Esophagogastric Junction Contractile Integral Research Articles

Manometric esophagogastric junction barrier metrics as predictors of gastroesophageal reflux.

High-resolution manometry (HRM) tools, like esophagogastric junction contractile integral (EGJ-CI), assess EGJ barrier function. This study aimed to evaluate the relationships between manometric EGJ metrics with esophageal acid exposure. We conducted a retrospective review of 284 patients who underwent HRM and ambulatory reflux testing between 11/2017-1/2020. EGJ-CI and total-EGJ-CI were manually calculated. Pathologic acid exposure was defined as pH < 4 with esophageal acid exposure time (EAET) exceeding 6.0%. Pearson's correlation, univariable and multivariable regression models were utilized to assess the relationships between pathologic acid exposure and EGJ parameters. Sensitivity and specificity thresholds for EGJ-CI and total EGJ-CI were optimized with ROC analyses. On univariable analysis, patients with pathologic acid exposure had increased odds of having lower mean basal LES pressures, EGJ-CI, and total EGJ-CI than patients without pathologic acid exposure. On multivariable analysis, age, EGJ-CI and mean DCI were significant predictors of pathologic acid exposure. There were significant, though weak, correlations between EAET and EGJ-CI and total EGJ-CI (r = - 0.18, - 0.19, p < 0.01, respectively). An EGJ-CI cutoff of 44.16 as a predictor for pathologic acid exposure had a sensitivity of 46% and specificity of 42% (AUC 0.60). Total EGJ-CI cutoff of 11,461.3 for pathologic acid exposure had a sensitivity of 44% and a specificity of 43% (AUC 0.62). EGJ-CI can independently predict pathologic acid exposure. However, the poor correlation between EGJ-CI and acid exposure, as well as the low sensitivity and specificity of calculated thresholds, indicate that mechanisms other than EGJ barrier function may impact acid exposure.

The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease.

A definitive diagnosis of gastroesophageal reflux disease (GERD) depends on endoscopic and/or pH-study criteria. However, high resolution manometry (HRM) can identify factors predicting GERD, such as ineffective esophageal motility (IEM), esophago-gastric junction contractile integral (EGJ-CI), evaluating esophagogastric junction (EGJ) type and straight leg raise (SLR) maneuver response. We aimed to build and externally validate a manometric score (Milan Score) to stratify the risk and severity of the disease in patients undergoing HRM for suspected GERD. A population of 295 consecutive patients undergoing HRM and pH-study for persistent typical or atypical GERD symptoms was prospectively enrolled to build a model and a nomogram that provides a risk score for AET>6%. Collected HRM data included IEM, EGJ-CI, EGJ type and SLR. A supplemental cohort of patients undergoing HRM and pH-study was also prospectively enrolled in 13 high-volume esophageal function laboratories across the world in order to validate the model. Discrimination and calibration were used to assess model's accuracy. Gastroesophageal reflux disease was defined as acid exposure time >6%. Out of the analyzed variables, SLR response and EGJ subtype 3 had the highest impact on the score (odd ratio 18.20 and 3.87, respectively). The external validation cohort consisted of 233 patients. In the validation model, the corrected Harrel c-index was 0.90. The model-fitting optimism adjusted calibration slope was 0.93 and the integrated calibration index was 0.07, indicating good calibration. A novel HRM score for GERD diagnosis has been created and validated. The MS might be a useful screening tool to stratify the risk and the severity of GERD, allowing a more comprehensive pathophysiologic assessment of the anti-reflux barrier. ClinicalTrials.gov (Identifier: NCT05851482).

Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility: Studies Using High-resolution Manometry.

This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. Codeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Effect of Body Weight and Obesity on Esophageal Function.

The incidence of obesity in the population is gradually increasing. Obesity can cause a variety of complications in the digestive system such as gastroesophageal reflux disease, and impacts the integrity of the esophageal mucosal barrier and esophageal motility. However, not many studies have focused on the effect of varying degrees of obesity on the esophagus. A total of 611 participants were included in this study. We divided them into three groups according to their body mass index (BMI): the normal weight group, the overweight group, and the obesity group. We performed a retrospective comparison between groups based on indicators from high resolution esophageal manometry (HREM) and 24-hour pH impedance monitoring, and did a correlation analysis on multiple indicators such as esophageal mucosal barrier, esophageal motility, and acid reflux. The mean nocturnal baseline impedance (MNBI) in the overweight and obesity groups was lower than that in the normal group. The MNBI of the subjects in Z5-Z6 channels in the overweight group was significantly lower than that in the normal group. With respect to Z3-Z6 channels, MNBI values in the obesity group were significantly lower than those in the normal group. 'The acid exposure time (AET), the DeMeester scores (DMS) and 24-hour total reflux episodes was significantly higher in the obesity group than those in the normal and overweight groups. The upper esophageal sphincter (UES) residual pressure, and intrabolus pressure (IBP) in the overweight and obesity groups were significantly higher than those in the normal group. In addition, lower esophageal sphincter (LES) resting pressure, and esophagogastric junction contractile integral (EGJ-CI) in the obesity group were significantly higher than those in the normal group. We found that increase in body weight affected the integrity of esophageal mucosa, and different degrees of increase associated with different degrees and different aspects of changes in esophageal motility.

Esophagogastric junction contractile integral (EGJ-CI) complements reflux disease severity and provides insight into the pathophysiology of reflux disease.

Esophagogastric junction contractile integral (EGJ-CI) has not come into routine use due to methodological discrepancies and its unclear clinical utility. We aimed to determine which method of calculating EGJ-CI was best at discriminating between common reflux disease states. High-resolution manometry (HRM) and pH-Impedance measurements were acquired for 100 patients; 25 Barrett's esophagus (>3 cm/acid exposure time (AET) > 6), 25 endoscopy-negative reflux disease (ENRD; AET >6), 25 borderline reflux (AET 4-6), 25 functional heartburn (FH; AET <4), constituting the developmental cohort. EGJ-CI was calculated at 20 mmHg, 2 mmHg, and 0 mmHg isobaric contour. Empirical associations, univariable, multivariable and ROC analyses were performed between EGJ-CI and manometric/pH-impedance metrics. A validation cohort (n = 25) was used to test the new EGJ-CI cutoff. Significant correlations with AET were observed when EGJ-CI was calculated with an isobaric threshold of 20 mmHg (p < 0.001). Significant differences in EGJ-CI were observed between patients with FH and Barrett's esophagus (p = 0.004) and with ENRD (p = 0.01); however, LES basal pressure was unable to differentiate between these disease states (p = 0.09, p = 0.25, respectively). ROC analysis on the developmental cohort found that EGJ-CI 21.2 mmHg.cm demonstrated sensitivity 72% and specificity 72% between patients with reflux (Barrett's esophagus/ENRD) and FH. In the validation cohort, 92.8% with a low EGJ-CI had good/moderate improvement in symptoms following therapy compared to 54.5% with raised EGJ-CI (p = 0.026). This study re-affirms EGJ-CI as a reliable discriminator between reflux disease (Barrett's esophagus/ENRD) and FH. In borderline reflux patients, patients with a lower EGJ-CI score (<21.2 mmHg) appear to respond better to anti-reflux therapies compared to those with a higher value.

Improving the Diagnostic Yield of High-Resolution Esophageal Manometry for GERD: The “Straight Leg-Raise” International Study

The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET). Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%. The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected. gov ID: NCT04813029.

Esophageal manometry findings in patients with refractory symptoms of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. High-resolution esophageal manometry (HREM) and 24-h pH study help to properly evaluate GERD patients. The aim of the present study was to classify patients with refractory GERD symptoms into various groups based on endoscopic and physiological testing.The present study is a retrospective analysis of patients referred for HREM and 24-h pH recording between 2019 and 2021. We included all adult patients (age > 18 years) who were referred for evaluation of refractory GERD symptoms. Upper gastrointestinal endoscopy findings, HREM, and 24-h pH findings were noted. Patients were divided into erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH) based on test results. Demographic details and HREM parameters were compared in the four groups. Statistics used are one-way analysis of variance (ANOVA) and Chi-squared tests. A p-value of <0.05 was considered statistically significant.A total of 144 patients were included-NERD (56, 38.9%), ERD (42, 29.2%), RH (28, 19.5%), and FH (18, 12.5%). Age (p 0.74), andsex distribution (p 0.47), and symptom profile (p 0.12) were similar. The presence of type 2/3 esophagogastric junction (EGJ) morphology was commoner in ERD and NERD (p <0.001). Moreover, the esophagogastric junction contractile integral (EGJ-CI) and basal inspiratory pressures were significantly lower in these two groups (p<0.05). EGJ-CI was low in 32 cases of ERD (76.2%), 41 cases with NERD (73.2%), 7 cases with RH (25%), and 3 cases with FH (16.7%), respectively (p-value < 0.00001).FH and RH account for 32% of cases with refractory GERD symptoms. Impaired EGJ function was more common in ERD and NERD patients compared to FH and RH patients.

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

Background/AimsThe 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.MethodsClinical 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.ResultsA 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.ConclusionEsophageal motor parameters on HRM are similar between pathologic and inconclusive GERD according to the Lyon consensus.

Esophagogastric junction contractile integral abnormalities in patients with proton pump inhibitor-refractory symptoms.

Esophagogastric junction contractile integral (EGJ-CI) is a novel indicator to evaluate quantitatively the esophagogastric junction (EGJ) barrier function. We aimed to assess the role of EGJ-CI in patients with refractory gastroesophageal reflux disease (GERD) symptoms and the correlation between EGJ-CI and impedance-pH monitoring characteristics. In total 82 patients with proton pump inhibitors (PPIs)-refractory gastroesophageal reflux symptoms (heartburn or regurgitation) were enrolled. These patients were further divided into two groups based on their EGJ-CI value (39 mmHg·cm). The mean nocturnal baseline impedance (MNBI) was measured to explore its association with EGJ-CI. The median EGJ-CI in patients with PPI-refractory symptoms was 30.8 mmHg·cm. EGJ-CI was inversely correlated with acid exposure time and reflux episodes; while it was positively correlated with MNBI, distal contractile integral, lower esophageal sphincter basal pressure and integrated relaxation pressure. Patients were further divided into the high (n=27) and low (n=55) EGJ-CI groups using a cut-off value of 39.0 mmHg·cm. Patients with a low EGJ-CI had a lower MNBI level than those with a high EGJ-CI (2703 Ω vs 3545 Ω, P = 0.034). In patients with PPIs-refractory symptoms, EGJ-CI is associated with acid exposure and conventional high-resolution manometry parameters. EGJ-CI may play an important role in the diagnosis and treatment of patients with refractory GERD.

Chicago Classification update (v4.0): Technical review of high-resolution manometry metrics for EGJ barrier function.

Esophagogastric junction (EGJ) barrier function is of fundamental importance in the pathophysiology of gastroesophageal reflux disease. Impaired EGJ barrier function leads to excessive distal esophageal acid exposure or, in severe cases, esophagitis. Hence, proposed high-resolution manometry (HRM) metrics assessing EGJ integrity are clinically important and were a focus of the Chicago Classification (CC) working group for inclusion in CC v4.0. However, the EGJ is a complex sphincter comprised of both crural diaphragm (CD) and lower esophageal sphincter (LES) component, each of which is subject to independent physiological control mechanisms and pathophysiology. No single metric can capture all attributes of EGJ barrier function. The working group considered several potential metrics of EGJ integrity including LES-CD separation, the EGJ contractile integral (EGJ-CI), the respiratory inversion point (RIP), and intragastric pressure. Strong recommendations were made regarding LES-CD separation as indicative of hiatus hernia, although the numerical threshold for defining hiatal hernia was not agreed upon. There was no agreement on the significance of the RIP, only that it could localize either above the LES or between the LES and CD in cases of hiatus hernia. There was agreement on how to measure the EGJ-CI and that it should be referenced to gastric pressure in units of mmHgcm, but the numerical threshold indicative of a hypotensive EGJ varied widely among reports and was not agreed upon. Intragastric pressure was endorsed as an important metric worthy of further study but there was no agreement on a numerical threshold indicative of abdominal obesity.

Comparison of high-resolution manometry parameters among type II diabetes patients and normal volunteers

Background: Gastrointestinal (GI) autonomic neuropathy and reflux esophagitis are common in chronic diabetics. To gauge the adequacy of peristalsis, high-resolution esophageal manometry is considered as a reliable test. Aim and Objective: To compare the GI symptoms and high-resolution manometry parameters between type II diabetes patients and normal volunteers. Materials and Methods: This comparative study was conducted on 35 known type II diabetes mellitus patients (hemoglobin A1c [HbA1c] levels ≥6.5%) and 35 normal volunteers between the age group of 35 and 70 years. Sociodemographic details, drug history, disease duration, and GI symptoms were elicited among the study participants. HbA1c and High-resolution manometry were measured for all the participants. Results: The frequency of epigastric pain (31.48%), heartburn (34.28%), pharyngeal irritation (31.43%), and loose stools (37.14%) were significantly higher in the diabetics. Significant difference (P < 0.05) was observed in mean basal expiratory pressure (MBEP) and mean basal inspiratory pressure (MBIP) values between diabetics and controls. There was a positive significant correlation between esophagogastric junction contractile integral and MBIP (r = 0.557), MBEP (r = 0.583), Median Integrated Relaxation pressure (r = 0.410). Conclusion: Hyperglycaemia seems to be an independent risk factor for gastroesophageal reflux disease (GERD). Obesity significantly increments the occurrence of GERD in diabetics. Strict adherence to preventive measures such as weight reduction, diet management, glycaemic control will have a great impact on the occurrence of GERD in diabetics.

Evaluation of the Esophagogastric Junction on High Resolution Manometry.

The esophagogastric junction (EGJ) is a complex barrier between the thoracic and abdominal luminal gut compartments, comprised primarily of the lower esophageal sphincter (LES) and crural diaphragm. Although closed at rest, the EGJ relaxes to allow antegrade bolus transit and retrograde venting of air. Abnormal relaxation is the hallmark of achalasia spectrum disorders, while increased frequency of transient lower esophageal sphincter relaxations and/or EGJ disruption are seen in gastroesophageal reflux disease. High resolution manometry (HRM) is the modern day gold standard for assessment of EGJ morphology and function, with better performance characteristics compared with endoscopy and barium esophagography. Conventional LES metrics defining EGJ function include resting LES pressure as well as postswallow residual pressures. Newer HRM-based metrics include EGJ contractile integral, which measures static barrier function at rest, and EGJ morphology, which characterizes the relationship between LES and crural diaphragm. Provocative maneuvers assess dynamic EGJ function during physiological or pharmacologic stress. The most useful of these maneuvers, the rapid drink challenge, assesses for latent obstruction, while multiple rapid swallows evaluate adequacy of deglutitive inhibition. Amyl nitrate and cholecystokinin administration can segregate motor from structural obstruction. Newer provocative tests (straight leg raise maneuver, abdominal compression) and novel diagnostic tools (functional lumen imaging probe) complement HRM evaluation of the EGJ. Although current HRM metrics and maneuvers show promise in identifying clinically relevant EGJ abnormalities, future investigations evaluating management outcomes will improve segregation of normal from abnormal EGJ morphology and function.

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

Background/AimsImpaired 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.MethodsClinical 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.ResultsOf 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.ConclusionsIntact 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.

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

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. 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. Of 28 pseudoachalasia patients (62.2±2.5years, 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±2.5years, 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. Pseudoachalasia manifests with a shorter history, greater weight loss, and incomplete HRM achalasia patterns compared to achalasia.

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

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. Adult patients being evaluated for reflux symptoms with esophageal physiologic testing off antisecretory therapy over a 12month 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. Of 122 patients, 70 (57.4%) had ≥50% peak intra-abdominal pressure increase during SLR (58.0±1.4years, 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). Analysis of intra-esophageal pressure gradients during SLR, a simple HRM maneuver, may augment evaluation of symptomatic GERD, and provide adjunctive evidence supporting GERD.

Influence of sildenafil on esophageal motor function in humans: Studies using high-resolution manometry.

Sildenafil induces smooth muscle relaxation of the esophagus by blocking type 5 phosphodiesterase that degrades cyclic guanine monophosphate. We aimed to characterize the effects of sildenafil on esophageal peristalsis and contraction reserve using high-resolution manometry (HRM). Fifteen healthy adults (12 men, age 21-39, mean 27years) participated in this study using HRM following either sildenafil 50mg or placebo. HRM with ten wet swallows and five multiple rapid swallows was performed in all participants. HRM metrics included esophagogastric junction contractile integral (EGJ-CI), basal lower esophageal sphincter (LES) pressure, 4-second integrated relaxation pressure (IRP-4s), distal contractile integral (DCI), distal latency, resting upper esophageal sphincter pressure (UESP), and the response to MRS. Sildenafil significantly lowered EGJ-CI (P<.001), LES pressure (P=.04), IRP-4s (P=.02), and DCI (P<.001). There was no difference in UESP (P=.87) between sildenafil and placebo. Sildenafil significantly decreased peristaltic vigor, inducing absent peristalsis in 12 subjects and ineffective esophageal motility in 3 subjects. Peristaltic response and augmentation following MRS were significantly inhibited following sildenafil (7% vs 100%, P<.001, and none vs 73%, P<.001). Sildenafil attenuates EGJ barrier function, resting LES pressure, and LES relaxation. Both esophageal body contractility and contraction reserve are inhibited by sildenafil in healthy adults.

Trans-esophagogastric junction pressure gradients during straight leg raise maneuver on high-resolution manometry associate with large hiatus hernias.

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. Consecutive patients undergoing esophageal HRM were included if they had adequate SLR (hip flexion with knees extended for≥5seconds 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<3cm; type 3: separation of≥3cm). 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<1mmHg denoted the equalization of pressures. Of 430 patients, 248 (57.5±0.9years, 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±1.8mmHg vs. -8.6±4.8mmHg, P=.01). More type 3 EGJ patients equalized peak (65%) pressures across EGJ compared with types 1 and 2 (27%, P<.001). The evaluation of intra-abdominal and intra-thoracic pressures with SLR during esophageal HRM can provide evidence of physiological disruption of the EGJ barrier.

Study on esophageal motility and anti-reflux barrier function in patients with heartburn symptom and negative endoscopic findings based on Rome IV criteria

Objective To evaluate esophageal motility and anti-reflux barrier function in patients with different phenotypes of heartburn and negative endoscopic findings based on the Rome Ⅳ criteria. Methods From March 2011 to November 2018, 136 patients with heartburn and negative endoscopic findings were retrospectively analyzed. The patients underwent high-resolution manometry (HRM), 24-hour pH monitoring and proton pump inhibitor (PPI) test and according to the Rome Ⅳ criteria and new diagnostic procedures, they were divided into non-erosive reflux disease (NERD) group, reflux hypersensitivity (RH) group, functional heartburn (FH) group and unclassified group. During the same period, 20 healthy volunteers were selected as healthy control group. The changes of esophageal motility and HRM were analyzed among different groups. Statistical analysis was performed using one-way analysis of variance, Kruskal-Wallis H test and chi-square test. Results According to Rome Ⅳ criteria, 35 patients were enrolled into the NERD group, 43 patients were enrolled into the RH group, 48 patients were included in the FH group, and 10 patients were enrolled into unclassified group. There were no significant differences between the NERD group, the RH group, the FH group, the unclassified group and healthy control group in the length of the lower esophageal sphincter (LES), end lower esophageal sphincter resting pressure (LESP), mean LESP, 4-second-integrated relaxation pressure (4 s-IRP), distal latency (DL) , upper esophageal sphincter residual pressure (UES-RP), upper esophageal sphincter relaxation time to nadir, upper esophageal sphincter (UES) recovery time and esophagogastric junction contractile integral (EGJ-CI, all P>0.05). The distal contractile integral (DCI) of NERD group and unclassified group were both lower than that of healthy control group (919.7 mmHg·s·cm (411.7, 1 417.9) mmHg·s·cm (1 mmHg=0.133 kPa), 535.6 mmHg·s·cm (321.4, 1 513.4) mmHg·s·cm vs. 1 322.1 mmHg·s·cm (841.6, 1 918.5) mmHg·s·cm), and the differences were statistically significant (Z=-2.62 and -2.20, P=0.01 and 0.03). The upper esophageal sphincter pressure (UESP) of the unclassified group was lower than that of the healthy control group(57.0 mmHg (31.3, 77.8) mmHg vs. 70.4 mmHg (49.4, 97.8) mmHg), and the difference was statistically significant (Z=-2.64, P=0.02). There was significant difference in esophagogastric junction (EGJ) subtypes between the NERD group, the RH group, the FH group and the unclassified group (χ2=10.85, P=0.02); the proportion of type Ⅲ patients was highest in unclassified group, followed by NERD group, which were both higher than those of RH group and FH group. There was no significant difference in the proportion of esophageal motility subtypes between NERD group, RH group, FH group and unclassified group (P>0.05). Conclusions Patients with different phenotypes of heartburn and negative endoscopy finding should be classified by efficient diagnostic procedure according to the Rome Ⅳ criteria combined with HRM, 24-hour pH monitoring and PPI test. The unclassified patients need further evaluation, especially for those with effective PPI test and negative pH monitoring. However, the evaluation of anti-reflux barrier function by the HRM parameters in patients with heartburn and negative endoscopic findings has certain limitations. Key words: Heartburn; Esophageal pH monitoring; Non-erosive reflux disease; Reflux hypersensitivity; Manometry; Rome Ⅳ

Effects of GABA-B agonist baclofen on esophageal motility: Studies using high-resolution manometry.

Baclofen inhibits transient lower esophageal sphincter (LES) relaxation. This study aimed to investigate the effect of baclofen on esophageal peristaltic function and contraction reserve in healthy adults using high-resolution manometry (HRM). Fifteen subjects underwent HRM with ten water swallows and five multiple rapid swallows (MRS) 90minutes after oral intake of either baclofen or placebo on separate days at least 1week apart. HRM parameters assessed included esophagogastric junction contractile integral (EGJ-CI), resting LES pressure, 4-second integrated relaxation pressure (IRP-4s), distal contractile integral (DCI), distal latency, peristaltic breaks, resting upper esophageal sphincter (UES) pressure, and contractile response to MRS. Baclofen significantly increased EGJ-CI (P=.007), IRP-4s (P=.003), and LES pressure (P=.004). UES pressure, latency, and DCI were similar between baclofen and placebo (P=.87, P=.84, and P=.54, respectively). There was no difference in contractile response and peristaltic augmentation following MRS between baclofen and placebo (93% vs 100%, P=.30; 53% vs. 73%, P=.26, respectively). Baclofen increases resting LES pressure and EGJ barrier function, but has no effect on primary peristalsis or contraction reserve.

Esophagogastric junction function and gastric pressure profile after minigastric bypass compared with Billroth II

BackgroundMinigastric bypass (MGB) is being performed widely with effective weight loss and improvement in co-morbidities. Because of similarity to Billroth II (BII), there are concerns about bile reflux. ObjectivesTo assess the esophagogastric junction (EGJ) function, esophageal peristalsis, and reflux exposure after MGB and BII. SettingUniversity Hospital, Italy; Public Hospital, Italy. MethodsObese patients underwent symptom questioning, endoscopy, high-resolution impedance manometry, and impedance-pH monitoring, before and 1 year after MGB. Esophageal motor function, EGJ, EGJ–contractile integral, intragastric pressure (IGP), and gastroesophageal pressure gradient were determined. Acid exposure time, number of refluxes, and symptom-association probability were assessed. A group of patients who underwent BII were studied with the same protocol and served as controls. ResultsTwenty-two MGB and 20 BII patients were studied. After surgery, none of the patients reported de novo heartburn or regurgitation. At endoscopic follow-up, esophagitis and bile findings were absent in all. High-resolution impedance manometry features did not vary significantly after MGB, whereas IGP and gastroesophageal pressure gradient statistically diminished (P < .01). BII patients had significantly lower values in IGP, sphincter pressure, and EGJ–contractile integral. In MGB patients, a marked decrease in number of refluxes (from median 41 to 7, P < .01) was observed, whereas BII patients had statistically significant higher acid exposure and number of refluxes (57, P < .001). ConclusionsIn contrast to BII, MGB does not increase any kind of reflux. Also, the differences in IGP and gastroesophageal pressure gradient suggest that bile reflux occurs more readily after BII than after MGB, and that these 2 operations share more differences than similarities.