2.02] Confocal endomicroscopy (CFE) in gastroenterology: Ready for prime time?

Abstract

Objective Confocal laser endomicroscopy (CFE), when implemented during endoscopy, enables in vivo microscopy of the mucosal layer of any tissue in the gastrointestinal tract with subcellular resolution. Endomicroscopy opens the door to immediate tissue and vessel analysis. Different types of diseases can be diagnosed with optical surface and subsurface analysis. Discrimination between normal and malignant cells is possible. Analysis of the in vivo microarchitecture can be used for targeting biopsies to relevant areas, and subsurface imaging can unmask microscopic diseases. The aim of our study was to validate this new technique further. Material and methods For CFE we used a Cellvizio® miniprobe, which is compatible for all endoscopes with an operating channel of 2.6 mm. Placed in contact with the mucosa, the miniprobe delivers real-time video sequences of the tissue microarchitecture at 12 images per second and a depth resolution of about 50 μm. We used CFE to perform “optical biopsies” in patients with known Barrett's esophagus, one with a known high-grade intraepithelial neoplasia, in the follow-up of a patient after small bowel transplantation, and in a patient with invasive cholangiocellular carcinoma of the bile duct. Additionally, we performed CFE in a newly established pig model of benign bile duct stenosis. The benign stenosis were induced by endoscopic retrograde cholangiography (ERC) with introduction of a 10 Fr-heater probe and application of HF energy (400 J) approximately 3 cm proximal of the papillae. Results Confocal imaging of the normal squamous epithelium of the esophagus demonstrated squamous cells at high resolution, showing capillaries (filled with red blood cells) within single papillae. The typical shape of Barrett's epithelium was villous, differing from the cardiac epithelium. High-grade intraepithelial neoplasias can be recognized by a distinct cell type in endomicroscopy. Nevertheless, this technique appears to require experience and is not an “easy-to-use-method” in the esophagus. In contrast, CFE appears to be safe and useful for monitoring patients for transplant rejection after small bowel transplantation. In bile duct cancer, CFE showed a deranged vascular architecture in contrast to the regular pattern obtained within the normal epithelium of this patient. In our pig model we were able to establish a reproducible benign bile duct stenosis. These fibrotic structures were characterized by virtually no CFE signal. This is in direct contrast to the normal bile duct epithelium of animals and to the bile duct cancer mentioned above. Conclusion CFE is feasible in a wide variety of gastrointestinal tissues using regular endoscopes and a thin miniprobe. Although real-time “optical biopsies” are achievable, the exact diagnosis still has to be made by the pathologist. CFE is helpful for discrimination between normal tissue and dysplasia or even carcinoma. The application in the bile duct system probably requires an additional cholangioscope for placing the miniprobe specifically in the suspected area. Further studies are necessary to evaluate this promising technique in bile-duct disorders in humans.