Probe-based confocal laser endomicroscopy: scientific toy or clinical tool?

The incidence of esophageal adenocarcinoma and associated death has risen significantly over the past decades in Western countries [1,2]. This coincides with the pandemic of obesity and associated increase in the incidence of reflux disease [3]. In tertiary referral patients, Barrett’s esophagus can be found in 4.9% of patients with atypical symptoms and in 4.5% of patients with typical reflux symptoms [4]. Screening for neoplasia in Barrett’s esophagus is a difficult but worthwhile effort. First, the annual combined incidence of adenocarcinoma or highgrade intraepithelial neoplasia in patients with a nondysplastic Barrett’s esophagus is estimated to be 1.3% [5]. This is comparable to the annual risk of colorectal cancer for which cancer screening programs with colonoscopy have been implemented in many countries [6]. Secondly, retrospective surgical series [7–12] have shown that patients who are diagnosed with adenocarcinoma while under surveillance have a higher rate of early stage lesions (76%) than patients who had their cancer diagnosed outside a Barrett’s surveillance setting (15%). This is reflected in a 3year survival of 80% and 31%, respectively [7]. Endoscopic surveillance comprises both thorough inspection for possible visible lesions and biopsies taken according to the Seattle protocol (fourquadrant biopsies every 2 cm). However, adherence to this protocol by gastroenterologists is generally poor [13] and it is often perceived as time consuming and uncomfortable for the patient. Confocal laser endomicroscopy (CLE) is a new endoscopic imaging technique that allows in vivo imaging with a (sub)cellular resolution, enabling the endoscopist to perform a histologic assessment during ongoing endoscopy [14–21]. Currently, two systems are available. In the first system, a confocal probe is incorporated into the tip of a conventional colonoscope (eCLE). The second system is a probe-based system (pCLE), which can be passed through the biopsy channel of any conventional endoscope. The basics for obtaining images are the same for both systems. The confocal unit is connected to a monochrome blue light laser source, necessary to excite a fluorophore. Themost commonly used fluorescent dye is intravenously administered fluorescein. Images can be obtained easily by applying the confocal window of the probe or endoscope onto the mucosa once the fluorescent dye is administered. Intravenously applied fluorescein causes a transient discoloration of the skin and concerns have been raised about its safety as a diagnostic aid. A recent multicenter study assessing fluorescein-assisted pCLE showed, however, that no major adverse events occurred in 2272 procedures and that mild adverse events were recorded in 1.4% of the procedures, including nausea, vomiting, transient hypotension, injections site erythema, rash, and epigastric pain [22]. With a lateral resolution of 0.7 μm and a magnification of × 1000, the eCLE system currently has the best resolution compared with pCLE, which has a lateral resolution of 1μm [23]. Although the absolute difference of 0.3 μm appears rather small, this constitutes a 43% decrease in resolution, which is comparable to the difference between standard video endoscopy and high-definition endoscopy. The eCLE system also allows the adjustment of the imaging plane in the Zaxis, which makes it possible to scan at different depths and visualize different histologic structures, such as blood vessels. The pCLE system has a fixed imaging plane but its use is more versatile as it can be used with any endoscope, at any moment. In addition, the temporal resolution of the pCLE system is higher (12 images/second) compared with the pCLE (± 1 image/second). Studies suggest that confocal endomicroscopy enables the endoscopist to differentiate gastric mucosa, specialized intestinal metaplasia, and neo-