• Radiation Oncology Journal
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• v.19 no.4
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• pp.335-344
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• 2001

Purpose : The aim of this study was to clarify the role of VEGF expression as an independent prognostic factor and to identify the patients at high risk for poor prognosis in stage IB cervical cancer. Materials and methods : A total of 118 patients with stage IB cervical cancer who had radical hysterectomy and pelvic lymph node dissection were included in the study. All known high risk factors of the patients were pathologically confirmed from the surgical specimen. Of the 118 patients, n patients were treated with postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded specimens of post-hysterectomy surgical materials. A semiquantitative analysis was made using a scoring system of 0, +, ++, and +++ for increasing intensity of stain. We classified the patients with scores from 0 to ++ as low VEGF expression and the patients with a score of +++ as high VEGF expression. Results : Of the 118 patients, 35 patients $(29.7\%)$ showed high VEGF expression. Strong correlations were found between the high VEGF expression and both deep stromal invasion (p=0.01) and the positive pelvic node (p=0.03). The 5-year overall and disease-free survival rates for all 118 patients were $95.5\%\;and\;93.8\%$. The 5-year overall (p=0.03) and disease-free survival (p<0.001) rates were $98.5\%\;and\;100%$ for low VEGF expression (0, +, and ++) and $85.5\%\;and\;79.7\%$ for high VEGF expression, respectively. Pelvic and distant failures for low versus high VEGF expression were $1.2\%$ versus $17.1\%$, (p=0.001) and $0\%$ versus $14.3\%$ (p<0.001), respectively. In a Cox multivariate analysis of survival, the high VEGF expression (p=0.02) and the bulky mass (p=0.02) were significant prognostic factors for overall survival. The high VEGF expression (p=0.002), and bulky mass (p=0.01) demonstrated as significant prognostic indicators for disease free survival. Conclusion : These results showed that VEGF expression was a highly significant predictor for pelvic and distant failure and the most significant prognostic factor of overall and disease free survival for the patients with stage IB cervix cancer treated with radical surgery. We strongly suggest that the immune-histochemistry for VEGF expression be performed in a routine clinical setting in order to identify the patients at high risk for poor prognosis in early stage cervical cancer. Furthermore, postoperative and/or chemotherapy did not reduce the pelvic failure and distant metastasis. To improve the cure rate for the patients with high VEGF expression in stage IB cervical cancer, antiangiogenic therapy including anti-VEGF Ab may be new treatment option.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.26 no.2
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• pp.101-103
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• 2015

There are no standard consensus about treatment results and prognostic factors based on randomized trials for benign vocal fold lesion. Currently, voice therapy is the treatment of choice for vocal nodules, and laryngomicroscopic surgery is for vocal polyps. There are no strong evidences to support it, based on randomized controlled trials, But, it's just a consensus among laryngologist. Considering the pathophysiology of benign vocal cord lesions, cognitive behavioral therapy that corrects the patient's bad voice habits and improves their vocal hygiene could be most important factor for treatment outcomes.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.142-148
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• 1995

Background: Despite modern diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. Method: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. Results: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. Conclusion: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.387-395
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• 1993

To identify pretreatment prognostic factors in carcinoma of the uterine cervix, a retrospective analysis was undertaken of 510 patients treated with curative radiation therapy in Seoul National University Hospital during the 7 year period, from March 1979 through December 1986. According to FIGO classification,35 patients were stage I B,89 were stage IIA, 232 were stage IIB,8 were stage IIIA, 134 were IIIB, and 12 were stage IVA. Five year locoregional control (LRC) rates in stage I B, II A, II B, IIIA, IIIB, and IVA were $79\%,78\%,70\%,58\%,51\%\;and\;27\%,$ respectively. Five year disease free survival (DFS) rates were $76\%,67\%,60\$,57\%,40\%,\;and\;25\%,$ respectively. Overall survival (OS) rates at five years were $82\%,72\%,67\%,67\%,51\%,\;and\;33\%,$ respectively. In univariate analyses, stage, age, initial hemoglobin level, type of histology, tumor size, and several CT findings including pelvic lymph node (LN) status, paraaortic lymph node (PAN) status, extent of parametrial invasion, bladder invasion, and rectal invasion were significant factors in terms of LRC. All these factors and elevation of BUN or creatinine were associated with DFS. In terms of overall survival, stage, initial hemoglobin level, type of histology, tumor size, elevation of BUN or creatinine, and five CT findings associated with LRC were prognostically significant. In multivariate analysis excluding CT findings, stage IV disease, non-squamous histology, and tumor size $\ge$4 cm were associated with poor LRC and DFS. Stage IV disease and tumor size significantly affected OS. in multivariate analysis including CT findings, histology, tumor size, and pelvic LN status on CT were uniformly significant in terms of LRC, DFS, and 05, PAN status on CT affected overall survival only.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.36-41
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• 1999

Purpose : We reviewed the treatment results for the patients with locally recurrent rectal carcinoma. The object was to evaluate the treatment outcome and to identify the prognostic factors influencing the survival. Methods and Materials: Twenty-eight patients with locally recurrent rectal carcinoma treated principally with external-beam radiation therapy between 1982 to 1996 in the Department of Radiation Oncology at Paik and Hanyang Hospital were reviewed retrospectively Of these, 17 patients had initially abdominoperineal resection, 9 had low anterior resection, and 2 had local excision. No patients had received adjuvant radiation therapy for the primary disease. There were 14 men and 14 women whose ages ranged from 31 to 72 years (median age:54.5). Median time from initial surgery to the start of radiation therapy for local recurrence was 11 months (4~47 months). Radiation therapy was given with total doses ranging from 27 to 64.8 Gy (median=51.2 Gy). Results : The median survival was 16.7 months. The 2-year and 5-year survival rates were 20.1%, 4.1% respectively. Upon multivariate analysis, overall survival was positively correlated with duration of intervals from initial surgery to local recurrence (P=0.039). Relief of pelvic symptoms was achieved in 17 of 28 patients (60.7%). Pain and bleeding responded in 40% and 100% of patients, respectively Conclusions : Patients with locally recurrent rectal carcinoma treated with radiotherapy have benefited symptomatically, and might have increased survivals with a small chance of cure. But, patient were rarely cured (median survival : 10 months, 5-year survival : less than 5%). Overall survival was positively correlated with long intervals from initial surgery to local recurrence. Future efforts should be directed to the use of effective therapy for patients with locally recurrent rectal carcinoma and adjuvant therapy for patients with rectal cancer to reduce the incidence of pelvic recurrence.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Radiation Oncology Journal
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• v.8 no.1
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• pp.59-64
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• 1990

From 1980 to 1986,26 patients with metastatic carcinoma of the neck node from an unknown primary site were seen in the Department of Therapeutic Radiology of Seoul National University Hospital. Among these, three patients were excluded from further analysis due to incomplete treatment. So a retrospective analysis was undertaken on 23 patients who had complete treat-ment with radiation therapy alone or in combination with surgical treatment and chemotherpay. The overall three year actuarial survival rate was $32\%$. According to the staging system of the American Joint Committee on Cancer, the three year survival rates with N2 and N3 patients were $43\%\;and\;13\%$, respectively. In 16 patients with squamous cell carcinoma and seven with non-squamous cell carcinoma, the three year survival rates were $34\%\;and\;29\%$, respectively. Analysis according to site of nodal involvement was also done. Patients with cervical node and supraclavicular node involvement recorded $44\%\;and\;17\%$ of three year survival, rate, respectively. In this study, six patients eventually manifested the primary sites (three in the lung, one in the esophagus, one in the stomach, one in the nasopharynx). Presence of the primary site seemed to influence the prognosis ($17\%\;vs\;38\%$). In analyzing the prognostic factors, the nodal stage and site of nodal involvement were important prognostic factors, and the presence of a primary site seemed to influence the patients' survival, but histology did not.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.57-70
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• 2003

Background : Small cell lung cancer represents approximately 20% of all carcinomas of the lung, and is recognized as having a poor long term outcome compared to non-small cell lung cancer. Therefore, this study investigated the prognostic factors in small cell lung cancer patients in order to improved the survival rate by using the proper therapeutic methods. Material and method : The clinical data from 394 patients who diagnosed with small cell lung cancer and treated from 1993 to 2001 at the Kosin University Gospel Hospital, were analyzed. Result : There were 314 male patients (79.7%), and 80 female patients (20.3%). The number of those with limited disease was 177 (44.9%), and the number of those with extensive disease was 217 (55.1%). Overall, 366 out of 394 enrolled patients had died. The median survival time was 215 days (95% CI : 192-237days). The disease stage, Karnofsky performance state, 5% body weight loss for the recent 3 months, chemotherapy regimens, and the additive chest radiotherapy were identified as being statistically significant factors for the survival time. The median survival times of the supportive care group, one anticancer therapy, and two or more treatment groups were 17 days, 211 days, and 419 day, respectively (p<0.001). These data emphasize the importance of anticancer treatment to improve survival time for patients. The group of concurrent chemoradiotherapy (30 patients) showed significantly longer survival time than the group given sequential chemoradiotherapy (55 patients) (528 days versus 373 days, p=0.0237). The favorable prognostic factors of laboratory study were groups of leukocyte =8,000/mm3, ALP=200 U/L, LDH=450 IU/L, NSE=15 ng/mL, s-GOT=40 IU/L. In extensive disease, there was no difference according to the number of metastatic site. However, the median survival time of patients with ipsilateral pleural effusion had longer than patients having other metastatic sites. According to the survey periods, three groups were divided into 1993-1995, 1996-1998, and 1999-2001. The median survival time was significantly prolonged after 1999 in comparison to previous groups (177 days, 194 days, 289 days, p=0.001, 0.002, respectively). Conclusion: Disease stage and 5% body weight loss for recent 3 months at diagnostic state were significant prognostic factors. In addition, the performance status, serum ALP, LDH, NSE, CEA levels also appear to be prognostic factors. The survival time of those patients with small cell lung cancer has been prologned in recent years. It was suggested that the used of the EP (etoposied and cisplatin) chemotherapy method and concurrent chemoradiotherapy for patients with a limited stage contributed to the improved survival time.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.379-388
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• 2002

Background : Although patients with stage IV non-small cell lung cancer are known to have a poor prognosis, the prognostic factors for survival have not been well evaluated. Such factors may be different from those for overall survival. This study was performed to analyze the prognostic factors for survuval and the variation of survival according to metastatic organ, in patients with stage IV non-small cell lung cancer. Materials and Methods : From January 1997 to December 2000, 151 patients with confirmed stage IV non-small cell lung cancer were enrolled into this study retrospectively. The clinical and laboratory data were analyzed using univareate Kaplan-Meied and Multivariate Cox regression models. Results : On univariate analysis, age, performance status, serum albumin level, weight loss, forced expiratory volume in one second (FEV1), systemic chemotherapy, the number of metastatic organs and serum lactate dehydrogenase (LDH) level were significant factors (p<0.05). In multivariate analysis, important factors for survival were ECOG performance (relative risk of death [RR]: 2.709), systemic chemotherapy (RR: 1.944), serum LDH level (RR: 1.819) and FEV1 (RR: 1.774) (p<0.05), Metastasis to the brain and liver was also a significant factor on univariate analysis). The presence of single lung metastasis was associated with better survival than that of other metastatic organs (p=0.000). Conclusion : We confirmed that performance status and systemic chemotherapy were independent prognostic factors, as has been recognized. The survival of stage IV non-small cell lung cancer patients was different according to the metastatic organs. Among the metastatic sites, only patients with metastasis to the lung showed bettrer survival than that of other sites, while metastasis of the brain or liver was associated with worse survival than that of other sites.