Single step treatment using radiofrequency ablation and endoscopic resection for Barrett esophagus containing early neoplasia .

Endoscopic resection (ER) and radiofrequency ablation (RFA) are effective
treatment modalities for high-grade dysplasia (HGD) and early cancer (EC) in
Barrett*s esophagus (BE).
ER of early BE neoplasia allows for resection deep into the submucosa, which
not only effectively removes superficial lesions but also permits accurate
histological staging. The histological evaluation of ER specimens is imperative
for proper patient selection: patients with mucosal lesions can be treated
endoscopically, whereas those with submucosal cancers are referred for surgery
given their significant risk of local lymph node metastasis.
RFA effectively removes BE mucosa but has only been used for flat type mucosa
without visible abnormalities since these require ER for effective removal and
staging.
Compared to ER, RFA is a relatively easy endoscopic procedure with a low risk
of complications and no significant esophageal scarring.
The combined treatment of ER and RFA currently requires two separate treatment
sessions. Generally, an interval of 6-8 weeks is used to allow the esophagus to
heal before RFA is applied.
Esophageal scarring after ER may, however, hamper the efficacy and safety of
subsequent RFA sessions. After ER, it may be more difficult to bring the
ablation balloon in full contact with the remaining BE. In addition, widespread
ER may cause so much stricturing that inflation of the balloon catheter may
cause esophageal laceration. For this reason most studies on the combined
treatment with ER and RFA have restricted the maximum extent of ER prior to RFA
to < 50% of the circumference and <2 cm in longitudinal length.

To test the use of RFA and ER in a single endoscopic session in 20 consecutive
patients with a BE containing visible abnormalities with HGD or EC upon biopsy.

Inclusion criteria:
1. Age between 18 and 85 years inclusive.
2. BE with a minimal circumferential extent of 2 cm.
3. An endoscopically visible abnormality of type 0-I, 0-IIa, 0-IIc or a
combination thereof, irrespective of its size.
4. A biopsy proven histological diagnosis of HGD and/or EC on two separate
endoscopic sampling procedures.
5. HGD, G1 or G2 cancer in the endoscopic resection specimens, without
involvement of the deeper resection margins, no lymphatic invasion, and a
maximum infiltration depth into the submucosa <500µm.
6. Written informed consent.

Exclusion criteria:
1. A BE with a maximum extent >12 cm.
2. Any prior endoscopic treatment for esophageal adenocarcinoma of BE
associated neoplasia.
3. Signs of local or distant metastasis on EUS (EUS is obligatory).
4. Signs of distant metastasis on CT-scan of thorax and/or abdomen (optional
for mucosal lesions).
5. Any of the following findings in any of the ER specimens: G3 or G4 tumor
differentiation; lymphatic invasion; infiltration into the submucosa >500µm, a
positive deeper resection margin.
6. Endoscopic signs of esophageal varices.
7. Esophageal stenosis not allowing passage of a therapeutic endoscope with an
ER-cap.
8. Prior esophageal surgery (except fundoplication).
9. Use of any anticoagulant therapy that can not be discontinued between one
week before and 1 week after every treatment session.

Procedures:
Endoscopic work-up:
Prior to the first therapeutic endoscopy all patients will undergo 2
endoscopies with targeted (i.e. 2 biopsies per lesion) and random biopsies
(i.e. 4QBx/1-2 cm).
Endoscopic ultrasound (EUS) will be performed using a radial scanning
electronic EUS endoscope, supplemented with EUS-FNA in case suspicious lymph
nodes are detected.
CT scan of thorax/abdomen is only required for those patients who show
submucosal invasion.

Endoscopic treatment protocol (see flow chart):
All patients will undergo a circumferential ablation using the HALO360+ system
according to current guidelines, followed by endoscopic resection of any
visible abnormality in the BE during the same procedure. Prior to the ablation,
the area to be resected will be marked by placing electrocoagulation markers.
After the ablation, the delineated area will be resected using either the
multi-band mucosectomy technique of the ER-cap technique, until all visible
markers have been removed.
The second ablation session is scheduled after 3 months followed by 2-monthly
ablation sessions until all endoscopically visible BE has been removed. A
maximum number of 2 HALO360+ (for circumferential ablation) and 3 HALO90
sessions (for focal ablation of residual islands) are allowed.
In case Barrett mucosa persists after completing the maximum number of ablation
sessions, an ER will be performed as an *escape*procedure to achieve complete
removal. An ER is also allowed if during the treatment phase visible
abnormalities are identified in the original BE.
In case complete endoscopic regression of the BE is observed, 4-quadrant random
biopsies will be obtained at 1-2 cm intervals throughout the original BE. In
addition, 4-quadrant random biopsies will be obtained immediately distal (i.e.
< 5-mm) of the neo-squamocolumnar junction.
After complete endoscopic and histological eradication of HGD, EC and BE has
been documented, patients will undergo follow-up at 6 and 12 months, and
annually thereafter, using the aforementioned biopsy protocol.
Focal ablation sessions with the HALO90 system and all follow-up endoscopies
will be performed with high-resolution endoscopy and narrow-band imaging.
Apart from the first treatment session, in which RFA and ER are combined, the
treatment protocol and follow-up regimen are identical to those of 5 previous
cohort studies by our group.

Post-treatment care and medication
After all therapeutic procedures, patients will be observed in the recovery
room for 2-4 hours and subsequently discharged with further instructions
concerning diet, acid suppressant therapy, and the use of analgetics. After the
first therapeutic session, the frequency, severity, and duration of symptoms
will be assessed by standardised questionnaires and patient diaries.
Patients will be contacted by telephone within 72 hours and will be rescheduled
for repeat procedures or follow-up endoscopies according to the aforementioned
schedule.

Histology
All pre-treatment histology, all ER specimens, and all follow-up biopsies will
be routinely processed and evaluated by a senior gastroenterologist. For the
purpose of this study, all materials will be reviewed by an expert
GI-pathologist with extensive experience in this field.

Resection of visible lesion with high grade dysplasia and/or early cancer and
total eradication of Barrett's esophagus.

We anticipate that ER immediately after RFA will not be associated with a
higher risk for complications. In fact, the risk for perforation, the most
feared complication of ER, is likely to be reduced due to the slight mucosal
thickening that occurs immediately after RFA.
RFA of visible lesions prior to their resection may effect the histological
evaluation of the superficial part of the resected specimen. The main purpose
of the histological evaluation of ER specimens, however, is the evaluation of
the deeper mucosal and superficial submucosal layers, which are left undamaged
by the RFA.
This allows for a combined treatment which otherwise would require 2 separate
procedures but more importantly, it preserves the diagnostic and therapeutic
efficacy of ER but prevents that RFA is hampered by esophageal scarring after
the ER. If this treatment regimen is found to be effective it will also allow
patients with larger visible abnormalities to be treated with the combination
of ER and RFA.