• Journal of Gastric Cancer
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• 제17권4호
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• pp.319-330
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• 2017

Introduction: The extent of lymphadenectomy in the surgical treatment of gastric cancer is a topic of controversy among surgeons. This study was conducted to analyze the American National Cancer Database (NCDB) and conclude the optimal extent of lymphadenectomy for gastric adenocarcinoma. Methods: The NCDB for gastric cancer was utilized. Patients who received at least a partial gastrectomy were included. Patients with metastatic disease, unknown TNM stages, R1/R2 resection, or treated with a palliative intent were excluded. Joinpoint regression was used to identify the extent of lymphadenectomy that reflects the optimal survival. Cox regression analysis and Bayesian information criterion were used to identify significant survival predictors. Kaplan-Meier was applied to study overall survival and stage migration. Results: 40,281 patients of 168,377 met the inclusion criteria. Joinpoint analysis showed that dissection of 29 nodes provides the optimal median survival for the overall population. Regression analysis reported the cutoff ${\geq}29$ to have a better fit in the prognostic model than that of ${\geq}15$. Dissection of ${\geq}29$ nodes in the higher stages provides a comparable overall survival to the immediately lower stage. Nonetheless, the retrieval of ${\geq}15$ nodes proved to be adequate for staging without a significant stage migration compared to ${\geq}29$ nodes. Conclusion: The extent of lymphadenectomy in gastric adenocarcinoma is a marker of improved resection which reflects in a longer overall survival. Our analysis concludes that the dissection of ${\geq}15$ nodes is adequate for staging. However, the dissection of 29 nodes might be needed to provide a significantly improved survival.

• Molecules and Cells
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• 제40권1호
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• pp.45-53
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• 2017

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

• Journal of Gastric Cancer
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• 제19권4호
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• pp.393-407
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• 2019

Purpose: To identify the potential therapeutic role of postoperative radiotherapy (RT) in patients with locally advanced (stage II and stage III) gastric signet ring cell carcinoma (SRC). Materials and methods: Patients with locally advanced gastric SRC from the Surveillance, Epidemiology, and End Results program database between 2004 and 2012 were included in our study. Univariate and multivariate Cox proportional models were performed, and survival curves were generated to evaluate the prognostic effect of postoperative RT and surgery alone on SRC patients. Propensity score matching (PSM) was used to avoid selection bias among the study cohorts. Results: We found that patients with postoperative RT had better probability of survival compared with those who did not receive RT (overall survival [OS], P<0.001; cancer-specific survival [CSS], P<0.001). After PSM, analysis of both overall and CSS showed that patients who underwent postoperative RT had better prognosis than those receiving surgery alone in the matched cohort (OS, P=0.00079; CSS, P=0.0036). Multivariate Cox proportional model indicated that postoperative RT had better effect on prognosis compared with surgery alone with respect to both overall (hazard ratio [HR], 0.716; 95% confidence interval [95% CI], 0.590-0.87; P=0.001) and CSS (HR, 0.713; 95% CI, 0.570-0.890; P=0.003). Conclusions: Postoperative RT had better prognosis compared with surgery alone for both overall and CSS for patients with locally advanced gastric SRC.

• 대한방사성의약품학회지
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• 제1권2호
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• pp.137-144
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• 2015

Hypoxia is an important adverse prognostic factor for tumor progression and is a major cause of failure of radiation therapy. In case of short-term hypoxia, the metabolism can recover to normal, but if hypoxia persists, it causes irreversible cell damage and finally leads to death. So a hypoxia marker would be very useful in oncology. In particular, 2-nitroimidazole can be reduced to form a reactive chemical species, which can bind irreversibly to cell components in the absence of sufficient oxygen, thus, the development of radiolabeled nitroimidazole derivatives for the imaging of hypoxia remains an active field of research to improve cancer therapy result. 2-nitroimidazole based hypoxia marker, [$^{18}F$]FMISO holds promise for the evaluation of tumor hypoxia by Positron emission tomography (PET), at both global and local levels. In the present study, [$^{18}F$]FMISO was synthesized using an automatic synthesis module with high radiochemical purity (>99%) in 60 min. Immunohistochemical analysis using pimonidazole confirmed the presence of hypoxia in xenografted CT-26 tumor tissue. A biodistribution study in CT-26 xenografted mice showed that the increased tumor-to-muscle ratio and tumor-to-blood ratios from 10 to 120 min post-injection. In the PET study, [$^{18}F$]FMISO also showed increased tumor-to-muscle ratios from 10 to 120 min post-injection. In conclusion, this study demonstrates the feasibility and utility of [$^{18}F$]FMISO for imaging hypoxiain mouse colon cancer model using small animal PET.

• Parasites, Hosts and Diseases
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• 제45권4호
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• pp.273-282
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• 2007

In acute uncomplicated falciparum malaria, there is a continuum from mild to severe malaria. However, no mathematical system is available to predict uncomplicated falciparum malaria patients turning to severe malaria. This study aimed to devise a simple and reliable model of Malaria Severity Prognostic Score (MSPS). The study was performed in adult patients with acute uncomplicated falciparum malaria admitted to the Bangkok Hospital for Tropical Diseases between 2000 and 2005. Total 38 initial clinical parameters were identified to predict the usual recovery or deterioration to severe malaria. The stepwise multiple discriminant analysis was performed to get a linear discriminant equation. The results showed that 4.3% of study patients turned to severe malaria. The MSPS = 4.38 (schizontemia) + 1.62 (gametocytemia) + 1.17 (dehydration) + 0.14 (overweight by body mass index; BMI) + 0.05 (initial pulse rate) + 0.04 (duration of fever before admission)-0.50 (past history of malaria in last 1 year). 0.48 (initial serum albumin)-5.66. Based on the validation study in other malaria patients, the sensitivity and specificity were 88.8% and 88.4%, respectively. We conclude that the MSPS is a simple screening tool for predicting uncomplicated falciparum malaria patients turning to severe malaria. However, the MSPS may need revalidation indifferent geographical areas before utilized at specific places.

• Journal of Genetic Medicine
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• 제9권1호
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• pp.1-10
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• 2012

About 7% of all breast cancer (BC) cases result from a genetic predisposition, and approximately 1,000 patients develop hereditary BC (HBC) every year in Korea. BRCA1 and BRCA2 are the primary genes underlying HBC. The average cumulative risks in BRCA1 mutation carriers at 70 years of age are 65% (95% confidence interval 44-78%) for BC and 39% (18-54%) for ovarian cancer (OC). The corresponding estimates for BRCA2 are 45% (31-56%) and 11% (2.4-19%), respectively. The penetrance of BRCA mutations is not the same between patients and can depend on factors such as race and birth-cohort. The Korean Hereditary Breast Cancer (KOHBRA) study is a large prospective nationwide study that includes 39 participating centers. Between May 2007 and May 2010, the first phase of the KOHBRA study was planned and fulfilled successfully. The primary aim of phase I was to estimate the prevalence of BRCA1/2 mutations and OC among a high-risk group of patients with HBC and their families. According to data collected during phase I of the study, the prevalence and penetrance of BRCA mutations were comparable to corresponding data from Western countries. For the second phase of the KOHBRA study, we are currently investigating a Korean BRCA mutation prediction model, prognostic factors in BRCA-related BC, environmental/genetic modifiers, and implementing a genetic counseling network. The final goal of the KOHBRA study is to create clinical practice guidelines for HBC in Korea. In this article, I review the genetics of HBC, summarize the characteristics of Korean HBC, and discuss current and future HBC research in Korea.

• 대한종양외과학회지
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• 제14권2호
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• pp.89-94
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• 2018

Purpose: To investigate the relationship between MUC expression and clinicopathologic factors in advanced gastric cancer. Methods: A total of 237 tumor specimens were assessed for MUC expression by immunohistochemistry. The clinicopathologic factors were investigated with MUC1, MUC2, MUC5AC, and MUC6. Results: MUC1, MUC2, MUC5AC, and MUC6 expression was identified in 148 of 237 (62.4%), 141 of 237 (59.5%), 186 of 237 (78.5%), and 146 of 237 (61.6%) specimens, respectively. MUC1 expression was correlated with age, human epidermal growth factor receptor 2 (HER2) status, lymphatic invasion, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC1expression and lymphatic invasion, diffuse type of Lauren classification. MUC5AC expression was correlated with HER2 status, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC5AC expression and HER2 status, diffuse and mixed type of Lauren classification. MUC2 and MUC6 expression were not correlated with clinicopathologic factors. The patients of MUC1 expression had poorer survival than those without MUC1 expression, but MUC2, MUC5AC or MUC6 were not related to survival. In an additional multivariate analysis that used the Cox proportional hazards model, MUC1 expression was not significantly correlated with patient survival independent of age, N-stage, and venous invasion. Conclusion: When each of these four MUCs expression is evaluated, in light of clinicopathologic factors, MUC1 expression may be considered as a prognostic factor in patients with advanced gastric cancer. Therefore, careful follow-up may be necessary because the prognosis is poor when MUC1 expression is present.

• Investigative and Clinical Urology
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• 제59권6호
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• pp.376-382
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• 2018

Purpose: The authors performed this study to investigate the risk factors for predicting stent failure and to evaluate its impact on prognosis. Materials and Methods: Between January 2002 and March 2017, we retrospectively reviewed 117 consecutive patients who underwent retrograde ureteral stenting and exchanging at least once every 3 months for malignant ureteral obstruction. The patients were classified according to their pre-stenting chronic kidney disease (CKD) stage. The factors affecting stent failure were analyzed using a logistic regression model. Overall survival (OS) was estimated, and the prognostic significance of each variable was estimated using Cox proportional-hazards regression modeling. Results: Before stenting, 91 patients were CKD stages 1-3 and 26 patients were CKD stages 4-5. These two groups differed significantly only in pre-stenting estimated glomerular filtration rate (eGFR), bilateral obstruction, and pre-stenting pyuria. Among the 117 patients, stent failure occurred in 30 patients (25.6%), and there were no differences between the groups. Pre-stenting pyuria and post-stenting complications were significant predictors of stent failure. There were 79 deaths in total, including 56 in the CKD stages 1-3 group and 23 in the CKD stages 4-5 group. In the multivariate analysis predicting patient OS, pre-stenting eGFR and post-stenting disease progression were significant factors. Conclusions: Internal ureteral stenting was effective for maintaining renal function in malignant ureteral obstruction. However, it did not restore renal function, which is related to the prognosis of the patients. Therefore, to improve patients' renal function and prognosis, patients who require stenting must be quickly recognized and treated.

• Journal of Gynecologic Oncology
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• 제29권6호
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• pp.82.1-82.13
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• 2018

Objective: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. Methods: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. Results: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ${\geq}60$ years, longer duration use (${\geq}1$ year), in patients with Charlson Comorbidity Index (CCI) ${\geq}3$, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (${\geq}180$ days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (${\geq}720$ days). In multivariate Cox proportional hazards model, longer duration of BB medication (${\geq}1$ year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. Conclusion: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ${\geq}3$).

• Journal of Gastric Cancer
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• 제21권2호
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• pp.155-168
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• 2021

Purpose: Previous studies have demonstrated the usefulness of the controlling nutritional status (CONUT) score in nutritional assessment and survival prediction of patients with various malignancies. However, its value in advanced gastric cancer (GC) treated with neoadjuvant chemotherapy and curative gastrectomy remains unclear. Materials and Methods: The CONUT score at different time points (pretreatment, preoperative, and postoperative) of 272 patients with advanced GC were retrospectively calculated from August 2004 to October 2015. The χ² test or Mann-Whitney U test was used to estimate the relationships between the CONUT score and clinical characteristics as well as short-term outcomes, while the Cox proportional hazard model was used to estimate long-term outcomes. Survival curves were estimated by using the Kaplan-Meier method and log-rank test. Results: The proportion of moderate or severe malnutrition among all patients was not significantly changed from pretreatment (13.5%) to pre-operation (11.7%) but increased dramatically postoperatively (47.5%). The pretreatment CONUT-high score (≥4) was significantly associated with older age (P=0.010), deeper tumor invasion (P=0.025), and lower pathological complete response rate (CONUT-high vs. CONUT-low: 1.2% vs. 6.6%, P=0.107). Pretreatment CONUT-high score patients had worse progression-free survival (P=0.032) and overall survival (OS) (P=0.026). Adjusted for pathologic node status, the pretreatment CONUT-high score was strongly associated with worse OS in pathologic node-positive patients (P=0.039). Conclusions: The pretreatment CONUT score might be a straightforward index for immune-nutritional status assessment, while being a reliable prognostic indicator in patients with advanced GC receiving neoadjuvant chemotherapy and curative gastrectomy. Moreover, lower pretreatment CONUT scores might indicate better chemotherapy responses.