Background. To enhance the diagnostic accuracy and to reduce the burden patients must endure in bronchoscopy for evaluations of peripheral lung lesions, we have recently employed the quick cytological examination. Objective. By making comparisons of the diagnostic rate before and after introduction, and by making comparisons with examinations, we strive to clarify the effectiveness of the quick cytological examination. Material and Methods. From April 2004 to December 2005, 269 patients underwent bronchoscopy in our division. In transbronchial lung biopsies (sampling) using bronchoscopy, we retrospectively analyzed and compared group A (without quick cytological examination; up to April 2005) with group B (with quick cytological examination; from May 2005) in diagnostic rates and in sampling numbers such as brushing, curet, washing and biopsy. Results. In malignant lesions, the diagnostic rates of group A and group B were 61.9% (39 of 63 patients) and 88.5% (23 of 26 patients), respectively. The diagnostic rate was significantly greater in group B than in group A. In non-malignant lesions, the diagnostic rates of group A and group B were 75% (6 of 8 patients) and 75% (3 of 4 patients), respectively. There was a little more sampling numbers in group B than in the sampling numbers in group A. Washing was performed in almost all patients of group A, but in only one patient of group B. A complication was confirmed in only one patient of group A. Conclusion. Trans-bronchial lung biopsy with quick cytological examination by using bronchoscopy contributes to increasing diagnostic accuracy and as a result, reduces the burden patients must bear. (JJSRE. 2006;28:557-560)

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Using bronchoscope insertion supportive system Plus by virtual bronchoscopic navigation, when the lesion is set as a target, the bronchus is isolated by automatic adjustment of the threshold, then, the route to the target is searched, and virtual images are obtained. In addition, during examination, virtual images can be displayed in comparison with actual images, allowing bronchoscope navigation to the target. We described this system and performed transbronchial biopsy (TBB) using it in combination with a thin bronchoscope and endobronchial ultrasonography using a thin guide sheath (thin GS-EBUS) for diagnosing twenty-three pulmonary peripheral lesions. Virtual images to a median of the 5th generation bronchus could be obtained. In all patients, the branching patterns on virtual images were the same as those on actual images. Twenty-one lesions could be visualized by EBUS, and biopsy confirmed 15 pulmonary cancerous lesions and 4 inflammatory lesions. Using this system, not only experienced radiologists but also any bronchoscopist can readily obtain virtual images on the route to the lesion. The combination of this system with a thin bronchoscope and thin GS-EBUS is not time-consuming, and can be readily performed. Therefore, this method is useful for the diagnosis of pulmonary peripheral lesions. (JJSRE. 2006;28:561-565)

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Purpose and Materials. We evaluated more than 700 CT-guided needle lung biopsy (CT-NB) during the past 25-year period to clarify the sphere of CT-NB indications. Methods. We analysed the relationships between the hitting rate or positive diagnostic rate and the size or location of the lung lesions. Results. Hitting rate of CT-NB were mainly affected by both the size and location of the lesions. The lesions that located at (1) deep in the lung, (2) just below the rib, (3) lateral, and (4) subpleural lung field were often difficult to be hit. Larger than 2 cm in caliber lesion could be hit in 2-3 times of needle insertions if it was not located at above (1)-(4) areas. It was often difficult to get enough specimen from the small lesions that were too hard to insert the needle or of poor cellularity. In 1992 we developed a new method in order to overcome these limitations. This new method consists of needle biopsy to get core specimen using biopsy gun before needle aspiration biopsy (NAB) by coaxial method. By this new method both the improvement of the positive rate for malignant lesions and the diagnostic rate for benign lesions were achieved(75%→95%,25→81%sequentially). (JJSRE. 2006;28:566-571)

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Objectives. We evaluated the efficacy of the intraoperative needle aspiration cytology (NAC) as a diagnostic approach for indeterminate pulmonary nodule. Patients and Methods. We performed intraoperative NAC in 197 patients who had not been obtained a definitive diagnosis preoperatively. We evaluated the accuracy of diagnosis, especially to analyze the difference of the accuracy after dividing the nodule by the tumor size and percentage of ground glass opacity (GGO%). Results. One-hundred and seventy three patients were diagnosed as NAC positive and the other 24 were negative and needed histological examination followed by partial resection. The definitive diagnosis of the 24 nodules were follows; primary lung cancer in 11 patients and benign disease in 13. In 173 patients who were diagnosed as malignancy by intraoperative NAC, 171 were primary lung cancer, one was metastasis from breast cancer, and the other one was atypical adenomatous hyperplasia. Eleven patients were false negative and one was false positive, resulting 94% diagnostic sensitivity, 92.9% specificity, and 93.9% accuracy for lung cancer were obtained. In 11 false negative patients, 9 patients had adenocarcinoma; 6 of 9 had bronchioloalveolar carcinomas. The diagnostic accuracy after dividing the nodule by the tumor size were follows; 100% (10/10) for 1-10 mm in diameter nodule, 90% (69/77) for 11-20 mm, 96% (55/57) for 21-30 mm, and 97% (37/38) for over 31 mm in diameter tumor. The accuracy after dividing by GGO% were follows; 96% (157/163) for GGO 0% (solid) nodule, 60% (6/10) for GGO 1-49%, and 89% (8/9) for GGO 50-100% nodule. We could not obtain high diagnostic accuracy for the nodules which include predominant GGO component. No patients who underwent intraoperative NAC suffered from severe complications after the procedure. Conclusion. Intraoperative NAC showed a good efficacy, with a high accuracy for the diagnosis of indeterminate pulmonary nodule regardless of the size. However, we could not achieve sufficient accuracy for the GGO predominant pulmonary nodule. (JJSRE. 2006;28:572-576)

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Transbronchial biopsy by bronchoscopy and percutaneous needle biopsy are useful diagnostic methods for peripheral pulmonary nodules. However, they are not always accurate indicators if they cannot assist in the decision of treatment guidance or management, or if the lesion is too small to obtain the specimen through biopsy. Diagnostic imaging is extremely important in judging whether these biopsies, or open lung and thoracoscopical biopsies are conducted. A precise diagnosis through imaging is necessary. (JJSRE. 2006;28:577-579)

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In order to improve the safety measures for thoracoscopy under local anesthesia, we studied the accomplishment rate of and complications due to thoracoscopy and examined the measure to be taken. Method. In all the cases in which thoracoscopy under local anesthesia was scheduled to be performed at our endoscopy room during the period from April 2000 to November 2005, we examined the schedule change, complications associated with thoracoscopy, and early death within one month after thoracoscopy. Results. Thoracoscopy was scheduled in 158 cases. Among them, 7 cases canceled thoracoscopy due to the difficulty in thoracic port placement and 151 cases underwent thoracoscopy under local anesthesia. Two of the 151 cases did not undergo pleural biopsy due to the difficulty in intrathoracic procedures. The schedule change was attributable to reduction of pleural effusion during thoracoscopy, severe thickening of the parietal pleura, and adhesive changes. Though the injury of visceral pleura, among complications associated with thoracoscopy, was caused by damaging the thickened visceral pleura during port insertion, the case was only carefully observed without treatment because there was no bleeding or air leak during and after thoracoscopy. Other complications included 1 case in which drain reinsertion was required due to the occurrence of subcutaneous emphysema, and 1 case each of subcutaneous infection and empyema after thoracoscopy. Both of the 2 early postoperative death cases were carcinomatous pleurisy, and diagnosed as death from the progression of the primary disease 12 and 28 days after thoracoscopy respectively. Accomplishment rate of intrathoracic observation and pleural biopsy was 94.3%, and the rate of complications that require treatment was 2.0%. The diagnosis of pleurisy using thin thoracic videoscope at endoscopy room showed a high accomplishment rate, which we believe demonstrated an acceptable level of safety. (JJSRE. 2006;28:582-584)

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Mycobacterial contamination during bronchoscopy was found out since six of eight samples of bronchial mucous showed existence of mycobacteria by Ziehl-Neelsen staining. All samples were not pathogeneic because both PCR and culture were negative. In order to prevent contamination, causes were investigated and countermeasures were assessed. Material and method. 1487 patients underwent bronchoscopy from June 2001 to March 2005. Rinse saline from bronchus of the patients and samples from scope washer and bronchoscope were investigated to examine mycobacterial contamination by Ziehl-Neelsen staining. Result of investigation. Many steps of surveillance lead to a result that mycobacteria in water flowed into scope washer were cause of contamination. Counter-measures. First step against contamination was to set double membrane filters with 0.2 μ and 0.5 μ pore to cut off mycobacteria in water flowed into washer. Second step was to set disinfectant device for water channel. Glutaraldehyde was replaced phtharal for third step. Result of countermeasures. No mycobacterial contaminations were found out after three steps of countermeasures. Conclusion. Although mycobacterial contamination of bronchoscopy is difficult to remove, safe bronchoscope can be provided by settings double membrane filters and disinfectant device for water channel and selection of effective disinfectant destroying mycobacterial DNA.(JJSJRE. 2006:28:585-591)

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Purpose. We newly developed a less invasive bronchoscopic microsampling (BMS) probe to assess biochemical substances in epithelial lining fluid (ELF). We have been reporting that measuring biomarkers in ELF was useful for diagnosis of pulmonary diseases in clinical setting. In the present study, we examined whether if proteomic analysis of ELF by BMS method is possible. Methods. 1) ELF in Lipopolysaccharide (LPS) induced lung injury model was collected using BMS probe specially designed for rats. 2) The BMS probe was inserted through a bronchoscope channel and regional ELF was collected selectively in patients with lung cancer. Two ul of ELF was analyzed by SELDI-ToF-MS (Proteintip System^<TM>, Ciphergen Biosystems) in both experiments. Results. 1) Increasing TNF-α level of ELF (ELISA method) in LPS rat model had been confirmed. Some peaks (31000,47000,63000 Da) were detected in LPS rats. These peaks were not detected in control rats and rats which were treated by TNF-α antagonist 2) Several peaks (3460,9280, 20800, 5230 Da) were detected in ELF that was collected from tumor side in patients with adenocarcinoma compared to contralateral side. Conclusion. Proteomic analysis of ELF by BMS method was possible. (JJSRE. 2006;28:592-596)

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Background. Retrospective analyses have been reported on the relationship between mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene and response to gefitinb in non-small cell lung cancers (NSCLCs). Objectives. In this study, we evaluated the EGFR mutation rate of NSCLC tumor samples obtained by several procedures and the correlation with response to gefitinib. Subjects. One hundred and seventeen patients with histologically confirmed NSCLCs diagnosed from November 2004 through January 2006 at each institute of the Hokkaido Lung Cancer Clinical Study Group were enrolled. Fifty-two surgically resected samples and 52 transbronchial biopsy (TBB) samples, and 13 other biopsy samples were used for analysis. Methods. Genomic DNA was extracted from tumors of paraffin-embedded tissues. Exons 18-21 of EGFR were amplified by PCR, and the resulting PCR amplicons were directly sequenced. Results. The overall proportion of patients with EGFR mutations were 29% (34/117). There was no significant difference in mutation rate between surgically resected samples (29%, 15/52) and TBB samples (27%, 14/52). Deletions in exon 19 and L858R in exon 21, which are reportedly correlated with gefitinib sensitivity, were detected in 26% of all the samples (30/117), 25% (13/52) of surgically resected samples, and 25% (13/52) of TBB samples, respectively. There was no significant difference either in response rate of gefitinib between surgically resected samples (70%, 7/10) and TBB samples (67%, 8/12). Conclusion. TBB samples are as useful as surgically resected samples in EGFR mutational analysis. (JJSRE. 2006;28:597-600)

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According to the hypothesis of multi-step carcinogenesis, we believe that squamous cell carcinoma appears in bronchial epithelium through the precancerous lesion (squamous metaplasia and dysplasia). We cannot distinguish in-situ carcinoma from dysplasia without a skillful diagnosis by experienced pathologists. However, such a pathological diagnosis is a universal criterion, isn't it? Recently, it is recommended that a small-sized bronchioloal-veolar carcinoma in the peripheral lung is enough for follow-up examinations, even though its lesion is recognized as a cancerous lesion. When we evaluate the necessity of therapeutic treatments of the intrabronchial lesion, we should regard the biological characteristics as important. We attempted to evaluate the biological characteristics of the intrabronchial lesions using cell proliferation, mutant p53 protein expression and the deficiency of cell to cell adhesion ability, and we concluded that these changes initially occurred in the neighborhood of the basement membrane. (JJSRE. 2006;28:601-606)

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Background. We tried bronchoscopic lung volume reduction (BLVR) with Endobronchial Watanabe Spigot (EWS) for patients with severe emphysema. However, the collateral ventilation seemed to interfere with its clinical effect. Therefore we developed the new endobronchial silicone valve (Endobronchial Miyazawa Valve, EMV) as more effective devise. The purpose of this study was to investigate the safety and feasibility of placing EMV in the lobar bronchi with severe emphysema and giant bulla. Methods. Seven patients (five patients with severe emphysema and two with giant bulla) were entered this pilot study. EMVs were placed in the lobar or segmental bronchi supplying the most hyperinflated parts of the lung. The EMVs were inserted under intravenous anesthesia and spontaneous ventilation, with visual and fluoroscopic control through a flexible bronchoscope and forceps. Spirometry, diffusing capacity of the lung carbon monoxide (D_<LCO>) and exercise tolerance testing (6 minutes walk distance and ADL) were performed at 1 month, 3 months and 6 months after procedure. Results. In this series no complication occurred. In the change ratio of respiratory functions, FVC increased by 7.6±6.7%(p=0.016), FEV_<1.0> increased by 10.1±11.7%(p=0.023), RV/TLC decreased by 18.0±18.9%(p=0.039), D_<LCO>/VA increased by 22.1±24.6%(p=0.008) and 6-min walk distance increased by 48.1±23.7%(p=0.008). ADL was improved slightly or moderately in 6 patients. Three patients revealed the effect of lung volume reduction in the chest X-ray films but no patient had lobar atelectasis. Conclusion. EMV which we developed has a wide orifice for easy excretion of secretion and little risk of damage by its simple structure. Therefore BLVR with EMV can be performed with acceptable short-term safety and worthwhile functional benefits. We considered that BLVR with EMV was the new and low invasive therapy for the patient with severe emphysema or giant bulla. (JJSRE. 2006;28:607-614)

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Background. Indication of airway stent for benign airway stenosis is controversial, however, majority of the opinions are negative because of its unknown long term-durability and inflammatory response of the airway wall with granulation. Method. Twelve patients with benign airway stenosis were treated with surgical resection/reconstruction (n=6), laser ablation (n=3) or airway stent (n=3). Results. After stent insertion, granulation and stricture were seen in all patients, whereas surgically treated patients recovered uneventfully. Discussion. Based on those experience regarding the treatments of benign airway stenosis, we suggest that the application of airway stent either silicone or metallic prosthesis should be carefully considered depending on individual bases. If the stricture includes less than 2 rings of tracheal cartilage, laser ablation or balloon bougie can be applied. Surgical resection and reconstruction should be selected as a first line treatment if the stenosis involves 3 or more tracheal cartilages. Airway stents or other interventional treatment should be considered if the surgical resection can not be considered because the length of the stenosis is too long for safe airway reconstruction or the patients are not tolerable for surgery. (JJSRE. 2006;28:615-619)

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It is well known that central type early-stage lung cancer less than 1.0 cm in diameter shows almost 100% CR to photodynamic therapy (PDT). However, we have encountered cases of local recurrence after CR of tumors with a surface diameter less than 1.0 cm. Ninety three patients with 114 lesions were followed up, and cases of recurrence after CR has been obtained with initial tumors that had a diameter less than 1.0 cm were examined. We compared the cytological findings of local recurrence after CR to the cytological findings before PDT. The relationship between the cell features and the depth of bronchial tumor invasion before PDT and on recurrence was evaluated. Recurrences after CR were recognized in 9 out of 77 lesions (11.7%) less than 1.0 cm. When the recurrent tumor cells showed Type I-II at the same site initially treated, CR could be obtained by a second PDT. Type III cells showed the characteristics of tumor cells from deeper layers of the bronchial wall. Local recurrence at the same site may be caused by residual tumor cells from deep layers because of inadequate laser irradiation and penetration. To reduce the recurrence rate, it is essential to accurately grasp the tumor extent and the depth of the bronchogenic carcinoma before performing PDT. Analysis of cell features of recurrent lesions after CR appears to be a useful source of information as to the depth of cancer invasion in the bronchial wall. The description of this manuscript was presented in Chest 2005;128:3269-3275. (JJSRE. 2006;28:620-627)

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Background and Purpose. Fiberoptic bronchoscopy (FB) is a simple and well-tolerated procedure that can provide both diagnostic and therapeutic benefits. Fever or pneumonia related with bronchoscopy has been frequently reported in adults. The purpose of the present study is to determine whether there are relations between nasopharyngeal flora and bacteria which is attached to the FB. Material and Methods. Twenty-one patients undergoing FB from January to March 2005 in our hospital were randomly divided into 2 groups. Eleven patients received bronchoscopy via transnasal route, 10 patients received it via transoral route. Nasal and oral swab samples were collected from each patient just before the procedure. Swab samples from bronchoscope were collected after the bronchoscopy. Samples were cultured for bacteriological examination. Results. Staphylococcus aureus (S. aureus) isolate was cultured from nasal samples in 5 patients. However S. aureus isolate was not found in pharyngeal samples from 21 patients. In cases of transnasal bronchoscopy, bacterial isolates which were found in nasopharyngeal flora were cultured from bronchoscope. In cases of transoral bronchoscopy, bacterial isolates which were found in pharyngeal flora were cultured from bronchoscope. S. aureus isolate was cultured from nasal samples in 3 patients undergoing transnasal bronchoscopy. S. aureus isolate was also found in swab samples from bronchoscope after the procedure in these 3 cases. Discussion. Results of the present study suggested that bronchoscope potentially carries pathogenic bacteria in nasopharyngeal flora to the lower respiratory tract. Therefore careful procedures including selection of the route of introduction probably reduce the risk of infection due to the bronchoscopy. (JJSRE. 2006;28:628-632)

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