Interrogation of esophagogastric junction barrier function using the esophagogastric junction contractile integral: an observational cohort study

Abstract

The esophagogastric junction contractile integral (EGJ-CI), designed similar to distal contractile integral (DCI), has been proposed as a metric to evaluate EGJ barrier function. We determined normative values and evaluated EGJ-CI in predicting esophageal acid exposure time (AET) and symptomatic outcome in this observational cohort study. High-resolution manometry (HRM) studies were reviewed in 188 patients (55.2 ± 0.9 years, 64% female) undergoing ambulatory pH monitoring off therapy. Dominant symptoms and global symptom severity (GSS) were determined on questionnaires initially and upon follow-up. EGJ-CI was measured using the DCI tool placed across the EGJ and compared to normal controls (n = 21, 27.6 ± 0.6 years, 52% female). EGJ-CI was calculated both for a single respiratory cycle (SRC, in mmHg.cm.s) and corrected for respiratory cycle (CRC, mmHg.cm). Univariate and multivariate analyses determined the predictive potential of EGJ-CI in terms of AET and post-therapy GSS at follow-up, controlling for medical versus surgical therapy. Mean EGJ-CI values were significantly lower when AET was abnormal; EGJ-CI/SRC and EGJ-CI/CRC were 86% concordant (r = 0.84). Using receiver operating characteristic analysis, values below 121.8 mmHg.cm.s (EGJ-CI/SRC) and 39.3 mmHg.cm (EGJ-CI/CRC) predicted abnormal AET best (sensitivity 0.61 and 0.65, specificity 0.61 and 0.57, respectively). On univariate and multivariate analysis, the EGJ-CI discriminated normal from abnormal AET better than conventional LES parameters (P ≤ 0.02). After 2.7 ± 0.1 years follow-up, EGJ-CI below identified thresholds predicted better symptom response to antireflux surgery compared to medical therapy (P = 0.009). EGJ-CI is a novel HRM metric that has potential to complement or replace currently used basal LES and EGJ parameters.

Keywords: esophagogastric junction; gastroesophageal reflux disease; high-resolution manometry.

Fig. 1

Calculation window for measurement of the esophagogastric junction contractile integral (EGJ-CI). (A) The software tool assessing contraction vigor (distal contractile vigor) is forced into a rectangle encompassing the proximal and distal extents of the EGJ, and covering exactly three respiratory cycles during a period of quiet rest and baseline breathing (landmark phase). EGJ-CI is recorded above the gastric baseline during the landmark phase. The value is divided by 3 to obtain EGJ-CI for a single respiratory cycle (EGJ-CI/SRC); division by the duration of the three respiratory cycles provides the EGJ-CI corrected for respiration (EGJ-CI/CRC). (B) In the presence of a measurable and consistent separation between the lower esophageal sphincter (LES) and the diaphragmatic crura, the distal contractile integral (DCI) rectangle is forced across the LES high-pressure zone for the duration of three respiratory cycles. The remainder of the calculations are exactly the same as described above.

Fig. 2

Receiver operating characteristic (ROC) curves defining optimal esophagogastric junction contractile integral (EGJ-CI) thresholds for segregating subjects with normal and abnormal esophageal acid exposure. Both EGJ-CI calculated for a single respiratory cycle (EGJ-CI/SRC) and corrected for respiration (EGJ-CI/CRC) provided equivalent segregation of subjects with and without abnormal acid exposure times. Threshold values provided sensitivity of 61–65% range and specificity of 58–65%, with modest area under the curve (0.6–0.7).

Fig. 3

Correlation between esophagogastric junction contractile integral (EGJ-CI) calculated for a single respiratory cycle (SRC) and corrected for respiration (CRC). The two metrics demonstrated excellent correlation of 86% (Pearson's r = 0.84, P < 0.0001), with most discordant values clustered around the identified thresholds for each value.

Fig. 4

Correlation between esophagogastric junction contractile integral (EGJ-CI) and conventional lower esophageal sphincter (LES) metrics. Both EGJ-CI calculated for a single respiratory cycle (SRC) and corrected for respiration (CRC) correlated very well with mean basal LES pressure (Pearson's r = 0.73–0.74, P < 0.0001) and end-expiratory LES pressure (Pearson's r = 0.66–0.67, P < 0.0001) indicating that the EGJ-CI can adequately replace conventional metrics.

Fig. 5

Symptomatic outcome segregated by esophagogastric junction contractile integral (EGJ-CI) thresholds after antireflux therapy. The likelihood of an excellent outcome (100-point visual analog score of <25 on follow-up) was significantly higher with antireflux surgery compared to medical management when EGJ-CI values were below the identified thresholds. This suggests that the EGJ-CI has values in predicting patients likely to improve following antireflux surgery in contrast to medical therapy.