Peroral endoscopic myotomy and its use in non-achalasia disorders.

The aim of this review is to provide an overview of per-oral endoscopic myotomy (POEM) and its utilization in non-achalasia disorders of the esophagus. POEM, a relatively novel endoscopic technique, involves submucosal tunneling to access esophageal muscle layers, enabling selective myotomy and mitigating the consequences of motor disorders of the esophagus. POEM is an effective treatment modality for diffuse esophageal spasm providing resolution of chest pain and dysphagia in a majority of patients who have refractory symptoms despite medical therapy. The results of POEM are more equivocal compared to esophagogastric junction outflow obstruction (EGJOO). POEM in EGJOO has been shown to have a 93% clinical success rate in 6 months. POEM appears to be more effective in motor disorders that affect the lower esophageal sphincter, such as EGJOO and opioid-induced esophageal dysfunction. While the current data for POEM in other entities such as DES and HE are positive, more supportive data are required to make POEM a consistent recommendation for patients.

Endoscopic submuscular dissection as a rescue for severe fibrosis after incomplete polypectomy.

Video 1Endoscopic submuscular dissection as a rescue for severe fibrosis after incomplete polypectomy.

Identification of Achalasia Within Absent Contractility Phenotypes on High-Resolution Manometry: Prevalence, Predictive Factors, and Treatment Outcome.

INTRODUCTION: Absent contractility on high-resolution manometry (HRM) defines severe hypomotility but needs distinction from achalasia. We retrospectively identified achalasia within absent contractility using HRM provocative maneuvers, barium esophagography, and functional lumen imaging probe (FLIP). METHODS: Adult patients with absent contractility on HRM during the 4-year study period were eligible for inclusion. Inadequate studies, achalasia after therapy, or prior foregut surgery were exclusions. Upright integrated relaxation pressure (IRP) >12 mm Hg, panesophageal pressurization, and/or elevated IRP on multiple rapid swallows and rapid drink challenge (RDC) were considered abnormal. Esophageal barium retention and abnormal esophagogastric junction distensibility index (<2.0 mm 2 /mm Hg) on FLIP defined achalasia. Clinical, endoscopic, and motor characteristics of patients with achalasia were compared with absent contractility without obstruction. RESULTS: Of 164 patients, 20 (12.2%) had achalasia (17.9% of 112 patients with adjunctive testing), while 92 did not, and 52 did not undergo adjunctive tests. Achalasia was diagnosed regardless of IRP value, but the median supine IRP was higher (odds ratio 1.196, 95% confidence interval 1.041-1.375, P = 0.012). Patients with achalasia were more likely to present with dysphagia (80.0% vs 35.9%, P < 0.001), with obstructive features on HRM maneuvers (83.3% vs 48.9%, P = 0.039), but lower likelihood of GERD evidence (20.0% vs 47.3%, P = 0.027) or large hiatus hernia (15.0% vs 43.8%, P = 0.002). On multivariable analysis, dysphagia presentation ( P = 0.006) and pressurization on RDC ( P = 0.027) predicted achalasia, while reflux and presurgical evaluations and lack of RDC obstruction predicted absent contractility without obstruction. DISCUSSION: Despite HRM diagnosis of absent contractility, achalasia is identified in more than 1 in 10 patients regardless of IRP value.

Chronic opioid users with dysphagia are indistinguishable from symptomatic nonusers on functional lumen imaging probe evaluation.

BACKGROUND: Opioid-induced esophageal dysmotility (OIED) includes spastic esophageal motility disorders, increasingly recognized in the contemporary opioid epidemic. We assessed functional lumen imaging probe (FLIP) findings in diagnosing OIED. METHODS: Symptomatic patients undergoing FLIP with no prior foregut surgery who completed validated questionnaires were identified and segregated into chronic opioid users and nonusers in this cohort study. Esophagogastric junction (EGJ) distensibility index (DI), EGJ diameter, and esophageal body contraction patterns were extracted. Symptom profiles were compared to FLIP findings between chronic opioid users and nonusers. Outcome was evaluated in a subset using the same validated questionnaires. RESULTS: Over the 18-months study period, of 116 patients (median age 62 years, 70.7% female), 33 (28.4%) were chronic opioid users, with median morphine milligram equivalent of 30 mg. While presenting symptoms were similar, chronic opioid users reported higher perceptive symptoms (p = 0.008) and worse quality of life (p = 0.01) compared to nonusers. Median DI trended lower in chronic opioid users (p = 0.08), with more retrograde repetitive contractions (p < 0.001) and less absent contractility (p = 0.007), but final FLIP diagnoses were similar compared to nonusers. There was no correlation between opioid dose and FLIP metrics. In the subset with follow-up, perceptive symptoms trended higher in chronic opioid users (p = 0.08), but symptom improvement following therapy was similar in both groups. CONCLUSIONS & INFERENCES: Symptomatic chronic opioid users have FLIP diagnoses that are similar to nonusers, despite higher perceptive symptoms and worse quality of life. Dominant symptoms improve both in chronic opioid users and nonusers following treatment directed by FLIP.

High-Resolution Manometry Thresholds and Motor Patterns Among Asymptomatic Individuals.

OBJECTIVE: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. DESIGN: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. RESULTS: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. CONCLUSIONS: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.

Validation of choledocholithiasis predictors from the "2019 ASGE Guideline for the role of endoscopy in the evaluation and management of choledocholithiasis."

BACKGROUND AND AIMS: Identifying patients likely to have CDL is an important clinical dilemma because endoscopic retrograde cholangiopancreatography (ERCP), carries a 5-7% risk of adverse events. The purpose of this study was to compare the diagnostic test performance of the 2010 and 2019 ASGE criteria used to help risk stratify patients with suspected CDL. METHODS: Consecutive patients evaluated for possible CDL from 2013 to 2019 were identified from surgical, endoscopic, and radiologic databases at a single academic center. Inclusion criteria included all patients who underwent ERCP and/or cholecystectomy with intraoperative cholangiogram (IOC) for suspected CDL. We calculated the diagnostic test performance of criteria from both guidelines and compared their discrimination using the receiver operator curve. Univariate and multivariate analysis was used to identify the strongest component predictors. RESULTS: 1098 patients [age 57.9 ± 19.0 years, 62.8% (690) F] were included. 66.3% (728) were found to have CDL on ERCP and/or IOC. When using the 2019 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 65.8, 78.9, 86.3, 54.1, and 70.4%, respectively. Using the 2010 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 50.5, 78.9, 82.5, 44.8, and 60.1%, respectively. The AUC for high-risk criteria using the 2019 guidelines [0.726 (0.695, 0.758)] was greater than for the 2010 guidelines [0.647 (0.614, 0.681)]. The key difference providing the increased discrimination was the inclusion of stones on any imaging modality, which increased the sensitivity to 55.0% from 29.1%. Not including CDL on imaging or cholangitis, a dilated CBD was the strongest individual predictor of CDL on multivariate analysis (OR 3.70, CI 2.80, 4.89). CONCLUSION: Compared to 2010, the 2019 high-risk criterion improves diagnostic test performance, but still performs suboptimally. Less invasive tests, such as EUS or MRCP, should be considered in patients with suspected CDL prior to ERCP.

Breaks in peristaltic integrity predict abnormal esophageal bolus clearance better than contraction vigor or residual pressure at the esophagogastric junction.

BACKGROUND: High-resolution impedance manometry (HRIM) evaluates esophageal peristalsis and bolus transit. We used esophageal impedance integral (EII), the ratio between bolus presence before and after an expected peristaltic wave, to evaluate predictors of bolus transit. METHODS: From HRIM studies performed on 61 healthy volunteers (median age 27 years, 48%F), standard metrics were extracted from each of 10 supine water swallows: distal contractile integral (DCI, mmHg cm s), integrated relaxation pressure (IRP, mmHg), and breaks in peristaltic integrity (cm, using 20 mmHg isobaric contour). Pressure and impedance coordinates for each swallow were exported into a dedicated, python-based program for EII calculation (EII ratio ≥ 0.3 = abnormal bolus clearance). Univariate and multivariate analyses were performed to assess predictors of abnormal bolus clearance. KEY RESULTS: Of 591 swallows, 80.9% were intact, 10.5% were weak, and 8.6% failed. Visual analysis overestimated abnormal bolus clearance compared to EII ratio (p ≤ 0.01). Bolus clearance was complete (median EII ratio 0.0, IQR 0-0.12) in 82.0% of intact swallows in contrast to 53.3% of weak swallows (EII ratio 0.29, IQR 0.0-0.57), and 19.6% of failed swallows (EII ratio 0.5, IQR 0.34-0.73, p < 0.001). EII correlated best with break length (ρ = 0.52, p < 0.001), compared to IRP (ρ: -0.17) or DCI (ρ: -0.42). On ROC analysis, breaks predicted abnormal bolus transit better than DCI or IRP (AUC 0.79 vs. 0.25 vs. 0.44, p ≤ 0.03 for each). On logistic regression, breaks remained independently predictive of abnormal bolus transit (p < 0.001). CONCLUSIONS & INFERENCES: Breaks in peristaltic integrity predict abnormal bolus clearance better than DCI or IRP in healthy asymptomatic subjects.

Patients With Definite and Inconclusive Evidence of Reflux According to Lyon Consensus Display Similar Motility and Esophagogastric Junction Characteristics.

BACKGROUND/AIMS: The role of esophageal high-resolution manometry (HRM) within Lyon consensus phenotypes, especially patients with inconclusive gastroesophageal reflux disease (GERD) evidence, has not been fully investigated. In this multicenter, observational study we aim to compare HRM parameters in patients with GERD stratified according to the Lyon consensus. METHODS: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH (MII-pH) studies performed off proton pump inhibitor therapy in patients with esophageal GERD symptoms were reviewed. Lyon consensus criteria identified pathological GERD, reflux hypersensitivity, functional heartburn, and inconclusive GERD. Patients, with inconclusive GERD were further subdivided into 2 groups based on total reflux numbers (≤ 80 or > 80 reflux episodes) during the MII-pH recording time. RESULTS: A total of 264 patients formed the study cohort. Pathological GERD and inconclusive GERD patients were associated with higher numbers of reflux episodes, lower mean nocturnal baseline impedance (MNBI) values, and a higher proportion of patients with pathologic MNBI compared to functional heartburn (P < 0.05 for each comparison). On multivariate analysis, pathological GERD and inconclusive GERD patients, both with ≤ 80 or > 80 reflux episodes, were significantly associated with pathologic esophagogastric junction contractile integral values and with presence of hiatus hernia (type 2/3 esophagogastric junction). Patients with inconclusive GERD and > 80 reflux episodes were significantly associated with fragmented peristalsis and ineffective esophageal motility whilst inconclusive GERD with ≤ 80 reflux episodes were significantly associated with fragmented peristalsis. CONCLUSION: Esophageal motor parameters on HRM are similar between pathologic and inconclusive GERD according to the Lyon consensus.

Duration of symptoms and manometric parameters offer clues to diagnosis of pseudoachalasia.

BACKGROUND: Pseudoachalasia manifests high-resolution manometry (HRM) findings of achalasia but results from a secondary process. We analyzed clinical and HRM characteristics of pseudoachalasia, including malignant and non-malignant subtypes. METHODS: High-resolution manometry was retrospectively reviewed in patients with confirmed pseudoachalasia, and corroborated with endoscopic and radiographic studies. A control cohort of idiopathic achalasia patients was identified. Clinical characteristics, Eckardt score, and HRM metrics were extracted from institutional records. Grouped data and medians (interquartile range) were compared between pseudoachalasia and idiopathic achalasia, and between malignant and non-malignant pseudoachalasia, using parametric and non-parametric statistical tests. KEY RESULTS: Of 28 pseudoachalasia patients (62.2 ± 2.5 years, 60.7% female), 18 (64.3%) had malignancy, and 10 (35.7%) had non-malignant obstruction. Although Eckardt score did not differentiate pseudoachalasia from 58 achalasia patients (55.9 ± 2.5 years, 53.4% female), weight loss was greater (median 9.1 [5.0-18.5] vs 3.6 [0-9.1] kg, P < .02) with shorter duration of symptoms (median 12.9 [8.0-38.6] vs 36.0 [25.7-45.0] weeks, P < .001] in pseudoachalasia. Esophagogastric junction (EGJ) metrics demonstrated lower mean IRP values and lower EGJ contractile integral in pseudoachalasia (P < .04 for each comparison with idiopathic achalasia). Type 1 pattern was more frequent in pseudoachalasia (39.3% vs 13.8%, P < .008). Pseudoachalasia demonstrated incomplete HRM patterns, with lower rates of lack of peristalsis (79.6%, vs 93.1% in achalasia, P < .05). Despite higher Eckardt scores in malignant vs non-malignant pseudoachalasia (median 8.0 [7.0-9.0] vs 6.0 [3.5-7.8], P < .03], no significant HRM differences were noted. CONCLUSIONS AND INFERENCES: Pseudoachalasia manifests with a shorter history, greater weight loss, and incomplete HRM achalasia patterns compared to achalasia.

Esophagogastric junction morphology and contractile integral on high-resolution manometry in asymptomatic healthy volunteers: An international multicenter study.

BACKGROUND: Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited. METHODS: Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions. RESULTS: Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P < 0.001). 5th percentile EGJ-CI values ranged from 6.9 to 12.1 mm Hg cm. EGJ-CI values were consistent across world regions, but different between manufacturers even within the same world region (P ≤ 0.001). Within Medtronic studies, EGJ-CI and basal LESP were similar in younger and older individuals (P ≥ 0.3) but higher in women (P < 0.001). CONCLUSIONS: EGJ morphology is predominantly type 1 in healthy adults. EGJ-CI varies widely in health, with significant gender influence, but is consistent within each HRM system. Manufacturer-specific normative values should be utilized for clinical HRM interpretation.

Postreflux swallow-induced peristaltic wave index from pH-impedance monitoring associates with esophageal body motility and esophageal acid burden.

BACKGROUND: Postreflux swallow-induced peristaltic wave (PSPW) on pH-impedance monitoring and contraction vigor on high-resolution manometry (HRM) both assess esophageal peristaltic response. We aimed to evaluate relationships between PSPW and esophageal peristalsis on HRM in the context of reflux disease in this multicenter cohort study. METHODS: pH-impedance and HRM studies performed on patients with persisting reflux symptoms were reviewed from 6 centers (5 in Europe and 1 in US). Total, upright and supine acid exposure time (AET) were evaluated from pH-impedance studies; PSPW index (PSPWI) and mean nocturnal baseline impedance (MNBI) were calculated using standard methodology. Esophageal body contraction vigor was analyzed using distal contractile integral (DCI), and DCI ratio > 1 between single swallows and multiple rapid swallows (MRS) defined presence of contraction reserve. Student's t test, ANOVA, and linear regression were utilized to investigate relationships between PSPW, contraction vigor, and contraction reserve. KEY RESULTS: Of 296 patients (52.8 ± 0.8 yr, 63% F), median PSPWI was 0.475. Only 24.0% had intact DCI; the remainder had varying degrees of hypomotility. As hypomotility increased, PSPWI and MNBI decreased significantly, while total AET and reflux episodes had an inverse response (P ≤ .002 for each). MRS data were available in 167 (56.4%), 72.5% had contraction reserve. MRS cohorts with normal PSPWI had significantly lower reflux burden compared to low PSPWI, regardless of presence or absence of contraction reserve (P ≤ .001). CONCLUSIONS AND INFERENCES: PSPWI correlates with esophageal hypomotility and reflux burden, and complements clinical reflux evaluation. Intact PSPW is more relevant to esophageal reflux clearance than contraction reserve.

Overlap of functional heartburn and reflux hypersensitivity with proven gastroesophageal reflux disease.

BACKGROUND: When esophageal acid exposure time (AET) is physiologic, ROME IV stratifies functional esophageal disorders into functional heartburn (FH, with negative reflux-symptom association) and reflux hypersensitivity (RH, with positive reflux-symptom association), and hypothesizes that FH/RH could overlap with proven gastroesophageal reflux disease (GERD). We compared conventional FH/RH diagnosed off antisecretory therapy with overlap FH/RH coexisting with proven GERD. METHODS: Adult patients with heartburn underwent pH-impedance testing on therapy (proven GERD) and off therapy (unproven GERD) and completed validated questionnaires defining symptoms (Reflux Diagnostic Questionnaire, RDQ), affective state (Hospital Anxiety and Depression Scale, HADS; Visceral Sensitivity Index, VSI), and functional diagnoses (irritable bowel syndrome, IBS; functional dyspepsia, FD on ROME diagnostic questionnaire). AET (pathologic: >6%, physiologic <4%) and mean nocturnal baseline impedance (MNBI) were calculated. Clinical, psychological, and functional profiles were compared between FH and RH and to a comparison cohort of non-erosive reflux disease (NERD, AET > 6%). KEY RESULTS: Study patients included 19 with RH (10 with overlap RH), 60 with FH (31 with overlap FH), and 26 patients with NERD. Clinical, psychological, and functional profiles of conventional FH/RH were similar to overlap FH/RH. Compared with NERD, combined FH and RH cohorts had higher anxiety scores, and lower proportions with IBS. Compared with FH with low MNBI, FH defined using both normal AET and normal MNBI had higher depression scores (p = 0.008), and trended toward higher anxiety scores (p = 0.059). CONCLUSIONS AND INFERENCES: Conventional and overlap FH and RH have similar clinical, psychological and functional profiles, thereby proving ROME IV hypotheses.

A Potential Role for Stress-Induced Microbial Alterations in IgA-Associated Irritable Bowel Syndrome with Diarrhea.

Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, this process is not well understood. Here, we find that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via the opening of goblet-cell associated passages. Notably, stress increases host immunity to gut bacteria as assessed by immunoglobulin A (IgA)-bound gut bacteria. Stress-induced microbial changes are necessary and sufficient to elicit these effects. Moreover, similar to mice, many diarrhea-predominant IBS (IBS-D) patients from two cohorts display increased antibacterial immunity as assessed by IgA-bound fecal bacteria. This antibacterial IgA response in IBS-D correlates with somatic symptom severity and was distinct from healthy controls or IBD patients. These findings suggest that stress may play an important role in patients with IgA-associated IBS-D by disrupting the intestinal microbial community that alters gastrointestinal function and host immunity to commensal bacteria.

High-resolution manometry features of paraesophageal hernia.

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.

Straight leg raise metrics on high-resolution manometry associate with esophageal reflux burden.

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.

High-resolution Manometry Determinants of Refractoriness of Reflux Symptoms to Proton Pump Inhibitor Therapy.

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.

Fragmented and failed swallows on esophageal high-resolution manometry associate with abnormal reflux burden better than weak swallows.

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.

High-resolution Manometry can Characterize Esophagogastric Junction Morphology and Predict Esophageal Reflux Burden.

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.

Mean Nocturnal Baseline Impedance Correlates With Symptom Outcome When Acid Exposure Time Is Inconclusive on Esophageal Reflux Monitoring.

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.

Correlation between reflux burden, peristaltic function, and mucosal integrity in GERD patients.

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.