The rate of developing a biopsy-bases diagnosis of High-Grade Dysplasia or Esophageal Adenocarcinoma in patients with Barrett*s esophagus, after an extensive baseline evaluation with random biopsies and Wide Area Transepithelial Sample Esophageal brush combined with Computer Assisted 3-Dimensional Tissue Analysis (WATS3D): The WATS-EURO2 Pilot study;The WATS-EURO2 Pilot study

Patients with BE are kept under endoscopic surveillance, since early detection
of esophageal adenocarcinoma (EAC) significantly improves the prognosis
compared to late detection. Current endoscopic surveillance strategies rely on
random sampling, which is time-consuming and has an inevitable risk for
significant sampling error. The WATS-3D brush samples a much wider area of the
esophageal epithelium, and prior studies have suggested that it detects more
dysplasia. However, the clinical value of these WATS-positive-biopsy-negative
cases is unknown. Ultimately, we aim to study the rate of developing a
biopsy-based diagnosis of HGD/EAC in Barrett*s patients at high risk of
progression (i.e. after endoscopic removal of visible lesions containing
HGD/EAC and/or a diagnosis of LGD) as well as in patients in a standard
Barrett*s surveillance program, in a large European multicenter, prospective
study. In these patients we will combine biopsy sampling with WATS brushing at
baseline and all follow-up endoscopies. This will allow us to study the natural
history of WATS-positive-biopsy-negative case and of WATS-specific outcomes
such as Basal-crypt dysplasia.
Prior to starting this large study, we first want to perform a pilot study to
assess the feasibility of our study infrastructure, sample processing and
online study database to optimize the final study.

To assess the feasibility of our study logistics and infrastructure, sample
processing and online study database.

This is an investigator initiated, multicenter, prospective, pilot study in 5
centers with a tertiary referral function for detection and treatment of early
Barrett*s neoplasia.

Our study population consists of patients with either a flat Barrett's
esophagus (BE) with low grade dysplasia (LGD) or high grade dysplasia (HGD) or
a flat BE after removal of visible lesions with LGD, HGD or early carcinoma. At
baseline, an imaging endoscopy will be performed and after confirmation of
absence of visible lesions, WATS brushing of the Barrett*s segment will be
performed followed by random 4 quadrant mucosal biopsies every 2 cm. If the
biopsies subsequently show HGD or esophagus adenocarcinoma (EAC), the patient
has reached the study endpoint and will be managed according to the
institution*s standard of care. If the baseline biopsies show LGD, indefinite
(IND) or non dysplastic BE, patient will not undergo ablation therapy and will
be scheduled for endoscopic follow-up. In case of prior endoscopic resection
for a visible lesion containing HGD/EAC the follow-up schedule consists of
endoscopies at 3, 6, 9, 12, 18, 24 and 36 months. For patients with a referral
diagnosis of LGD, the follow-up consists of endoscopies at 6 and 12 months and
annually thereafter


It is undisputed that patients referred with LGD, HGD or early cancer should
have all visible lesions removed by ER techniques. In general, the endoscopic
resection specimen will then show a diagnosis of HGD or early cancer. Follow-up
studies have shown that the chance of the development of metachronous HGD/EAC
in the remaining BE segment is about 10% per year. Therefore ablation therapy
is advised for the remaining BE segment. The same 10% annual progression rate
to HGD/EAC applies for patients with a confirmed diagnosis of LGD. For this
category guidelines suggest that ablation therapy may be indicated for cases in
which this diagnosis, apart from being confirmed by an expert pathologist, is
also reproduced in subsequent endoscopies. The actual decision to ablate the
remaining segment after endoscopic resection of HGD/EAC or to prophylactically
ablate for LGD, is made on a per patient basis in which age and comorbidity are
important factors to regard. Follow-up studies after ER of visible lesions
containing HGD/EAC have found that metachronous lesions are found to be
endoscopically treatable with the majority of patients not developing recurrent
disease. The same holds for prophylactic ablation in cases with LGD: a
significant proportion of patients will not progress or not even manifest their
baseline diagnosis of LGD upon follow-up. In the SURF-study, 30% of the
LGD-patients randomized to endoscopic surveillance did not have their LGD
diagnosis reproduced during 4 subsequent endoscopies in 3-years follow-up and
all cases that progressed to HGD/EAC were diagnosed at an endoscopically
curable stage.
Furthermore, RFA still is accompanied by complications such as esophageal
stenosis and requires multiple hospital visits. Even upon complete endoscopic
eradication of all Barrett*s mucosa, guidelines still dictate endoscopic
surveillance after ablation virtually at the same frequency as for Barrett*s
cases that are not prophylactically treated.
Therefore, keeping Barrett*s patients under strict endoscopic surveillance
after ER of visible lesions or for flat LGD is a very acceptable treatment
strategy that does not divert from current guidelines.