Recently micromachine technology has been actively introduced to the endoscope. It makes endoscopes more compact to get into the organs more easily. And also it makes various functions integrated to enhance the ability of endoscopes. This will lead to advanced diagnosis and therapy. As examples of the above, the following devices are introduced; Active bending catheter with SMA(Shape Memory Alloy)realizes accurate bending of the distal end by remote control and ensures clear observation. Micro tactile sensor, which is fabricated by micromachining technique, can measure the hardness of tissue. Ultra-thin video endoscope is the thinnest video endoscope in the world. We developed Ultra-thin video endoscope by using micro fabricating technology and micro assembling technology. Endoscopic Optical Coherence Tomography is a novel technique based on low-coherence interferometery that provides noninvasive, surface, high-resolution imaging of biological ultrastructure. The optical component inside the probe is fabricated using miniaturization technology. Micro confocal scanning microscope is a laser-scanning microscope extremely miniaturized with micromachine technology and is built into the distal end of the probe. It will realize the observation of the cellular architecture of biological tissue with resolution on the micro scale in vivo without biopsies. Micromachine technology has enhanced the diagnostic capability of endoscopes. It enables endoscopes to reach various organs more easily and obtain much more diagnostic information. Consequently, endoscopes can contribute to less-invasive and more precise diagnosis. Technical challenges is continued to realize the Capsule Endoscope as a dream endoscope.

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Despite increasing the number of peripheral-type adenocarcinoma of the lung, the diameter of daily-use bronchoscope is large to go through narrow bronchi. Fine needle fiberoptic bronchoscopy(FNFB)with 2.8 mm of outer diameter and 1.2 mm of biopsy channel was developed to reach small mass(BF-XP40, Olympus). To investigate the usefulness of FNFB, we compared the ability of BF-XP40 and usual-type videoscope(BF240 or BF-1T200, Olympus). From December 1998 to July 2000, we performed comparative bronchoscopic examinations in 49 patients suspected to have peripheral lung cancer. In the diagnostic approach to the lesion, we recorded the level of most distal bronchus reached, and the level of most distal bronchus observed by FNFB and videoscope respectively in the same examination. Median age was 60(range 36-80), and 37 were male. Diagnoses were adenocarcinoma in 24, squamous cell in 9, large cell in 3, small cell in 1, non-small cell in 1, metastases in 3, tuberculoma in 2, inflammation in 2, and unknown in 4. Right lung lesions were 23, and left 26. FNFB could reach more peripherally in all cases. Median difference of levels of bronchi to reach was 3(range 1-5)in the right side, and 2(range 1-5)in the left lung. In 15% of all cases, FNFB could reach 4 levels or more distally. In observations, median difference of levels of bronchi was 2(range 0-4)in the right, and 1(range 0-4)in the left. In 15% of the patients, FNFB could observe 3 levels or more distally. FNFB was easy to reach mediastinal-side lesions. We experienced less bleeding from the biopsied site. Final pathological diagnostic sensitivity was 80%. FNFB could reach more distally and more closely to the peripherally located mass and could obtain enough specimens.

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Dual wavelength autofluorescence(AF)imaging bronchoscopy is optimized by studying the AT excitation-emission matrix over a wide spectral range. This study was carried out under endoscopic conditions in patients with various stages of malignancy as proven by biopsy. The results show major AF spectral differences between(1)healthy bronchial mucosa, (2)metaplasia or inflammation, and(3)dysplasia or carcinomain situ. The optimal AF excitation wavelength at the applied conditions was found to be near 410 nm. It is suggested that red backscattered light may be a better reference for the disease-related decrease in green AF intensity than the red fluorescence itself. An imaging AF bronchoscope was constructed based on these findings which was tested on 50 patients. The AF results appear to be superior to those obtained by white light bronchoscopy. The combined use of both techniques leads to a much improved positive predictive value for the identification of early stage central lung squamous cell malignancy as compared to each technique used by itself.

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The early detection of premalignant and malignant lesions in the endobronchial tree is crucial to survival in lung cancer patients. Autofluorescence bronchoscopy, e.g., the LIFE system has been developed for these patients and is now applied clinically. Many investigators in the world have demonstrated the effectiveness of this system for the early detection of endobronchial malignancies. Recently, a system of autofluorescence endoscopy(SAFE-1000, Asahi Pentax Co.Tokyo Japan)has been developed. This system is equipped with a conventional xenon lamp with a special bandpass filter as an excitation light source instead of laser light. The objective of this study was to judge if this simple fluorescence endoscopy system could be as useful as the LIFE system in detecting premalignant and malignant lesions of the bronchial tree. A total of 108 cases were studied and 234 sites were biopsied. The subjects were classified into three categories: cases with lung cancer(56 cases), abnormal sputum findings(32 cases), and smokers with current symptoms(20 cases). Bronchial biopsies were performed at the area of abnormal findings discovered by conventional bronchoscopy(CB)or SAFE-1000, and specimens were investigated histopathologically. The respective results of sensitivity for cancer plus dysplasia and dysplasia were 74% and 64% by CB and 89% and 85% by SAFE-1000. Positive predictive value(P.P.V.)was 64%(CB)and 70%(SAFE-1000). This data showed almost the same results obtained using the LIFE system by our group(sensitivity: 95% for cancer plus dysplasia, 90% for dysplasia, P.P.V.: 73%). Sensitivity for dysplasia increased in the fluorescence bronchoscopy compared with CB. The SAFE-1000 was developed for detection of mucosal autofluorescence without the application of any photosensitizers or use of any lasers was evaluated in this study. The result suggests the possibility of autofluorescence diagnosis of subtle bronchial lesions with this simple device.

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Photodynamic therapy utilizing Photofrin has proven to be an effective modality that can be used in the treatment of a wide variety of solid tumors and luminal cancers. Over the past decade, 285 patients(338 lesions)with central type lung cancers have been treated in our hospital. Overall complete remission was obtained in 50.3% of the 170 lesions, significant remission in 48.9% and no remission was obtained in 0.8%. However, among 161 early stage lesions CR was obtained in 139(86.3%)and 48 cases were disease free in 2 to 228 months. We have been also studying the new clinical trial to expand the indication of PDT for the treatment of bronchogenic carcinoma. Twenty eight lung cancer patients were received the preoperative PDT for the purpose of either reducing the extent of resection or increasing operability. The initial purpose of PDT, i.e.either to reduce the extent of resection or convertinoperable disease to operablestatus, was achieved in 24 out of 28 patients treated. We conclude that PDT is efficacious for the advanced bronchogenic carcinoma combined with surgery as well as in the treatment of superficial lung cancer where complete remission may be achieved.

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The inflammatory changes in small airways have been believed to be important in the pathogenesis of chronic obstructive pulmonary disease(COPD). We successfully harvested epithelial cells from these sites by using an ultrathin fibroptic bronchoscope BF2.7(Chest 106; 1443, 1994). We first evaluated IL-8 and ICAM-1 expression in small airway epithelium, both being important in the recruitment and activation of inflammatory cells such as neutrophils. The IL-8 and ICAM-1mRNA levels corrected by beta-actin transcripts were significantly more increased in COPD patients and smokers than non-smokers. Secondly, we studied the levels of TGF β-1 expression, an important growth factor in tissue remodeling. Heavily smoking volunteers(>1 packs/day), COPD patients and never-smokers underwent bronchoscopic examination after an informed consent, and epithelial cells from small airways were harvested. Levels of TGF β-1 mRNA/bata-actin transcripts were significantly higher in smokers and COPD patients than in non-smokers. The levels showed a positive correlation with daily cigarette consumption. Importantly, there was an inverse correlation between TGF β-1 mRNA and V25 on flow-volume curves. In conclusion, small airway epithelium of smokers and COPD expresses higher levels of IL-8, ICAM-1 and TGF β-1, which may be involved in neutrophil inflammation and irreversible airway obstruction found in small airways.

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Based on our BAL panel of interstitial lung diseases(ILD)and current classification of interstitial pneumonia(IP), we tried to summarize whether BAL fluid(BALF)cell findings are a feasible diagnostic indexes for differentiation, and whether the BALF cell findings predict prognosis. In an analysis of 400 healthy subjects and 151 patients with idiopathic IP(IIP)histologically diagnosed by surgical lung biopsy, we investigated how BALF cell findings were related with histology, disease severity, and prognosis. The BALF cell findings were found to be useful for differentiating between UIP and non-UIP lesions, and also to be related to prognosis among the IIP subjects. However, the BALF cell findings were not useful for differentiating between IIP and IP-CVD, and for predicting the prognosis in patients with IP-CVD.

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