Barrett's esophagus (BE) is a premalignant condition of the distal esophagus, predisposing to dysplasia and esophageal adenocarcinoma. Therefore, in BE patients, current guidelines recommend endoscopic surveillance with four-quadrant biopsies every 2 centimeters of the Barrett's length. These biopsies need to be of optimal quality for adequate histopathological assessment. Larger biopsies can facilitate adequate histopathological assessment because (1) more tissue is available, (2) larger biopsies usually result in less superficial biopsies, with all mucosal layers present in the biopsy specimen, and (3) larger biopsies will ease orientation of the specimen. In a pilot study, the investigators found a median increase of nearly 30% in surface area when the biopsies were obtained by BE-expert endoscopists in comparison with non BE-expert endoscopists. A possible explanation for this difference can be biopsy method or technique. BE-expert endoscopists use the single biopsy method and turn-and-suction technique, whereas the double biopsy method and the advance-and-close technique are the more generally used biopsy techniques within non BE-expert endoscopists.

The BITE study is therefore designed to identify the preferred biopsy technique and method in BE patients in order to optimise biopsy quality and histopathological assessment.

This study will consist of three consecutive parts: a retrospective analysis, a two-by-two factorial randomised study, and a prospective before after study. The results of the preceding part of the BITE study will determine the continuation with subsequent part. If the second part of the BITE-study fails to identify a specific technique as the optimal biopsy technique (i.e. biopsy size is not significantly increased by using the single-biopsy turn-and-suction technique), the investigators will not proceed with the third step of the BITE-study.

Part I - retrospective analysis The retrospective analysis will be performed. This analysis of biopsy size aims to properly compare biopsy size of esophageal biopsies taken by BE-expert en non-expert endoscopists.

Part II - Two-by-two factorial design randomised study The second part of the BITE study is a two-by-two factorial design randomised study. This is a prospective, individually randomised study and will be performed in two different hospitals in the Netherlands: St. Antonius Hospital Nieuwegein and University Medical Centre Utrecht (UMCU). Patients who are willing to participate will be randomised into four different groups: in group A, biopsies will be taken using the single-biopsy advance-and-close technique; in group B, biopsies are obtained by the single-biopsy turn-and-suction technique; in group C the double-biopsy advance-and-close technique will be used; and group D, biopsies will be taken by the double-biopsy turn-and-suction technique. All upper endoscopies will be performed by BE-expert endoscopists.

Part III - retrospective before-after study The third and last part of the BITE study is a prospective before-after study. If the single-biopsy turn-and-suction technique proves to be the superior biopsy technique, this technique will be implemented among non BE-expert endoscopists. Non BE-expert endoscopists will be trained in the turn-and-suction technique, and data will be collected of biopsies before and after the training. If the second part of the BITE-study fails to identify the single-biopsy turn-and-suction technique as the optimal biopsy technique (i.e. biopsy size is not significantly increased by using the single-biopsy turn-and-suction technique), the investigators will not proceed with the third step of the BITE-study.

Inclusion Criteria:

• Age 18 years or older
• A diagnosis of Barrett's esophagus (maximum length ≥ 1cm)
• Scheduled for surveillance endoscopy with random biopsies
• In addition to the abovementioned inclusion criteria, a subject must meet the following criteria to participate in:

Part I: endoscopy performed by BE expert or non-BE expert endoscopists Part II: endoscopy performed by BE expert endoscopist Part III: endoscopy performed by non-BE expert endoscopist

Exclusion Criteria:

• Very long BE segment (maximum length ≥ 10cm)
• Any known clinical contraindication for obtaining biopsies (e.g. oesophageal varices, uncontrolled coagulopathy)
• Biopsies of suspicious lesions in the Barrett's epithelium will be excluded from analysis in all parts of this study. In case of suspicious lesions, endoscopists (in part II and part III of the BITE study) are allowed to obtain biopsies according to the technique they prefer.