• Journal of Chest Surgery
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• v.30 no.3
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• pp.308-314
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• 1997

A retrospective review of the histopathology and clinical information of primary lung cancer was performed to investigate the trends in the histologic type related to sex, age, and smoking history. During January 1988 and July 1995, 541 pateints were diagnosed as primary lung cancer at the Korea Univeristy Anam Hospital. Male (423) to female(118) ratio was 3. 6:1. The most frequent histologic type of lung cancer in male patients was squamous cell carcinoma (223 patients, 52.7%) followed by adenocarcinoma (86, 20.3%) and small cell carcinoma (85, 20.1 %). In female patients, adenocarcinoma (64, 54.2%) wa most common, which was followed by squamous cell carcinoma (22, 18.6%) and small cell carcinoma (22, 18. 6%). The incidence of adenocarnimoma had an increased tendency recently (14.3% in 1988, 33.3% in 1995)(P=0.019). The predominant type in smokers was squamous cell carcinoma; whereas adenocarcinoma was the most frequent type in non-smokers. The proportion of patients aged less than 40 years (younger group) was 4. 0% (n=22). Of them, adenocarcinoma (7) and small cell carcinoma (7) were most common. In patients older than 40 years (older group, n=519), 243 (46.8%) patients had squamous cell carcinoma, and 143 (27.6%) adenocarcinoma. As age increased, the prevalence of squamous cell carcinoma was increased (P=0.0005), adenocarcinoma decreased (P=NS), and small cell carcinoma remained unchanged. We suggest above data as a clinical guidance for management of primary lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.63 no.3
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• pp.242-250
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• 2007

Background: Abnormal angiogenesis can induce hypoxia within a highly proliferating tumor mass, and these hypoxic conditions can in turn create clinical problems, such as resistance to chemotherapy. However, the mechanism by which hypoxia induces these changes has not yet been determined. Therefore, this study was conducted to determine how hypoxia induces changes in cell viability and extracellular microenvironments in an in vitro culture system using non-small cell lung cancer cells. Methods: The non-small cell lung cancer cell line, A549 was cultured in DMEM or RPMI-1640 media that contained fetal bovine serum. A decrease in the oxygen tension of the media that contained the culture was then induced in a hypoxia microchamber using a $CO_2-N_2$ gas mixture. A gas analysis and an MTT assay were then conducted. Results: (1) The decrease in oxygen tension was checked the anaerobic gas mixture for 30 min and then reoxygenation was induced by adding a 5% $CO_2-room$ air gas mixture to the chamber. (2) Purging with the anaerobic gas mixture was found to decrease the further oxygen tension of cell culture media. (3) The low oxygen tension resulted in a low pH, lactic acidosis and a decreased glucose concentration in the media. (4) The decrease in glucose concentration that was observed as a result of hypoxia was markedly different when different types of media were evaluated. (5) The decrease in oxygen tension inhibited proliferation of A549 cells. Conclusion: These data suggests that tumor hypoxia is associated with acidosis and hypoglycemia, which have been implicated in the development of resistance to chemotherapy and radiotherapy.

• Journal of Chest Surgery
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• v.30 no.9
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• pp.899-907
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• 1997

Recently, primary lung cancer has increased markedly in incidence & prevalence in korea. Prom July 1979 to June 1996, 183 patients were diagnosed and operated for primary non-small cell lung cancer, and evaluated clinically. 1. There were 164 males and 19 females(M:P=8.6: 1), and the peak incidence of age was 50th and 60th decade of life(73.7%). 2. Most of symptoms were respiratory, whitch were cough(44.8%), chest pain(30.1%), dyspnea(20.8%), hemoptysis or blood tinged sputum(19.7%), sputum(15.3%), and asymptomatic cases were 12.0%. 3. Histopathologically, sguamous cell carcinoma was 68.9%, adenocarcinoma 19.7%, bronchioloalveol r cell carcinoma 2.2%, adenosguamous cell carcinoma 1.6%, and large cell carcinoma 7.7%. 4. In the operation, pneumonectomy was 41.0%, lobectomy 42.1%, bilobectomy 13.1%, stagmentectomy or wedge resection 1.6%, and explore tharacotomy 2.2%, and the overall resectability was 97.8%. 5. Postoperative complications were developed in 31.9%, and operative mortality was 1.6%. 6. In postoperative stagings, stage I was 38.3%, stage H 14.8%, stage llla 31.1%, and stage IIIb 15.8%. 7. The overall cumulative survival rates were 1 year 77.8%, 3 year 42.7%, and 5 year 39.5%. The 5 year survival rate according to stage were stage 153.0%, stage H 46.5%, stage I[la 28.2%, and stage IIIb 13.8%(p<0.05), according to operation method were lobectomy 45.0%, and pneumonectomy 30.3%(p<0.05), and according to mediastinal involvement were Nl 32.0%, and N2 11.1%(p<0.05). The 5 year survival rate according to histologic type were squamous cell carcinoma 43.1%, adenocarcinoma 23.3%, and large cell carcinoma 30.3 (p>0.05).

• Korean Journal of Veterinary Research
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• v.49 no.1
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• pp.1-8
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• 2009

The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.323-327
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• 2002

Purpose : To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy alone and define the optimal radiotherapeutic regimen for these patients. Materials and Methods : A retrospective review was peformed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 59 Gy. No patients were lost to follow-up. Results : The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and $21\%$, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and $25\%$, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was $43\%$. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented $78\%$ of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm $(0\%\;vs\;36\%)$. Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70 $(25\%\;vs\;26\%,\;p>0.05)$. Conclusion : Radiation therapy 리one is an effective and safe treatment for early stage non-small ceil lung cancer patients who are medically inoperable or refuse surgery. Also we believe that a higher radiation dose to the primary site could improve the local control rate, and ultimately the overall survival rate.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.100-107
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• 1999

Purpose: This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Materials and Methods Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45~67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in T2, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal Iymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intravenous cis-Platin (100 mg/m$^{2}$) on day 1 and oral Etoposide (50 mg/m$^{2}$/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Results : Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred In 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/l3) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor stagings were pT0 in 3 patients, pTl in 6, and pT2 in 3. Lymph node status findings were pN0 in 8 patients, pN1 in 1, and pN2 in 3. Pathologic tumor down-staging was 61.5% (8/13) including complete response in three patients ($23.7%). Tumor stage was unchanged in four patients (30.8%) and progression was in one (7.7%). Conclusions : Pre-operative concurrent chemoradiotherapy for Stage IIIA (N2) non-small cell lung cancer demonstrated satisfactory results with no increased severe acute complications. This treatment shceme deserves more patinet accrual with long-term follow-up.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.233-241
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• 1997

Purpose : This study was done to evaluate the survival rate and Prognostic factors of patients with inoperable non-small cell lung cancer(NSCLC) treated with radiation therapy. Materials and Methods A retrospective analysis was undertaken of 62 Patients who had inoperable NSCLC treated with radiation therapy from January 1991 through December 1993. According to AJCC slaging, stage IIIA was 14 patients and stage IIIB was 48 patients. Forty Gy to 70.2Gy to the primary tumor site was delivered with daily fractions of 1.8Gy or 2Gy, 5days per week. Thirty-seven patients received neoadjuvant chemotherapy. Results : Complete, partial and no response to radiation therapy were 3 patients, 34 Patients and 25 patients, respectively The median survival period of all patients was 11 month. One rear survival rate, 2 year survival rateand 5 rear survival rate for all patients were 45.0%, 14.3%, and 6.0% respectively The median survival period was 6.5 months in stage IIIA and 13 months in stage IIIB. One year survival rates were 28.6% in stage IIIA and 50.3% in stage IIIB In univariaite analysis, prognostic factors affecting survival were T-s1aging, AJCC staging, and response after radiation therapy (P<0.05) . Pretreatment peformance status affected survival but was not statistically significant (0.050.1). In multivariate analysis, Pathology and response to radiation therapy are independently significant prognostic factor. T stage was marginally significant (P=0.0809). During follow-up duration, distant metastasis developed in 20 patients-bone metastasis in 10 patients, brain metastasis in 3 patients, liver mentastasis in 3 patients, contralateral lung metastasis in 1 patients and multiple metastases in 3 patients. Conclusion :　Conventional radiotherapy alone or combined chemoradiotherapy are unlikely to achieve long term survival in patients with NSCLC.　Surgery after concurrent chemoradiotherapy is Ivied to improve the local　control in our hospital

• Journal of Chest Surgery
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• v.44 no.2
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• pp.169-177
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• 2011

Background: Video-assisted thoracic surgery (VATS) lobectomy has been performed with increasing frequency over the last decade. However, there is still controversy as to its indications, safety, and feasibility. Especially regarding lung cancer surgery, it is not certain whether it can reduce local recurrences and improve overall survival. Materials and Methods: We retrospectively reviewed 1,067 cases of VATS lobectomy performed between 2003 and 2009, including the indications, postoperative morbidity, mortality, recurrence, and survival rate. Results: One thousand and sixty seven patients underwent VATS lobectomy for the following indications: non-small cell lung cancer (NSCLC) (n=832), carcinoid tumors (n=12), metastatic lung cancer (n=48), and benign or other diseases (n=175). There were 63 cases (5.9%) of conversion to open thoracotomy during VATS lobectomy. One hundred thirty one (15.7%) of the 832 NSCLC patients experienced pathologic upstaging postoperatively. The hospital mortality rate was 0.84% (9 patients), and all of them died of acute respiratory distress syndrome. One hundred forty-nine patients (14.0%) experienced postoperative complications. The median follow-up was 22.9 months for patients with NSCLC. During follow-up, 120 patients had a recurrence and 55 patients died. For patients with pathologic stage I, the overall survival rate and disease-free survival rate at 3 years was $92.2{\pm}1.5%$ and $86.2{\pm}1.9%$, respectively. For patients with pathologic stage II disease, the overall survival rate and disease-free survival rate at 3 years was $79.2{\pm}6.5%$ and $61.9{\pm}6.6%$, respectively. Conclusion: Our results suggest that VATS lobectomy is a technically feasible and safe operation, which can be applied to various lung diseases. In patients with early-stage lung cancer, excellent survival can be also achieved.

• Progress in Medical Physics
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• v.26 no.4
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• pp.229-233
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• 2015

We retrospectively reviewed lung cancer patients who were treated with stereotactic ablative radiotherapy (SABR). We investigated the value of response evaluation after treatment by measuring the volume change of tumors on serial chest computed tomography (CT) examinations. The study included 11 consecutive patients with early-stage (T1-T2aN0M0) non-small cell lung cancer (NSCLC) who were treated with SABR. The median dose of SABR was 6,000 cGy (range 5,000~6,400) in five fractions. Sequential follow-up was performed with chest CT scans. Median follow-up time was 28 months. Radiologic measurement was performed on 51 CT scans with a median of 3 CT scans per patient. The median time to partial response ($T_{PR}$) was 3 months and median time to complete remission ($T_{CR}$) was 5 months. Overall response rate was 90.9% (10/11). Five patients had complete remission, five had partial response, and one patient developed progressive disease without response. On follow-up, three patients (27.2%) developed progressive disease after treatment. We evaluated the the response after SABR. Our data also showed the timing of response after SABR.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.109-113
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• 2007

Background: In non-small cell lung cancer (NSCLC), malignant pleural effusion is a frequently observed com-plication, and is an important negative prognostic factor. Although many studies concerned to diagnosis and treatment of malignant pleural effusion have been performed, prognostic factors of malignant pleural effusion have rarely been investigated. This study was performed to determine the prognostic factors of malignant pleural effusion n non-small cell lung cancer. Material and Method: We evaluated 33 NSCLC patients with malignant effusion treated between January 2002 and December 2003. We analyzed possible factors: gender, age, TNM Stage, fluid analysis (pH, CEA, LDH, glucose, albumin) and treatment modality. Median survival time of each factor was calculated by Kaplan-Meier method and difference of median survival time between groups of factor compared by log-rank test. The Cox proportional hazards regression model was used to confirm the significance of prognostic factor. Results: Of the 33 patients, 23 (69.7%) patients were adenocarcinoma. The median interval of the diagnosis of lung cancer and malignant effusion was 7.3 months ($25^{th}{\sim}75^{th}:\;3.9{\sim}11.8$), and the median survival time was 3.6 months (95% Confidence Interval: $1.14{\sim}5.99$). In the univariate analysis, using the log-rank test, those with an adenocarcinoma showed a relatively longer median survival time than those of a non-adenocarcinoma (4.067 vs. 1.867 months, p=0.067) without statistical significance. In the multivariate analysis, using the Cox regression, those with a non-adenocarcinoma showed a trend of high risk of cancer death than those with an adenocarcinoma without statistical significance (Relative risk; 2.754, 95% Cl: $0.988{\sim}7.672$, p=0.053). Conclusion: We could not find an independent prognostic factor of malignant pleural effusion in NSCLC. As there was a trend of high risk of cancer death according to histology, further study will be needed.