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1.  Prognostic factors in patients with middle and distal bile duct cancers 
AIM: To identify the influence of the surgery type and prognostic factors in middle and distal bile duct cancers.
METHODS: Between August 1990 and June 2011, data regarding the clinicopathological factors of 194 patients with surgical and pathological confirmation were collected. A total of 133 patients underwent resections (R0, R1, R2; n = 102, 24, 7), whereas 61 patients underwent nonresectional surgery. Either pancreaticoduodenectomy (PD) or bile duct resection (BDR) was selected according to the sites of tumors and co-morbidities of the patients after confirming resection margin by the frozen histology in all cases. Univariate and multivariate analyses of clinicopathologic factors were performed, utilizing the Kaplan-Meyer method and Cox hazard regression analysis.
RESULTS: The overall 5-year survival rate for the 133 patients who underwent resection (R0, R1, and R2) was 41.2%, whereas no patients survived longer than 3 years among the 61 patient who underwent nonresectional surgeries. The 5-year survival rate of the patients who underwent a PD (n = 90) was higher than the rate of those who underwent BDR (n = 43), although the difference was not statistically significant (46.6% vs 30.0% P = 0.105). However, PD had a higher rate of R0 resection than BDR (90.0% vs 48.8%, P < 0.0001). If R0 resection was achieved, PD and BDR showed similar survival rates (49.4% vs 46.5% P = 0.762). The 5-year survival rates of R0 and R1 resections were not significantly different (49.0% vs 21.0% P = 0.132), but R2 resections had lower survival (0%, P = 0.0001). Although positive lymph node, presence of perineural invasion, presence of lymphovascular invasion (LVI), 7th AJCC-UICC tumor node metastasis (TNM) stage, and involvement of resection margin were significant prognostic factors in univariate analysis, multivariate analysis identified only TNM stage and LVI as independent prognostic factors.
CONCLUSION: PD had a greater likelihood of curative resection and R1 resection might have some positive impact. The TNM stage and LVI were independent prognostic factors.
PMCID: PMC4047355  PMID: 24914391
Distal extrahepatic bile duct cancer; Lymphovascular invasion; Tumor node metastasis; Pancreaticoduodenectomy; Bile duct resection; Prognostic factor
2.  Prevalence of Trichomonas vaginalis by PCR in Men Attending a Primary Care Urology Clinic in South Korea 
Trichomonas vaginalis, a causative agent of trichomoniasis, may trigger symptomatic or asymptomatic nongonococcal urethritis and chronic prostatitis in men. Despite the availability of highly sensitive diagnostic tests, such as nucleic acid amplification tests, including PCR, few prospective studies present data on male T. vaginalis infection in South Korea. In the present study, the prevalence of T. vaginalis and associated clinical conditions were evaluated in 201 male patients from a primary care urology clinic in South Korea. The prevalence of T. vaginalis infection in our cohort was 4% (8/201) by PCR. T. vaginalis infection was common in men older than 40 years (median age, 52 years). Among the 8 Trichomonas-positive patients, 87.5% (7/8) had prostatic diseases, such as prostatitis and benign prostatic hyperplasia, and 25.0% (2/8) and 12.5% (1/8) were coinfected with Chlamydia trachomatis and Mycoplasma genitalium, respectively. Our results suggest that T. vaginalis infection is not rare in men attending primary care urology clinics in South Korea, especially in those older than 40 years, in whom it may explain the presence of prostatic disease. The possibility of T. vaginalis infection should be routinely considered in older male patients with prostatic diseases in South Korea.
PMCID: PMC4210741  PMID: 25352707
Trichomonas vaginalis; sexually transmitted disease; diagnosis; PCR; multiplex PCR
3.  Effect of Body Mass Index on Global DNA Methylation in Healthy Korean Women 
Molecules and Cells  2014;37(6):467-472.
Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and 30 kg/m2. However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship.
PMCID: PMC4086340  PMID: 24938226
Alu; BMI; methylation; pyrosequencing; U-shape
4.  Development of Loop-Mediated Isothermal Amplification Targeting 18S Ribosomal DNA for Rapid Detection of Azumiobodo hoyamushi (Kinetoplastea) 
Ascidian soft tunic syndrome (AsSTS) caused by Azumiobodo hoyamushi (A. hoyamushi) is a serious aquaculture problem that results in mass mortality of ascidians. Accordingly, the early and accurate detection of A. hoyamushi would contribute substantially to disease management and prevention of transmission. Recently, the loop-mediated isothermal amplification (LAMP) method was adopted for clinical diagnosis of a range of infectious diseases. Here, the authors describe a rapid and efficient LAMP-based method targeting the 18S rDNA gene for detection of A. hoyamushi using ascidian DNA for the diagnosis of AsSTS. A. hoyamushi LAMP assay amplified the DNA of 0.01 parasites per reaction and detected A. hoyamushi in 10 ng of ascidian DNA. To validate A. hoyamushi 18S rDNA LAMP assays, AsSTS-suspected and non-diseased ascidians were examined by microscopy, PCR, and by using the LAMP assay. When PCR was used as a gold standard, the LAMP assay showed good agreement in terms of sensitivity, positive predictive value (PPV), and negative predictive value (NPV). In the present study, a LAMP assay based on directly heat-treated samples was found to be as efficient as DNA extraction using a commercial kit for detecting A. hoyamushi. Taken together, this study shows the devised A. hoyamushi LAMP assay could be used to diagnose AsSTS in a straightforward, sensitive, and specific manner, that it could be used for forecasting, surveillance, and quarantine of AsSTS.
PMCID: PMC4096644  PMID: 25031473
Azumiobodo hoyamushi; LAMP; diagnostic method; soft tunic syndrome; ascidian aquaculture
5.  Obsessive-Compulsive Symptoms and Their Impacts on Psychosocial Functioning in People with Epilepsy 
Background and Purpose
Obsessive-compulsive symptoms (OCS) in people with epilepsy (PWE) have not been studied systematically. We evaluated the severity, predictors, and psychosocial impact of OCS in PWE.
We recruited PWE who visited our epilepsy clinic and age-, gender-, and education-matched healthy controls. Both PWE and healthy controls completed the Maudsley Obsessional-Compulsive Inventory (MOCI), which measures OCS. PWE also completed the Beck Depression Inventory (BDI) and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31). We examined the severity of OCS in PWE relative to healthy controls. Predictors of OCS and the QOLIE-31 score were measured by regression analyses. A path analysis model was constructed to verify interrelations between the variables.
The MOCI total score was significantly higher in PWE than in healthy controls (p=0.002). OCS were found in 20% of eligible patients. The strongest predictor of the MOCI total score was the BDI score (β=0.417, p<0.001), followed by EEG abnormality (β=0.194, p<0.001) and etiology (β=0.107, p=0.031). Epileptic syndrome, the side of the epileptic focus, and action mechanisms of antiepileptic drugs did not affect the MOCI total score. The strongest predictor of the QOLIE-31 overall score was the BDI score (β=-0.569, p<0.001), followed by seizure control (β=-0.163, p<0.001) and the MOCI total score (β=-0.148, p=0.001). The MOCI total score directly affected the QOLIE-31 overall score and also exerted indirect effects on the QOLIE-31 overall score through seizure control and the BDI score.
OCS are more likely to develop in PWE than in healthy people. The development of OCS appears to elicit psychosocial problems directly or indirectly by provoking depression or uncontrolled seizures.
PMCID: PMC4017015  PMID: 24829598
obsessive-compulsive symptom; MOCI; predictor; epilepsy; quality of life; depression
6.  The Reliability and Validity of the Korean Version of the Child Sexual Behavior Inventory 
Psychiatry Investigation  2013;10(4):336-345.
This study examined the reliability and validity of the Korean version of the Child Sexual Behavior Inventory (CSBI) in Korean children aged from 6 to 12 years old and the suitability of and potential for clinical application of the CSBI in Korean population.
The participants consisted of 158 typically growing children and 122 sexually abused children. The subjects were evaluated using the Korean version of the Child Sexual Behavior Inventory (CSBI), the Child Behavior Checklist (CBCL), and the Trauma Symptom Checklist for Young Children (TSCYC). Internal consistency was examined as a measure of reliability. To investigate the concurrent validity, Pearson's correlations were calculated. One-way ANCOVA was used to demonstrate discriminant validity.
The Cronbach's α value was 0.84. The CSBI total score was moderately correlated with the CBCL subscales and mildly correlated with the sexual concern subscale of the TSCYC. The total score of the CSBI for the sexually abused children group was significantly higher than that of typically growing children group.
This study demonstrated that the Korean version of the Child Sexual Abuse Inventory (CSBI) is a reliable and valid tool. It can be applied in the clinical field for assessing the sexual behavior of Korean children aged from 6 to 12 who are suspected to have been sexually abused.
PMCID: PMC3902150  PMID: 24474981
Child sexual abuse; Korea; Screening; Validation study; Child Sexual Abuse Inventory
7.  A1c Variability Can Predict Coronary Artery Disease in Patients with Type 2 Diabetes with Mean A1c Levels Greater than 7 
Endocrinology and Metabolism  2013;28(2):125-132.
Recent studies suggested that the association of acute glucose variability and diabetic complications was not consistent, and that A1c variability representing long term glucose fluctuation may be related to coronary atherosclerosis in patients with type 1 diabetes. In this study, we attempt to determine whether or not A1c variability can predict coronary artery disease (CAD) in patients with type 2 diabetes.
We reviewed data of patients with type 2 diabetes who had undergone coronary angiography (CAG) and had been followed up with for 5 years. The intrapersonal standard deviation (SD) of serially-measured A1c levels adjusted by the different number of assessments among patients (adj-A1c-SD) was considered to be a measure of the variability of A1c.
Among the 269 patients, 121 of them had type 2 diabetes with CAD. In patients with A1c ≥7%, the mean A1c levels and A1c levels at the time of CAG among the three groups were significantly different. The ratio of patients with CAD was the highest in the high adj-A1c-SD group and the lowest in the low adj-A1c-SD group (P=0.017). In multiple regression analysis, adj-A1c-SD was an independent predictor for CAD in subjects with A1c ≥7% (odds ratio, 2.140; P=0.036).
Patients with higher A1c variability for several years showed higher mean A1c levels. A1c variability can be an independent predictor for CAD as seen in angiographs of patients with type 2 diabetes with mean A1c levels over 7%.
PMCID: PMC3811710  PMID: 24396666
A1c variability; Coronary artery disease; Diabetes mellitus, type 2
8.  Estimation of True Serum Thyroglobulin Concentration Using Simultaneous Measurement of Serum Antithyroglobulin Antibody 
We investigated the analytical interference of antithyroglobulin antibody (TgAb) to thyroglobulin (Tg) measurement and tried to convert measured Tg concentration to true Tg concentration using a mathematical equation which includes a concentration of TgAb. Methods. Tg was measured by immunoradiometric assay and TgAb by radioimmunoassy. Experimental samples were produced by mixing Tg and TgAb standard solutions or mixing patients' serum with high Tg or high TgAb. Mathematical equations for prediction of expected Tg concentration with measured Tg and TgAb concentrations were deduced. The Tg concentration calculated using the equations was compared with the expected Tg concentration. Results. Measured Tg concentrations of samples having high TgAb were significantly lower than their expected Tg concentration. Magnitude of TgAb interference with the Tg assay showed a positive correlation with concentration of TgAb. Mathematical equations for estimation of expected Tg concentration using measured Tg and TgAb concentrations were successfully deduced and the calculated Tg concentration showed excellent correlation with expected Tg concentration. Conclusions. A mathematic equation for estimation of true Tg concentration using measured Tg and TgAb concentration was deduced. Tg concentration calculated by use of the equation might be more valuable than measured Tg concentration in patients with differentiated thyroid cancer.
PMCID: PMC3626228  PMID: 23606837
9.  Telomerase Activity and the Risk of Lung Cancer 
Journal of Korean Medical Science  2012;27(2):141-145.
Telomerase play a key role in the maintenance of telomere length and chromosome integrity. We have evaluated the association between telomerase activity and the risk of lung cancer in peripheral blood. Telomerase activity in peripheral blood mononuclear cells was measured by a PCR-designed telomeric repeat amplification protocol in 63 lung cancer patients and 190 healthy controls that were matched for age, gender, and smoking status. Telomerase activity was significantly lower in the lung cancer patients than in controls (mean ± standard deviation; 1.32 ± 1.65 vs 2.60 ± 3.09, P < 1 × 10-4). When telomerase activity was categorized into quartiles based on telomerase activity in the controls, the risk of lung cancer increased as telomerase activity reduced (Ptrend = 1 × 10-4). Moreover, when the subjects were categorized based on the median value of telomerase activity, subjects with low telomerase activity were at a significantly increased risk of lung cancer compared to subjects with high telomerase activity (adjusted odds ratio = 3.05, 95% confidence interval = 1.60-5.82, P = 7 × 10-4). These findings suggest that telomerase activity may affect telomere maintenance, thereby contributing to susceptibility to lung cancer.
PMCID: PMC3271286  PMID: 22323860
Lung Cancer; Telomerase Activity; Susceptibility
10.  Changes in Dietary Behavior Among Adolescents and Their Association With Government Nutrition Policies in Korea, 2005-2009 
This study was conducted to observe recent changes in adolescents' dietary behavior and indirectly evaluate the effects of the government's nutritional policies in Korea.
We analyzed the secular trends in seven dietary behaviors using the Korea Youth Risk Behavior Web-based Survey data from 2005 to 2009. Through literature review, we included the policies implemented for the improvement of adolescents'dietary behaviors during the same periods.
The significant linear trends were observed in all dietary behaviors (p<0.05). Overall, all behaviors except the fruit intake rate were desirably changed during five years but undesirable changes were observed between 2008 and 2009 in all behaviors. Within those periods, several policies were implemented including 'Ban on carbonated-beverages in school', 'Green Food Zone', etc. Despite confirmed evidence of their effects, the policies on individual behavior such as nutrition education didn't influence the prevalence of dietary behaviors because they were conducted to too limited persons. Polices on the school environmental improvement, such as ban on carbonated beverage in school, were more effective because they decreased the exposure of undesirable food environment. However, for effect of Green Food Zone improving community environment we couldn't come to a conclusion because of too short period after full implementation.
Among government nutrition policies conducted from 2005 to 2009, those on environmental improvement, especially in school, were more effective than those on individual behavior. Therefore, the development and implement of policies on school environmental improvement are needed in Korea.
PMCID: PMC3278604  PMID: 22389758
Adolescent; Food habits; Policy; Trends
11.  Polymorphisms in Apoptosis-Related Genes and TP53 Mutations in Non-Small Cell Lung Cancer 
Journal of Korean Medical Science  2011;26(11):1527-1530.
Apoptosis plays an essential role in the elimination of mutated or transformed cells from the body. Therefore, polymorphisms of apoptosis-related genes may lead to an alteration in apoptotic capacity, thereby affecting the occurrence of TP53 mutations in lung cancer. We investigated the relationship between potentially functional polymorphisms of apoptosis-related genes and TP53 mutations in non-small cell lung cancer (NSCLC). Twenty-seven single nucleotide polymorphisms in 20 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay in 173 NSCLCs and the associations with TP53 mutations in the entire coding exons (exons 2-11), including splicing sites of the gene, were analyzed. None of the 27 polymorphisms was significantly associated with the occurrence of TP53 mutations. This suggests that apoptosis-related genes may not play an important role in the occurrence of TP53 mutations in lung cancer.
PMCID: PMC3207061  PMID: 22065914
Lung Neoplasms; Apoptosis; TP53 Mutation; Polymorphism, Genetic
12.  Trends in Cigarette Use Behaviors Among Adolescents by Region in Korea 
Understanding recent trends in cigarette smoking among adolescents is important in order to develop strategies to prevent cigarette smoking. The aim of this study was to compare recent trends in cigarette smoking for adolescents living in rural areas, small towns and metropolitan cities in Korea.
The raw data from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) from 2005 to 2009 were used. Data were analyzed by using the method of complex survey data analysis considering complex sampling design. Logistic regression models were used to evaluate significant linear time trends in cigarette smoking. The indicators of cigarette use behaviors were 'current smoking rate', 'frequent smoking rate', 'heavy smoking rate' and 'smoking experience rate before 13 years of age'. All analyses were conducted according to gender.
Statistically significant increasing trends in current smoking rate and frequent smoking rate were observed and borderline significant increasing trends in heavy smoking rate were shown among rural boys. Among metropolitan city boys, statistically significant increasing trends were also seen for frequent smoking. Statistically significant decreasing trends in current smoking rate were observed among small town and metropolitan city girls. Smoking experience rate before 13 years of age for rural girls decreased significantly.
Cigarette smoking prevalence among adolescents in the rural areas has increased in the last five years especially among boys. Our findings suggest that anti-tobacco program for adolescents should be conducted primarily for those in rural areas.
PMCID: PMC3249254  PMID: 21894066
Smoking; Trends; Adolescent; Rural health; Korea Youth Risk Behavior Web-based Survey (KYRBWS)
13.  SERPINE2 Polymorphisms and Chronic Obstructive Pulmonary Disease 
Journal of Korean Medical Science  2009;24(6):1119-1125.
A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesized that the SERPINE2 gene, which is one of the genes located at the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of four SERPINE2 single nucleotide polymorphisms (SNPs; rs16865421A>G, rs7583463A>C, rs729631C>G, and rs6734100C>G) with the risk of COPD was investigated in a case-control study of 311 COPD patients and 386 controls. The SNP rs16865421 was associated with a significantly decreased risk of COPD in a dominant model for the polymorphic allele (adjusted odds ratio [OR]=0.66, 95% confidence interval [CI]=0.45-0.97, P=0.03). In haplotype analysis, the GACC haplotype carrying the polymorphic allele at the rs16865421 was associated with a significantly decreased risk of COPD when compared to the AACC haplotype (adjusted OR=0.58, 95% CI=0.38-0.89, P=0.01), and this effect was evident in younger individuals (adjusted OR=0.30, 95% CI=0.14-0.64, P=0.002). This study suggests that the SERPINE2 gene contributes to the susceptibility to COPD.
PMCID: PMC2775861  PMID: 19949669
Serpine2; Polymorphism; Pulmonary Disease, Chronic Obstructive
14.  Polymorphisms in the epidermal growth factor receptor gene and the risk of primary lung cancer: a case-control study 
BMC Cancer  2007;7:199.
Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population.
We first examined the frequencies of 39 candidate polymorphisms in the EGFR gene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C>T, 142285G>A, 162093G>A, 181946C>T and 187114T>C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls.
Of the 5 polymorphisms, the 181946C>T genotype distribution was significantly different between the cases and controls (P = 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45–0.88, P = 0.007). When the analyses were stratified by smoking status, the protective effect of the TT genotype was statistically significant in ever-smokers (adjusted OR = 0.59, 95% CI = 0.41–0.86, P = 0.007), but not in never-smokers (adjusted OR = 0.89, 95% CI = 0.45–1.75, P = 0.73; P = 0.08, test for homogeneity). Consistent with the results of the genotyping analysis, the CGGCT haplotype with the 181946C allele was associated with a significantly increased risk of lung cancer compared to the CGGTT haplotype carrying the 181946T allele (adjusted OR = 1.50, 95% CI = 1.09–2.07, P = 0.012 and Bonferroni corrected P-value = 0.048).
These results suggest that the EGFR polymorphisms, particularly the 181945C>T polymorphism, could be used as markers for the genetic susceptibility to lung cancer.
PMCID: PMC2129097  PMID: 17956637
15.  Relationship between cyclooxygenase 8473T>C polymorphism and the risk of lung cancer: a case-control study 
BMC Cancer  2006;6:70.
Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the 8473T>C polymorphism in the 3'-untranslated region of the COX-2 gene and the risk of lung cancer in a Korean population.
The COX-2 genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender.
The distribution of the COX-2 8473T>C genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined 8473 TC + CC genotype was associated with a significantly decreased risk of adenocarcinoma as compared with the 8473 TT genotype (adjusted OR = 0.64; 95% CI = 0.46–0.90, P = 0.01). On the stratification analysis, the protective effect of the combined 8473 TC + CC genotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91, P = 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93, P = 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87, P = 0.01, respectively).
These findings suggest that the COX-2 8473T>C polymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung.
PMCID: PMC1468421  PMID: 16542464

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