by Harwood Academic Publishers Printed in Singapore Early Localization of Bronchogenic Cancerous/

The result of the clinical trial using the lung imaging fluorescence endoscope (LIFE) was reported. A total of 77 biopsy confirmed sites from 30 patients were evaluated. The sensitivity for metaplasia detection by the LIFE system was 96% compared to 28% by conventional bronchoscopy. The LIFE system was found to be useful in detecting subtle cancerous/precancerous lesions.


INTRODUCTION
The increasing numbers of lung cancer deaths throughout the world are mainly due to the detection of the disease at late stage. Since lung cancer is highly malignant, its prevention and early detection are essential to decrease the death rate. However, the detection of early lung cancer, especially carcinoma in situ, is a diagnostic challenge for bronchoscopists because these lesions do not always show endoscopically visible changes [1]. Photodynamic diagnosis is a modality to enhance the lesions using photosensitizer which has an affinity to tumor tissue [2][3][4]. However, photosensitizers can have side effects and are not commonly used. To overcome this problem, fluorescence detection system has been created. The lung imaging fluorescence endoscope (LIFE) system was developed to detect precancerous and CIS lesions, based on differences in normal and abnormal tissue auto-fluorescence [5][6][7]. In this study, the authors will report the result of a clinical trial using the LIFE system performed at our institution.

MATERIAL AND METHOD
Lung Imaging Fluorescence Endoscope (LIFE) [5] Normal bronchial tissue fluoresces green when excited by blue light, but abnormal tissue lacks green auto-fluorescence [8,9]. Sophisticated application of this principle produced the LIFE system [8]. The   Biopsy of this area showed carcinoma in situ (Fig. lc). Normal fluorescence decreased at the site of CIS. Metaplasia (moderate or more severe in all cases) was detected at 25 sites. The sensitivity for metaplasia detection by conventional bronchoscopy was 28% (7/25) compared to 96% (24/25) by the LIFE system (Table II). Figure 2a shows a fight basal bronchus which seems to be normal on conventional bronchoscopy. Figure 2b shows the LIFE image of the same site. A cold spot can be detected in the bifurcation of B8 and biopsy revealed metaplasia with moderate atypia (Fig. 2c). In relation to specificity, the LIFE system had a slightly higher false positive (16/36, 44%) rate than the white light bronchoscopy (14/36, 39%) but the difference was not statistically significant.
The definition of positive was atypical metaplasia or cancer.
FIGURE 1C Biopsy revealed squamous cell carcinoma.  [1,4]. The concept of fluorescence endoscopy depends on the fact that an abnormal area has different autofluorescence from that of normal areas. The normal area of the bronchus shows green autofluorescence when excited by blue light, but abnormal areas such as cancer or metaplasia show cold spots due to decreased green autofluorescence [6]. Several investigations have been performed to prove the possible cause of decreased autofluorescence: thickened cell layers, decreased amount offlavin in tissue [9], but no definite conclusion has yet been obtained. In the present study, the diagnostic rate for cancerous lesions is almost same by conventional bronchoscopy and the LIFE system (Only easily be evaluated by the LIFE system, which is helpful in the preoperative determination of the resection line or the extent of photoradiation when performing photodynamic therapy. Certain areas of metaplasia develop cancer and this theory was confirmed by experiment in dogs 10]. However endoscopic findings of metaplasia have not been intensively studied.

RESULTS
Thickening of the bifurcation with a whitish color is the only endoscopically recognizable sign of metaplasia. The sensitivity of metaplasia detection by conventional fiberoptic bronchoscope and LIFE was 28% and 96%, respectively. Lam, a pioneer ofthis system, reported the sensitivity to be 40% by white light endoscopy and 91% by LIFE [7]. Concerning this point, the LIFE system is useful to estimate the effect of chemopreventive treatment. A total of 36 normal/inflamed sites existed in this study. Using the LIFE system, 16 sites were diagnosed as abnormal. Pathological examination revealed that 5 sites demonstrated truly normal histology and 11 sites demonstrated chronic inflammation. False positive results due to inflammation (basal cell hyperplasia, thickened basement membrane) in 11 sites resulted from autofluorescence being absorbed and diminished by thickened cell layers. The reason for false positive result in the remaining 5 normal sites was not clear. Lam reported that some false positive auto fluorescence lesions appeared to progress rapidly after the examination while some false negative CIS cases regressed spontaneously during follow-up [7]. It is possible biological behavior may have some influence on autofluorescence or endogenous fluoropores.
Our study suggests that fluorescence endoscopy is useful in the detection of early lung cancer as well as in the detection of precancerous lesions not detectable by conventional methods. This method requires no photosensitizer or some specific contrast. On the average, the fluorescence examination took another 10 minutes after the standard bronchoscopy procedure so that this modality could be routinely used. Fluorescence endoscopy should contribute to the detection of early stage lung cancer and therefore to the improvement of prognosis of this disease, as well as functioning as a method to investigate the pathogenesis of pulmonary disease.