• Journal of Chest Surgery
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• v.31 no.12
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• pp.1195-1199
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• 1998

Bafckground: Thr role and indication of surgery in the treatment of small cell lung cancer(SCLC) is currently limited and unsettled. Material and Method: We analyzed the surgical results of 9 patients with SCLC at Yosei Medical Center from January 1990 to December 1996. There were 8 males and 1 female, and their mean age was 57.2 years (range; 35-76). Preoperatively SCLC was confirmed in 5, but the other 4 cases were diagnosed as undifferentiated squamous cell carcinoma. All patients underwent pulmoinary resection(lobectomy;5, lobectomy, segmentectomy and en-bloc resection of rib;1, bilobectomy; 2, pneumonectomy;1) and mediastinal lymph node dissection. Results: There were no operative mortality with two complications(postoperative bleeding;1, arrhythmia;1). All cases were diagnosed as SCLC histologically and their TNM staging were confirmed as follows: T1N0M0;1, T2N0M0;4, T3N0M0;1, T3N1M0;1, T2N2M0; 1, T4N0M0;1. All patients had received postoperative chemotherapy, and radiotherapy was combined in 4 patients. During follow up period(range 1-63 months; mean 33.0months), there was only one metastasis to pelvic bone among 8 patients without lymph node metastasis, and all patients were alive. On the other hand, among 3 patients who had regional and/or mediastinal lymph node metastasis or T4 lesion, all patients had recurrences(local;2, brain;1), and 2 patients died. Conclusion: We suggest that the use of TNM staging is beneficial, and surgical resection should be recommended in the patients with early staged SCLC as an important treatment modality.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.367-377
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• 1993

Background: The benefits of combination chemotherapy in unresectable non-small cell lung cancer remain uncertain. But, according to the recent reports, the response rates of cisplatin-based polychemotherapy regimens are higher than those of single agent. Also, the response rates of high-dose cisplatin group are higher than those of low-dose cisplatin group. In attemp to answer the question whether treatments, combination chemotherapy (high VPP) and combination chemotherapy with radiation therapy, improve survival in advanced non-small cell lung cancer, we begin to study. Method: Thirty-five patients above stage III, diagnosed histologically as non-small cell lung cancer, were enrolled. Among them, nineteen received a combination chemotherapy consisting of VP-16 & high-dose cisplatin (100 $mg/m^2$) and/or radiation therapy. The other group (16 subjects) received no therapy. To investigate the differences of survival and response rates between two groups and the side effects related to therapy, we reviewed patients' records. Results: 1) The overall objective response rate was 47%(9/19) with one complete remission. 2) In patients who received polychemotherapy and radiation therapy, the response rate was 60%(6/10) with one complete remission and survival rates of 3 months, 6 months and 12 months were 100%, 70% and 40%. 3) In patients who received polychemotherapy, the response rate was 33% (3/9) with no complete remission and survival rates of 3 months, 6 months and 12 months were 78%, 67% and 33%. 4) Overall, treated patients survived significantly longer (p<0.05) than non-treated patients (median survival 307 days versus 95 days). 5) Analysis of the various prognostic factors disclosed that good performance status, stage III and squamous cell type showed the good response rates. 6) The toxicities were nausea and/or vomiting (100%), alopecia (90%), anemia (79%), leukopenia (69%), thrombocytopenia (2%), increased creatinine (16%) and neurotoxicity (5%). Conclusion: According to above results, there are relatively good results that high VPP combination chemotherapy in advanced non-small cell lung cancer improves survival in the treated group than in the non-treated group. Thus, it is considerd that we select the patients with proper indications and treat them with effective chemotherpy and radiation therapy. But, because improvement related to high VPP ploychemotherapy is not marked in this study, it is necessary that we should investigate follow-up studies in many cases.

• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.60-71
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• 2000

Backgrounds : Cathepsin D, an aspartic lysosomal proteinase, is believed to be involved in local invasion and metastasis of tumor cells by its proteolytic activity and has been described to be associated with tumor progression and prognosis in some human malignancies including breast cancer. But, its prognostic value for human lung cancer remains to be determined. The purpose of this study is to determine clinicopathological and prognostic significance of cathepsin D expression in non-small cell lung cancer. Method : Using a polyclonal antibody, immunohistochemical analysis of cathepsin D was performed on paraffin embedded sections of tumors obtained surgically from 54 patients with non-small cell lung cancer (37 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, and 1 undifferentiated carcinoma). Results : Eighteen patients (33.3%) showed positive immunoreactivities of cathepsin D in tumor cells. No significant correlation of cathepsin D expression in tumor cells was found in p-stage (surgical-pathologic stage), tumor size, tumor factor, nodal involvement, and differentiation. Of 54 patients, 29 (53.7%) patients showed moderate to massive cathepsin D-positive stromal cells within the tumor tissues, while the rest (46.3%) showed few cathepsin D-positive stromal cells within the tumor tissues. Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung canær (p=0.031). No significant correlation of the degree of cathepsin D-positive stromal cells was found in tumor size, T -factor, nodal involvement, differentiation Cathepsin D expression status in tumor cells and stromal cells was not significantly associated with prognosis expressed by survival rate. The results of multivariate analyses of variables possibly associated with prognosis showed that nodal involvement was the only independent prognostic factor in all patients. Conclusion : Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung cancer. However, it was not related to other clinicopathologic features and prognosis, and Cathepsin D expression in tumor was not related to p-stage and prognosis.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.576-584
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• 2000

Background : With the increase of cigarette consumption by women and the young, the incidence of lung cancer is expected to increase during the next three or four decades in Korea. The purpose of this study was to analyze the smoking habits in patients with lung cancer and to identify the gender differences in terms of their susceptibility to cigarette related carcinogens. Method : This investigation was a hospital-based case control study, which included the data of 178 case subjects (72 females, 106 males) with lung cancer and 218 control subjects (97 females, 121 males) with diseases unrelated to smoking. The information was obtained through a direct personal interview and a questionnaire related to personal smoking history. Results : The relative frequency of the squamous cell carcinoma was substantially higher in males than in females (61.3% in males, and 29.2% in females), while adenocarcinoma including bronchoalveolar cell carcinoma was higher in females(31.9% in females, 18.9% in males). Kreyberg I lung cancer was of relatively higher frequencies in males and smokers, while Kreyberg II lung cancer was higher in females and never smokers. The odds ratios (ORs) at each exposure level were consistently higher in females than males. For all cell types, the risk of lung cancer was increased with the quantity of smoked cigarettes, duration of smoking, and depth of inhalation. Odds ratio was distinctly higher in Kreyberg I lung cancer than in total lung cancer and a steeper gradient of risk with increased smoking was observed in females. Conclusion : The relative risk for lung cancer was consistently higher in females than in males at every level of exposure to cigarette smoke. This is believed to be due to the higher susceptibility of females to tobacco carcinogens, such as gender associated differences of carcinogen activation and/or the elimination of smoking related metabolites.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.5
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• pp.341-347
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• 2020

Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck cancer. MicroRNAs, as new biomarkers, are recommended for diagnosis and treatment of different types of cancers. Bevacizumab, sold under the trade name Avastin, is a humanized whole monoclonal antibody that targets and blocks VEGF-A (vascular endothelial growth factor A; angiogenesis) and oncogenic signaling pathways. Materials and Methods: This study comprised 50 cases suffering from OSCC and 50 healthy participants. Peripheral blood samples were collected in glass test tubes, and RNA extraction was started immediately. Expression levels of miR-155, miR-191, and miR-494 biomarkers in the peripheral blood of OSCC-affected individuals and healthy volunteers in vivo were evaluated using real-time PCR. The influence of Avastin on the expression levels of the aforementioned biomarkers in vitro and in the HN5 cell line was also investigated. Results: Expression levels of miR-155, miR-191, and miR-494 in the peripheral blood of individuals affected by OSCC were higher than in those who were healthy. Moreover, Avastin at a concentration of 400 μM caused a decrease in the expression levels of the three biomarkers and a 1.5-fold, 3.5-fold, and 4-fold increase in apoptosis in the test samples compared to the controls in the HN5 cell line after 24, 48, and 72 hours, respectively. Conclusion: The findings of this study demonstrate that overexpression of miR-155, miR-191, and miR-494 is associated with OSCC, and Avastin is able to regulate and downregulate the expression of those biomarkers and increase apoptosis in cancerous cells in the HN5 cell line.

• Journal of Chest Surgery
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• v.30 no.2
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• pp.179-186
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• 1997

The frequency of primary lung cancer is increasing compared to other cancer. Complete surgical resection is the most effective method of treatment, but it is limited to only 25 to 30 percent of patients after initial clinical presentation. The survival rate is different by the subtypes of carcinoma, stages, and general condition of patients. The author investigated the survival rate of 87 patients with squamous cell carcinoma of the lung after surgery. Age ranged from 31 to 73 years, with Lean 57.1) $\pm$ 7.15 and 80.5% (70 cases) was initially diagnosed at sixth and seventh decades. Male to female ratio was 8.9'1. Initial complaints were cough with sputum in 78.1%, weight loss in 31.0%, chest pain and discomfort in 29.9%, and hemoptysis in 24.1%. The location of the tumor was right side in 44.8% and left slde in 55.2% ; LUL in 39.1%, RLL in 20.7%, LLL in'16. 1%, RUL in 14.9% and RML in 9.2%. Stage I was 19.5%, stage II 25.3%, stage olla 54.1% and stage lIIb 1.1%. Operative procedures were as follow : pneumonectomy in 52.9%, lobectomy in 47.1%, sleeve upper lobectomy in 4 cases. Single mediastinal Iymph node involvement was observed in 17 cases, and multi-level mediastinal Iymph node involvement in 23 cases. Lower paratracheal Iymph node and subcarinal Lymph node were more frequently involved in right side lung cancer, with 8 and 10 cases, respectively and subaortic Iymph node was most frequently involved in left side lung cancer with 9 cases. Operative complications were hoarseness, wound infection and chylothorax in 7, 5 and 4 cases, respectively. The operative mortality was 2.2% and the cause of death was pulmonary edema. Postoperative follow-up period ranged from 1 month to 99 months with a mean of 29.95 $\pm$ 17.21 months. Overall one-year survival rate was 75.1 % and five-year survival rate was 29.8%. One-year and five-year survival rates were 93.7% and 52.4% for stage 1, 92.2% and 30.5% for st ge ll, and 61.2% and 17.4% for stage llla, respectively. These findings correlate survival rate with tumor size, mediastinal Iymph node metastasis and surgical resectability, and long-term survival can be expected with small sized tumor, absent mediastinal Iymph node metastasis and complete surgical resection.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.73-80
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• 1994

From December 1989 to February 1993, 108 patients with Non-Small Cell Lung Cancers(NSCLC) were studied retrospectively to evaluate radiotherapeutic significance of serum levels of NSE. We considered elevated serum neuron specific enolase(S-NSE) level as one of the neuroendocrine features in NSCLC. Histopathologic evaluation revealed 86 squamous cell carcinomas, 11 adenocarcinomas.3 large cell carcinomas, 3 mucoepidermoid carcinomas, and 5 unknown pathology. Eight Patients had stage 1,40 stage IlIA, and 60 stage lIIB.S-NSE level greater than 15 ng/ml was considered as elevated, and below this considered as normal. All patients recieved radiotherapy as primary treatment modality. The responders to radiotherapy had significantly higher mean S-NSE level than non-responders (28.5 ng/ml vs 20 ng/ml, p=0.01). Overall 2-year survival rate(YSR) was 23.6$ \% $. According to radiotherapy response, 2 YSR for Patients with CR, PR, and NR were 39.2$ \% $, 28.6$ \% $, and 6.2$ \% $ respectively(p=0.001). 2 YSR for patients with elevated and normal S-NSE were 14.6$ \% $ and 31.7$ \% $(p=0.02). The patients with NR showed no difference in survival according to S-NSE level. When we considered all patients, S-NSE level showed no significant impact on response. But for squamous cell carcinomas alone, patients with elevated S-NSE had more responders(80$ \% $ vs 61$ \% $, p=0.05). There was no correlation between tumor characteristics and S-NSE level. But the patients with elevated S-NSE had more patients with higher nodal stage, Based on our and other datas, NSCLC with neuroendocrine features have different response to treatment and clinical behavior compared to other NSCLC. Thus, this subgroup may need different treatment modality, and S-NSE level may have prognostic significance.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.200-205
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• 2008

Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.543-548
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• 1999

Background: These days, lung volume reduction surgery (LVRS) is used as an alternative or a bridge operation to lung transplantation in treating patients with severe emphysema. The procedure can be used in patients with pulmonary nodules combined with severe emphysema. We report the results of 21 months follow up after lung volume reduction surgery in 7 cases including 2 cases of concurrent resection of pulmonary nodules. Material and Method: Seven patients with emphysema, including 2 cases of preoperatively suspected lung cancer were operated with LVRS technique between July 1996 and June 1997. Result: Postoperative mortality was observed in a case of squamous cell carcinoma in LUL with brain metastasis, detected at postoperative 13months. Average of 21months(19-25months) follow up was done for other cases without specific events. Conclusion: LVRS is a useful operation in the treatment of patients with severe emphysema, but further evaluation should be done about the long term results and precise criteria for patient selection. Simultaneous LVRS and tumor resection could be done in patients with emphysema with marginal reserve in the hope of maximizing postoperative lung functions.

• Journal of Chest Surgery
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• v.43 no.1
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• pp.39-46
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• 2010

Background: Preoperative chemotherapy has been adopted in our hospital as a standard treatment for non-small cell lung cancer patients with N2 disease. However, there have been cases of pathologic N2 disease that have been detected after curative-intent surgical resection. We retrospectively studied the outcomes of initial surgical treatment without neoadjuvant therapy in patients with unexpected N2 non-small cell lung cancer. Material and Method: Between January 1995 and June 2007, 225 patients were diagnosed with pathologic N2 disease after they underwent initial pulmonary resection without neoadjuvant therapy. Among them, 170 patients were preoperatively diagnosed with lymph node stage N0 or N1. We retrospectively reviewed their medical record and analyzed the outcomes. Result: The overall 5-year survival rate was 35.4%. The prognostic factors that were significantly associated with survival were no adjuvant therapy, histologic cell types other than adenocarcinoma or squamous cell carcinoma, a pathologic T stage more than T1, old age (${\geq}$70 years) and no mediastinoscopic biopsy. During the follow-up, 79 patients (46.5%) experienced tumor recurrence, including loco-regional recurrence in 20 patients (25.3%) and distant metastasis in 56 (70.9%). The 5-year recurrence-free survival rate was 33.7%. Conclusion: Based on our findings, the survival was good for patients with unexpected N2 non-small cell lung cancer and who underwent initial pulmonary resection without neoadjuvant therapy. A prospective comparative analysis is needed to obtain more conclusive and persuasive results.