• Radiation Oncology Journal
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• v.21 no.1
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• pp.27-34
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• 2003

Purpose : To evaluate the efficacy of radiotherapy, and the factors affecting survival in patients of extrahepatic bile duct cancer, by analyzing the results of postoperative radiotherapy Materials and Methods : Between October 1991 and July 2001, 21 patients with extrahepatic bile duct cancer, who received radiotherapy after a radical resection, were retrospectively reviewed. The patients' ages ranged from 39 to 75 years, with a median of 61 years, and a male to female ratio of 16 to 5. The numbers of patients with proximal and distal bile duct cancer were 14 and 7, respectively. From the postoperative pathological examination, 19 of the patients were found to have microscopic residues, and 7 to be lymph node positive. Patients with AJCC stages I, II and III were 10, 10 and 1, respectively. The total radiation dose administered was 4,500$\~$6,300 cGy, with a median dose of 5,040 cGy. The follow up period was 20$\~$81 months, with a median of 57.5 months. Results : The overall and disease free survival rates at 3 and 5 years were 41.0 and 29.3$\%$, and 41.6 and 29.7$\%$, respectively. The influences of age, sex, tumor location, differentiation, microscopic residue, neural invasion, 7 and N stage, the stage itself, the dose of radiation and chemotherapy, on survival were evaluated. The T stage and the stage itself were found to be significant from a univariate analysis (p<0.05), but the degree of significance was limited by the small number of patients. A recurrence occurred in 12 patients (57.1$\%$), 5 in locoregional sites, 4 in distant sites and 3 in a combination of locoregional and distant sites, and the sites of distant metastasis were the liver, 6, and the bone, 1 Grade 2 or 3 acute leucopenias occurred in 2 patients and grade 2 chronic peptic ulcers occurred in 4, who were all recovered by conservative management. Conclusion : Postoperative radiotherapy is feasigbls in extrah데atic bile duct cancer, with tolerable toxicity, but prospective studies, with a large patient enrollment, are needed for the evaluation of the effects of postoperative radiotherapy and the related prognostic factors.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, 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 increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• 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.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.97-102
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• 2006

Purpose: The prognosis for patients with a Borrmann type IV gastric cancer is extremely poor despite an aggressive surgical approach. We evaluated the clinicopathological features for Borrmann type IV cancers to find treatment strategy. Materials and Methods: The 1098 patients with advanced gastric cancer who underwent surgical resection between 1990 and 2001 were analyzed. These patients were divided into two groups: 81 patients with a Borrmann type IV carcinoma, and 1017 patients with all other types of gastric carcinomas. Results: Patients with a Borrmann type IV carcinoma were younger than those with other types, and female was prevalent (p=0.000). Of the patients with a Borrmann type IV gastric carcinoma, 68 patients (84%) were classified as stage III or IV at the initial diagnosis. The histologic type was commonly undifferentiated and serosal infiltration; nodal involvement and lymphatic invasion were more frequent in patients with a Borrmann type IV than in those with other types of cancer. Multivariate analysis confirmed that the extent of lymph node metastasis was a negative prognostic factor for Borrmann type IV gastric carcinomas. The curability for a Borrmann type IV carcinoma was only 53.1%, and peritoneal dissemination rate was 25.9%. The predominant pattern of recurrence for a Borrmann type IV gastric carcinoma was peritoneal dissemination, and it was significantly different with other types (93.1% vs 55.8%, P<0.05). The 5-year survival rate of patients with a Borrmann type IV gastric carcinoma was significantly lower than those of patients with other types of cancer, even though a curative resection had been accomplished (26% vs 63%, p<0.005). The 5-year survival rates of patients with a Borrmann type IV carcinoma following a curative resection were 44.9%, 24%, and 0% for stages II, III and IV, respectively (p<0.05). Conclusion: Because the prognosis for patients of a Borrmann type IV gastric cancer is extremely poor despite a curative resection, preoperative and/or intraperitoneal chemotherapy should be considered. And diagnostic laparoscopy and peritoneal cytology may be used to play an important role in accurate staging workup. (J Korean Gastric Cancer Assoc 2006;6:97-102)

• Journal of Chest Surgery
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• v.37 no.8
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• pp.684-690
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• 2004

Background: Primary thymic epithelial neoplasm is a type of mediastinal tumors that have various biologic and morphologic features. In this study, we reclassified 59 cases of thymic epithelial tumors by the new WHO classification. We inquired whether the new WHO classification has independent prognostic relevance by analyzing clinical characteristics of thymic epithelial tumors including Masaoka's clinical stage. Material and Method: From December 1986 to August 2003, 59. patients who underwent surgery in the Keimyung University Dongsan Medical Center with definite diagnosis of thymic epithelial tumor were studied. We analyzed the histologic subtype (WHO classification). clinical stage (Masaoka's clinical stage) and patient's characteristics (sex, age, myasthenia gravis, tumor size, invasion. recurrence, metastasis) as prognostic factors. We analyzed the relationship between histologic subtype and clinical stage. Result: 32 patients were male and 27 were female. Mean age was 50.1$\pm$14.2. From WHO A to C, all thymic epithelial tumors were reclassified by the new WHO classification. Six patients (10.2%) had Type A, 7 (11.9%) had Type AB, 7 (11.9%) had Type B$_1$, 10 (16.9%) had Type B$_2$ and 7 (11.9%) had Type B$_3$, 22 (37.3%) had Type C. Two factors were shown by multivariate analysis to be associated with a favorable prognosis: completeness of resection (p=0.003) and non-invasiveness (p=0.001). The overall 5-year survival of the 59 patients was 53%, subtype A and AB were 92.3%, B$_1$ and B$_2$ were 70.2%, and B$_3$ and C were 26.1%. The association between histologic subtype and invasive behavior (stage) was statistically significant (p<0.001). Conclusion: The WHO classfication is not only a histologic classfication of the thymic epithelial tumors but also a significant prognostic factor that influence the survival of thymic epithelial tumors.

• The Journal of the Korean bone and joint tumor society
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• v.18 no.1
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• pp.7-13
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• 2012

Purpose: The purpose of this study is to compare general survival rate and survival rate according to expectable prognostic factors by analyzing the result of treating a patient of squamous cell carcinoma. Materials and Methods: From Mar. 1999 to Feb. 2011, 151 patients were pathologically confirmed as squamous cell carcinoma of limbs and body in our hospital, and among those patients, 51 patients underwent the surgical treatment. This study included 41 patients who underwent the surgical treatment and were followed-up for more than 12 months. The mean age of population was 64.4 years. 31 males and 10 females were included. Wide excision with following skin grafts or flaps for reconstruction (29 cases) was mostly performed, but amputation (12 cases) was also performed for cases with extremities where resection margin was difficult to obtain and cases with neural or vascular invasion. 8 patients underwent chemotherapy or radiotherapy after resection, and 33 underwent the operation only. Stages were classified by AJCC Classification, survival rate was calculated by Kaplan-Meier method and survival rate of groups was compared by Log-rank test. For the expectable prognostic factors related to survival rate, location of primary lesion, cause of disease, pathologic grade, staging, surgical method, additional anticancer therapy were examined and each survival rate was compared. Results: The average follow-up period was 65.2 (12-132) months. Thirty patients survived out of 41 patients till last follow up. The overall survival rate in 5 years was 77%. Three cases (7.3%) had local recurrence, and 7 cases (17.0%) had metastasis. The average period of recurrence from operation was 27 (18-43) months. Possible prognostic factors such as location of primary lesion, cause of disease, pathologic grade, staging, additional anticancer therapy showed no significant difference in survival rates. However, patients with amputation showed significantly lower survival rate than those with wide excision. Conclusion: In analysis the results of treating 41 cases of squamous cell carcinoma, the overall 5-year survival rate was 77%. And, among the several prognostic factors, only the surgical method was significant statistically.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.29-33
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• 2005

Purpose: To determine the prognostic values of the hematologic parameters checked preoperatively in gastric cancer patients, we evaluated and compared the relationship between hematologic parameters and clinicopathologic factors of gastric cancer patient. Materials and Methods: The medical records of 357 consecutive patients who had undergone surgery for gastric cancer at the Department of Surgery, Hanyang University Hospital, between Dec. 2,000 and Dec. 2003 were reviewed. To exclude any adverse effect of invasive procedures to hematologic parameters, the samples taken immediately at outpatient department was used. The normal range of serum albumin was defined above 3.5 g/dl, serum hemoglobin above 12 g/dl, and serum platelet count under $400\times10^{3}{\mu}l$. Patients were defined as group 1 when any of these parameters was abnormal, and defined as group 2 when all parameters were normal. The relationships between hematologic parameters and survival rate were investigated. Results: The mean values of platelet count increased, but level of serum albumin and serum hemoglobin decreased significantly according to the advancement of the disease stage (P=0.000). The differences of depth of tumor invasion and lymph node metastasis between the group 1 and the group2 was statistically significant (P=0.001). Three-year survival difference between group 1 and group 2 was significant (P=0.037). Conclusion: The hematologic parameters checked preoperatively in patients of gastric cancer are simple and cheap, meanwhile reflect the general condition of the patients. Any presence of anemia, hypoalbuminemia, or thrombocytosis can predict the progression of the disease and poor survival rates.

• 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.

• Journal of Gastric Cancer
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• v.8 no.3
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• pp.136-140
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• 2008

Purpose: Stage IV early gastric carcinoma (EGC) is a rare disease. We report here on 10 cases of EGC that showed metastasis in more than 15 lymph nodes. Materials and Methods: A total of 8354 cases of gastric carcinoma in patients who underwent surgical procedures between January 2001 and January 2007 at Samsung Medical Center were studied, and 10 cases were classified as stage IV EGC. We investigated their clinicopathologic characteristics. Results: There were 5 males and 5 females. Their ages at operation ranged from 46 to 76 years with a mean age of 61. All of the 10 patients had undergone curative resection for gastric cancer. The pathological diagnosis confirmed that all of the patients had tumor confined to the submucosa. The median size of the tumors was 5.3cm and the mean number of dissected nodes was 45.5 with a mean number of 22.2 involved nodes. Six cases were classified as the diffuse type and 4 were classified as the intestinal type by Lauren's classification. Histologically, 3 cases were signet ring cell carcinoma, 3 were poorly differentiated, 2 were moderately differentiated and 2 were well differentiated adenocarcinoma. Endolymphatic invasion was found in 9 cases. The median follow-up was 31 months. Adjuvant chemotherapy was done in 9 patients, and the patient who did not receive chemotherapy died by cerebrovascular accident. 2 patient had recurrence of gastric cancer and 7 survived without recurrence. Conclusion: More cases should be collected and further studies on the molecular and cellular tumor characteristics are required to characterize these tumors that show aggressive lymphatic spread.