• Journal of Korean Neurosurgical Society
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• v.64 no.2
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• pp.271-281
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• 2021

Objective : Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

• Journal of Chest Surgery
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• v.34 no.12
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• pp.917-923
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• 2001

Background : Bronchial sleeve resection for centrally located primary lung cancer is a lung-parenchyma-sparing operation in patients whose predicted postoperative lung function is expected to diminished markedly. Because of its potential bronchial anastomotic complications, it is considered to be an alternative to pneumonectomy. However, since sleeve lobectomy yielded survival results equal to at least those of pneumonectomy, as well as better functional results, it became and accepted standard procedure for patients with lung cancer who have anatomically suitable tumors, regardless of lung function. In this study, from analyzing of occurrence rate of postoperative complication and survival rate, we wish to investigate the validity of sleeve resection for primary lung cancer. Material and Method : From January 1989 to December 1998, 45 bronchial sleeve resections were carried out in the Department of Thoracic Surgery of Seoul National University Hospital. We included 40 men and 5 women, whose ages ranged from 23 to 72 years with mean age of 57 years. Histologic type was squamous cell carcinoma in 35 patients, adenocarcinoma in 7, and adenosquamous cell carcinoma in 1 patients. Right upper lobectomy was peformed in 24 patients, left upper lobectomy in 11, left lower lobectomy in 3, right lower lobectomy in 1, right middle lobecomy and right lower lobectomy in 3, right upper lobectomy and right middle lobecomy in 2, and left pneumonectomy in 1 patient. Postoperative stage was Ib in 11, IIa in 3, IIb in 16, IIIa in 13, and IIIb in 2 patients. Result: Postoperative complications were as follows; atelectasis in 9, persistent air leakage for more than 7 days was in 7 patients, prolonged pleural effusion for more than 2 weeks in 7, pneumonia in 2, chylothorax in 1, and disruption of anastomosis in 1. Hospital mortality was in 3 patients. During follow-up period, bronchial stricture at anastomotic site were found in 7 patients under bronchoscopy, Average follow-up duration of survivals(n=42) was 35.5$\pm$29 months. All of stage I patients were survived, and 3 year survival rate of stage II and III patients were 63%, 21%, respectively. According to Nstage, all of N0 patients were survived and 3 year survival rates of Nl and N2 were 63% and 28% respectively. Conclusion: We suggest that this sleeve resection, which is technically demanding, should be considered in patients with centrally located lung cancer, because ttlis lung-saving operation is safer than pneumonectomy and is equally curative.

• Journal of Chest Surgery
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• v.30 no.9
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• pp.854-861
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• 1997

CYPRA 21-1 is known to be a cytokeratin 19 fragment, and it can be detected by using two specific monoclonal antibodies (KS 19-1 and BM 19-21) and can be clinically applied as a useful circulating tumor marker The epidermal growth factor receptor (EGF-R) expression was evaluated and characterized by its tyrosine protein kinase activity and by its ligand-stimulated autophosphorylation, a property shared with other peptide growth factor receptors. Autocrine or para'urine action was initiated by a growth factor, or by a transforming growth factor o, which had an extensive homology with EGP and which also stimulated tyrosine kinase activity on the EGF-R. The CYFRA 21-1 and the EGF-R levels in 30 patients with primary lung tumors were investigated. There were 24 patients with squamous cell carcinomas and 6 patients with adenocarcinomas. Specimen 5 mm3 in size were sampled at three different locations ; the main lesion, the boundary between the lesion and the unaffected tissue, and the unaffected tissue of the patients. The results were as follows 1. The CYPRA 21-1 concentration in the cancer boundary, the most malignant region,(348.6 : 89.9 ng/ml) was the lowest value. The CYFRA 21-1 concentration in unaffected tissue,(718.4$\pm$77.8 ng/ml) was higher than that in the main lesion. which had intact cellularity. 2. The EGF-R concentration in the main lesion was higher than that in the unaffected tissue, and the EGF-R concentration in a squamous cell cacinoma was higher than that in an adenocarcinoma. also, the EGF-R concentration in the cancer b undary was highest at stage 1, ll. The EGF-R concentration was higher in the main cancer lesion that in the unaffected tissue at stage 111, IV. 3. The CYFRA 21-1 was a cytoplasmic skeleton and the EGF-R was a cell-wall component; there was no correlation. In conclusion, CYFRA 21-1 was abundant in the cytoplasm but had a higher concentration in the unaffected tissue than in the main cancer lesion. The CYFRA 21-1 concentration of the tissue did not reflect the amount of cancer activity, the EGP-R was located in the cell membrane, the level of tissue that reflects cancer activity, so the main cancer lesion had a higher concentration than the unaffected tissue. CYFRA 21-1 is not a useful tumor maker at the tissue level. Because the EGF-R concentration re(looted the cancer activity, its a useful tumor marker for lung cancer.

• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.38-43
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• 2005

Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

• Journal of Chest Surgery
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• v.40 no.8
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• pp.564-568
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• 2007

Background: Pulmonary hamartomas are the most common form of pulmonary benign tumors, and they occur in approximately $2{\sim}5%$ of all pulmonary neoplasm. However, only a few reports have been published on the clinical characteristics of pulmonary hamartoma in Korea. Material and Method: The charts, X-rays and pathological specimens of 37 pulmonary hamartoma patients who were diagnosed by a pathological examination from January of 2000 to May of 2005 at the Catholic Medical Center were retrospectively reviewed. Result: The peak incidence of the tumor occurred in the seventh decade of life (32.4%), There were 23 men (62.6%) and 14 women (37.8%), with mean age of 55.6 years. Twenty-six patients (70.3%) were asymptomatic and 11 patients (29.7%) had symptoms. A total of 29 tumors (78.4%) were parenchymal, and 8 (21.6%) were endobronchial. Twenty cases (54.1%) were in the right lung and 17 cases (45.9%) were in the left lung. The right lower lobe was most commonly involved. Thirty-two (86.5%) hamartomas were diagnosed by surgical resection, 4 cases (10.8%) were diagnosed by bronchoscopic biopsy and 1 case (2.7%) was diagnosed by a fine needle aspiration biopsy. Thirty-four hamartomas (91.9%) were managed by surgical resection without complication. No recurrence or malignant changes were seen during the follow up period. Conclusion: Pulmonary hamartomas are most common in males during their fifth to seventh decade and they more commonly involve the right lung. No recurrence or malignant changes were seen during the follow up period.

• Journal of Chest Surgery
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• v.36 no.10
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• pp.711-720
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• 2003

Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.

• 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.

• 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.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.536-542
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• 1999

Background: The purpose of this study is to improve the quality of the diagnostic procedures in the preoperative evaluation so as to reduce the unnecessary thoracotomy and to ensure resectability in non-small cell lung cancer. Material and Method: Of 616 patients who underwent thoracotomy for primary lung cancer from January 1990 to December 1996, 59 patients(9.6%) turned out to have inoperable lesions after the thoracotomy. We reprospectively reviewed the bronchoscopic findings, methods of tissue diagnosis, CT scans, pulmonary function test and lung perfusion scan, reasons for nonresectability, and adjuvant therapy, and then followed up on the survival rate after exploratory thoracotomy. Result: The cell types were squamous cell carcinoma in 38, adenocarcinoma in 15, large cell carcinoma in 3 and others in 3. Primary loci were RUL in 20, RML in 6, RLL in 8, LUL in 13, LLL in 4 and others in 8. The reasons for non-resectability were various; direct tumor invaison to mediastinal structures(n=41), seeding on pleural cavity(n=8), poor pulmonary function(n=2), invasions to extranodal mediastinal lymph node(n=2), technical non- resectability due to extensive chest wall invasion (n=3), small cell carcinoma (n=1), malignant lymphoma(n=1), and multiple rib metastases(n=1). In the follow-up of 58 patients, 1-year survival rate was 55.2% and 2-year survival rate was 17.2% and the mean survival time was 14 months. When compared according to cell types or postoperative adjuvant therapeutic modalities, no significant difference in the survival rates were found. The squamous cell carcinoma was frequently accompanied by local extension to contiguous structures and was the main cause of non-resectability. In adenocarcinoma, pleural seeding with malignant effusion was frequently encountered, and was the major reason for non-resectability. Conclusion: These data revealed that if appropriate preoperative diagnostic tools had been available, many unnecessary thoracotomies could have been avoided. Both the use of thoracoscopy in selected cases of adenocarcinoma and the more aggressive surgical approach to the locally advanced tumor could reduce the incidence of unnecessary thoracotomies for non-small cell lung cancers.

• 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.