abnormalities of gastroduodenal motility, visceral hypersensitivity, disturbances along the brain-gut axis, and psychological factors; all of these causative mechanisms have potential to partially explain symptoms in some functional dyspepsia patients, thus providing a rationale for the efficacy of a diversity of therapeutic approaches to functional dyspepsia. Management of dyspepsia symptoms relies upon both pharmacologic treatments and non-pharmacologic approaches, including psychological and complementary interventions. The evidence in support of established functional dyspepsia therapies is reviewed, and forms the basis for an effective functional dyspepsia treatment strategy emphasizing the patient's current symptom severity, pattern, and impact on the function and quality of life of the individual.

Background & Aims: Esophageal motor disorders (EMD) and pathologic reflux are often identified in obese individuals, but it is not clear how obesity contributes to these symptoms. We examined the relationships among symptom burden, EMD, acid exposure time (AET), symptom association probability, and body mass index (BMI)., Methods: We performed a retrospective study of 1089 consecutive patients who underwent high-resolution manometry, of which 426 patients also underwent reflux monitoring off acid suppression, over a 2-year period at a tertiary referral center. Symptom burden was assessed by questionnaires to determine dominant symptom intensity (DSI; product of symptom severity, and frequency, on 5-point Likert scales) and global symptom severity (GSS; global esophageal symptoms on 10-cm visual analog scales) at the time of esophageal testing; BMIs were recorded. We compared proportions of patients with EMD and abnormal reflux burden among BMI categories and correlated them with symptom burden., Results: Four-hundred thirty-three patients (39.8%) met the criteria for EMD. Esophageal outflow obstruction was observed in higher proportions of patients with low BMIs (underweight, 25.9%; normal, 14.1%; overweight, 13.9%; and obese, 9.8%; P = .037), but EMDs were less frequent in obese patients (P = .047), despite higher symptom burden compared with non-obese patients (DSI, 10.5 ± 0.3 vs 9.7 ± 0.2; P = .03 and GSS, 6.5 ± 1 vs 5.9 ± 1; P = .01). Among the 426 patients who underwent reflux monitoring, the proportions with total AET (P = .02), and upright AET (P < .001) increased among BMI categories, supine AET trended strongly (P = .06), in combination with increasing DSI and GSS (P ≤ .001 for each comparison). BMI correlated with symptom burden, higher AET, and positive symptom association probability (P < .01 for each analysis)., Conclusions: Increased symptom burden in obese individuals correlates with esophageal acid burden but not with motor disorders., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Straight leg raise (SLR) while supine increases intra-abdominal pressure. We hypothesized that elevations in intra-abdominal pressure would transmit into the thoracic cavity if the esophagogastric junction (EGJ) was disrupted., Methods: Consecutive patients undergoing esophageal HRM were included if they had adequate SLR (hip flexion with knees extended for ≥ 5 seconds while supine). EGJ morphology was subtyped based on lower esophageal sphincter (LES) and crural diaphragm (CD) location (type 1: LES and CD overlap; type 2: separation of < 3 cm; type 3: separation of ≥ 3 cm). EGJ tone was assessed using EGJ contractile integral (EGJ-CI). HRM studies were analyzed according to Chicago Classification v3.0. Mean and peak intra-thoracic and abdominal pressures were measured at baseline and during SLR using on-screen software tools. Trans-EGJ gradients were compared, and pressure gradient < 1 mmHg denoted the equalization of pressures., Key Results: Of 430 patients, 248 (57.5 ± 0.9 years, 69.4% F) completed SLR. EGJ morphology was type 1 in 122 (49.2%), type 2 in 56 (22.6%) and type 3 in 40 (16.1%). In types 1 and 2 EGJ, neither the mean nor peak trans-EGJ pressure gradient changed with SLR (P ≥ .17 for each). In contrast, in type 3 EGJ, peak pressure gradient decreased significantly following SLR (3.5 ± 1.8 mmHg vs. -8.6 ± 4.8 mmHg, P = .01). More type 3 EGJ patients equalized peak (65%) pressures across EGJ compared with types 1 and 2 (27%, P < .001)., Conclusions and Inferences: The evaluation of intra-abdominal and intra-thoracic pressures with SLR during esophageal HRM can provide evidence of physiological disruption of the EGJ barrier., (© 2020 John Wiley & Sons Ltd.)

Background: The functional lumen imaging probe (FLIP) system is an FDA-approved tool for dynamic evaluation of the esophagogastric junction (EGJ). Even though commercially available since 2009, FLIP utilization remains low, partly due to lack of consensus in methodology and interpretation. Therefore, we aimed to analyze the influence of concurrent endoscopy on FLIP measurements., Methods: In this single-center study, we reviewed data from 93 patients undergoing FLIP for symptomatic esophageal motility disorders between 2016 and 2018. During sedated endoscopy, we measured luminal values (distensibility, cross-sectional area (CSA), and balloon pressure) at the EGJ and distal esophagus using 30, 40, and 50 mL distension volumes, with and without concurrent endoscope presence. All recorded values were compared at the various distension volumes between the two measurements using a Wilcoxon rank sum test., Key Results: There was a significant difference in distensibility and CSA with index distension volume (40 mL) at the EGJ comparing the two measurements: Lower median distensibility was 2.1 mm 2  mm Hg -1 in the group with concurrent inserted endoscope, respectively, 3.4 mm 2  mm Hg -1 without endoscope (P < .001), and median CSA was 86.0 resp. 110.0 mm 2 (P < .001). No significant difference could be found in the measurements of the distal esophagus., Conclusions & Inferences: Our results show a significant difference in FLIP measurements with and without endoscope presence. This underlines the importance of establishing a consensus of a standardized FLIP protocol to define normal luminal values and guiding future FLIP diagnostic studies., (© 2020 John Wiley & Sons Ltd.)

BEST PRACTICE ADVICE 1: A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. BEST PRACTICE ADVICE 2: A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 3: Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 4: PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. BEST PRACTICE ADVICE 5: Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. BEST PRACTICE ADVICE 6: Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. BEST PRACTICE ADVICE 7: Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Abnormal acid exposure time (AET) is associated with good outcomes of symptoms from antireflux therapy. Low esophageal mean nocturnal baseline impedance (MNBI) is an additional marker of reflux disease. We aimed to evaluate the value of MNBI when analysis of AET produces borderline or inconclusive results., Methods: We studied a retrospective cohort of 371 patients (mean age, 54.5 ± 0.7 y; 60.0% female) who had persistent reflux symptoms after treatment and underwent ambulatory pH-impedance monitoring off antisecretory therapy at 1 tertiary center in Europe or 1 in the United States. Total AET was determined from pH impedance studies (pathologic, >6%; physiologic, <4%; borderline or inconclusive, 4%-6%). Baseline impedance values were calculated at the 5-cm impedance channel at 3 nocturnal 10-minute periods and averaged to yield MNBI (abnormal, <2292 ohms). The primary outcome was response to antireflux therapy, defined as global symptom improvement of 50% or greater on patients' answers on standardized visual analog scales., Results: Among the 371 patients, 107 (28.8%) had pathologic AET and 234 (63.1%) had abnormal MNBI. Low MNBI was concordant in 99.1% of patients with pathologic AET, in 91.2% with borderline AET, and in 33.7% with physiologic AET. During 38.7 ± 0.8 months of follow-up evaluation, 43.0% of patients had improved symptoms with medical therapy and 76.2% had improved symptoms with surgical antireflux therapy (P < .0001). When MNBI was low, response to medical therapy did not differ significantly between patients with borderline AET and patients with pathologic AET (P = .44), but did differ significantly when each group was compared with patients with physiologic AET, regardless of whether MNBI was normal or low (P < .0001 for each comparison)., Conclusions: When low, MNBI identifies patients with pathologic and borderline AET who respond to antireflux therapy. MNBI analysis complements AET in defining esophageal reflux burden. MNBI correlates with response of symptoms to antireflux therapy., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Mean nocturnal baseline impedance (MNBI) augments the diagnostic yield of multichannel intraluminal impedance-pH (MII-pH) monitoring. While acid exposure time (AET) correlates with MNBI, it remains unclear whether esophageal motility affects MNBI values. The present study was aimed at evaluating the respective roles of esophageal motor function and AET on MNBI., Methods: High-resolution manometry (HRM) studies and ambulatory 24-hour MII-pH monitoring tracings were retrospectively analyzed from consecutive endoscopy-negative GERD patients with typical symptoms responsive to previous acid-suppressive therapy from three tertiary care centers. Univariate and multivariate analyses were performed to determine predictors of pathologic MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES)., Key Results: Patients with pathological AET displayed lower MNBI values at 3 cm and 5 cm (P < .01) compared to patients with non-pathological AET. Similarly, significantly lower MNBI values were also noted at both sites with type 3 EGJ compared to type 1 EGJ (P ≤ .02 for each comparison), and with absent contractility compared to normal peristalsis (P ≤ .02 for each comparison). On multivariate analysis, the presence of type 2 or 3 EGJ and absent contractility were associated with a significantly higher probability of pathological MNBI values at 3 cm and 5 cm above the LES., Conclusions and Inferences: Disruption of the EGJ and absent contractility on HRM are both associated with lower MNBI values. HRM findings complement reflux testing using MII-pH monitoring., (© 2019 John Wiley & Sons Ltd.)

Objectives: Symptoms are inconsistently associated with esophageal motor findings on high-resolution manometry (HRM). We aimed to evaluate predictors of dysphagia severity, including esophageal hypervigilance and visceral anxiety, among patients evaluated with HRM., Methods: Adult patients undergoing HRM at 4 academic medical centers (United States and France) were prospectively evaluated. HRM was completed and analyzed per the Chicago Classification v3.0. Validated symptom scores, including the Brief Esophageal Dysphagia Questionnaire and Esophageal Hypervigilance and Anxiety Scale, were completed at the time of HRM., Results: Two hundred thirty-six patients, aged 18-85 (mean 53) years, 65% female, were included. Approximately 59 (25%) patients had a major motor disorder on HRM: 19 achalasia, 24 esophagogastric junction outflow obstruction, 12 absent contractility, and 4 jackhammer. Approximately 177 (75%) patients did not have a major motor disorder: 71 ineffective esophageal motility and 106 normal motility. Having a major motor disorder was a significant predictor of dysphagia severity (Radj = 0.049, P < 0.001), but the Esophageal Hypervigilance and Anxiety Scale score carried a predictive relationship of Brief Esophageal Dysphagia Questionnaire that was 2-fold higher than having a major motor disorder: Radj = 0.118 (P < 0.001). This finding remained when evaluated by the major motor disorder group. HRM metrics were nonsignificant., Discussion: In a prospective, international multicenter study, we found that esophageal hypervigilance and visceral anxiety were the strongest predictors of dysphagia severity among patients evaluated with HRM. Thus, an assessment of esophageal hypervigilance and visceral anxiety is important to incorporate when evaluating symptom severity in clinical practice and research studies.

Irritable bowel syndrome with diarrhea (IBS-D) and NAFLD are both common conditions that may be influenced by shared pathways of altered bile acid (BA) signaling and homeostatic regulation. Pathophysiological links between IBS-D and altered BA metabolism include altered signaling through the ileal enterokine and fibroblast growth factor 19 (FGF19) as well as increased circulating levels of 7α-hydroxy-4-cholesten-3-one, a metabolic intermediate that denotes increased hepatic BA production from cholesterol. Defective production or release of FGF19 is associated with increased BA production and BA diarrhea in some IBS-D patients. FGF19 functions as a negative regulator of hepatic cholesterol 7α-hydroxylase; therefore, reduced serum FGF19 effectively de-represses hepatic BA production in a subset of IBS-D patients, causing BA diarrhea. In addition, FGF19 modulates hepatic metabolic homeostatic response signaling by means of the fibroblast growth factor receptor 4/klotho beta receptor to activate cascades involved in hepatic lipogenesis, fatty acid oxidation, and insulin sensitivity. Emerging evidence of low circulating FGF19 levels in subsets of patients with pediatric and adult NAFLD demonstrates altered enterohepatic BA homeostasis in NAFLD. Conclusion: Here we outline how understanding of shared pathways of aberrant BA homeostatic signaling may guide targeted therapies in some patients with IBS-D and subsets of patients with NAFLD., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Sleep disturbance and fatigue are commonly reported among patients with Crohn's disease (CD). In this prospective study, we aimed to define sleep quality in CD patients at various disease activity states and compare to healthy controls using objective and subjective measures. A prospective observational cohort study of CD patients seen at a tertiary academic inflammatory bowel diseases (IBD) clinic was compared to healthy volunteers. CD activity was assessed using the Harvey-Bradshaw Index (HBI). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) and objectively over 1-week using actigraphy (motion-based) and morning urinary melatonin metabolite. 121 subjects (CD patients N = 61; controls N = 60) completed the study. 34 had active CD (HBI > 4). Sleep disturbance was more frequently reported by CD subjects than controls (PSQI: 57% vs. 35%, p = 0.02) and in patients with active CD versus in remission state (PSQI 75.8% vs. 33.3%, p < 0.01; ESS: 45.5% vs. 19%, p = 0.03). Sleep parameters as measured by actigraphy and urine melatonin metabolite did not vary by group. Crohn's patients report significantly more disturbed sleep than controls. However, poor sleep was not confirmed by objective measures of sleep quality. Excessive daytime sleepiness in CD patients may be driven by factors beyond objectively measured poor sleep.

Background: Association between proportions of hypomotile swallows on esophageal high-resolution manometry (HRM) and esophageal reflux burden remains incompletely understood. We investigated relationships between hypomotility, acid exposure time (AET), and mean nocturnal baseline impedance (MNBI) on ambulatory reflux monitoring., Methods: Clinical data, HRM, and ambulatory pH-impedance studies (performed off acid suppression) from patients with persisting reflux symptoms were reviewed from five international centers. AET (abnormal > 6%) and MNBI (abnormal < 2292 ohms) were extracted from pH-impedance studies. Distal contractile integral (DCI) designated esophageal peristalsis into normal (DCI > 450 mmHg.cm.s), fragmented (DCI > 450 mmHg.cm.s with breaks > 5 cm), weak (DCI 100-450 mmHg.cm.s), and failed (DCI < 100 mm mmHg.cm.s) sequences. Univariate and multivariate analyses were performed to identify motor associations of abnormal reflux burden., Key Results: Of 351 patients (52.1 ± 0.8 years, 67%F), 29.3% had AET > 6% and 61.8% had MNBI < 2292 ohms. On univariate analysis, both fragmented peristalsis and IEM associated with abnormal AET (P ≤ .01) and MNBI (P ≤ .03); reflux burden was more profound with >70% fragmented as well as ineffective sequences compared to ≤70% for each (P < .05 for each comparison). When weak and failed sequences within IEM were separately analyzed, ≥50% failed sequences predicted abnormal AET (P ≤ .009), and ≥50% weak sequences did not (P = .14). On multivariate regression, ≥50% failed sequences predicted abnormal AET (P = .02), and >70% ineffective sequences trended strongly (P = .069); >70% ineffective sequences predicted abnormal MNBI (P = .046), and >70% fragmented sequences trended strongly (P = .076)., Conclusions and Inferences: Breaks in esophageal peristaltic integrity seen with fragmented and failed sequences are more relevant to abnormal esophageal acid burden than weak sequences., (© 2019 John Wiley & Sons Ltd.)

Background: High-resolution manometry (HRM) allows characterization of esophagogastric junction (EGJ) morphology and identification of hiatus hernia using novel software tools., Aim: The main purpose of this study was to determine the impact of HRM-based EGJ and lower esophageal sphincter (LES) metrics in predicting abnormal reflux burden., Methods: Total, upright, and supine acid exposure times (AETs) were extracted from ambulatory reflux monitoring performed off therapy in 482 patients (54.2±0.6 y, 63.3% female patients). EGJ morphology was categorized into type 1 (superimposed LES and crural diaphragm), type 2 (<3 cm separation between LES and crural diaphragm), and type 3 (≥3 cm separation). EGJ-contractile integral (EGJ-CI) and distal contractile integral (DCI) were extracted. Conventional EGJ and LES metrics, including basal and end-expiratory LES pressure, and LES length were also analyzed. Univariate and multivariate analyses were performed to determine the value of HRM parameters in predicting abnormal esophageal reflux burden., Results: Type 1 EGJ was noted in 298 (61.8%), type 2 in 125 (25.9%), and type 3 in 59 (12.2%); EGJ-CI and mean DCI were lower with abnormal EGJ morphology. Mean AET, and proportions with abnormal AET increased as EGJ morphology became progressively disrupted (P<0.0001 across groups); low EGJ-CI was additive in predicting abnormal AET. All HRM parameters assessed (EGJ morphology, EGJ-CI, and DCI) were independent predictors for abnormal AET (P≤0.02). Conventional LES and EGJ metrics were also associated with abnormal reflux burden, but intra-abdominal LES length, and hiatus hernia size did not independently predict total AET., Conclusions: HRM-based EGJ morphology and EGJ barrier assessment independently predict esophageal reflux burden.

Background and Aims: A novel device that provides real-time depiction of functional luminal image probe (FLIP) panometry (ie, esophagogastric junction [EGJ] distensibility and distension-induced contractility) was evaluated. We aimed to compare real-time FLIP panometry interpretation at the time of sedated endoscopy with high-resolution manometry (HRM) in evaluating esophageal motility., Methods: Forty consecutive patients (aged 24-81 years; 60% women) referred for endoscopy with a plan for future HRM from 2 centers were prospectively evaluated with real-time FLIP panometry during sedated upper endoscopy. The EGJ distensibility index and contractility profile were applied to derive a FLIP panometry classification at the time of endoscopy and again (post-hoc) using a customized program. HRM was classified according to the Chicago classification., Results: Real-time FLIP panometry motility classification was abnormal in 29 patients (73%), 19 (66%) of whom had a subsequent major motility disorder on HRM. All 9 patients with an HRM diagnosis of achalasia had abnormal real-time FLIP panometry classifications. Eleven patients (33%) had normal motility on real-time FLIP panometry and 8 (73%) had a subsequent HRM without a major motility disorder. There was excellent agreement (κ = .939) between real-time and post-hoc FLIP panometry interpretation of abnormal motility., Conclusions: This prospective, multicentered study demonstrated that real-time FLIP panometry could detect abnormal esophageal motility, including achalasia, at the endoscopic encounter. Additionally, normal motility on FLIP panometry was predictive of a benign HRM. Thus, real-time FLIP panometry incorporated with endoscopy appears to provide a suitable and well-tolerated point-of-care esophageal motility assessment., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery., Design: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous., Results: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett's oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis., Conclusion: With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms., Methods: This study enrolled 303 consecutive patients with proton pump inhibitor treatment-naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non-dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances., Results: There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms., Conclusions: Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Ineffective esophageal motility (IEM) is a heterogenous minor motility disorder diagnosed when ≥50% ineffective peristaltic sequences (distal contractile integral <450 mm Hg cm s) coexist with normal lower esophageal sphincter relaxation (integrated relaxation pressure < upper limit of normal) on esophageal high-resolution manometry (HRM). Ineffective esophageal motility is not consistently related to disease states or symptoms and may be seen in asymptomatic healthy individuals., Purpose: A 1-day symposium of esophageal experts reviewed existing literature on IEM, and this review represents the conclusions from the symposium. Severe IEM (>70% ineffective sequences) is associated with higher esophageal reflux burden, particularly while supine, but milder variants do not progress over time or consistently impact quality of life. Ineffective esophageal motility can be further characterized using provocative maneuvers during HRM, especially multiple rapid swallows, where augmentation of smooth muscle contraction defines contraction reserve. The presence of contraction reserve may predict better prognosis, lesser reflux burden and confidence in a standard fundoplication for surgical management of reflux. Other provocative maneuvers (solid swallows, standardized test meal, rapid drink challenge) are useful to characterize bolus transit in IEM. No effective pharmacotherapy exists, and current managements target symptoms and concurrent reflux. Novel testing modalities (baseline and mucosal impedance, functional lumen imaging probe) show promise in elucidating pathophysiology and stratifying IEM phenotypes. Specific prokinetic agents targeting esophageal smooth muscle need to be developed for precision management., (© 2019 John Wiley & Sons Ltd.)

Background: Megaesophagus (ME) carries a poor long-term prognosis in dogs. In people, lower esophageal sphincter (LES) disorders causing functional obstruction are rare causes of ME that may respond to targeted treatment. Functional LES disorders are reported rarely in dogs because of challenges in diagnostic methodologies., Hypothesis/objectives: To identify dogs with videofluoroscopic swallow study (VFSS) features of LES achalasia-like syndrome (LES-AS). We hypothesized that dogs with LES-AS could be distinguished from normal dogs using standardized VFSS criteria., Animals: Dogs with LES-AS by VFSS (n = 19), healthy normal dogs (n = 20)., Methods: Retrospective study. One-hundred thirty dogs presented to the University of Missouri Veterinary Health Center (MU-VHC) between April 2015 and December 2017 for a free-feeding VFSS; 20 healthy dogs were included as controls. Swallow studies were evaluated for failure of the LES to relax during pharyngeal swallow (LES-AS). Affected dogs subsequently were evaluated using standardized criteria to identify metrics important for identifying and characterizing dogs with LES-AS., Results: Nineteen dogs with LES-AS were identified out of 130 VFSS. Megaesophagus was present in 14 of 19 (73.7%) dogs with LES-AS. A baseline esophageal fluid-line and "bird beak" were present in 68.4% (95% confidence interval [CI], 47.5%-89.3%) and 63.2% (95% CI, 41.5%-84.8%) of affected dogs, respectively. The esophagus was graded as acontractile (8/19), hypomotile (8/19), or hypermotile (3/19)., Conclusions and Clinical Importance: Dogs with LES-AS may successfully be identified by VFSS using a free-feeding protocol. These data are of critical clinical importance because a subpopulation of dogs with functional LES obstruction may be candidates for targeted intervention., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Esophageal hypercontractility can manifest with and without esophagogastric junction (EGJ) outflow obstruction. We investigated clinical presentations and motility patterns in patients with esophageal hypercontractile disorders., Methods: Esophageal HRM studies fulfilling Chicago Classification 3.0 criteria for jackhammer esophagus (distal contractile integral, DCI >8000 mmHg.cm.s in ≥ 20% swallows) with (n = 30) and without (n = 83) EGJ obstruction (integrated relaxation pressure, IRP > 15 mm Hg) were retrospectively reviewed from five centers (4 in Europe, 1 in US). Single swallows (SS) and multiple rapid swallows (MRS) were analyzed using HRM software tools (IRP, DCI, distal latency, DL); MRS: SS DCI ratio >1 defined contraction reserve. Comparison groups were achalasia type 3 (n = 72, positive control for abnormal inhibition and EGJ obstruction) and healthy controls (n = 18). Symptoms, HRM metrics, and MRS contraction reserve were analyzed within jackhammer subgroups and comparison groups., Key Results: The esophageal smooth muscle was excessively stimulated at baseline in jackhammer subgroups, with lack of augmentation following MRS identified more often compared with controls (P = .003) and type 3 achalasia (P = .07). Consistently abnormal inhibition was identified in type 3 achalasia (47%), and to a lower extent in jackhammer with obstruction (37%, P = .33), jackhammer esophagus (28%, P = .01), and controls (11%, P < .01 compared with type 3 achalasia). Perceptive symptoms (heartburn, chest pain) were common in jackhammer esophagus (P < .01 compared with type 3 achalasia), while transit symptoms (dysphagia) were more frequent with presence of EGJ obstruction (P ≤ .01 compared with jackhammer without obstruction)., Conclusions and Inferences: The balance of excessive excitation and abnormal inhibition defines clinical and manometric manifestations in esophageal hypercontractile disorders., (© 2019 John Wiley & Sons Ltd.)

Background & Aims: Dysphagia is a consequence of antireflux surgery (ARS) for gastroesophageal reflux disease (GERD). We studied patient management and symptomatic outcomes., Methods: We performed a retrospective study of 157 consecutive adult patients with GERD (mean age, 65.1 ± 1.0 y; 72% female) who underwent ARS at a tertiary care center from 2003 through 2014. We characterized postfundoplication dysphagia using a self-reported Likert scale, which ranged from a low score of 0 (no dysphagia) to a high score of 4 (severe daily dysphagia); scores of 2 or more indicated clinically significant dysphagia. Postfundoplication dysphagia was categorized as early (≤6 wk after ARS) or late (>6 wk after ARS), and Kaplan-Meier analyses were used to assess the time to development of clinically significant dysphagia. We performed univariate and multivariate analyses to assess management response and identify factors associated with dysphagia. The primary aim was to determine the prevalence and clinical course of postfundoplication dysphagia in patients with GERD treated with ARS., Results: Of the 157 patients, 54.8% had early postfundoplication dysphagia (clinically significant in 20.4%); only 3.5% required endoscopic intervention. Over 2.1 ± 0.2 years of follow-up evaluation, 29 patients (18.5%) developed late postfundoplication dysphagia. Based on Kaplan-Meier analysis, the median time to clinically significant late postfundoplication dysphagia was 0.75 years (95% CI, 0.26-1.22). Of 13 patients (44.8%) who underwent endoscopic dilation, improvement was reported by 92.3%, with a mean decrease in dysphagia severity of 1.55 ± 0.3, based on the Likert scale. Prefundoplication dysphagia, early postfundoplication dysphagia, recurrent hiatal hernia, and lack of contraction reserve following multiple rapid swallows were univariate predictors of late postfundoplication dysphagia (P ≤ .04); lack of contraction reserve was associated independently with late postfundoplication dysphagia, based on multivariate logistic regression analysis (odds ratio, 3.73; 95% CI, 1.11-12.56)., Conclusions: Early and late postfundoplication dysphagia can be successfully managed conservatively or with endoscopic dilation, respectively. Lack of contraction reserve on multiple rapid swallows is associated independently with late postfundoplication dysphagia., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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 & Aims: Diagnostic testing for chronic esophageal disorders relies on histopathology analysis of biopsies or uncomfortable transnasal catheters or wireless pH monitoring, which capture abnormal intraluminal refluxate. We therefore developed a balloon mucosal impedance (MI) catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy over a long segment of the esophagus. We performed a prospective study to evaluate the ability of a balloon-incorporated MI catheter to detect and evaluate esophageal disorders, including gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE)., Methods: We performed a prospective study of 69 patients undergoing esophagogastroduodenoscopy with or without wireless pH monitoring. Patients were classified as having GERD (erosive esophagitis or abnormal pH; n = 24), EoE (confirmed with pathology analysis of tissues from both distal and proximal esophagus; n = 21), or non-GERD (normal results from esophagogastroduodenoscopy and pH tests; n = 24). Receiver operating characteristic curves and area under the operating characteristic curve (AUC) were used to compare the accuracy of balloon MI in diagnosis. Probabilities of assignment to each group (GERD, non-GERD, or EoE) were estimated using multinomial logistic regression. Association between MI patterns and diagnoses were validated using data from patients seen at 3 separate institutions., Results: MI pattern along the esophageal axis differed significantly (P < .01) among patients with GERD, EoE, and non-GERD. Patients with non-GERD had higher MI values along all measured segments. The MI pattern for GERD was easily distinguished from that of EoE: in patients with GERD, MI values were low in the distal esophagus and normalized along the proximal esophagus, whereas in patients with EoE, measurements were low in all segments of the esophagus. Intercept and rate of rise of MI value (slope) as distance increased from the squamocolumnar junction identified patients with GERD with an AUC = 0.67, patients with EoE with an AUC = 0.84, and patients with non-GERD with an AUC = 0.83 in the development cohort. One patient had an adverse event (reported mild chest pain after the procedure) and was discharged from the hospital without further events., Conclusions: We developed a balloon MI catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy and found it to be safe and able to identify patients with GERD, EoE, or non-GERD. We validated our findings in a separate cohort for patients. ClinicalTrials.gov ID NCT03103789., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)