• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.54-62
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• 1996

Background: $^{99m}Tc$ MIBI(Methoxyisobutylisonitrile complex), a member of the isonitrile class of coordination compounds, is a lipophilic cation presently under investigation for clinical use as myocardial perfusion imaging agent and is widely used to detect myocardial infarction. Preliminary reports indicate that $T_1$-201 accumulate in human neoplasm and several authors reported $^{99m}Tc$ MIBI may also localized in primary malignant tumor and metastatic deposits from lung cancer. We evaluated the uptake of $^{99m}Tc$ MIBI in lung cancer and localization of mediastinal and other site metastasis, and compared the benign lesion of the lung. Method: Thirty four patients of lung cancer and ten patients of benign lung lesion were studied with chest CT and $^{99m}Tc$ MIBI Lung SPECT. $^{99m}Tc$ MIBI uptake ratio was assessed by TR/NL(Lung lesion/ Normal area), HT/NL (Heart/Normal area) and HT/TR(Heart/Lung lesion). Results: 1) All lung cancer patients showed increased uptakes of $^{99m}Tc$ MIBI in malignant lung lesion and Tc-99m MIBI uptake was also increased in mediastinal and lymph node metastasis except two cases. 2) There was significant different ratio of TR/NL between malignant and benign lesion, $3.79{\pm}1.82$ and $1.67{\pm}0.63$ on planar images, respectively(p<0.001). 3) There was no significant difference of $^{99m}Tc$ MIBI uptake ratio between squamous cell carcinoma, small cell carcinoma and adeno carcinoma($3.64{\pm}1.66$, $3.57{\pm}0.72$, $4.31{\pm}2.28$ respectively). Conclusion: $^{99m}Tc$ MIBI lung SPECT was useful in the localization of tumor and mediastinal or other site metastatic lesion in lung cancer and also in the differential diagnosis between benign and malignant lesion.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.108-121
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• 2001

Background : The $p16^{INK4a}$ (p16) twnor suppressor gene is frequently inactivated in hwnan non-small cell lung cancers (NSCLCs), predominantly through homozygous deletion or in association with aberrant promotor hypermethylation. Death-associated protein kinase (DAPK) gene influences interferon $\gamma$-induced apoptotic cell death and has important role in metastasis of lung cancer in animal model. Hypermethylation of promoter region of DAP kinase gene may suppress the expression of this gene. Methods : This study was performed to investigate the aberrant methylation of p16 or DAP kinase in 35 resected primary NSCLCs by methylation-specific PCR (MSP), and demonstrated frequency, diagnostic value and clinical implication of aberrant methylation of two genes. Results : Thirty-two cases were male patients, and 3 cases were female patients with an average age was 57. $8{\pm}10.5$ years. The histologic types of lung cancer were 22 of squamous cell carcinoma, 12 of adenocarcinoma, 1 of large cell carcinoma. Pathologic stages were 11 cases of stage I (1 IA, 10 IB), 13 cases of stage II (1 IIA, 12 IIB), and 11 cases of stage III (9 IIIA, 2 IIIB). Regarding for the cancer tissue, p16 aberrant methylation was noted in 13 case of 33 cases (39.4%), DAP kinase in 21 cases of 35 cases (60%). Age over 55 year was associated with p16 aberrant methylation significantly (p<0.05). Methylation status of two genes was not different by smoking history, histologic type, size of tumor, lymph node metastasis and disease progression of lung cancer. There was no correlation between p16 and DAP kinase hypermethylation. Conclusion: This investigation demonstrates that aberrant methylation of p16 tumor suppressor gene or DAP kinase showed relatively high frequency (74.3%) in NSCLCs, and that these genes could be a biologic marker for early detection of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.147-154
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• 2001

Background : Bronchoscopy has been widely used for a histologic diagnosis through a transbronchial lung biopsy or for staging of patients with peripheral lung cancer. However a transthoracic needle aspiration (TTNA) has been used more widely for a histologic diagnosis in patient with a small size nodule or a nodule located in the outer portion of the lung because of the low diagnostic yield of bronchoscopy in these cases. The role of bronchoscopy for staging is not well established in patients with peripheral lung cancer diagnosed by a TTNA or patients who are undergoing surgery without a histologic diagnosis. Method: To evaluate the role of bronchoscopy for the staging in patients with peripheral lung cancer, who were diagnosed by TTNA, the medical records of 86 patients with peripheral lung cancer who underwent bronchoscopyat Kyungpook National University Hospital between January 1995 and May 1997 were reviewed. Results : While 53 cases had normal bronchoscopic findings, 33 cases had abnormal bronchoscopic findings comprising 9 cases of tumor, 10 cases of infiltration and 14 cases of compression of which there were 25 cases of T1 and 8 T2 endoscopically. The bronchoscopic staging did not influence the changes of the clinical stage of lung cancer. The frequencies of bronchial involvement tended to increase as the sizes of the nodule increased. Among the 42 patients who underwent surgery, 9 patients staged higher after operation because of lymph node involvement in 8 patients and the involvement of the pulmonary artery in 1 patient. No case staged above after operation due to a bronchial invasion. Conclusion : These findings suggests that bronchoscopy is not useful for staging in patients with peripheral lung cancer diagnosed by a TTNA.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.265-272
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• 2004

Background : RASSF1A, which is one of tumor suppressor genes, is frequently inactivated by hypermethylation of the promoter region in a variety of human cancers, including lung cancer. This study was performed to investigate the association between RASSF1A methylation and the clinicopathological factors in patients with squamous cell carcinoma of the lung. Methods : Eighty-one samples from the patients with squamous cell carcinoma of lung were examined. The promoter methyation of RASSF1A was analyzed by methylation specific PCR and sequencing. Statistical analysis was made to examine the association between RASSF1A methylation and the clinicopathological parameters. Results : RASSF1A methylation was observed in 37.0 % (30 of 81) of the patients with squamous cell carcinoma of the lung. RASSF1A methylation was found to be associated with cellular differentiation(p=0.0097) and the overall survival(p=0.0635). However, there was no association between RASSF1A methylation and the other clinicopathological parameters, such as the pathological TNM stage, the recurrence rate, lymph node invasion and the amount of cigarettes smoked. Conclusion : RASSF1A methylation might be associated with a poor prognosis in patients with squamous carcinoma of the lung. A larger scale study is needed.

• Tuberculosis and Respiratory Diseases
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• v.41 no.6
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• pp.616-623
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• 1994

Objectives: Careful evaluation about mediastinal involvement is important in the management of patients with non-small cell lung cancer. Invasive staging procedure such as mediastinoscopy is advocated because of the unreliability of noninvasive staging methods such as CT, MRI. We compared differences between pre- and postoperative staging in non-small cell lung cancer without lymphadenopathy on CT scan and investigated the methods for more accurate preoperative staging. Methods & Results: 1) Records of a total of 41 patients with preoperative $T_{1-3}N_0M_0$ non-small cell lung cancer were reviewed and the histologic types of tumors were squamous cell carcinoma in 32 cases, adenocarcinoma in 6 cases and large cell carcinoma in 3 cases. Twenty-four cases were central lesions and seventeen cases were peripheral lesions. 2) Among the 32 cases with preoperative $T_2$, 2 cases were identified postoperatively as $T_3$ with invasion of chest wall and among 6 cases with preoperative $T_3$, 1 case was identified postoperatively as $T_4$ with invasion of aorta and pulmonary arteries. 3) After the operation of 35 cases with $T_{1-2}$, 5 cases were $N_1$ and 3 cases were $N_2$ postoperatively. After the operation of 6 cases with $T_3$, 2 cases were $N_1$ and 3 cases were $N_2$ postoperatively. Preoperative $T_3$ showed more intrathoracic lymph node metastases and higher $N_2/N_1$ involvement ratio than preoperative $T_{1-2}$. 4) Complete surgical resections were done in 34 out of 41 cases. Incomplete resection were done in all postoperative $N_2$ tumors. Conclusion: Invasive staging procedures such as mediastinoscopy should be considered in the case of preoperative $T_3$ non-small cell lung cancer even though mediastinal lymphadenopathy is not recognized on the CT scan of the chest.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.591-598
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• 2001

Background : Primary adenoid cystic carcinoma arising in the bronchus is an uncommon disease that is histologically and ultrastructurally identical to the salivary gland tumor of the same name and regarded as a slow growing low-grade malignancy. We examined its clinical characteristics. Method : We collected 13 Korean cases of primary adenoid cystic carcinoma arising in the bronchus including 5 cases of our own and 8 cases from the literature. Result : The patients ages ranged from 20 to 74. Men numbered 9 and women 4. The presenting symptoms were cough, dyspnea, and hemoptysis. The fiberoptic bronchoscopic findings were primarily hypervascular polypoid mass with a smooth surface that obstructed airway totally or near totally. There were three inoperable cases including two cases with distant metastasis to bone or cervical lymph node and one case with mediastinal invasion. The remaining 10 patients underwent surgical resection. Among them, two patients received postoperative radiotherapy. The median survival was 21 months in the 8 surgical and evaluable cases. One patient lived 13 years without recurrence. The prognosis was relatively favorable in operable cases. Conclusion : It was not common for primary adenoid cystic carcinoma arising in the bronchus to have distant metastasis or invasion to the mediastinum on presentation. The prognosis was relatively favorable in operable cases. It would be important to perform flexible bronchoscopy for early diagnosis and to do surgical treatment if possible.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.45-56
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• 1998

Background: Lung cancer continues to increase worldwide. Also, the proportion of female patients incease and adenocarcinoma is the predominant histological type among lung cancer in many western countries. So, we studied these current trends of lung cancer by clinical approach of recent patients from our department Method: We conducted a retrospective analysis on 212 subjects who were diagnosed with lung cancer at the department of chest medicine in National Medical Center between January 1990 and July 1996. The contents of analysis were patient's profile, clinical manifestation, smoking habits, accuracy of diagnostic methods, histological cell type, staging and treatment, etc. Results: The results were as follows. 1) The ratio of male to female was 5.2 : 1. The peak incidence of age was 7th decade(35.4%). 2) Chief complaints were cough, dyspnea and chest pain, etc. The most common duration of symptoms before the first admission was less than 3 months(57.7%). On the other side, duration more than 1 year represented 6.5%. The early diagnosed patients has been increased from the 1980s. 3) Smokers among the total patients were 77.2%. The proportion of smokers in sqamous cell carcinoma, small cell carcinoma and adenocarcinoma were 88.4%, 85.7% and 55.7%, respectively. Smoking history and histological cell type were correlated in squamous and small cell carcinoma. 4) Squamous cell carcinoma is still the predominant histological type (44.8%), but, adenocarcinoma increased more than the previous study(30.7%). The other histological types were small cell carcinoma(17.0%) and large cell carcinoma(3.8%) in order of their proportions. 5) The accuracy of diagnostic methods were as follows: sputum cytology 75.3%, bronchoscopic biopsy 65.7%, lymph node aspiration cytology 95.8%, percutaneous lung aspiration cytology 94.6% and open lung biopsy 100%. The general accuracies of diagnostic methods were improved than previous studies. 6) Performance status scales on admission were relatively good. After diagnosis, chemotherapy and/or radiotherapy were undertaken in 69.3% of the patients, and only 7.5% of the patients were operated. Conclusion: In our study, squamous cell carcinoma is still the predominant histological cell type, but, adenocarcinoma continues to increase. Because adenocarcinoma is less correlated with smoking habits, further evaluation of other carcinogens than smoking is requested. Screening and early diagnosis of lung cancer is important for good performance status scales in spite of advanced stages. But, we think that the prevention, for example, stop smokings is more important as because of no perfect treatment for lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.516-524
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• 1997

Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{\pm}0.3ng/mL$ in controls, $1.0{\pm}0.3ng/mL$ in benign lung disease patients and $0.9{\pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{\pm}6.7ng/mL$ in controls, $14.9{\pm}6.3ng/mL$ in benign lung disease patients, and $22.1{\pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{\pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{\pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{\pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{\pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{\pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{\pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{\pm}0.6ng/mL$ in stage II, $0.7{\pm}0.4ng/mL$ in stage IIIA, $0.7{\pm}0.4ng/mL$ in stage IIIB, and $0.7{\pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{\pm}8.7ng/mL$ in stage II, $18.4{\pm}4.9ng/mL$ in stage IIIA, $25.3{\pm}9.0ng/mL$ in stage IIIB, and $21.5{\pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{\pm}0.4ng/mL$ in T1-3 and $0.7{\pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{\pm}5.6ng/mL$ in T1-3 and $26.1{\pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{\pm}0.4ng/mL$ in M0 and $0.7{\pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{\pm}8.3ng/mL$ in M0 and $21.5{\pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.