Barrett's esophagus (BE) is considered to result from prolonged gastroesophageal reflux and
is the only known precursor of esophageal adenocarcinoma.
The clinical management of BE patients aims to control esophageal reflux to reduce mucosal
injury and neoplastic progression, and to detect early neoplastic lesions in Barrett’s mucosa,
suitable for curative endoscopic treatment.
The first part of this thesis evaluates the effect of a stepwise increase in the dose of proton
pump inhibitors (PPI), on esophageal acidic reflux, symptoms and histology in long segment
BE patients (group 1, n=24). We also compare these outcomes in BE patients under PPI with
the results of BE patients after clinically successful fundoplication (group 2, n=30). In all but
one patient in group 1, it was possible to normalize acid reflux with PPI, resulting in
improvements in symptom scores. However, symptomatic amelioration was only significant
in the first step of PPI treatment. Patients with PPI or fundoplication had the same levels of
symptom scores. Normalization of the acid reflux in both groups was associated with
reductions of papillary length, thickness of the basal cell layers, dilation of intercellular
spaces, and acute and chronic inflammation of the squamous epithelium. We did not find a
significant change in markers of proliferation and differentiation in Barrett’s mucosa
associated with normalization of acid reflux in either group.
The second part of this thesis assesses 3 different endoscopic classification systems,
Amsterdam, Kansas and Nottingham, developed for the characterization of Barrett’s mucosa.
These classifications use magnification endoscopy with narrow band imaging (ME-NBI) for
the identification of intestinal metaplasia and dysplasia in Barrett’s mucosa. We used 84
video segments from Barrett’s mucosa, that were randomly selected and blindly evaluated by
9 observers with different expertise in the field. All classifications were feasibly but showed
suboptimal accuracy and low inter-observer agreement, with slightly better results for the
Amsterdam classification.
The last part of this thesis evaluates the role of a structured learning program for the
application of the Amsterdam classification system. We used the first 70 videos from the 84
randomly selected videos from the previous study. While, during the learning process, there
was a decrease in the time spent for evaluation and an increase in declared certainty of
prediction, the accuracy in histological prediction did not improve. This classification system
was found to be suboptimal in terms of accuracy and inter- and intra-observer agreements.
This thesis shows that, in long segment BE patients, acid reflux and symptom scores
correlated through several steps of the PPI treatment process, achieving the same level as
after a successful fundoplication. If a single dose of PPI is associated with marked
improvement of symptoms, higher doses still may be needed for complete acid suppression.
Minor changes were found among morphological markers of reflux disease, both in the
glandular and in the squamous epithelium, irrespective of medical or surgical treatment. Our
results underscore the questionable utility of ME-NBI classification systems for clinical
routine practice in BE
