Back-to-back high-definition white light endoscopy versus single-pass high-definition white light endoscopy and chromoendoscopy in IBD surveillance (HELIOS study)

Patients with long-standing inflammatory bowel disease (IBD) have an increased
risk of developing colorectal cancer (CRC)(1). In IBD, chronic inflammation may
lead to the development of mucosal dysplasia that can progress to
colitis-associated CRC. To decrease CRC-related mortality and morbidity,
guidelines recommend enrolling patients in an endoscopic surveillance program
in order to detect and remove dysplasia before progressing to more advanced
lesions.

High-definition endoscopic visualisation techniques have improved the dysplasia
detection rate compared to standard-definition white light endoscopy (2). To
further enhance the image contrast, dye-based chromoendoscopy (CE) can be used.
The current international guidelines recommend as first choice the use of CE,
and as an alternative high-definition white light endoscopy (HDWLE) for optimal
dysplasia detection, based on data from clinical trials (3, 4). However, data
on the superiority of CE over HDWLE are not consistent in literature (5, 6). We
hypothesize that the better performance of CE in some clinical trials is the
result of the associated longer procedural time of 11 minutes with CE (7), and
the fact that every colon segment is examined twice due to the need for
spraying every colon segment before re-examination. Indeed, previous studies
have shown that a longer procedural time and procedures during which the mucosa
is visualized twice (back-to-back) are associated with a higher adenoma
detection rates in non-IBD patients (8, 9). Currently, no studies have been
published evaluating the dysplastic yield of back-to back HDWLE compared to
HDWLE with a single pass or CE in patients with IBD.

In the present study, we aim to compare the yield of dysplasia/CRC between 1)
regular HDWLE, 2) HDWLE back-to-back, and 3) CE.

Assessment of the detection of neoplastic lesions in patients with longstanding
inflammatory bowel disease, using different endoscopic imaging techniques.
Colonoscopy will be performed with either A) HDWLE, B) back-to-back HDWLE or C)
CE.

A multi-center, prospective, non-blinded randomized trial. In all participating
centers, eligible patients will be randomized between groups A, B or C. The
study will be performed at the following centers: Radboudumc Nijmegen,
University Medical Center Utrecht, Leiden University Medical Center, and
Amsterdamumc location AMC.

A) HDWLE, B) back-to-back HDWLE or C) CE.

Colonoscopy is a commonly performed procedure with a very low overall serious
adverse event (SAE) rate of approximately 2.8 per 1000 colonoscopies.
Diagnostic colonoscopy has a bleeding risk of 0.1% and a perforation risk of
0.01% of subjects. These risks are associated with regular surveillance
colonoscopies in daily practice and not expected to increase due to our
intervention. The bleeding risk of multiple biopsies is considered extremely
low (0.008% to 0.03% (10)). The burden related to this study includes the
additional burden of a second look in a select group of patients. There are
also some substantial benefits. Although a single pass with HDWLE is currently
part of standard practice when CE is not applied, it has been shown that a
single examination has a miss-rate of polyps of 16.8% to 28% (11-13).
Back-to-back colonoscopy may result in the detection (and subsequent removal)
of more neoplastic lesions, which has been shown to be inversely correlated
with the development of interval carcinomas(14).