Endoluminal fundoplication with the Esophyx*-device versus proton-pump-inhibition in treatment of Gastro-esophageal reflux disease (GERD).

Gastro-esofageal refluxdisease (GERD) is common in Western society. This reflux
is not only painful and uncomfortable, but can severely damage the oesophageal
lining, cause chronic inflammation, and can lead to permanent damage and cancer
of the oesophagus. In severe or chronic GERD, regurgitation occurs regularly,
spilling chime not only into the esophagus, but also into the lungs, mouth and
pharyx, causing astma-like symptoms, dental erosions and ENT-disaeses.

The primary treatments for gastroesophageal reflux disease (GERD) were
lifestyle changes, medications or surgery, until today, when an additional
option that mimics surgery but involves no abdominal or internal incisions has
become available.
Current medical treatment of GERD includes drugs, such as H2 blockers and
proton pump inhibitors, which neutralize or suppress the stomach acid and help
relieve symptoms. However, these drugs are expensive, they don*t work for
everyone, (5-20% non-responders) and there are many people who do respond worse
to them over time. These drugs however do not correct the root cause of GERD
(anatomic disintegration of the antireflux barrier) so symptoms return when the
medication is stopped.

The primairy treatement of GERD were medications or surgery (Nissen
Fundoplication). Medication neutralize or suppress the stomach acid and help
relieve symptoms, However, these drugs are expensive, they don*t work for
everyone, (5-20% non-responders) and there are many people who do respond worse
to them over time. These drugs however do not correct the root cause of GERD
(anatomic disintegration of the antireflux barrier) so symptoms return when the
medication is stopped. Antireflux surgery (ARS) is the alternative in case of
failed medical therapy.
For the non-responders to drug treatment, the Nissen fundoplication is proven
effective and the current standard of treatment, however, this surgery is an
invasive therapy.

A new technique was intoduced recently: the endoluminal fundoplication with the
Esophyx-device. To evaluate this new technique we would like to set up a
randomised trial. In this trial the Esophyx will be comared to PPI-treatment.
End-points will be: quality of life, use of medication and reflux-measurements.

The purpose of this prospective randomized controlled trial is to demonstrate
that the EsophyX-TIF procedure will be more effective than PPI therapy as a
short and long-term treatment of GERD.

Intervention: Endoluminal fundoplication with the EsophyX-device.

In general, the work up for ELF is similar to the usual workup that is done for
laparoscopic fundoplication surgery. After the patient has discontinued PPI *s
for at least 5 days, the following workup will be performed at their evaluation
visit:
* GERD medication status documenting > 5 days off PPI
* Gastroscopy
Gastroscopy is typically the first test performed to confirm a symptom-based
diagnosis of GERD and is most valuable for excluding gastric and duodenal
pathologic conditions and detecting the presence of Barrett's esophagus
* 24-hour pH or pH-impedance testing
Ambulatory pH monitoring is the most reliable test for the diagnosis of GERD,
with a sensitivity and specificity of about 92%.It is of key importance in the
workup for the following four reasons.
1. It determines whether abnormal reflux is present. Obviating the continuation
of inappropriate and expensive drugs (e.g., PPIs) or the performance of a
fundoplication. In addition, normal pH monitoring prompt further investigation
that in a number of cases points to other diseases (e.g., cholelithiasis and
irritable bowel syndrome).
2. It establishes a temporal correlation between symptoms and episodes of
reflux. Such a correlation is particularly important when atypical GERD
symptoms are present because 50% of these patients experience no heartburn and
50% do not have esophagitis on gastroscopy.
3. It allows staging on the basis of disease severity. Specifically, pH
monitoring identifies a subgroup of patients characterized by worse esophageal
motor function (manifested by a defective LES or by abnormal esophageal
peristalsis), more acid reflux in the distal and proximal esophagus, and slower
acid clearance. These patients more frequently experience stricture formation
and Barrett metaplasia and thus might benefit from early antireflux surgery.
4. It provides baseline data that may prove useful postoperatively if symptoms
do not respond to the procedure.

* Manometry
Oesophageal manometry provides useful information about the motor function of
the esophagus by determining the length and resting pressure of the lower
oesophageal sphincter (LES) and assessing the quality (i.e., the amplitude and
propagation) of esophageal peristalsis. In addition, it allows proper placement
of the pH probe for ambulatory pH monitoring (5 cm above the upper border of
the LES).

* Upper GI Barium swallow (to assess hiatal hernia)
An upper GI series is useful for diagnosing and characterizing an existing
hiatal hernia. The size of the hiatal hernia helps predict how difficult it
will be to reduce the esophagogastric junction below the diaphragm. In
addition, large hiatal hernias are associated with more severe disturbances of
esophageal peristalsis and esophageal acid clearance. Esophagograms are also
useful for determining the location, shape, and size of a stricture and
detecting a short esophagus.

* GERD-HRQL score, EuroQol and GESRS

ELF-procedure

Discontinuation of all anticoagulants and platelet agents (including aspirin) >
10 days before the elf procedure will be organized if applicable. The patient
should be instructed not to eat of drink for at least 12 hours before the ELF
procedure

The ELF procedure will be performed under full endoscopic visualization and
under general anesthesia (naso-tracheal intubation). The patient is positioned
in supine position. Pre- and post procedure Functional Lumen Imaging Probe
(FLIP) will be inserted for dynamic evaluation of the integrity of the GE-
junction. FLIP will be performed again after 6 month follow-up. The Esophyx*
device is placed over the gastroscope, inserted trans-orally through a bite
block and advanced into the insufflated stomach. The z-line is visualized
through the window in the shaft of the esophyx device, and the invaginator
(vacuum suction) is engaged to hold the esophagus. The device is advanced
distally until the z-line is at the level of the diaphragm to reduce hiatal
hernia. Now that the esophagus and stomach are in the correct position, back in
the stomach the helical retractor is deployed to engage stomach tissue to the
level of the serosa and a long flap of tissue (3-5 cm) is pulled. This
serosa-to-serosa flap of tissue is drawn into the tissue mold and locked in
place. Polypropylene fasteners are delivered across the serosa-to-serosa fundus
tissue using a stylet to penetrate the tissue ahead of the fastener and a
pusher to advance the over-the-wire fasteners. This forms a full-thickness
serosa-to-serosa plication. The system is now disengaged by releasing the
tissue mold, helical retractor and invaginator. The process is then repeated
circumferentially until a 220- 270º valve that is 3-5 cm deep is created
(generally involving placement of ~14 fasteners).
A post-procedure endoscopy is performed to assess for any procedure related
complications and to evaluate, measure, and grade the newly created valve.
Photos of the valve should be obtained and submitted. The patient will be
monitored in a hospital setting for 24 hours after the procedure, to continue
observing for any side effects. Before the patient is discharged, they will be
given a patient brochure of post-procedure (dietary-)instructions. Medications
are stopped one week post procedure, but can be taken on demand and noted in a
medication-diary.

Medication-group

This group is a control-group. No intervention will be done, this group will
continue GERD-medication (step-down regime). Follow-up period has a minimum of
6 months. After 6 months the control-group will have the opportunity to undergo
the actual ELF-procedure (cross-over-design).

Discontinuation of all anticoagulants and platelet agents (including aspirin) >
10 days before the elf procedure will be organized if applicable. The patient
should be instructed not to eat of drink for at least 12 hours before the ELF
procedure

The ELF procedure will be performed under full endoscopic visualization and
under general anesthesia (naso-tracheal intubation). The patient is positioned
in supine position. The Esophyx* device is placed over the gastroscope,
inserted trans-orally through a bite block and advanced into the insufflated
stomach. The z-line is visualized through the window in the shaft of the
esophyx device, and the invaginator (vacuum suction) is engaged to hold the
esophagus. The device is advanced distally until the z-line is at the level of
the diaphragm to reduce hiatal hernia. Now that the esophagus and stomach are
in the correct position, back in the stomach the helical retractor is deployed
to engage stomach tissue to the level of the serosa and a long flap of tissue
(3-5 cm) is pulled. This serosa-to-serosa flap of tissue is drawn into the
tissue mold and locked in place. Polypropylene fasteners are delivered across
the serosa-to-serosa fundus tissue using a stylet to penetrate the tissue ahead
of the fastener and a pusher to advance the over-the-wire fasteners. This forms
a full-thickness serosa-to-serosa plication. The system is now disengaged by
releasing the tissue mold, helical retractor and invaginator. The process is
then repeated circumferentially until a 220- 270º valve that is 3-5 cm deep is
created (generally involving placement of ~14 fasteners).
A post-procedure endoscopy is performed to assess for any procedure related
complications and to evaluate, measure, and grade the newly created valve.
Photos of the valve should be obtained and submitted. The patient will be
monitored in a hospital setting for 24 hours after the procedure, to continue
observing for any side effects. Before the patient is discharged, they will be
given a patient brochure of post-procedure (dietary-)instructions. Medications
are stopped two weeks post procedure, but can be taken on demand (step-down
regime) and noted in a medication-diary.

This group is a control-group. No intervention, this group will continue
GERD-medication (step-down regime). Follow-up period has a minimum of 6 months.
After 6 months the control-group will have the opportunity to undergo the
actual ELF-procedure (cross-over-design).

Interventiongroup: narcosis, bleeding, esophageal perforation
Control-group: risk of PPI-use