• Journal of Chest Surgery
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• v.34 no.8
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• pp.615-620
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• 2001

The new stage of metastatic lung cancer based upon resectability, disease-free interval, and the number of pulmonary metastases was proposed in 1998 by Ginsberg, et al. We evaluated the validity of the new staging proposal for pulmonary metastases through the analysis of experiences at Severance Hospital. Material and Method: The cases of 111 patients who underwent resection of metastatic lung cancer during the eleven-year period (1990-2000) were reviewed. Of these patients, 103(92.8%) underwent compete surgical resection. The primary tumor was carcinoma in 60 cases, sarcoma in 46, and others in 5. The disease-free interval(DFI) was 0 to 35 months in 79 cases adn more than 36 months in 32 cases. Single metastasis accounted for 53 cases and multiple lesions for 58 cases. Mean follow-up was 49 months. Result: The actuarial survival after complete metastasectomy was 48.2% at 3 years and 32.6% at 5 years; the corresponding values for incomplete resection were 21.9% at 3 years. The 3-year survival rate(3-YSR) for complete resction was 40.5% and 5-year survival rate(5-YSR) was 30.4% for patients with a DFI less than 36 months, the 3-YSR, 75.8% and 5-YSR, 39.0% for those with a DFI equal or more than 36 moths; 45.8% and 30.5% for single lesions, 50.0% and 34.4% for multiple lesions. The 3-YSR and 5-YSR were 58.5% and 43.8% for stage I patients, 54.0% and 37.4% for stage II, 38.2% and 27.9% for stage III and 21.9% for stage IV. Conclusion: The result of the analysis of new stage of pulmonary metastases showed that the survival rate was different according to stage and there was no statistical significance. We need more experiences and long-term follow up to determine the prognostic factor of metastatic lung cancer surgery.

• Journal of Chest Surgery
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• v.35 no.3
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• pp.199-208
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• 2002

Background: The washing of packed red blood cells could remove pro-inflammatory mediators, cell debris, and micro-particles contained in packed red blood cells, and the preci-rculation-ultrafiltration (recirculation and ultrafiltration of circuit itself before cardiopulmonary bypass) could attenuate the initial inflammatory reaction and remove the initial proinflam-matory mediators. This study was performed to evaluate whether the washing of packed red blood cells and precirculation-ultrafiltration can reduce the production of cytokines that have an important role in myocardial reperfusion injury. This study investigated the effects of washing the packed red blood cells and precirculation-ultrafiltration on the production of cytokines during and after cardiopulmonary bypass and open heart surgery. Material and Method: Forty eight infants with VSD undergoing open heart surgery under cardiopulmonary bypass were randomized into control group (group C, n=12), washing group (group W, n= 12), precirculation-ultrafiltration group (group F, n: 12), and combined group(washing and precirculation-ultrafiltration, group WF, n=12). Blood samples were obtained before, during, and after the bypass to assess plasma level of tumor necrosis factor-$\alpha$(TNF-$\alpha$), interleukin-6(IL-6), and interleukin-8 (IL-8). Results: Expressions of TNF-$\alpha$ were significantly reduced in combined group (group WF) compared with group C, group W, and group F (p<0.05). Expression of IL-6 were significantly reduced in group W, group F, and group WF compared with group C (p<0.05), but similar among group W, group F, and group WF (p=0.053). Expression of IL-8 were reduced in group W and group WF compared with group C (p<0.05), but similar among group W, group F, and group WF (p=0.067). Conclusion: In conclusion, the washing of packed red blood cells and precirculation-ultrafiltration blunted the increase of TNF-$\alpha$ , IL-6, and IL-8 during and after open heart surgery with cardiopulmonary bypass. However, the clinical benefits of these treatments remains unproven.

• 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.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.1-10
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• 2004

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.177-184
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• 2007

Purpose: To evaluate the palliative effect of endobronchial brachytherapy (EBB) for patients with lung cancer that previously received external beam radiotherapy (EBRT). Materials and Methods: From July 1992 to May 2003, 29 patients with a recurrent or persistent lung cancer were treated with palliative EBB at our institute. EBB consisted of three fractions (once a week) of a dose of 5 Gy using the high dose-rate remote afterloader. Symptomatic improvement was assessed subjectively, and patients were divided into two groups according to whether symptoms were improved or not. Factors such as age, performance status, duration from EBRT to EBB and the location of the tumor were compared between the improved and unimproved groups of patients. Results: Overall symptomatic improvement was found in 27 out of 52 symptoms (52%). Improvement as to the type of symptoms was seen in 41 %, 50%, 82% and 33% of patients with cough, dyspnea, hemoptysis, and obstructive pneumonia respectively. The rate of improvement of hemoptysis was more than that of cough (p<0.05). The median time to symptom relapse was 5 months. The improved patient group (n=17, 59%) had a better performance status and longer duration from EBRT to EBB than the unimproved patient group (p<0.05). Lesions located in the distal trachea and/or main bronchus were found more frequently in the improved group of patients than in the unimproved group of patients, but the difference was not statistically significant (p=0.06). Fatal complications developed in two patients (7%), which were a hemoptysis and bronchopleural fistula respectively. Conclusion: Symptom improvement was found in 60% of patients after EBB and improvement was maintained for 5 months. Palliative EBB, even when EBRT was given previously, can be effective for a patient that has an endobronchial symptom, such as hemoptysis, and for a patient with good performance and a long duration from previous EBRT to EBB.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.502-512
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• 1995

Background: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. Method: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. Result: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. Conclusion: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.79-92
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• 2007

[ $\underline{Purpose}$ ]: For the first time, a nationwide survey in the Republic of Korea was conducted to determine the basic parameters for the treatment of esophageal cancer and to offer a solid cooperative system for the Korean Pattern of Care Study database. $\underline{Materials\;and\;Methods}$: During $1998{\sim}1999$, biopsy-confirmed 246 esophageal cancer patients that received radiotherapy were enrolled from 23 different institutions in South Korea. Random sampling was based on power allocation method. Patient parameters and specific information regarding tumor characteristics and treatment methods were collected and registered through the web based PCS system. The data was analyzed by the use of the Chi-squared test. $\underline{Results}$: The median age of the collected patients was 62 years. The male to female ratio was about 91 to 9 with an absolute male predominance. The performance status ranged from ECOG 0 to 1 in 82.5% of the patients. Diagnostic procedures included an esophagogram (228 patients, 92.7%), endoscopy (226 patients, 91.9%), and a chest CT scan (238 patients, 96.7%). Squamous cell carcinoma was diagnosed in 96.3% of the patients; mid-thoracic esophageal cancer was most prevalent (110 patients, 44.7%) and 135 patients presented with clinical stage III disease. Fifty seven patients received radiotherapy alone and 37 patients received surgery with adjuvant postoperative radiotherapy. Half of the patients (123 patients) received chemotherapy together with RT and 70 patients (56.9%) received it as concurrent chemoradiotherapy. The most frequently used chemotherapeutic agent was a combination of cisplatin and 5-FU. Most patients received radiotherapy either with 6 MV (116 patients, 47.2%) or with 10 MV photons (87 patients, 35.4%). Radiotherapy was delivered through a conventional AP-PA field for 206 patients (83.7%) without using a CT plan and the median delivered dose was 3,600 cGy. The median total dose of postoperative radiotherapy was 5,040 cGy while for the non-operative patients the median total dose was 5,970 cGy. Thirty-four patients received intraluminal brachytherapy with high dose rate Iridium-192. Brachytherapy was delivered with a median dose of 300 cGy in each fraction and was typically delivered $3{\sim}4\;times$. The most frequently encountered complication during the radiotherapy treatment was esophagitis in 155 patients (63.0%). $\underline{Conclusion}$: For the evaluation and treatment of esophageal cancer patients at radiation facilities in Korea, this study will provide guidelines and benchmark data for the solid cooperative systems of the Korean PCS. Although some differences were noted between institutions, there was no major difference in the treatment modalities and RT techniques.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.17-25
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• 1998

Purpose : Although local recurrence rates of stomach cancer after radiocal surgery have been reported in the range of $30-70\%$, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. Materials and Methods : From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiornyosarcoma. The numbers of patients with stage I B, II, III A, III B, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion Minimum and median follow-up periods were 12 months and 18 months, respectively, Results : Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than $15\%$ of their pretreatment weight. But hematemesis. melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient Peritoneal seeding occurred in 6, liver metastases months and median disease free survival time was 26 months. Stages andradiation dose were not significant prognostic factors for locoregional in 2, and distant nodes in 2 patients. Four year disease specificsurvival rate was $40\%$ and disease free survival was $48\%$. Median survival was 35 failures. Conculsion : Although all patients in this study had positive surgical margins, locoregional failure rate was $28\%$, and 4 year disease specific survival rate was $40\%$. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences. but we could find a Possibility of the role of postoperative radiotherapy in Patients with high risk factors.