Ultralong-segment Barrett*s esophagus: towards a capsule-sponge surveillance strategy (ULSBE-Endosign study).

Barrett*s esophagus (BE) surveillance using conventional
esophagogastroduodenoscopy (EGD) aims to detect dysplasia and esophageal
adenocarcinoma (EAC) at an early, treatable stage. However, given the
relatively low progression rates of BE, the number of EGDs required is a burden
to patients and society. The capsule-sponge Endosign test is a non-invasive
test which might be able to replace EGD. Developed for BE screening, recent
work has shown it might also be suitable to detect dysplasia in BE patients
under surveillance. Patients at presumed high risk of neoplastic progression
are patients with an ultralong-segment (>10cm) Barrett*s esophagus (ULSBE).

The primary objective is to investigate the concordance between the Endosign
test and EGD by an expert endoscopist for detecting dysplasia and/or EAC in a
high-risk category of ULSBE patients. Secondary objectives are to determine the
acceptability and sensitivity and specificity of the Endosign test in a ULSBE
surveillance cohort, to develop a clinical and p53 risk stratification model to
identify a high-risk ULSBE group and to investigate if novel sequencing-based
panels on the Endosign test could increase its diagnostic accuracy.

In this clinical trial we will recruit two cohorts, the first cohort consists
of patients who have dysplasia and/or early stage EAC who require treatment.
The second cohort consists of ULSBE patients under surveillance. Both groups
will swallow the Endosign test prior to their endoscopy. Patients who are
treated will swallow the Endosign test once. The surveillance cohort will be a
longitudinal cohort, in which the participants are asked to swallow the
Endosign test a second time at their next surveillance endoscopy. The study
will run for 3 years. Additionally, we will use p53 immunohistochemistry (IHC)
to investigate its potential to risk stratify ULSBE patients, and we will test
a novel biomarkers including a sWGS panel on the capsule-sponge test.

The participants will be asked to swallow the Endosign test prior to their
standard-of-care endoscopy on the same day. The capsule-sponge test is a pill
on a string which the patient swallows under guidance of a dedicated nurse or
doctor. Once the pill reaches the stomach, it dissolves and a mesh unfolds
within approximately 7 minutes. After this period the nurse or doctor will pull
back the sponge, and on the way out the sponge scrapes cells from the esophagus
which can be analyzed in the laboratory. Using p53 and morphological features
the sponge is able to identify high-risk features corresponding with dysplasia.

Patients will undergo the Endosign test prior to their endoscopy. This test is
usually tolerated well, and has been extensively tested in prior trials for BE
screening. The risks associated with this procedure are extremely low with a
risk of severe adverse events <1:2000. Although there are no direct benefits
for the individual patient, this study could benefit all ULSBE patients in the
near future by reducing the need for endoscopies and by improving our ability
to predict patients at higher risk of developing cancer.