Advances in Barrett’s Esophagus Surveillance and Improved Prediction of Prognosis and Therapy Response in Patients with Esophageal Adenocarcinoma

Patiënten met een Barrett slokdarm, waarbij het normale plaveiselcelepitheel is vervangen door intestinale metaplasia met slijmbekercellen, hebben een verhoogde kans op het ontwikkelen van een adenocarcinoom. Het doel van dit proefschrift was te onderzoeken of toepassing van biomarkers de risicostratificatie van patiënten met een Barrett slokdarm voor het ontwikkelen van een adenocarcinoom kan verbeteren. Tevens evalueren we het effect van surveillance op kosteneffectiviteit en overleving en is de waarde van biomarkers voor het voorspellen van prognose en therapie response in patiënten met een slokdarm adenocarinoom onderzocht. Vele immunohistochemische bioma

Use of immunohistochemical biomarkers as independent predictor of neoplastic progression in Barrett's oesophagus surveillance

__Introduction:__ The low incidence of oesophageal adenocarcinoma (EAC) in Barrett's oesophagus (BE) patients reinforces the need for risk stratification tools to make BE surveillance more effective. Therefore, we have undertaken a systematic revi

Value of cyclin A immunohistochemistry for cancer risk stratification in Barrett esophagus surveillance A multicenter case-control study

The value of endoscopic Barrett esophagus (BE) surveillance based on histological diagnosis of low-grade dysplasia (LGD) remains debated given the lack of adequate risk stratification. The aim of this study was to evaluate the predictive value of cyclin A expression and to combine these results with our previously reported immunohistochemical p53, AMACR, and SOX2 data, to identify a panel of biomarkers predicting neoplastic progression in BE. We conducted a case–control study within a prospective cohort of 720 BE patients. BE patients who progressed to high-grade dysplasia (HGD, n=37) or esophageal adenocarcinoma (EAC, n=13), defined as neoplastic progression, were classified as cases and patients without neoplastic progression were classified as controls (n=575). Cyclin A expression was determined by immunohistochemistry in all 625 patients; these results were combined with the histological diagnosis and our previous p53, AMACR, and SOX2 data in loglinear regression models. Differences in discriminatory ability were quantified as changes in area under the ROC curve (AUC) for predicting neoplastic progression. Cyclin A surface positivity significantly increased throughout the metaplasia–dysplasia–carcinoma sequences and was seen in 10% (107/1050) of biopsy series without dysplasia, 33% (109/335) in LGD, and 69% (34/50) in HGD/EAC. Positive cyclin A expression was associated with an increased risk of neoplastic progression (adjusted relative risk (RRa) 2.4; 95% CI: 1.7–3.4). Increases in AUC were substantial for P53 (+0.05), smaller for SOX2 (+0.014), minor for cyclin A (+0.003), and none for AMARC (0.00). Cyclin A immunopositivity was associated with an increased progression risk in BE patients. However, compared to p53 and SOX2, the incremental value of cyclin A was limited. The use of biomarkers has the potential to significantly improve risk stratification in BE

Identification of patients at high risk for infections after liver transplantation

C