Improved screening of esophageal cancer by optical detection of field cancerization.

Esophageal adenocarcinoma (EAC) is a deadly disease with a poor prognosis at
advanced stage. When detected in early stage, disease can be managed by minimal
invasive endoscopic treatment, thereby avoiding surgery and/or
chemo-radiation-therapy. Patients with Barrett*s esophagus (BE) have an
increased risk for developing EAC and therefore undergo regular endoscopic
surveillance. These surveillance programs are hampered with several problems
that compromise efficacy and cost-effectiveness. Thus new technologies for
improving risk stratification for BE patients are dearly needed.
Field cancerization is based on the concept that focal cancers arise in mucosa
or tissue areas (*field*) with random genetic changes. Recent studies have
suggested that light scattering spectroscopy is able to detect this field
carcinogenesis by measuring the light scattering properties of tissue in vivo
using small fiberoptic catheters. Optical spectroscopy may, therefore, be an
innovative approach to improve detection of prevalent neoplasia in BE and to
identify BE patients at risk for malignant progression in the future. Elastic
Scattering Spectroscopy, ESS, is a specific form of optical spectroscopy that
uses optical fibres.
In this study, ESS will be combined with Optical Coherence Tomography (OCT), an
imaging technique also based on scattering of light. The combination of ESS and
OCT will enable better documentation of the specific locations where the
measurements are taken, but also to quantify the light scattering properties of
the tissue in an independent way.
We will compare our spectroscopic data with brush cytology and multicolor DNA
fluorescent in situ hybridization DNA (FISH), a technique to assess genetic
changes in cytology specimens.

Risk stratification of BE patients based on the detection of
field-carcinogenesis with spectroscopy has several theoretically advantages for
improving the cost-effectiveness of BE surveillance:
1. Spectral diagnostic probes can be reusable, easily cleaned, sustainable and
cheap.
2. Data acquisition is rapid and real-time.
3. No particular training in image analysis is necessary, since data are
automatically acquired and analyzed, and the reading is objective (positive or
negative).
4. Tissue characteristics otherwise not visualized on histology can be assessed
(chemical composition, tissue ultrastructure).
5. Enables direct decision making during ongoing endoscopy.
6. Only a small part of the organ has to been sampled, allowing for
low-complex, minimal invasive screening avoiding obtaining numerous biopsy
samples and decrease patient burden.

1. Evaluate the feasibility of ESS for detection of field cancerization in BE
patients.
2. Investigate the biological background of field cancerization by studying:
a) (ultra)structural changes in the tissue and b) genetic abnormalities and
clonal diversity.

This study will consist of two phases: a pilot-phase, in which we will use two
separate optical fibres, and a second phase, in which we will use a dual core
fibre.

Spectroscopy is non-invasive in nature. The type of light delivered by the
optical probe is equivalent in intensity to the standard light source used en
delivered by an standard endoscope; the excitation of tissue by the light
energy delivered by spectroscopy systems that are used in-vivo is non-damaging
and does not result in any thermal effects on tissue. During this study
patients will undergo extra spectroscopy measurements and cytology-brush.
Standard clinical practice according to diagnosis and treatments is not
influenced by these additional spectroscopy measurements. For study purposes,
two extra biopsies will be obtained, in addition to random biopsies according
to general practice. The endoscopy will take 15 minutes longer compared to the
standard endoscopy for the additional spectroscopy measurements and
cytology-brush.