Endoscopic fluorescence detection of low and high grade dysplasia in Barrett's oesophagus using systemic or local 5-aminolaevulinic acid sensitisation

Abstract

Background and aims: Barrett's oesophagus is associated with an increased risk of cancer. As dysplasia is not visible during routine endoscopy, random biopsies in the four quadrants every 1-2 cm are recommended. Endoscopic fluorescence detection (EFD) after sensitisation with 5-aminolaevulinic acid (5-ALA) with different modes and concentrations was assessed to optimise the technique for detection of dysplasia or early cancers. 5-ALA is converted intracellularly to protoporphyrin IX which accumulates in malignant tissue and can be detected by typical red fluorescence after illumination with blue light.

Methods: In 47 patients with Barrett's oesophagus, 10 with known dysplasia, 58 fluorescence endoscopies were performed after sensitisation with different concentrations of 5-ALA given orally (5, 10, 20, 30 mg/kg) or locally (500-1000 mg) by spraying the mucosa via a catheter. EFD was performed 4-6 hours after systemic and 1-2 hours after local sensitisation using a special light source delivering white or blue light. A total of 243 biopsies of red fluorescent (n=113) and non-fluorescent areas (n=130) were taken.

Results: In three patients, two early cancers and dysplasia, not visible during routine endoscopy, were detected by EFD. Thirty three biopsies revealed either low or high grade dysplasia. Sensitivity for detection of dysplastic lesions ranged from 60% after local sensitisation with 500 mg to 80%, 100%, and 100% after systemic application of 5-ALA 10, 20, and 30 mg/kg, respectively. However, specificity was best for local sensitisation (70%) while systemic administration revealed values between 27% and 56%. Using 5 mg/kg, no red fluorescence in dysplastic lesions was found. No severe side effects were noted.

Conclusion: EFD is a promising tool to detect non-visible dysplastic lesions in Barrett's oesophagus using 5-ALA sensitisation. A randomised controlled study is now indicated to compare the efficacy of EFD with the standard technique of four quadrant random biopsies.

Figure 1

Endoscopic fluorescence pictures. Comparative presentation of regular endoscopy with white light (A) and fluorescence endoscopy (B), four hours after sensitisation with 20 mg/kg 5-aminolaevulinic acid. Selective red fluorescence area within the Barrett's segment presented high grade dysplasia.

Figure 2

Fluorescence microscopy. (A, B) Frozen section (20 µm) from a biopsy of endoscopically red fluorescent positive mucosa in Barrett's oesophagus. (A) Fluorescence of the section and subsequent haematoxylin-eosin stained identical section (B). Enlargement 25×. Fluorescence was limited to the epithelium, mature foveolar epithelium was negative (left side, surface), and distinct and patchy positive fluorescence was related to intestinal metaplasia (specialised epithelium with goblet cells) and to dysplasia (arrows). (C, D) Frozen section (20 µm) from a biopsy of endoscopically red fluorescent negative mucosa in Barrett's oesophagus. (C) Fluorescence of section indicating only green autofluorescence, and subsequently haematoxylin-eosin stained identical section (D), showing the histology of the gastric mucosa (simple metaplasia). Enlargement 25×. Comment: diagnosis was verified by adjacent regular 5 µm sections but identical 20 µm sections are shown here to precisely relate fluorescence to morphology.