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Confocal imaging of colon pathology  
Colorectal cancer is still one of the leading causes of cancer-related death in the Western world. Screening colonoscopy is widely accepted as the gold standard for early diagnosis of cancer. The prognosis for patients with colonic neoplasms is strictly dependent on the depth of infiltration, and therefore depends on early detection of preinvasive and neoplastic changes. Early detection makes it possible to cure the patient by immediate endoscopic resection.

In 2003, Sakashita et al. reported initial experience with real-time confocal endoscopy in ex vivo specimens. The prototype endomicroscope that was used (Olympus Optical Ltd., Tokyo, Japan) was passed through the working channel of an endoscope. The aim of the study was to establish new criteria for distinguishing between benign lesions and high-grade dysplasia or cancer. The authors examined 100 endoscopically or surgically resected colorectal lesions from 90 patients. Nuclei could not be visualized in normal colonic mucosa or hyperplastic polyps, but were more often visible in neoplastic lesions. Conversely, goblet cells were visible less often in malignant or premalignant lesions. However, it should be noted that it was not individual nuclei, but rather dark areas in irregular cells that were visible. The study found a statistically significant difference between nonneoplastic and neoplastic lesions in relation to the detection rate of nuclei (dark areas) in laser-scanning confocal microscopy images.

On the basis of these results, the authors recommended preliminary criteria for a confocal imaging classification of high-grade intraepithelial neoplasia and cancer. Neoplasia was characterized by the presence of any structural abnormality and clear visualization of nuclei. However, the sensitivity of this method for predicting neoplasms in the colorectumwas only 60%, reflecting the limited resolution of the system that was used.

In a recently published study (Kiesslich et al., Gastroenterology 2004) using the newly developed endomicroscopic system, 42 patients with indications for screening or surveillance colonoscopy after previous polypectomy underwent in vivo endomicroscopy with the confocal laser endoscope. The aim of the study was to assess the histology in vivo during ongoing colonoscopy in order to diagnose intraepithelial neoplasias and colon cancer. Fluorescein-guided endomicroscopy of intraepithelial neoplasias and colon cancers showed a tubular, villous, or irregular architecture, with a reduced number of goblet cells. In addition, neovascularization in neoplasms is characterized by an irregular vessel architecture with fluorescein leakage.
  Confocal Pattern Classification for colonic neoplasias  
 
A simple classification of the confocal pattern (Table 1), based on initial experience with confocal endomicroscopy, was developed to allow differentiation between neoplastic and nonneoplastic tissue. Macroscopic and microscopic images were taken together to allowan immediate prediction of the histopathology. A total of 13020 confocal images from 390 locations were compared with the histological data from 1038 biopsies. It was possible to predict the presence of neoplastic changes using the newly developed confocal pattern classification with a sensitivity of 97.4 %, a specificity of 99.4 %, and an accuracy of 99.2%, respectively.