• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.180-185
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• 2005

Purpose: Among tumor-associated antigens, MAGE (melanoma antigen) was named as cancer/testis specific antigens because they are detected exclusively in the testis or cancer cells, including gastric carcinomas. Due to the elicitation of autoimmunitiy to tumors by these antigens either in vitro or in vivo and their tumor specificity, these antigens, thus, appear to be potential targets for tumor-specific immunotherapy. Materials and Methods: The fresh tumor tissue and normal gastric tissue samples were obtained from resected surgical specimens in 53 patients with gastric carcinomas. From the obtained cells, total cellular mRNA was extracted, and RT-PCR and nested PCR were run in 30 and 35 cycles respectively, with two different kinds of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results: In the 53 normal tissue, there was no expression of MAGE, but in the 53 cancer tissues, MAGE was expressed in 13 tissues (24.5%). Our data did not exhibit any correlation with the expression of the MAGE gene and clinicopathological factors. Conclusion: In our data, since 24.5% of gastric cancer tissues expressed MAGE, it should become possible to immunize a significant proportion of patients with advanced gastric carcinomas against the antigens encoded by these genes, provided that more antigenic peptides encoded by the genes of the MAGE family can be identified in the near future. (J Korean Gastric Cancer Assoc 2005;5:180-185)

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.550-558
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• 2001

Background : It has been reported that younger patients with lung cancer have characteristic features that differ from those in older patients. The prognosis for young patients with this disease is controversial. This study aimed to determine the clinicopathological characteristics, the survival rate, and the risk factors associated with the overall survival rate in younger patients with lung cancer. Methods : The records of 120 young(age${\leq}40$) patients with histologically confirmed lung cancer in the Korea Caneer Center Hospital(KCCH) between Jan. 1992 and Dec. 1998 were retrospectively reviewed. Of 5,082 lung cancer patients registered at the KCCH from 1992 to 1998, 120 older(age>40) patients were randomly selected as the controls. Results : More female patients(45.0% vs. 20.0%, p<0.001) and more adenocarcinoma cases(64.2% vs.38.3%, p<0.001) were found in the younger group, when compared to the older patients. In NSCLC, advanced disease(stage IIIB and IV) was more common in the younger patients(90.2%) than in the older patients(62.7%) (p<0.001). The Median survival was 8.6 months in the younger patients and 12.2 months in the older(p=0.003). In a multivariate analysis, only the advanced-stage was an independent negative prognostic factor. Conclusions : Lung cancer in the younger age group presents with a more advanced stage resulting in a poor survival rate, which suggests that lung cancer in this population is more aggressive than in older patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2935-2940
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• 2016

Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

• Journal of Breast Disease
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• v.6 no.2
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• pp.52-59
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• 2018

Purpose: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. Methods: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (${\geq}3cm$), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). Results: Small tumor size (p<0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. Conclusion: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.152-159
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• 2007

Purpose: Recently, the use of laparoscopic assisted gastrectomy for early gastric cancer has been on the increase and the procedure has been quickly adopted by clincians. However, there are few reports regarding the safety and risk of this type of surgery. The aim of this study is to evaluate the morbidity and to verify the safety of laparoscopic assisted gastrectomy for early gastric cancer. Materials and Methods: A total of 376 patients that had undergone laparoscopic assisted gastrectomy for early gastric cancer between April 2004 and December 2006 were reviewed retrospectively. The clinicopathological characteristics, operative complications, and factors related to complications were evaluated. Results: The overall operative morbidity and mortality rates were 10.6% and 0%, intraoperative morbidity was 1.1% (4 of 376 patients) and post operative morbidity was 9.6% (36 of 376 patients). Most complications required no surgery except for an intestinal obstruction in two cases. Multivariate analysis of risk factors related to operative morbidity determined that age was an independent factor associated with morbidity (P=0.021). Conclusion: The complication rate of laparoscopic assisted gastrectomy is low and most complications can be managed by conservative methods rather than with surgery. There were no specific predicting factors for complications except old age. Laparoscopy is a technically feasible and acceptable surgical modality for early gastric cancer.

• Journal of Gastric Cancer
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• v.7 no.4
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• pp.193-199
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• 2007

Purpose: Combined resection of an invaded organ in advanced gastric cancer (AGC) with infiltration of adjacent organs is essential to achieve R0 resection. However, when the tumor invades the head of the pancreas or duodenum, R0 resection interferes with the lower resectability and results in a higher morbidity. Wereviewed these cases retrospectively and considered the proper extent of the surgical resection. Materials and Methods: We retrospectively analyzed cases where patients underwent surgery for gastric adenocarcinoma at the Department of Surgery, Presbyterian Medical Center, between January 1998 and December 2003. Among the 45 patients who were suspected to have pancreatic head or duodenum invasion by a primary tumor or metastatic lymph nodes based on the operative findings, we included 22 patients without incurable factors. The patients were classified into three groups: 4 patients that underwent a combined resection (PD group), 12 patients that underwent a palliative subtotal gastrectomy (STG group) and 6 patients that underwent bypass surgery only (GJ group). We analyzed the clinicopathological features, operative data and results. Results: The patients of the PD group achieved R0 resection by PD with D3 Dissection in all Patients. A pancreatic fistula was observed in one patient (morbidity 25%). There was no surgery-associated mortality (mortality 0%). All patients of the PD group were in stage IV. However, the 2-year survival rate (SR) was 75% and the 5-year SR was 50%. Six patients of the STG group underwent surgery with marginal resection and the other six patients of the STG group had a positive distal resection margin. The 2-year SR was 41.7% and the 5-year SR was 16.7%. Most of the patients of group GJ were of old age (mean age: $72.7{\pm}8.6$ years) or had chronic diseases. The 2-year SR was 0%. Conclusion: Combined resection of the pancreas and duodenum in AGC with pancreatic head invasion is relatively safe with moderate morbidity and a lower mortality. One can expect long-term survival if combined resectionis performed in cases without incurable factors.

• 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.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.117-123
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• 2007

Purpose: The surgical treatment of gastric cancer that invades adjacent organs is a radical gastrectomy with combined resection including the adjacent organs or a palliative operation by performing either a gastrojejunostomy or gastrectomy. However, since it is impossible to determine the exact stage of the cancer, either T or N, in the case of palliative surgery, it is inappropriate to predict patient prognosis. This study analyzes the prognoses for patients whose final TNM stages are determined by a combined resection performed due to macroscopical infiltration into the adjacent organs. Materials and Methods: Of 2,452 patients that underwent surgery for gastric cancer at our hospital from 1983 to 2002, we evaluated 102 patients where a combined resection was performed because direct infiltration into the adjacent organs was discovered. Results: Univariate analysis showed that the survival rate differed by the depth of invasion into the gastric walls, the degree of lymph node metastasis, distant metastasis, pathological TNM stage, surgical curability, the location of tumor, and histological differentiation. By multivariate analysis, it was found that the surgical curability, the location of the tumor and the degree of lymph node metastasis were independent prognostic factors. Conclusion: It is suggested that even when infiltration into adjacent organs is suspected, radical surgery should be performed as to allow a prediction of prognosis through an exact determination of disease stage, and to improve the survival rate.

• Journal of Gastric Cancer
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• v.8 no.1
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• pp.27-34
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• 2008

Purpose: Many recent studies have reported on the feasibility and usefulness of laparoscopy assisted distal gastrectomy (LADG) for treating early gastric cancer. On the other hand, there has been few reports about laparoscopy assisted total gastrectomy (LATG) because upper located gastric cancer is relatively rare and the surgical technique is more difficult than that for LADG, We now present our procedure and results of performing LATG for the gastric cancer located in the upper or middle portion of the stomach. Materials and Methods: From Jan 2005 to Sep 2007, 96 patients underwent LATG by four surgeons at the Asan Medical Center, Seoul, Korea. Among them, 48 consecutive patients who were operated on by asingle surgeon were analyzed with respect to the clinicopathological features, the surgical results and the postoperative courses with using the prospectively collected laparoscopy surgery data. Results: There was no conversion to open surgery during LATG. For all the reconstructions, Roux-en Y esophago-jejunostomy and D1+beta lymphadenectomy were the standard procedures. The mean operation time was $212{\pm}67$ minutes. The mean total number of retrieved lymph nodes was $28.9{\pm}10.54$ (range: $12{\sim}64$) and all the patients had a clear proximal resection margin in their final pathologic reports. The mean time to passing gas, first oral feeding and discharge from the hospital was 2.98, 3.67 and 7.08 days, respectively. There were 5 surgical complications and 2 non-surgical complications for 5 (10.4%) patients, and there was no mortality. None of the patients needed operation because of complications and they recovered with conservative treatments. The mean operation time remained constant after 20 cases and so a learning curve was present. The morbidity rate was not different between the two periods, but the postoperative course was significantly better after the learning curve. Analysis of the factors contributing to the postoperative morbidity, with using logistic regression analysis, showed that the 8MI is the only contributing factor forpostoperative complications (P=0.029, HR=2.513, 95% CI=1.097-5.755). Conclusions: LATG with regional lymph node dissection for upper and middle early gastric cancer is considered to be a safe, feasible method that showed an excellent postoperative course and acceptable morbidity. BMI should be considered in the patient selection at the beginning period because of the impact of the BMI on the postoperative morbidity.

• Journal of Gastric Cancer
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• v.8 no.2
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• pp.70-78
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• 2008

Purpose: VEGF-C and VEGF-D are angiogenetic factors, and abnormal expression of E-cadherin hasa role in the progression of gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of E-cadherin, VEGF-C and VEGF-D with the presence of lymph node metastases (LNM) using cytokeratin 18 in early gastric cancer (EGC). Materials and Methods: Immunohistochemical staining for E-cadherin, VEGF-C and VEGF-D was performed in 49 EGC patients from March 1997 to December 2002. To evaluate the real extent of LNM, 1,562 lymph nodes from 49 patients were re-examined with the use of cytokeratin 18. Results: Eleven (0.7%) LNM were newly found in 12.2% (n=6) of patients. The real LNM rate was 3.6% in mucosal invasive (m) cancer and 38.1% in submucosal invasive (sm). Stage migration was seen in three patients (6.1%). Abnormal expression of E-cadherin was detected in 36.7% of the patients and expression of VEGF-C and VEGF-D was detected in 16.3% and 36.7% of the patients, respectively. Abnormal expression of E-cadherin was significantly correlated with tumor differentiation (P=0.0103) and Lauren classification (P<0.0001). There was no positive relationship of VEGF-C and VEGF-D expression with the clinicopathological findings for EGC including LNM. However, the frequency of lymph node metastases was significantly higher in patients that demonstrated abnormal expression of E-cadherin with positive immunoreactivity of VEGF-C or VEGF-D (P=0.031). Conclusion: In present study, we could not demonstrate a relationship between the presence of LNM and expression of VEGF-C and VEGF-D in EGC. However, VEGF-C or VEGF-D expression, in addition to the abnormal expression of E-cadherin, was correlated with the real extent of LNM in EGC.