Background: /Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. Methods: A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. Results: The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Conclusions Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

BACKGROUND/AIMS: This study compared the outcomes of patients with small hepatocellular carcinomas (HCCs) who were treated using transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). METHODS: This was a post-hoc analysis of a prospective study that evaluated the diagnostic efficacy of magnetic resonance imaging (MRI) and computed tomography (CT). We analyzed 41 small hepatic nodules in 32 patients that showed typical radiologic hallmarks on both CT and gadoxate-enhanced MRI (typical nodules) and 25 small hepatic nodules from 22 patients that showed atypical radiologic hallmarks on CT and typical radiologic hallmarks on MRI (discrepant nodules). RESULTS: There were no significant differences in the baseline characteristics of the patients with typical and discrepant nodules. Complete response rates 1 month after TACE or RFA were 75.0% (18/24) and 94.1% (16/17; P=0.20), respectively, for the patients with typical nodules and 58.8% (10/17) and 100% (8/8; P=0.05), respectively, for the patients with discrepant nodules. Treatment failure rates after TACE or RFA were 33.3% (8/24) and 5.8% (1/17; P=0.15), respectively, for the patients with typical nodules and 47.0% (8/17) and 0.0% (0/8; P=0.02), respectively, for the patients with discrepant nodules. Among patients achieving complete response, there were no significant differences in the risk of marginal recurrence. CONCLUSIONS: RFA provided higher complete response rates and significantly lower treatment failure rates than TACE for patients with discrepant nodules of HCC. Therefore, a treatment modality such as RFA may be preferable for small HCCs which show discrepancy on two imaging modalities.
Carcinoma, Hepatocellular* ; Catheter Ablation* ; Humans ; Magnetic Resonance Imaging* ; Multidetector Computed Tomography ; Prospective Studies ; Recurrence ; Treatment Failure

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-gamma agonists and increased in OLETF rats using microarrays in two different models. METHODS: In the first microarray analysis, PPAR-gamma agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats). RESULTS: Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-gamma agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count. CONCLUSION: Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-gamma agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.
Adipocytes ; Adipokines ; Animals ; Body Mass Index ; Carrier Proteins ; Genes, Overlapping ; Humans ; Interleukin-6 ; Intra-Abdominal Fat ; Leukocyte Count ; Mice ; Microarray Analysis ; Models, Animal ; Obesity ; Peroxisomes ; Polymerase Chain Reaction ; PPAR gamma ; Rats ; Rats, Inbred OLETF ; Reverse Transcription ; Transcriptome*

BACKGROUND/AIMS: Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated. METHODS: We collected HCC tissues from 83 HCC patients who underwent surgical resection for an immunohistochemical study of PDI. Overall survival (OS) was measured from the date of surgical resection until the date of death from any cause. Radiological progression was evaluated using the modified Response Evaluation Criteria in Solid Tumors in an independent radiological assessment. RESULTS: PDI expression was found to be increased in human HCC compared to adjacent nontumor tissues. Increased immunopositivity for PDI was associated with a high Edmondson-Steiner grade (p = 0.028). Univariate analysis of patients who had undergone surgical resection for HCC showed that tumor PDI upregulation is a significant risk factor for poor OS (p = 0.016; hazard ratio [HR], 1.980) and time to progression (TTP; p = 0.007; HR, 1.971). Multivariate analyses revealed that high PDI expression was an independent predictor of a shorter TTP (p = 0.015; HR, 1.865) and poor OS (p = 0.012; HR, 2.069). CONCLUSIONS: Upregulated PDI expression is associated with aggressive clinicopathological features of HCC; thus, PDI might serve as an independent prognostic factor and a potential therapeutic target for HCC patients.
Carcinoma, Hepatocellular/*enzymology/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/*enzymology/pathology ; Male ; Middle Aged ; Prognosis ; Protein Disulfide-Isomerases/*metabolism ; Retrospective Studies ; Tumor Markers, Biological/metabolism

BACKGROUND/AIMS: Primary aldosteronism (PA) is now widely recognized to have a higher prevalence than was once thought. In view of its increasing prevalence, we compared chronological changes in clinical manifestations of PA according to different times of diagnosis. METHODS: In total, 85 patients diagnosed with PA from January 1986 through March 2012 were reviewed retrospectively, based on their medical records. During two periods-1986 to 2005 and 2006 to 2012-41 and 44 patients, respectively, were diagnosed with PA. We compared the clinical and biological characteristics of PA between these periods. RESULTS: The results demonstrate an increasing trend in the prevalence of idiopathic hyperaldosteronism (IHA; p = 0.19). In the 2006 to 2012 period, patients with PA presented with higher serum potassium levels at the time of diagnosis than in the 1986 to 2005 period (p < 0.0002). Adrenal vein sampling (AVS) was performed mostly in the latter period (82.3%) and the diagnostic accuracy of adrenal computed tomography, compared with AVS, was only 56.2%. About 78.0% versus 86.3% of patients had at least one target organ damage (TOD) in the 1986 to 2005 and 2006 to 2012 periods, respectively (p = 0.39). However, patients with TOD were older and had longer durations of hypertension than patients without, in both periods. CONCLUSIONS: PA is becoming more prevalent. There was an increasing tendency for IHA, and more PA patients presented with normokalemia than in the earlier period. Early and accurate diagnosis of PA with AVS and proper treatment should have substantial prognostic value.
Adrenal Cortex Neoplasms/diagnosis/epidemiology ; Adrenal Glands/radiography ; Adrenocortical Adenoma/diagnosis/epidemiology ; Adult ; Biological Markers/blood ; Female ; Humans ; Hyperaldosteronism/blood/*diagnosis/epidemiology/therapy ; Hyperkalemia/diagnosis/epidemiology ; Hyperplasia ; Hypertension/diagnosis/epidemiology ; Male ; Middle Aged ; Potassium/blood ; Predictive Value of Tests ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome

BACKGROUND/AIMS: The aim of this study was to examine the distribution of range of liver enzymes according to age and BMI in each gender using large-scale data. METHODS: Data were gathered from 65,715 subjects who underwent a routine health check-up and did not have HBsAg and anti-HCV. Boxplot analysis was used to examine the distribution of range of liver enzymes according to age and BMI in each gender. Multivariate linear regression analysis was performed for assessment of the association of liver enzymes with age and BMI, and to determine whether the range of liver enzymes was affected by risk factors for metabolic syndrome in each gender. RESULTS: ALT, AST, and GGT levels showed significant association with BMI in both male and female after adjusting for age. The range of ALT, AST, and GGT levels varied more widely according to the increase in BMI in males than in females, and this finding was more prominent in younger subjects than in older subjects. All risk factors for metabolic syndrome were shown to affect liver enzyme levels in male subjects. However, although most risk factors for metabolic syndrome affected liver enzyme levels, there might be weak or no effect of fasting hyperglycemia on AST, and low serum HDL-cholesterol level on GGT in female subjects. CONCLUSIONS: Age, BMI, and other risk factors for metabolic syndrome had a significant effect on the distribution of range of liver enzymes in each gender, even in this study conducted from Korean health checkup subjects.
Alanine Transaminase ; Aspartate Aminotransferases ; Body Mass Index* ; Fasting ; Female ; Hepatitis B Surface Antigens ; Humans ; Hyperglycemia ; Linear Models ; Liver* ; Male ; Metabolic Syndrome X ; Risk Factors

BACKGROUND: Several epidemiologic studies showed the significant association of insulin resistance with asthma. OBJECTIVE: The aim of this study was to evaluate the association of insulin resistance with airway hyperresponsiveness (AHR) in adult population. METHODS: 1,058 subjects who visited to the Seoul National University Hospital Gangnam Center from October 2007 to January 2009 for a routine health check-up were enrolled. All subjects completed a questionnaire, anthropometric measurements such as body mass index (BMI) and waist circumference, blood tests, pulmonary function test, and methacholine bronchial provocation test (MBPT). Insulin resistance was estimated from the homeostasis model of assessment of insulin resistance (HOMA-IR).
Adult ; Asthma ; Body Mass Index ; Bronchial Hyperreactivity ; Bronchial Provocation Tests ; Epidemiologic Studies ; Fasting ; Female ; Forced Expiratory Volume ; Glucose ; Hematologic Tests ; Homeostasis ; Humans ; Insulin Resistance ; Insulin ; Logistic Models ; Lung ; Male ; Methacholine Chloride ; Obesity ; Odds Ratio ; Respiratory Function Tests ; Risk Factors ; Seoul ; Waist Circumference

This study aimed to investigate the status of primary liver cancers found through a routine health check-up. The data of subjects who were diagnosed with primary liver cancer for the first time through a routine health check-up during a period of 8-yr were analyzed. Primary liver cancers were detected for the first time in 34 subjects among 91,219 routine health check-up subjects. Only 11.8% of primary liver cancer subjects had been under previous surveillance. Of them, 55.8% were positive for HBsAg, 17.7% were positive for anti-HCV, and 8.8% were heavy alcohol comsumers. However, 17.7% of the subjects were neither heavy alcohol consumers nor positive for both HBsAg and anti-HCV. Of the subjects, 50.0% had a single nodular tumor, 23.5% had multi-nodular tumors, and 26.5% had an infiltrative tumor. A routine health check-up may provide beneficial opportunities to detect a liver cancer in a very early stage. It is beneficial to start surveillance in high-risk subjects for liver cancer or to detect any liver cancer in subjects without risk factors of chronic viral hepatitis or heavy alcohol consumption.
Age Factors ; Alcohol Drinking ; Early Detection of Cancer ; Hepatitis B Surface Antigens/blood ; Hepatitis C Antibodies/blood ; Humans ; Liver Neoplasms/*diagnosis/epidemiology/ultrasonography ; Questionnaires ; Sex Factors ; Smoking ; Tomography, X-Ray Computed

BACKGROUND: Thyroid function depends on ethnic and environmental factors. North Korean refugees have the same genetic background as South Koreans, but they have been exposed to different environments. This study examines the prevalence and pattern of thyroid disorders in North Korean women living in South Korea, focusing on subclinical hypothyroidism (SCH). METHODS: The intended sample was a total of 327 North Korean women residing in Seoul. Health questionnaires and medical examinations, including serum thyrotropin (thyroid stimulating hormone, TSH), free thyroxine, and thyroid autoantibodies, were conducted. RESULTS: The prevalence of SCH was 9.4%. In logistic regression analysis, smoking, menopause, length of stay in South Korea, body mass index, history of thyroid disease, and metabolic syndrome were not associated with the risk of SCH. Whereas, the positivity of autoantibodies were associated with a high risk for SCH (odds ratio [OR], 4.840; 95% confidence interval [CI], 1.80-13.017; P = 0.002), and age was associated with a low risk for SCH (OR, 0.94; 95% CI, 0.888-0.994; P = 0.031). The serum TSH levels also decreased with increasing age, and in particular, there was significant difference between 30-39 years, and over 60 years (2.33 +/- 1.51 microIU/mL vs. 1.54 +/- 0.73 microIU/mL, P = 0.028). CONCLUSION: In North Korean women, the positivity of autoantibodies was associated with a high risk for SCH. But interestingly, a younger age was associated with a high risk for SCH. Considering that they suffered from severe famine at the period of growth, and this led to malnutrition, their thyroid dysfunction might be associated with the peculiar environment that they experienced.
Autoantibodies ; Body Mass Index ; Female ; Humans ; Hypothyroidism ; Length of Stay ; Logistic Models ; Malnutrition ; Menopause ; Prevalence ; Refugees ; Republic of Korea ; Smoke ; Smoking ; Starvation ; Thyroid Diseases ; Thyroid Gland ; Thyrotropin ; Thyroxine ; Surveys and Questionnaires

BACKGROUND: Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats. METHODS: Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks. RESULTS: Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-beta1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups. CONCLUSION: Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.
Aldosterone ; Animals ; Collagen Type IV ; Connective Tissue Growth Factor ; Diabetic Nephropathies ; Fibronectins ; Lisinopril ; Mineralocorticoid Receptor Antagonists ; Peptidyl-Dipeptidase A ; Plasminogen Activators ; Rats ; Rats, Inbred OLETF ; Receptors, Mineralocorticoid ; Renin-Angiotensin System ; RNA, Messenger ; Spironolactone