Improving practicality of radiofrequency ablation for eradication of Barrett*s mucosa: a randomized trial comparing two different treatment regimens for circumferential ablation using the HALO360 System

Endoscopic ablation therapy is used for treatment of selected patients with
HGIN in a Barrett*s esophagus.(7;8) Endoscopic ablation therapy is used as an
adjuvant treatment after ER for early Barrett*s cancer to treat any hidden
areas of synchronous neoplasia and/or to reduce the rate of recurrences during
follow-up. Photodynamic therapy (PDT) and Argon Plasma Coagulation (APC) are
the most widely used techniques in this respect.(9-11) Both are associated with
significant drawbacks: PDT is expensive and uncomfortable to the patient. In
addition, the genetic abnormalities of the Barrett*s mucosa remain unaltered
after PDT and may even increase the genetic damage of the remaining
epithelium.(12) APC is most effective at higher energy settings where it may be
associated with perforation and stenosis, and requires multiple treatment
sessions.(13) After PDT and APC, a substantial number of patients have residual
Barrett*s epithelium or buried Barrett*s. (10;11)
Radiofrequency ablation (RFA) is a new endoscopic ablation technique that has
been shown to be an easy, safe and effective treatment modality for complete
eradication of Barrett*s esophagus (BE) containing early neoplasia. (23)
Compared to PDT and APC, RFA seems to be more easy to use, better tolerated by
patients, and is not associated with esophageal stricturing or the occurrence
of buried Barrett*s. (15;16)
In RFA, the Barrett*s segment is ablated by radiofrequency energy through two
specially designed devices for circumferential and focal ablation respectively.
The HALO360 System consists of a balloon which contains a spindle-shaped
electrode on its outer surface. Balloons with different diameters and lengths
of electrodes are available. For focal ablation a cap-based electrode, the
HALO90 System is used. The instruments have been developed by BÂRRx Inc,
California, USA and are FDA approved for ablation of Barrett*s mucosa.
Radiofrequency ablation (RFA, BÂRRX Medical, Sunnyvale, CA, USA) has been shown
to be an easy, safe and effective treatment modality for complete eradication
of Barrett*s esophagus (BE) containing early neoplasia. (15;16;17;18;19)
Currently, most patients undergo primary circumferential ablation with a
balloon based electrode, the HALO360 System, followed by additional focal
ablation using a cap-based electrode, the HALO90 System. The advised treatment
regimen for HALO360 procedures consists of two ablation runs with extensive
cleaning of the ablation zone after the first ablation. This procedure consists
of many different steps and requires multiple introductions and removals of the
endoscope, sizing catheters and ablation balloons which are impractical and
uncomfortable to the patient. We propose a simplified HALO360 ablation
procedure in which prior mucolysis with acetylcysteine is omitted, the ablation
zone is cleaned only with the use of a small distal attachment cap without
additional high-pressure waterjet cleaning and without removal of the ablation
balloon. We hypothesize that the simplified HALO360 ablation procedure results
in an easier and faster ablation procedure, while maintaining efficacy and
safety.

The aim of the study is to develop a shorter, less technical demanding and
therefore less uncomfortable for the patient, procedure for the HALO360
treatment of Barrett's esophagus with early neoplasie, high-grade or low-grade
dysplasia, without loosing efficacy and safety.

Patients eligible for a HALO360 procedure will be randomized to the currently
used standard HALO360 procedure or a simplified HALO360 procedure, both at an
energy level of 2x12 J/cm2.

Treatment protocol: HALO360 procedure
The esophagus is evaluated using white light (WL) high-resolution endoscopy and
narrow band imaging (NBI). The extent of columnar lined esophagus is documented
according to the Prague C&M classification and the number and localization of
islands of Barrett*s are noted. A pullback video recording (WL+NBI) of the
Barrett*s segment is obtained. If this is not possible, still images (WL+NBI)
for every cm of the BE while pulling back from the top of the gastric folds
(TGF). Patients are subsequently randomized to circumferential ablation with
the HALO360 system using the simplified or the standard ablation regimen.

Standard HALO360 ablation regimen:
After mapping and randomization, the Barrett*s segment is flushed with the
mucolytic agent acetylcysteine (1%) followed by flushing with tap water.
Subsequently, a guide wire is inserted into the duodenum and the endoscope is
removed. A non-compliant sizing balloon (BÂRRX Medical, Sunnyvale, CA) is then
introduced over the guide wire and positioned 5 cm above the proximal margin of
BE. The balloon is then automatically inflated to 4 psi (0.28 atm) and the
internal esophageal diameter is automatically calculated based on baseline
balloon volume/geometry and the inflated pressure/volume. Sizing is repeated
moving distally, for every 1 cm of BE until the transition to cardia is
detected by a rapid increase in calculated diameter. After previous ER, the
advice is to use an ablation catheter that is one step smaller in diameter than
the diameter advised by the sizing procedure. After the ablation catheter has
been introduced over the guide wire, the endoscope is introduced and under
visual control the BE is ablated at an energy level of 12 J/cm2 at 300 Watt
with working proximal to distal using visual repositioning. A small overlap
(i.e. <1cm) between ablation zones is allowed. The endoscope is removed
followed by removal of the ablation catheter and the guide wire. Before the
second ablation pass, the coagulum is cleaned off the balloon catheter. The
endoscope is reintroduced to irrigate and suction the ablation zone. A distal
attachment cap will be attached to the tip of the endoscope to gently wipe of
the coagulum from the ablated segment. After irrigating and suctioning the
debris away as much as possible, the ablation zone is cleaned by forcefully
flushing water through a spraying catheter. The stomach is emptied and deflated
and the endoscope is removed, after reintroduction of the guide wire. The
ablation catheter is reintroduced over the guide wire to repeat the ablation,
after reintroduction of the endoscope to allow for ablation under vision. After
this second ablation no additional cleaning of the ablation zone is required.
First, the endoscope is removed, followed by careful removal of the ablation
catheter.

Simple HALO360 ablation regimen:
In the simplified ablation regimen flushing with the mucolytic agent
acetylcysteine (1%) is not performed, but the esophageal wall will be flushed
with water through the flushing channel of the endoscope. Pre-RFA sizing,
selection of the appropriate ablation balloon, and the first ablation pass are
performed according to the guidelines description above. After the first
ablation the ablation balloon is not removed but advanced distally into the
stomach. The treated surface is cleaned by pushing of the debris with the
distal cap, which has been attached to the endoscope before ablation. No
high-pressure flushing is performed after cleaning the ablation zone with the
cap. After cleaning of the treatment area, a second ablation at 12 J/cm2 at 300
Watt is performed.
During the HALO360 procedure the following items will be specifically recorded
for the purpose of this study:
1. Time of the first introduction of the endoscope and the time of final
removal of the ablation balloon.
2. The number of introductions and removals of endoscope, sizing balloon and
ablation balloon.
3. Kind and amount of sedatives used.
After the procedure the patients* discomfort will be quantified using a
VAS-score-questionnaire. Patients will be asked to complete a questionnaire
after the ablation procedure and after recovery from sedative medication.

At three months patients will undergo a high resolution endoscopy. The
esophagus will be evaluated in the same way as at the pre-treatment
endoscopy.The percentage of endoscopically visible surface regression of BE
will be scored by two endoscopists, blinded for the administered treatment
regimens, using images/videos taken immediately prior to HALO360 treatment and
at the first post-HALO360-treatment endoscopy.

Radiofrequency ablation to eradicate Barrett's mucosa

Patients will be treated with the HALO360 system according to the current
protocol or the shorter procedure. There is no additional risk in case the
patient is randomized to the shorter procedure. There are less introductions
and removal of the endoscope and balloons. The procedure is also shorter in
time.