Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high‐resolution manometry (HRM). Fifty‐two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two‐years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.

GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symptoms persist and endoscopy does not reveal evidence of GERD, oesophageal function tests are performed, including oesophageal manometry and ambulatory reflux monitoring. However, reflux episodes can be physiological, and some findings on endoscopy and manometry can be encountered in asymptomatic individuals without GERD symptoms. The diagnosis of GERD on the basis of functional oesophageal testing has been previously reported, but no updated expert recommendations on indications and the interpretation of oesophageal function testing in GERD has been made since the Porto consensus over a decade ago. In this Consensus Statement, we aim to describe modern oesophageal physiological tests and their analysis with an emphasis on establishing indications and consensus on interpretation parameters of oesophageal function testing for the evaluation of GERD in clinical practice. This document reflects the collective conclusions of the international GERD working group, incorporating existing data with expert consensus opinion.

Background Mean nocturnal baseline impedance (MNBI), a novel pH-impedance metric, may be a surrogate marker of reflux burden. Aim To assess the predictive value of MNBI on symptomatic outcomes after antireflux therapy. Methods In this prospective observational cohort study, pH-impedance studies performed over a 5-year period were reviewed. Baseline impedance was extracted from 6 channels at three stable nocturnal 10-min time periods, and averaged to yield MNBI. Distal and proximal esophageal MNBI values were calculated by averaging MNBI values at 3, 5, 7, and 9 cm, and 15 and 17 cm, respectively. Symptomatic outcomes were measured as changes in global symptom severity (GSS, rated on 100-mm visual analog scales) on prospective follow-up after medical or surgical antireflux therapy. Univariate and multivariate analyses assessed the predictive value of MNBI on symptomatic outcomes. Results Of 266 patients, 135 (50.8%) were tested off PPI therapy and formed the study cohort (52.1±1.1 yrs, 63.7% F). The 59 with elevated acid exposure time (AET) had lower composite and distal MNBI values than those with physiologic AET (p<0.0001), but similar proximal MNBI (p=0.62). Linear AET negatively correlated with distal MNBI, both individually and collectively (Pearson's r=−0.5, p<0.001), but not proximal MNBI (Pearson's r=0, p=0.72). After prospective follow-up (94 patients followed for 3.1±0.2 yrs), univariate and multivariate regression models showed that distal MNBI, but not proximal MNBI, was independently predictive of linear GSS improvement. Conclusions Distal esophageal MNBI negatively correlates with AET and, when assessed off PPI therapy, is independently predictive of symptomatic improvement following antireflux therapy.

OBJECTIVES pH-impedance testing detects reflux events irrespective of pH, but its value in predicting treatment outcome is unclear. We prospectively evaluated subjects treated medically after pH-impedance testing to determine predictors of symptom improvement. METHODS Subjects referred for pH-impedance testing completed questionnaires in which dominant symptoms and global symptom severity (GSS) were recorded. Acid-reflux parameters (acid-exposure time, AET; symptom association by Ghillebert probability estimate, GPE; symptom index, SI) and impedance reflux parameters (reflux-exposure time, RET; number of reflux events; GPE and SI with impedance data) were extracted. Symptoms and GSS were prospectively reevaluated after medical therapy. Univariate and multivariate analyses determined predictors of GSS improvement following medical management. RESULTS Over 5 years, 128 subjects (mean 53.3 ± 1.3 years, 66.4% female; typical symptoms 57.0%, 53.9% tested on therapy) underwent pH-impedance testing and subsequent medical therapy for reflux symptoms, and completed required questionnaires. On follow-up 3.35 ± 0.14 years later, mean GSS declined by 45.0%, with 42.2% patients reporting ≥50% GSS improvement. On univariate analysis, total AET, AET ≥4.0%, and GPE for all reflux events predicted both linear and ≥50% GSS improvement, but RET and number of reflux events did not. On multivariate analysis, controlling for testing on or off therapy, only AET (P = 0.003) and GPE for all reflux events (P = 0.029) predicted GSS improvement. CONCLUSIONS Acid-based reflux parameters offer greater value over impedance-based nonacid-reflux parameters in predicting symptomatic responses to proton pump inhibitor (PPI) therapy. Our findings support conducting pH-impedance studies off PPI therapy to maximize clinical utility in predicting outcome.

Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term "refractory GERD" has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term "refractory GERD symptoms" only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.

The functional luminal imaging probe (FLIP) utilizes impedance planimetry technology to assess lumen dimensions along the length of the esophagus and esophageal distensibility (ie, the relationship of dimension with distensive pressure) during controlled volumetric distension. We developed a technique to assess esophageal motility using FLIP and a volume distention protocol, FLIP panometry,

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

ObjectiveLimitations 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.DesignOf 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).ResultsConsensus 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.ConclusionNormal 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.