| Background and aimsEndoscopy has gradually become the major means of diagnosing gastrointestinal diseases since the emergence of gastrointestinal endoscope. Though the improvements in endoscopic instruments and technology have enhanced the accuracy of endoscopic diagnosis, however, histological analysis of biopsy specimen still remains the gold standard for the final diagnosis of gastric lesions. There are several disadvantages that may be associated with white-light endoscopy with biopsies. First, the fixation and staining of biopsy specimen requires 2-3 days, as for those lesions which can be endoscopic resected, resulting in the need for repeate endoscopies. In addition, the diagnosis can be underestimated due to sampling error. If real-time pathological examination was performed during ongoing endoscopy, the diagnostic efficiency of endoscopy would be significantly enhanced.Confocal endomicroscopy is a newly developed endoscopic imaging technology, and confocal endomicroscope is the integration of a miniaturized laser scanning confocal microscope into the distal tip of a conventional endoscope. Confocal microscopy is well suited to the visualization of microscopic structures in intact tissues and generates a sequence of high resolution fluorescent images from successive focal planes within the specimen. Confocal laser endomicroscopy produces 1000-fold magnification virtual histological images of the gastrointestinal surface and subsurface tissue during routine endoscopy.There have been few reports on the application of confoal laser endomicroscopy in gastrointestinal diseases because it was only several years since the emergence of confocal laser endoscope. Up to date, there has no study about the application of confoal laser endomicroscopy for gastric diseases. The aim of the present study is to explore the various confocal appearances of various kinds of gastric diseases, to construct the diagnostic criteria of gastric cancer using confocal laser endomicroscopy, and to assess the validity and repeatability of confocal laser endomicroscopy for the diagnosis of gastric cancer. So this can establish the foundation for the extensive clinical application of confocal laser endomciroscopy.Methods1. In order to identify the feasibility of confocal laser endomicroscopy for the diagnosis of gastric disease, 7 healthy volunteers and 10 patients with gastric adenocarcinoma confirmed by histological examination underwent confocal laser endomicroscopy, and the appearances of normal gastric mucosa and cancerous mucosa in confocal images were observed. In order to evaluate the validity of confocal laser endomicroscopy for the diagnosis of gastric cancer, the confocal images obtained from the normal mucosa and from cancrous lesions were interpreted by two pathologists independently and compared with the histological findings.2. During the early period of the study, the confocal images obtained from 7 healthy volunteers, 10 patients with gastric adenocarcinoma and 6 chronic atrophic gastritis and the histopathological findings were reviewed in an unblinded manner. Insight gained from the exploratory meeting and previously published classification when using magnification endoscopy was used to develop the classification of gastric pit patterns by confocal laser endomicroscopy. The classification was then prospectively applied to a"validation set" (the 132 patients). The standardized location and every macroscopic lesion were examined using the confocal laser imaging system.The confocal images obtained from the 132 patients were compared with the histopathological findings of the biopsy specimens from the corresponding confocal imaging sites in a prospective and blinded fashion.3. A total of 193 consecutive patients underwent confocal laser endomicroscopy, and 117 lesions from 103 patients were examined by chromoendoscopy-guided confocal laser endomicroscopy. Confocal images were graded according to the changes of pit architecture and correlated with the conventional histological findings in a prospective and blinded fashion. In the second part of the study, the confocal images obtained from 200 sites were presented to five endoscopists in a blinded manner on 2 separate occasions in order to examine inter- and intra-observer variability.Results1. Confocal laser endomicroscopy was able to visualize precisely the structure of pits, including the superficial columnar epithelial cells, the lumens of pits, and stroma between pits. Normal mucosa with fundic glands mainly showed round pits with round mouth, and normal mucosa with pyloric glands mainly showed continuous short rod-like pits with slit-like mouth. The confocal images of gastric adenocarcinoma were obvious different from those of the normal mucosa, and the architecture of normal gastric pits disappeared, which were replaced by obviously allotypic cells and architecture representing tumour. In the results for the interpretation by the two pathologists, the accuracy for the diagnosis of gastric cancer was 95%, and 92.5%, respectively.2. The gastric pit patterns were classified into seven types. Gastric pit patterns were classified into 7 types. Normal mucosa with fundic glands mainly showed type A (round pits), and corporal mucosa with histologic gastritis showed type B (non-continuous short rod-like); normal mucosa with pyloric glands mainly showed type C (continuous short rod-like), and antral mucosa with histologic gastritis showed type D (elongated and tortuous branch-like). With the appearance of atrophic gastritis, the confocal endoscopic pit pattern became type E. The number of pits descreased and the lumen became enlarged. Intestinal metaplasia mucosa showed type F, goblet cells which showed big and dark cells appeared with or without villous-like architecture. Cancerous mucosa showed type G. Mucosa with undifferentiated carcinoma showed type G1, normal pits disappearing, with the appearance of diffusely atypical cells; Mucosa with differentiated carcinoma showed type G2, normal pits disappearing, with the appearance of atypical glands. The sensitivity and specificity of the type E pattern for predicting gastric atrophy were 83.6% and 99.6% respectively. Corresponding values of the type G pattern for predicting gastric cancer were 90.0% and 99.4%.3. The diagnostic sensitivity, specificity, and accuracy of chromoendoscopy-guided confocal laser endomicroscopy for gastric cancer were 93.8%, 99.2% and 98.3%, respectively. The mean kappa values for inter-and intra-observer agreement on the classification of confocal images in groups were 0.875 and 0.922, respectively.Conclusions1. Real-time virtual histologial examination which is consistent with conventional histology can be performed during ongoing conventional endoscopy using confocal laser endomicrocopy, and it is feasible to diagnose gastric diseases using confocal laser endomicroscopy.2. The patterns of gastric pits identified by confocal laser endomicroscopy correlate well with the histopathological findings. Confocal endomicroscopy may prove useful in predicting the histopathological diagnoses during routine endoscopic procedures.3. The validity and reproducibility of chromoendoscopy-guided confocal laser endomicroscopy for the diagnosis of gastric cancer are satisfactory. Chromoendoscopy-guided confocal endomicroscopy is useful in the diagnosis of gastric cancer.SignificanceIn the present study, the application of confocal laser endomicroscopy in gastric diseases was firstly explored. The diagnostic criteria of gastric cancer using confocal laser endomicroscopy were constructed, and the validity and repeatability of confocal laser endomicroscopy for the diagnosis of gastric cancer was assessed. So this established the foundation for the extensive clinical application of confocal laser endomciroscopy. |
