Towards improved risk stratification in Barrett’s esophagus

Barrett’s esophagus (BE) is a premalignant condition, increasing the risk to develop esophageal adenocarcinoma (EAC). Advanced EAC knows a poor prognosis, with a 5-year survival rate of 20%. It is believed malignant progression to EAC occurs gradually from non-dysplastic BE to, low-grade dysplasia (LGD), high-grade dysplasia and eventually EAC. Patients with BE undergo endoscopic surveillance to detect EAC at an early and curable stage. The majority of patients with BE, however, will never progress to EAC. This generates the need for better risk stratification of BE patients.
The first part of this thesis focuses on expert pathology in BE and the development of an expert review panel. In multiple studies a group of expert pathologists was evaluated on their assessments of BE biopsies with the use of quality criteria and benchmark scores. In addition the assessment of endoscopic resection specimens of BE neoplasia was evaluated, showing significant interobserver variability.
The second part of this thesis focuses on identification and validation of biomarkers and risk factors for malignant progression. One study describes a mutational load score that did not predict progression as was described earlier. In a large multi-community based center prospective cohort study we identified clinical and endoscopic risk factors for neoplastic progression. The long-term follow-up results of the SURF study, where endoscopic surveillance was compared to radiofrequency ablation (RFA) in patients with LGD are reported in the last chapter of this part. RFA treatment showed an absolute risk reduction of 32.4% and confirmed earlier results.