it was reported that there were 8,284 new cases of lung cancer in korea diagnosed in 2001 ( 1 ) , and the incidence and the number of lung cancer deaths continue to increase . since the overall 5-yr survival for patient with lung cancer is < 15% ( 2 ) , the future line in both the prevention of new disease by reducing the prevalence of tobacco use , and being able to accurately identify early stage disease will be amenable to curative therapy .
( 3 ) described the cellular progression of bronchial tissue from atypical metaplasia to dysplasia to carcinoma in situ ( cis ) and invasive carcinoma .
it has also been shown that the identification and treatment of these pre - invasive lesions in other organs , such as the cervix and colon , can lead to significant improvement in cancer related mortality ( 4 , 5 ) .
unfortunately , early detection has not been shown to improve survival in lung cancer patients , and physicians usually do not recommend screening for lung cancer , such as sputum cytology , chest radiology or bronchoscopy .
recent advances in screening include the use of ultra - fast ct , serum biomarkers , and sputum dna , however their role remains to be defined ( 6 , 7 ) .
bronchoscopy for the detection of early lung cancer may be helpful for two reasons : first , carcinogenesis is slow process evolving over years ( 3 ) .
secondly , about 50 - 60% of all lung cancer , especially squamous cell carcinoma , develops in the central airways .
these cancers can be detected by bronchoscopy , but are generally roentgenographically occult ( 8) . the main problem for conventional bronchoscopy is its low sensitivity and specificity for detection of early malignant cancer ( 9 ) .
pre - invasive lesions usually are small and only some cell layer thick ( 10 ) .
their endoscopic signs therefore are very subtle and can be missed even by experienced bronchoscopists . to improve the sensitivity and specificity of conventional endoscopy ,
autofluorescence bronchoscopy ( afb ) is an emerging endoscopic tool that can identify pre - cancerous lesions in the central tracheobronchial tree , predominantly squamous cell carcinoma .
there are four available systems of afb around the world , but the two most widely used systems are lung imaging fluorescence endoscopic device ( life ) and d - light / afb system .
there was only one report ( 12 ) of using life , but no report with d - light / afb system in korea .
the aim of this study was to compare the utility of d - light / afb versus the standard white light bronchoscopy ( wlb ) in the detection of pre - cancerous lesions .
the study was done during 15 november 2001 to 31 august 2002 in kosin university gospel hospital , busan , korea .
the criteria for enrollment were as follows : 1 ) patients with known or suspected bronchogenic cancer who scheduled for bronchoscopy as a part of standard diagnostic workup , 2 ) follow - up patients who were completely treated with surgery or radiotherapy , 3 ) positive cytological findings , and 4 ) smokers older than 40 yr and/or evidence of chronic obstractive pulmonary disease .
the exclusion criteria were suspected lung infection , in state of cancer treatment , pregnancy , bleeding disorders , and known reaction to topical lidocaine .
bronchoscopy was performed with local anesthesia with or without sedation using d - light / afb ( karl storz , tuttlingen , germany ) and the standard white light bronchoscopy ( wlb : bf-1t200 , olympus , tokyo , japan ) .
d - light / afb system can be used without the application of a photosensitive drug such as ala .
1 ) , while malignant abnormal tissues appearing as red / brown areas against a normal gray / blue background . fig .
2 shows the abnormal florescence and white light bronchoscopic findings of a 74 yr old male patient with cis in left upper lobe bronchus .
he was positive in sputum cytology , but he showed roentgenographically occult chest radiography finding .
details of d - light / afb systems have been reported elsewhere ( 13 ) .
the investigation was done first with white light mode , and then switching to blue light mode for the detection of the specific autofluorescence .
additionally , in almost all patients random biopsies were taken from normally appearing bronchial tissue ( 2 point classification system used ; normal and abnormal finding ) .
the duty pathologist without knowledge of clinical findings evaluated biopsy slides first , and then one lung pathologist who was blinded to the previous results reviewed all .
all biopsies were classified into one of eight groups as follows : normal , hyperplasia , metaplasia , mild atypia , moderate atypia , severe atypia , carcinoma in situ ( cis ) , and invasive carcinoma .
intraepithelial neoplasia was defined as lesions that were graded as moderate / severe dysplasia or cis .
thus the sensitivity was defined as the percentage ( visually suspicious and histologically positive / total number of histologically positive ) , and specificity also by the similar way .
positive predictive values and negative predictive values were also calculated for both wlb and afb in a similar manner .
the relative sensitivity , or the ratio of sensitivity of wlb+afb as compared with wlb alone was calculated to evaluate the contribution of the fluorescence examination to detect neoplastic lesions .
for the per lesion analysis , each biopsy specimen was evaluated and considered positive if the final diagnosis was positive .
there were 113 patients ( male 106 , female 7 ) with median age of 62 yr ( range 40 - 80 ) .
almost all patients ( 86.9% ) were current or ex - smokers with mean pack - years of 44.6 ( table 1 ) .
a total of 364 biopsy specimens were obtained . of these , 81 were not valuable ; inflammation in 63 and inadequate specimens in 18 .
the final pathologic diagnoses of the specimens were as follows : normal in 96 ; hyperplasia in 69 ; metaplasia in 32 ; mild dysplasia in 13 , moderate dysplasia in 6 , severe dysplasia in 4 ; cis in 6 ; invasive carcinoma in 57 ( table 2 ) . thus , 73 biopsy specimens ( 25.7% ) were graded as moderate dysplasia or worse ; this was then used as the standard to determine the relative sensitivity in intraepithelial neoplasia of the bronchoscopic procedure . on the lesion - by - lesion analysis , wlb alone detected severe dysplasia 2 among 4 , cis 2 among 6 , but moderate dysplasia could not be found .
in addition of afb , we missed only 1 moderate dysplasia ( table 3 ) .
the sensitivity of wlb was 30.6% , adjunctive afb to wlb 79.2% , the specificity of wlb 92% , adjunctive afb to wlb 70% in hyperplasia or worse lesions .
the sensitivity of wlb was 30.6% , wlb+afb 79.2% , the specificity of wlb 92% , wlb+afb 70% in moderate dysplasia or worse lesions .
the relative sensitivity of adjunctive afb to wlb vs. wlb alone was 2.6 in hyperplasia or worse and 1.5 in moderate dysplasia or worse lesions ( table 4 ) .
the addition of the afb identified 15 sites . therefore , the relative sensitivity of wlb+afb vs. wlb alone for intraepithelial lesions was 3.2 .
the specificity of adjunctive afb and wlb alone were 0.5 and 0.91 , respectively ( table 5 ) .
the fluorescent system is based on the different fluorescence emissions of normal tissue and tumor tissue , either spontaneously as autofluorescence ( af ) light or as drug induced fluorescence by selective accumulation of exogenous applied photosensitizer in the tumor tissue . when a surface is illuminated by light , the light
additionally , light also causes the tissue to fluoresce , however this af can not be seen during conventional wlb as the intensity of fluorescence is very low , and is overwhelmed by the reflected and back - scattered light .
tissue af revealed the underlying biochemical changes occurring in the cells , specifically the electronic structure of absorption chromophores .
the normal airway fluoresces green when exposed to light in the violet - blue spectrum ( 400 - 450 nm ) , and as sub - mucosal disease progresses from normal , to metaplasia , to dysplasia , to cis , there is a progressive loss of the green af , causing a red - brown appearance of the airway wall .
this results from reductions in certain chromophores , increasing thickness of the epithelium , as well as an increase in angiogenesis that develops with more advanced disease ( 15 ) .
as intraepithelial neoplastic lesions are only a few cell layers thick , the surface mucosa typically appears relatively normal during wlb .
lam et al . ( 17 ) introduced fluorescence bronchoscopy that is effective without the use of protoporphyrins for the purpose of localizing endobronchial lesions of moderate dysplasia or more malignant tissue .
they initially used a 100 mw helium - cadmium laser to illuminate the airways with blue light ( 442 nm ) .
lam 's group found that the red / green ratios from areas with moderate dysplasia , severe dysplasia and cis were significantly higher than those from normal areas ( 18 ) .
the system of karl - storz system is based on a modified xenon light source . on a filter in the ocular of the bronchoscope and an optional integrating camera ,
. there has been one study ( 19 ) comparing life and d - light system .
the examination time was significantly shorter with the d - light system , which may be explained by the more comfortable handling and the direct switch between white light and af imaging . when compared to the other studies , the relative sensitivity of 3.2 finding rate in the intraepithelial lesion is similar .
we gained 3.2-folds sensitivity in detecting pre - cancerous lesions by addition of afb , but lost 0.55-folds decrease in specificity .
the relative sensitivity of 1.5 in moderate dysplasia or worse lesions was also similar to the other report ( 20 ) .
that study was a large study with 1,173 patients ( 916 men ) of mean age 58.7 yr using d - light system .
overall pre - invasive lesions ( moderate to severe dysplasia , and cis ) were detected in 3.9% of the patients .
the biopsy based sensitivity of wlb alone and wlb+afb for detecting intraepithelial lesion was 57.9% compared with 82.3% ( 1.42-fold increase ) .
the corresponding specificity was 62.1% compared with 58.4% ( 0.94-fold decrease ) . in an initial study of afb , lam et al .
found a sensitivity of 48% for wlb , and sensitivity of 73% for afb , a 50% improvement ( 17 ) .
published data in more than 1,400 patients suggest that wlb alone detects on average only 40% of high - grade dysplasia and cis , whereas afb increased the detection rate up to 88% ( 21 ) .
the variation in results of both wlb and afb can be explained by the quality of conventional wlb as well as the reproducibility of the bronchoscopic and pathologic interpretation ( 22 ) .
the latter problem will hopefully be addressed by utilizing a standardized classification of pre - invasive lung cancer developed by the who ( 14 ) .
they investigated the additional yield afb had on wlb in 39 current or former smokers , and found no significant increase in the detection of squamous cell metaplasia or dysplasia .
a possible explanation for this is the fact that the prevalence of advanced disease was low in the population studied .
the majority of patients were former smokers who had stopped smoking for median of 8 yr prior to the study .
this contrasts to the studies where afb has shown to be beneficial , in that enrolled patients had known or suspected lung cancer , and therefore a higher prevalence of advanced dysplasia / cis ( 18 ) .
it appears that the increased sensitivity is associated with decreased specificity , resulting in many false - positive biopsies . aside from the cost of the autofluorescence unit , the major downside to afb is the lack of specificity .
the specificity of afb has been found to be low , with up to one third of area of abnormal fluorescence being found to be false positives ( 24 ) .
this results in a greater number of abnormal lesions being identified at the time of bronchoscopy , prolonging the procedure in order to biopsy the negative lesions , and added time and expense for the pathologist , who is required to examine all of the obtained tissue ( 25 ) .
there are many trials to increase the specificity . quantitative fluorescence imaging or combined fluorescence - reflectance imaging
however it has been suggested that up to 50% of biopsies obtained from these areas carry molecular genetic lesions associated with malignancy , despite their normal histological appearance ( 26 ) . in conclusion ,
the adjunctive afb to the standard wlb increased the detection rate of the localized pre - invasive lesions .
our findings do not support the general use of afb as a screening tool for lung cancer , but suggest that it may be of use in certain groups .
 autofluorescence bronchoscopy ( afb ) is one of the newly developed diagnostic tools to detect the pre - cancerous lesions in the bronchial tissue . 
 the utility of d - light / afb in the detection of pre - cancerous lesions was compared to the standard white light bronchoscopy ( wlb ) . in 113 patients ( male 106 , female 7 ) , who visited hospital for evaluation of lung cancer , wlb and afb were done and 364 biopsy specimens were obtained from november 2001 to august 2002 . 
 the bronchoscopic findings on wlb and afb were compared to the pathological findings . 
 the pathologic diagnoses of the specimens were as follows : normal in 96 ; hyperplasia in 69 ; metaplasia in 32 ; mild dysplasia in 13 , moderate dysplasia in 6 , severe dysplasia in 4 ; carcinoma in situ in 6 ; invasive carcinoma in 57 . 
 the relative sensitivity of adjunctive afb to wlb vs. wlb alone was 1.5 in moderate dysplasia or worse lesions , and 3.2 in intraepithelial neoplasia . 
 the specificity of adjunctive afb and wlb alone were 0.91 and 0.5 , respectively . 
 the adjunctive afb to the standard wlb increased the detection rate of the localized pre - invasive lesions . 
 however , there was high rate of false positive in afb . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION