Gastroesophageal flap valve reflected EGJ morphology and correlated to acid reflux

The dysfunction of anti-reflux barrier was a main cause for gastroesophageal reflux disease (GERD). The esophagogastric junction (EGJ) plays the fundamental role for the barrier. The anatomical structures of EGJ are complex, containing lower esophageal sphincter (LES), crural diaphragm (CD), His angle and flap valve.

The gastroesophageal flap valve (GEFV) is a 180-degree musculomucosal fold apposite to the lesser curvature of stomach as viewed with a retroflexed endoscope [1]. It is created by the intraluminal extension of His angle. The GEFV was first described by Thor et al. in 1987 [2], and the grading system was created by Hill et al. in 1996 [1]. Respiration and taking meal can influence GEFV. Decrease of His angle degree during expiration allows the contact to be closer. The proximal fundus becomes more spherical in the transverse plane when the gastric is filled, which may enhance the strength of anti-reflux barrier [3]. The GEFV grade IV is associated with hiatus hernia [1]. Several studies have reported that the GEFV grades were associated with acid reflux and may be helpful to predict the response of proton pump inhibitor (PPI) treatment [4‐7]. LES and CD are recognized as the main determinants of EGJ pressure, but the contribution of GEFV in the strength of anti-reflux barrier is still controversial, because the presence of intact GEFV is not enough to exclude the diagnose of GERD [7]. Transoral incisionless fundoplication (TIF) is useful in reinforcing the valve strength. TIF can reduce the distensibility of EGJ, associated with a decreased volume of refluxte [8, 9]. These results suggest that the intact flap valve may play an assistant role in the anti-reflux barrier and reporting the Hill classification on endoscopy would be helpful in identifying GERD patients.

The high-resolution manometry (HRM) is a useful tool in assessing EGJ function. With the advantage of synchronous and fine fidelity on presenting the peristalsis of whole esophagus, HRM can distinguish EGJ more accurately [10, 11]. There are three traditional metrics used to evaluate the EGJ function. Integrated relaxation pressure (IRP) indicates the adequacy of EGJ relaxation after swallowing. EGJP-insp and EGJP-exp. represent the barrier pressure during respiration separately [12, 13]. Recently a new metric, EGJ contractile integral (EGJ-CI) was developed by F.Nicodeme et al. [13]. EGJ-CI integrates the contraction length and amplitude of EGJ, as well as exclude the influence of respiration rate, so it is superior to those above. Several studies have showed that defective EGJ-CI was more frequently found in GERD patients with pathological acid reflux and lower EGJ-CI was associated with better symptom response after antireflux surgery [14, 15]. The EGJ-CI value would be increased after antireflux surgery [16]. These results support that the new metric is useful in evaluating anti-barrier function of GERD patients and revealing the role of defective flap valve on reflux.

In the study, we aimed to assess the association between GEFV grades and acid reflux, and to explore the impact of GEFV on the anti-reflux barrier by using the HRM metrics.

The dysfunction of EGJ implied the abnormal flow of gastric content into the esophagus. The LES and crural diaphragm are recognized as the two key components of the anti-reflux barrier [21]. GEFV is a special musculomucosal fold reflecting the contact of proximal gastric fundus with the esophageal cavity. The connection between proximal stomach and the esophagus would be closer when the GEFV grade decreased [1]. It seems that GEFV may play a synergistic role in the anti-reflux barrier, but there is still lack of sufficient research. HRM has the advantage to better identify the anatomic structure of EGJ and could display the barrier as the distal high pressure zone (DHPZ) [22]. EGJ-CI is a new HRM metric, which was first calculated by Nicodeme et al. [13], and they found that in patients with refractory GERD, its value was lower only in the group fulfilled all the criteria of GERD. It seems that the metric is useful in evaluating the contraction of EGJ at rest. So we assessed the correlation between GEFV grades and the acid reflux in the study and used EGJ-CI and other traditional HRM metrics to explore the impact of GEFV on the anti-reflux barrier function. It turned out that the grades of flap valve was associated with esophageal acid exposure weakly, and the differences on EGJ-CI were not significant within patients with different GEFV grades.

The increasing separation between LES and CD can cause an increase in AET% and reflux episodes [23]. EGJ subtype III means that the separation of CD and LES peaks is >2 cm. It is more common to be found in patient with higher GEFV grade. This suggested that the grade of GEFV was indeed a reflection of anti-reflux barrier. Contractor et al. showed that the GEFV grades were correlated with the severity of esophagitis positively [24], and Chang et al. reported that the grade I and II was less to be found in EE patients [25]. This was in line with our results. In fact, the grades I and II of GEFV were commonly found in healthy controls [1]. This result suggested that the dysfunction of GEFV may be benefit for pathological acid reflux. Because grade I implies that the fold of tissue along the lesser curvature would grip the endoscope closely, it was not surprising to find that the esophageal acid exposure in this group was not severe. The difference on AET% between patients with GEFV I and that without was more significant when the patients were in supine position. This may due to the lack of gravity effect in this position, thus the anti-reflux barrier became more important in the protection from regurgitation. EGJ subtypes were correlated to supine AET%. This result supported that GEFV could be the reflection of EGJ morphology. The GEFV grade IV is known to be associated with hiatus hernia [1], so it was reasonable to find that the AET% values in this group seemed higher than the others no matter in supine or upright position. The GEFV grade II and III also indicated a defect on anti-reflux barrier, so there was an ascending trend on the AET% and reflux episodes. Routinely reporting the impaired GEFV grades on endoscopy would be helpful in finding out the potential patients with excessive esophageal acid exposure.

Koch et al. showed that the flap valve had no significant effect on the LES pressure [7]. EGJ-CI was a comprehensive reflection of the EGJ contraction at rest. It captures more factors attributing to the barrier function. Tolone S et al. found that patients with defective EGJ-CI may have positive 24 h MII-pH monitoring more frequently [26]. We had found that EGJ-CI was correlated with esophageal acid exposure in the supine position [27]. These results supported that calculating EGJ-CI was useful in evaluating the defect of barrier function. In the study, though the impaired GEFV benefitted acid reflux in the same position and the values of EGJ-CI seemed lower when the grades increased, there were not significant differences within the four groups. We also found that the EPT metrics reflecting EGJ contraction during respiration were similar within different GEFV groups. These results suggested that the GEFV function was not the determining factor of the barrier function, though the patients with lower EGJ-CI and higher GEFV grades may be benefit from the antireflux surgery [14‐16]. A reasonable interpretation was that the role of GEFV was not as important as that of LES and crural diaphragm in the strength of anti-reflux barrier. In fact, the barrier strength is not a simple sum of the effect of all the structures located in EGJ, the LES tone may hinder the transmission of extrinsic pressure [21]. This was supported by the result that no correlation was found between GEFV grades and the HRM metrics reflected EGJ contractility. This may explain why the correlation between AET% and GEFV grades was weak and the difference on AET% in patients with impaired GEFV was not significant. Further research on the function of GEFV demands measurements using technique with higher sensitivity in differentiating EGJ pressure components, such as 3D–HRM technology.

There were two limitations in our study. One was that the mucosal erosion of most EE patients was not severe. If more patients with LA-C or LA-D grades were enrolled in the study, more patients with higher GEFV grades could be included. This would be useful in acquiring a greater depth on the correlation between impaired GEFV grades and acid reflux. The other limitation was that we did not included “functional heartburn (FH)” patients in the study. The comparison of the distribution of GEFV grades between GERD and FH patients would be useful in further revealing the valve function on the protection from regurgitation.

In summary, our findings in the study suggested that the GEFV grades had weak impact on the esophageal acid exposure, and it was a good reflection of EGJ morphology in HRM. The valve may play an assistant role on the strength of anti-reflux barrier and was needed to report on endoscopy. Further research on the therapeutic value of impaired valve was still needed for the long-term management of GERD patients.