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

doi:10.1016/j.gie.2005.07.025

Gastrointestinal Endoscopy

Volume 64, Issue 2, August 2006, Pages 195-199

https://doi.org/10.1016/j.gie.2005.07.025 Get rights and content

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.

Section snippets

Patients

All surveillance patients with a diagnosis of dysplasia in Barrett's esophagus from 2001 to 2003 and below 80 years of age were identified from computerized histopathology records. Patients with known dysplasia within mucosal ulceration, mucosal irregularity, or cancer were excluded. Patients who had received treatment (surgery, photodynamic therapy, argon plasma coagulation, endoscopic mucosal resection) for dysplasia also were excluded. We restricted our choice of patients to those with a

Results

Between January 2001 and January 2003, 72 patients under the age of 80 years were identified with a history of all grades of dysplasia. The study period itself was from April 2003 to February 2004. Thirty-seven patients were excluded before randomization (20 declined to participate, and 17 had received recent treatment for dysplasia). Hence, 35 of 55 patients (64%) accepted our invitation to participate in the study. These were randomized: 17 patients had MBDB and 18 patients had RB at their

Discussion

The use of MB as an aid to the diagnosis of Barrett's esophagus has generated interest since it was first introduced by Canto et al¹⁰ in 1996. Its use initially was attractive because the technique seemed relatively simple to learn, apparently safe, and appeared to be cost effective. A number of studies9, 10, 11, 16, 17 showed an increased yield of intestinal metaplasia in MBDB compared with RB. Other studies,18, 19 however, did not produce similar results. One study¹¹ had shown a significant

Acknowledgments

We thank our nurse endoscopist, Andrea Reilly, all the endoscopy staff, and the gastroenterologist specialist registrars at Leeds General Infirmary, Wharfedale General Hospital, Seacroft Hospital, and St James University Hospital, Leeds, United Kingdom for their participation as investigators in this study. We also thank all the consultant gastroenterologists, GI surgeons, and histopathologists at the above hospitals for their agreement and participation in this study.

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El esófago de Barrett es un trastorno premaligno del esófago en el cual el epitelio escamoso de la porción distal del esófago es reemplazado por epitelio columnar. Debido a que la incidencia de adenocarcinoma esofágico se encuentra al alza, la mayoría de las sociedades de Gastroenterología han emitido sus propias recomendaciones para el tamizaje y la vigilancia. Factores específicos como la obesidad, la raza blanca, la edad por encima de los 50 años, el inicio del ERGE a edad temprana, el tabaquismo y la hernia hiatal han sido identificados como factores que incrementan el riesgo de esófago de Barrett y adenocarcinoma. El diagnóstico requiere tanto de la identificación endoscópica de mucosa con revestimiento columnar como de la confirmación histológica con biopsia. La mayoría de las sociedades médicas recomiendan tamizar a todas las personas con ERGE, así como aquellos con otros factores de riesgo con endoscopia; sin embargo, otras alternativas que utilizan métodos menos invasivos se encuentran bajo estudio en la actualidad. Las estrategias de vigilancia varían dependiendo de los hallazgos endoscópicos y se recomienda el protocolo de biopsias de Seattle con un muestreo de 4 cuadrantes aleatorizado. Algunos biomarcadores han mostrado resultados prometedores, aunque se requieren de más estudios en el futuro. La endoscopia de luz blanca es el estándar en la práctica, sin embargo, otras modalidades de imagen más avanzadas han mostrado resultados variables y, por lo tanto, se esperan más estudios para obtener validación adicional. Las técnicas de erradicación endoscópica, incluyendo tanto la resección como la ablación, han mostrado buenos resultados, aunque variables, en el tratamiento de lesiones displásicas confinadas a la mucosa. Los procedimientos de resección para remover las lesiones visibles seguida por la ablación de la mucosa displásica han mostrado los mejores resultados, con tasas de erradicación más altas y menores tasas de recurrencia. El manejo quirúrgico está reservado para lesiones con invasión de la submucosa y propagación a ganglios linfáticos con un riesgo incrementado de metástasis.
Barrett's esophagus is a premalignant condition of the esophagus in which the squamous epithelium of the lower end of the esophagus is replaced with columnar epithelium. Since the incidence of esophageal adenocarcinoma is on the rise, the major gastroenterology societies have come up with their recommendations for screening and surveillance. Specific factors like obesity, white race, age over 50 years, early age of onset of GERD, smoking and hiatal hernia have been identified as increasing the risk of Barrett's esophagus and adenocarcinoma. The diagnosis requires both endoscopic identification of columnar-lined mucosa and histological confirmation with biopsy. Most medical societies recommend screening people with GERD and other risk factors with endoscopy, but other alternatives employing less invasive methods are currently being studied. Surveillance strategies vary depending on the endoscopic findings and the Seattle biopsy protocol with random 4-quadrant sampling is recommended. Biomarkers have shown promising results, but more studies are needed in the future. White light endoscopy is the standard practice, but other advanced imaging modalities have shown variable results and hence more studies are awaited for further validation. Endoscopic eradication techniques, including both resection and ablation, have shown good but variable results for treating dysplastic lesions confined to the mucosa. Resection procedures to remove visible lesions followed by ablation of the dysplastic mucosa have shown the best results with higher eradication rates and lower recurrence rates. Surgical management is reserved for lesions with sub-mucosal invasion and lymph node spread with increased risk of metastasis.
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There is no significant difference in the detection of dysplastic lesions using HDMEMBI with targeted collection of biopsy specimens vs SDWLE with 4-quadrant biopsy specimen collection. However, HDMEMBI requires the collection of significantly fewer biopsy specimens, providing better value for health care providers. ClinicalTrials.gov number: NCT01694511.
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The accuracy and effectiveness of targeted oesophageal biopsies in Barrett's oesophagus to detect dysplasia using new magnification techniques are unknown. Aim of this study was to investigate whether the combined use of acetic acid, magnification and electronic filters allows the same accuracy as the four-quadrant random biopsies pattern; pathologist interobserver agreement both in low grade and high grade dysplasia was also assessed.
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Original ArticleRandomized crossover study that used methylene blue or random 4-quadrant biopsy for the diagnosis of dysplasia in Barrett's esophagus

Background

Objective

Design

Setting

Patients

Interventions

Main Outcome Measurements

Limitations

Results

Conclusions

Section snippets

Patients

Results

Discussion

Acknowledgments

Gastroenterology

Gastroenterology

Am J Gastroenterol

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Lancet

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

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