Confocal laser endomicroscopy in Barrett's esophagus and endoscopically inapparent Barrett's neoplasia: a prospective, randomized, double-blind, controlled, crossover trial

Abstract

Background: The detection of high-grade dysplasia and cancer in Barrett's esophagus (BE) can be challenging. Confocal laser endomicroscopy (CLE) allows in vivo visualization of mucosal histology during endoscopy.

Objective: To determine whether CLE with optical biopsy and targeted mucosal biopsy improves the diagnostic yield of endoscopically inapparent, BE-associated neoplasia compared to standard endoscopy with a 4-quadrant, random biopsy protocol.

Design: Prospective, double-blind, randomized, crossover study.

Setting: Single, tertiary-care academic center.

Patients: This study involved patients with BE undergoing routine surveillance or referred for treatment of nonlocalized, endoscopically inapparent, BE-associated neoplasia.

Intervention: All participants underwent both a confocal endomicroscopy with a targeted biopsy procedure and standard endoscopy with a 4-quadrant biopsy procedure in a randomized order.

Main outcome measurements: Increase in diagnostic yield for neoplasia, reduction in mucosal biopsy number, final pathologic diagnosis.

Results: CLE with targeted biopsy almost doubled the diagnostic yield for neoplasia and was equivalent to the standard protocol for the final diagnosis of neoplasia. Two thirds of patients in the surveillance group did not need any mucosal biopsies at all.

Limitation: Single-center study.

Conclusion: CLE with targeted biopsy significantly improves the diagnostic yield for endoscopically inapparent BE neoplasia compared to a standard endoscopy with a random-biopsy protocol. CLE with targeted biopsy also greatly reduces the number of biopsies needed per patient and allows some patients without neoplasia to completely forgo mucosal biopsy.

Trial registration: ClinicalTrials.gov NCT00487695.

Figure 1

Overall study design. Patients are referred for Barrett’s esophagus (BE) or BE with high grade dysplasia (HGD) BE-HGD. All patients have confocal laser endomicroscopy (CLE) with targeted biopsy (TB) and standard endoscopy (SE) with random biopsy (RB) in a randomized order. For patients randomized to CLE first, endoscopist A performed CLE - TB. Two to 6 weeks later, the patient has SE with 4 quadrant random biopsy. All biopsies undergo histopathologic examination and the yield for neoplasia between CLE and SE is compared.

Figure 2

Study Participants

Figure 3

(A) Unmagnified standard white light endoscopic image of a tiny island of Barrett’s esophagus obtained with the endomicroscope prior to endomicroscopic imaging. (B and C) Confocal endomicroscopy images of the island shows glands with irregularly-shaped, distorted dark cells, indistinct cell borders, and loss of normal crypt architecture suggestive of high grade dysplasia (D) Histopathology confirmed Barrett’s esophagus with HGD in the endoscopic mucosal resection specimen

Figure 3

(A) Unmagnified standard white light endoscopic image of a tiny island of Barrett’s esophagus obtained with the endomicroscope prior to endomicroscopic imaging. (B and C) Confocal endomicroscopy images of the island shows glands with irregularly-shaped, distorted dark cells, indistinct cell borders, and loss of normal crypt architecture suggestive of high grade dysplasia (D) Histopathology confirmed Barrett’s esophagus with HGD in the endoscopic mucosal resection specimen

Figure 3

(A) Unmagnified standard white light endoscopic image of a tiny island of Barrett’s esophagus obtained with the endomicroscope prior to endomicroscopic imaging. (B and C) Confocal endomicroscopy images of the island shows glands with irregularly-shaped, distorted dark cells, indistinct cell borders, and loss of normal crypt architecture suggestive of high grade dysplasia (D) Histopathology confirmed Barrett’s esophagus with HGD in the endoscopic mucosal resection specimen

Figure 3

(A) Unmagnified standard white light endoscopic image of a tiny island of Barrett’s esophagus obtained with the endomicroscope prior to endomicroscopic imaging. (B and C) Confocal endomicroscopy images of the island shows glands with irregularly-shaped, distorted dark cells, indistinct cell borders, and loss of normal crypt architecture suggestive of high grade dysplasia (D) Histopathology confirmed Barrett’s esophagus with HGD in the endoscopic mucosal resection specimen