Endomicroscopy-targeted Endoscopic Mucosa Resection for Barrett's Oesophagus-associated Neoplasia

Introduction

Barrett's oesophagus is a common complication in patients suffering from gastro-oesophageal reflux disease (GERD). By means of chronic acid exposure the squamous epithelium of the oesophagus turns into a specialised columnar epithelium (SCE) with goblet cells. This histological change is prevalent in 1% of the normal population, and in up to 4, 9% of patients with reflux symptoms [1]. Although the Barrett's epithelium itself does not necessarily cause additional symptoms, its presence has to be diagnosed accurately, since affected patients are at increased risk of 0.5% per year of developing Barrett's associated cancer. An important prognostic factor is made up by the grade of dysplasia within the Barrett's mucosa. While most patients with no dysplasia or low-grade dysplasia remain clinically inconspicuous, the annual risk of developing cancer is up to 10% in those patients with high-grade dysplasia. If a Barrett's associated neoplastic lesion is found during endoscopy, Barrett's associated cancer is also present at another site of Barrett's oesophagus in up to 30% [2].

Consequently, they undergo periodically screening, consisting of endoscopy of the oesophagus with 4-quadrant biopsy every 2 to 3 cm or, in case of HGIN, local ablative therapy. The time period between controls depends on the grade of dysplasia diagnosed at upper gastrointestinal endoscopy. If no dysplasia is present, the recommended follow-up period is less than 5 years. In case of low grade dysplasia endoscopic controls should be performed every year. Patients with high grade dysplasia should be examined every 3 months or prepared for a therapeutic intervention [3].

Early detection of Barrett's associated neoplasms, which can be histologically classified as adenocarcinoma, has important therapeutic implications. Cancerous infiltration of submucosal structures is associated with a significant risk of lymph node metastases and should be therefore treated by surgery. However, oesophagectomy has been shown to suffer from mortality rates between 3 and 12%, apart from substantial short- and long-term morbidity. Hence it is essential to detect early neoplastic lesions to have a broader range of therapeutic options at disposal. Patients with high grade intraepithelial neoplasia (HGIN) or mucosal cancer are perfect candidates for curative endoscopic interventions like endoscopic ablation (with radiofrequency, for example), endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR). The latter techniques are preferred as the resected specimens can be evaluated histologically, which provides definite information about the invasion depth and whether the resection borders are free from neoplastic tissue. Because of high rates of newly occurring neoplasia, remaining areas of Barrett's mucosa should be ablated or resected after histological confirmation of Barrett's oesophagus associated neoplasia [3, 4].

Trying to improve the diagnostic yield in the surveillance of patients with high risk for Barrett's oesophagus associated neoplasia, many new endoscopic inventions have been introduced into the management of Barrett's oesophagus in order to optimize the detection rates of early lesions. Among those are developments that improved the image quality of conventional white light endoscopes like high-resolution and high-definition endoscopes. Another approach, called chromoendoscopy, uses in vivo staining with methylene blue, indigo carmine or acetic acid. These dyes help to increase the tissue contrast which leads to improvement of detection rates comparable to high-resolution endoscopy. High contrast levels without staining agents can be achieved by the use of narrow band imaging (NBI). This technology additionally improves the visibility of capillaries, veins and other subtle tissue structures by the use of light with wavelength restricted to small bands in the blue and green spectrum. In a prospective randomized crossover study it showed equal results to high-resolution endoscopy plus indigo carmine [4, 5].