Long term outcomes of EGJ distensibility, rate of TLESRs and reflux mechanisms in patients unresponsive and responsive to anti-reflux surgery

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 compromised 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 are not induced by swallowing. GERD
can be further complicated by the existence of a hiatal hernia4. A hiatal
hernia is an anatomical abnormality characterized by a displaced LES which no
longer coincides with the crural diaphragm at the esophageal gastric junction.
This can lead to dysfunction of anti-reflux barrier and is therefore often
associated with GERD4.

Initial management in GERD patients is medical therapy using proton pomp
inhibitors (PPI) 5. In patients that are intolerant for PPI therapy or patients
that keep persistent troublesome symptoms despite PPI therapy, anti-reflux
surgery is indicated 5. Recently, Broeders et al reported 10 year outcomes of
anti-reflux surgery, the so called Nissen fundoplication 6. Although initial
response is often good, as many as 25% - 28% of the patients has become daily
PPI-dependent again and/or has reflux symptoms 10-years after anti-reflux
surgery. GERD could be objectified in 30% - 40% of this subgroup of patients
and abnormal pH-metry was measured in 20%-30% 6. Furthermore, 5% - 10% of the
patients underwent surgical revision due to recurrent GERD within 10 years 6.
Despite the problems that can occur after anti-reflux surgery it is not
completely understood why some do not respond to anti-reflux surgery and why
others (72% - 75%) have a good response to anti-reflux surgery and do not
require further medical therapy and/or have symptoms.
The exact mechanisms by which anti-reflux surgery prevents gastro-esophageal
reflux are still unclear, currently, it is believed that three mechanisms play
a role. The first mechanism is anatomical restoration of the EGJ by repairing a
hiatal hernia if present. Second, the rate of TLESRs has been demonstrated to
decrease in patients that underwent anti-reflux surgery as well as a decrease
in the association of TLESRs with acid reflux7. The third mechanism, , is a
decreased distensibility of the EGJ 8,9.
We hypothesize that in patients that do not respond to anti-reflux surgery
there is an absent or less pronounced decrease in rate of TLESRs and its reflux
association, as well as a less pronounced decrease in EGJ distensibility.

The aim of this study is to determine whether differences in rate of TLESRs,
acid reflux associated TLESRs and EGJ distensibility can provide an explanation
for different responses to anti-reflux surgery by comparing long term reflux
mechanisms in patients unresponsive to and responsive to anti-reflux surgery.

A prospective study using combined high-resolution manometry/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.