Randomized crossover study that used methylene blue or random 4-quadrant biopsy for the diagnosis of dysplasia in Barrett's esophagus

Gastrointest Endosc. 2006 Aug;64(2):195-9. doi: 10.1016/j.gie.2005.07.025.


Background: Barrett's esophagus is generally accepted to be a premalignant condition. Previous studies have suggested the use of methylene blue (MB) chromoendoscopy to aid the identification of dysplasia in Barrett's esophagus surveillance programs, but a recent study has raised the concern that MB might induce oxidative damage of DNA.

Objective: The aim of this study was to compare MB directed biopsies (MBDB) with our current standard, which is random 4 quadrant biopsies (RB).

Design: A randomized prospective crossover study.

Setting: Single center.

Patients: Patients with a diagnosis of dysplasia identified in Barrett's esophagus within a 2-year period before entering the study.

Interventions: Either 4 random quadrant biopsies taken every 2 cm through the length of the Barrett's esophagus or MBDB from unstained or heterogenously stained mucosa.

Main outcome measurements: The number of patients with a diagnosis of dysplasia by each intervention.

Limitations: Thirty-six percent of eligible patients declined the invitation to participate.

Results: Thirty patients completed the crossover study. The median length of Barrett's esophagus was 5 cm (interquartile range [IQR] 3-9 cm). At baseline histology, grades were as follows: 17 low-grade dysplasia (LGD), 3 high-grade dysplasia (HGD), and 10 no dysplasia. At completion, there were 10 LGD, 8 HGD, and 12 no dysplasia. Overall, dysplasia was identified in 17 of 18 patients by RB and in 9 of 18 by MBDB (McNemar test, p = 0.02).

Conclusions: Our study showed MBDB to be significantly less sensitive in detecting dysplasia than RB in Barrett's esophagus. Hence, we discourage its use during routine surveillance of Barrett's esophagus.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Barrett Esophagus / pathology*
  • Biopsy / methods
  • Coloring Agents*
  • Cross-Over Studies
  • Female
  • Humans
  • Image Enhancement
  • Male
  • Methylene Blue
  • Middle Aged
  • Mucous Membrane / pathology
  • Prospective Studies
  • Sensitivity and Specificity


  • Coloring Agents
  • Methylene Blue