The pathophysiological importance of lower esophageal sphincter distensibility in gastroesophageal reflux disease

Background
Gastric content is prevented from re-entering the esophagus by the
esophagogastric junction (EGJ) formed by the lower esophageal sphincter (LES)
and crural diaphragm(1). In patients suffering from gastroesophageal reflux
disease (GERD) this barrier function is usually disturbed and reflux of gastric
content can occur freely causing symptoms (heartburn, regurgitation) as well as
damage to the esophagus (esophagitis)(2). Most reflux episodes occur during
Transient Relaxations of the Lower Esophageal Sphincter (TLESR)(3). These are
spontaneous sphincter relaxations, and not induced by swallowing. The rate of
TLESRs as well as associated gastroesophageal reflux differs between
postprandial and fasting condition in both GERD patients and healthy
volunteers(4,5).. However, the rate of TLESRs in GERD patients does not differ
from healthy volunteers and therefore does not offer an explanation for the
occurrence of pathologic reflux in GERD patients suggesting a different
underlying mechanism(6).
GERD patients can be further divided in patients with and without a hiatal
hernia(7). A hiatal hernia is an anatomical abnormality characterized by a
displaced LES which no longer coincides with the crural diaphragm at the EGJ.
This abnormality is associated with a higher prevalence of GERD. It has been
shown that TLESRs, although still partially responsibly, play a less pronounced
role in GERD patients with hiatal hernia(8). Since a hiatal hernia is present
in a large number of healthy subjects and a hiatal hernia comparable in size
and nature can be present in GERD patients, with different severity of disease,
the existence of a hiatal hernia is not solely responsible for the increased
rate of esophageal reflux in GERD patients suggesting a different underlying
mechanism.

EGJ barrier function can be assessed by measuring its distensibility (9). We
hypothesize that a difference in EGJ distensibility is responsible for the
failure of EGJ barrier function. An increased distensibility in GERD patients
could theoretically lead to an increase in the rate of reflux which contributes
to GERD severity and symptoms.
Furthermore, we hypothesize that there is a difference between GERD patients
with and without a hiatal hernia. Since the EGJ no longer consists of two
contributing muscles, EGJ distensibility could theoretically be increased in
GERD patients with hiatal hernia(7) leading to an increase in the rate of
reflux which contributes to GERD severity and symptoms.

Traditionally, barrier function of the EGJ is studied by manometry and
esophageal pH measurement. Basal LES pressure and rate of TLESRs is measured by
high-resolution manometry(10), the occurrence of gastroesophageal reflux is
measured by pH/impedance measurement(11). Previous research has not shown a
clear relationship between LES pressure and rate of reflux. Recently, a new
method has been developed that enables measurement of EGJ distensibility, the
so-called functional luminal imaging probe (EndoFLIP®, Crospon Inc., Carlsbad,
USA)(12). Before development of the EndoFLIP it was not possible to measure EGJ
distensibility. Kwiatek and coworkers assessed EGJ distensibility in GERD
patients with EndoFLIP and observed that symptomatic GERD patients exhibit a
more distensible EGJ compared to controls. Kwiatek et al suggested that this
increased distensibility may be an important mechanism by which greater
refluxate volume enters the esophagus(13). However, the role of EGJ
distensibility in the pathogenesis of GERD is not known and insights in the
role of EGJ distensibility on reflux characteristics and esophageal
characteristics that are known to play a role in the pathogenesis of GERD are
lacking.

Therefore, the aim of this study is to determine whether differences in EGJ
distensibility lead to different rates of esophageal reflux by comparing EGJ
distensibility with esophageal reflux characteristics, esophageal pressure
characteristics and GERD symptoms in GERD patients with and without hiatal
hernia and healthy volunteers.

Study Design:
A prospective study using combined high-resolution pressure/pH/impedance
measurements, ambulant pH/impedance measurement and EndoFLIP measurement.

Patients have to stop PPI or medication influencing GI-motility and have to
travel to the AMC. There are no known risks associated with the investigations.