• Journal of Chest Surgery
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• v.13 no.1
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• pp.66-71
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• 1980

This is one case report of coexisting two histologically different carcinomas in the different lobes of the right lung, which operated the right pneumonectomy in the Dept. of Thoracic and Cardiovascular Surgery Hanyang University Hospital. The 43 years old male patient complained coughing, blood tinged sputum and weight loss. The chest films [PA and lateral view] showed a small round hazy shadow in the posterior segment of the right upper lobe and irregular hazy densities in the right middle lobe and hilar area. Histopathologically, the tumor in the posterior segment of the right upper lobe was consisted of a tissue of adenocarcinoma and the tumor in the right middle lobe was consisted of a tissue of well-differentiated bronchial squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.188-198
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• 2013

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.685-694
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• 1995

Introduction: Transthoracic fine needle aspiration biopsy(TNAB) has shown to be a resonably safe, simple, and accurate procedure in diagnosis of intrathoracic lung lesions. We reviewed the results of 1,005 TNAB of chest lesions performed on 930 patients with 20 or 22-gauze needles over a period of 10 years. Methods: From November 1983 to June 1995, 1,005 cases in 930 patients with an undiagnosed lung lesion underwent TNAB at the Hanyang University Hospital: 66% were men and 34% were women. Most of the patients were 40~60 years old and the youngest patient was 3 years of age. Result: 540 patients had various malignant chest lesions and 322 patients had benign pulmonary lesions. The diagnostic accuracy of TNAB was 96.1 percent in malignant diseases with one false positive result and 90.1% in benign diseases. A definitive diagnosis was not obtained in the remaining 68 patients. The most common diagnoses among 519 malignancy chest lesions with TNAB were the following: squamous cell lung carcinoma, 31.7%; adenocarcinoma, 24.7%; small cell lung carcinoma, 16.7%; metastatic cancer, 14.2%; large cell lung carcinoma, 6.2% and so on. Complications included pneumothorax in 12.3% necessitating chest tube drainage in 0.6%. Minor hemoptysis occurred in 3.6%. There was no death directly attributable to the procedure. Conclusion: We concluded that TNAB permits a direct approach to all kinds of localized lung lesions with a high degree of accuracy and without major complications.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.480-489
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• 2005

Background : Dysregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. This study was designed to assess the pattern of expression and the prognostic value of XIAP in radically resected non-small cell lung carcinoma (NSCLC) patients. Method : The expression of XIAP and its relationship with clinicopathologic parameters (patient age, TNM stage, TNM-pT, TNM-pN, histologic type, VEGF expression, microvessel density, PCNA index) and overall survival were analysed with formalin-fixed, paraffin-embedded blocks from eighty cases of NSCLC. In addition, the apoptotic index (AI) was also assessed. Results : In a regard to histologic type, squamous cell carcinoma (SCC) showed XIAP expression in 91.3%(42/46) and adenocarcinoma (AC) in 61.8%(21/34). The difference was significant(p=0.001). There was no correlation between XIAP expression and other parameters. In the group of AC, XIAP expression showed the signifcant correlation with older age group ${\geq}58years$ and VEGF expression(p=0.028, p=0.014, respectively). The AI in the group with or without XIAP expression were $2.5{\pm}4.9%$ and $18.5{\pm}28.9%$, respectively(p=0.001). Both groups just aforementioned showed no significant difference in median survival time (42.5 months, 29.8 months, respectively). Conclusion : This study suggests that the XIAP expression in NSCLCs could have relation to inhibition of apoptosis, and show differential expression according to histologic type. However, its prognostic role during the progression of NSCLC needs to be further defined.

• Tuberculosis and Respiratory Diseases
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• v.71 no.1
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• pp.8-14
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• 2011

Background: MicroRNAs (miRNAs) have demonstrated their potential as biomarkers for lung cancer diagnosis. In recent years, miRNAs have been found in body fluids such as serum, plasma, urine and saliva. Circulating miRNAs are highly stable and resistant to RNase activity along with, extreme pH and temperatures in serum and plasma. In this study, we investigated serum miRNA profiles that can be used as a diagnostic biomarker of non-small cell lung cancer (NSCLC). Methods: We compared the expression profile of miRNAs in the plasma of patients diagnosed with lung cancer using an miRNA microarray. The data from this assay were validated by quantitative real-time PCR (qRT-PCR). Results: Six miRNAs were overexpressed and three miRNAs were underexpressed in both tissue and serum from squamous cell carcinoma (SCC) patients. Sixteen miRNAs were overexpressed and twenty two miRNAs were underexpressed in both tissue and serum from adenocarcinoma (AC) patients. Of the four miRNAs chosen for qRT-PCR analysis, the expression of miR-23a was consistent with microarray results from AC patients. Receiver operating characteristic (ROC) curve analyses were done and revealed that the level of serum miR-23a was a potential marker for discriminating AC patients from chronic obstructive pulmonary disease (COPD) patients. Conclusion: Although a small number of patients were examined, the results from our study suggest that serum miR-23a can be used in the diagnosis of AC.

• Journal of Chest Surgery
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• v.36 no.5
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• pp.348-355
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• 2003

Background: The prognostic significance of lymph node micrometastasis in non-small cell lung cancer remains controversial. We therefore investigated the clinicopathologic factors related to lymph node micrometastsis and evaluated the clinical relevance of micrometastasis with regard to recurrence. Material and Method: Five hundred six lymph nodes were obtained from 41 patients with stage 1 non-small ceil lung cancer who underwent curative resection between 1994 and 1998. Immunohistochemical staining using anti-cytokeratin Ab was used to detect micrometastasis in these lymph nodes. Result: Micrometastatic tumor cells were identified in pN0 lymph nodes in 14 (34.1%) of 41 patients. The presence of lymph node micrometastasis was not related to any clinicopathoiogic factor (p) 0.05). The recurrence rate was higher in patients with micrometastasis (57.1%) than in those without (37.0%), but the difference was not significant (p=0.22). Patients with micrometastasis had a lower 5-year recurrence-free survival rate (48.2%) than those without micrometastasis (64.1%), with a borderline significance (p=0.11), The S-year recurrence-free survival rate (25.0%) in the patients with 2 or more micrometastatic lymph nodes was significantly lower than that in the patients with no or single micrometastasis (p=0.02). In multivariate analysis, multiple lymph node micromestasis us was a significant independent predictor of recurrence (p=0.028, Risk ratio=3.568). Conclusion: Immunehistochemical anti-cytokeratin staining was a rapid, sensitive, and easy way of detecting lymph node micrometastasis. The presence of lymph node micrometastasis was not significantly associated with the recurrence, but had a tendency toward a poor prognosis in stage 1 non-small cell lung cancer. Especially, the presence of multiple micrometastatic lymph nodes was a significant and independent predictor of recurrence.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.489-496
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• 2003

To clarify the prognostic implication of the location and number of the metastatic mediastinal nodes in resected stage IIIA N2 non-small cell lung cancer. Material and Method: One hundred and seventy-four patients with resected non-small cell lung cancer who eventually proved to have pathologic stage IIIA N2 disease were studied. Patients who received preoperative induction therapy, non-curative operation or defined as operative mortality were excluded from this study. Result: In upper lobe tumors, there was no difference in 5-year survival according to the involvement of lower mediastinal nodes (32.3% vs 25.6%, p＝0.86). In lower lobe tumors, no difference was found in 5-year survival according to the involvement of upper mediastinal nodes (25.1% vs 14.1%, p＝0.33). There was no significant difference in 5-year survival between patients with or without metastatic subcarinal node (20.9% vs 25.6%, p＝0.364). In terms of the number of metastatic mediastinal nodes, 5-year survival was better in single station group (26.3%) than multiple station group (18.3%) (p＝0.048). In multiple station N2 group, the patients who received postoperative chemotherapy and radiation therapy had better 5-year survival (34.2%) (p＝0.01). Cox's proportional hazards model revealed that the age $\geq$60 (O.R: 1.682, p＝.006), multiple station N2 (O.R: 1.503. p＝0.021), pneumonectomy (O.R: 1.562, p＝0.018), postoperative chemotherapy and radiation therapy (O.R: 0.625, p＝0.012) were the factors affecting the postoperative survival. Conclusion: Multiple station N2 disease was the important prognostic factor for postoperative survival in resected stage IIIA N2 non-small cell lung cancer. Postoperative chemotherapy and radiotherapy were thought to improve the survival in case of multiple station N2 disease.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.237-242
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• 2006

$\underline{Purpose}$: We evaluated retrospectively the outcome of locally advanced non-small cell lung cancer patients treated with definitive radiotherapy to find out prognostic factros affecting survival. $\underline{Materials\;and\;Methods}$: 216 cases of stage IIIB non-small cell lung cancer were with treated radiotherapy at our Hospital between 1991 to 2002 and reviewed retrospectively. Cases were classified by mode of treatment and response to treatment. Patients showing complete response or partial response to treatment were included in the "response group", while those showing stable or progressive cancer were included in the "non-response group". $\underline{Results}$: 30 patients completed the planned radiotherapy treatments and 39 patients completed combined treatments or chemoradiotherapy. Median survival was 4.6 months for patients treated with radiotherapy and 9.9 months for those undergoing combined radiotherapy and chemotherapy. Survival rates for the first year were 13.3% with radiotherapy and 35.9% with chemoradiotherapy. In the second year, 3.3% of the radiotherapy patients survived and 20.5% of the patients receiving chemoradiotherapy survived. By the third year, 15.4% of the patients receiving the combined treatments survived. None of the patients treated with radiotherapy alone lived to the third year, however. Overall survival was significantly different between the radiotherapy patients and the combined chemoradiotherapy patients (p<0.001). In the response group, median survival was 7.2 months with radiotherapy and 16.5 months with combined therapy. In the non-response group, median survival was 4.4 months with radiotherapy and 6.7 months with combined treatments. Severe acute complications (grade 3) occurred in 2 cases using radiotherapy, and in 7 cases using combined therapy. $\underline{Conclusion}$: When the patients with stage IIIB non-small cell lung cancer received chemoradiotherapy, treatment response rate and overall survival was greater than with radiation alone.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.441-452
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• 2002

Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.35-41
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• 1999

Background: Sleeve lobectomy of the main bronchus has been proposed to spare lung tissue in patients who cannot tolerate pneumonectomy because of impaired lung function. The purpose of this study was to evaluate whether sleeve lobectomy can preserve lung function as expected from preoperative evaluation of lung function in patients with non-small cell lung cancer. Method: Between January 1995 and March 1998, 15 patients with non-small cell lung cancer who underwent sleeve resection were evaluated. Preoperative evaluations included spirometry and quantitative lung perfusion scan, from which predicted postoperative $FEV_1$ was calculated. At least 3 months after operation follow up spirometry and bronchoscopy were performed. Predicted FEVj was compared with measured postoperative $FEV_1$. Result: Fourteen men and one woman, with median age of 58 years, were reviewed. The diagnosis was squamous cell carcinoma in 13 patients and adenocarcinoma of lung in 2 patients. Our results showed a excellent preservation of pulmonary function after sleeve lobectomy. Correlation between the predicted (mean, $2180{\pm}570mL$) and measured $FEV_1$ (mean, $2293{\pm}499mL$) was good(r=0.67, P<0.05). Furthermore, patient with low $FEV_1$ (<2L) showed improved lung function after sleeve lobectomy. Conclusion: These findings indicated a complete recovery of the reimplanted lung lobes after sleeve lobectomy. Therefore, this technique could be safely used in lung cancer patients with impaired lung function.