Barrett*s Esophagus and Adenocarcinoma STudy (EAST); The inflammatory background

Barrett*s esophagus (BE) is an acquired premalignant condition that results
from chronic gastro esophageal reflux disease (GERD) and predisposes to the
development of esophageal adenocarcinoma (EAC). In BE, the normal esophageal
squamous epithelium is replaced by intestinal columnar epithelium: intestinal
metaplasia. The prognosis of EAC is poor and the incidence of EAC is rising
faster than that of any other malignancy in the Western world. The
pathophysiology of BE is largely unknown, but it is commonly accepted that the
disease is initiated by chronic exposure to acid and bile (components of
reflux). Diagnostic strategies to identify BE patients and the subgroup at
increased risk of developing EAC are currently insufficient and critical to
improve.
There is increasing evidence that chronic inflammation in the gastrointestinal
tract predisposes to changes in tissue morphology and may lead to development
of cancer. As reflux disease may result in inflammation, it is plausible that
inflammatory cells, - receptors or - mediators play a role in the esophageal
metaplastic and neoplastic tissue transition, contributing to the development
of reflux esophagitis (RE), BE and EAC.
Insight in these immunological processes could lead to a better understanding
how RE, BE and EAC develop and could pave the way for new diagnostic
strategies. Therefore, a study elucidating the pathogenesis of BE and EAC is
urgently needed.

To determine the composition of immune cells and the expression of
immunological factors in normal squamous esophagus, RE, BE and EAC.

This is a cross-sectional study, in which extra biopsies will be taken during
upper gastrointestinal endoscopy at the outpatient Gastroenterology department
of the UMC Utrecht adn CMH (BE and EAC groups). Patients with reflux symptoms,
aspecific complaints, BE and EAC (associated with BE) scheduled for endoscopy
of the esophagus will be asked to participate in this study. A different
patient information brochure is distributed for each of the three endoscopy
indications (reflux symptoms or aspecific complaints/ BE/ EAC).
During upper gastrointestinal endoscopy the following extra biopsies are taken
(if indicated): 5 biopsies in patients without endoscopic abnormalities, 7 in
RE, 8 in BE, 8 in EAC in the absence of BE (but with a prehistory of BE) and 11
in EAC in the presence of BE. The biopsies will be obtained from the involved
esophageal segments, from normal esophageal squamous epithelium and from the
duodenum as a control for intestinal tissue. The selected patients will be
asked to complete the *Barrett slokdarm*- questionnaire concerning
socio-demographic and medical information and two blood samples (12ml) will be
taken by venepuncture. The composition of immune cells and the expression of
immunological factors will be assessed in biopsies and blood samples.

The burden associated with participation is limited; filling out a
questionnaire, which takes 15 minutes, undergoing a venepuncture and extending
the duration of the endoscopic procedure with 2 minutes. Patients do not have
to bring an additional visit to the hospital. The risk of participation is
considered low. A total of 12 ml blood will be withdrawn from the patient and a
hematoma may develop after venepuncture. The endoscopical procedures are
routinely performed and considered as safe. No minors or incapacitated adults
are included in this study. There are no direct benefits for the patients in
this study.