PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.
Biopsy ; Chemoradiotherapy* ; Disease-Free Survival ; Follow-Up Studies ; Glioblastoma* ; Humans ; Korea* ; Methylation ; Radiotherapy ; Retrospective Studies* ; Survival Rate

OBJECTIVE: We aimed to assess disturbances in postural and gait balance and functional connectivity within the brain regions controlling balance in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Thirteen children with ADHD and 13 age- and sex-matched controls were recruited. Gait balance was assessed by the difference in the center of pressure (COP) between the left and right foot, as well as the difference in plantar pressure between the left and right foot during gait. Neuroimaging data were acquired using a 3.0 Tesla MRI scanner. Functional connectivity between the vermis of the cerebellum and all other brain regionswas assessed. RESULTS: The difference in plantar pressure between the left foot and right foot in the ADHD group was greater than that observed in the control group. The average COP jerk score of the right foot in the ADHD group was higher than that observed in the control group. A higher functional connectivity between the cerebellum and the right middle frontal gyrus (premotor cortex) and medial frontal gyrus (cingulate gyrus) was observed in the control group relative to the ADHD group. In the ADHD group, the difference in plantar pressure between the left and right foot was also negatively correlated with the beta-value within the middle frontal gyrus. CONCLUSION: Children with ADHD had disturbance of balance as assessed by plantar pressure. Decreased brain connectivity from the cerebellum to the premotor cortex and anterior cingulate was associated with disturbances of posture and balance in children with ADHD.
Brain* ; Cerebellum ; Child* ; Foot ; Gait ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Motor Cortex ; Neuroimaging ; Posture ; Prefrontal Cortex

BACKGROUND/AIMS: Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion. METHODS: A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. RESULTS: The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively). CONCLUSIONS: The survival of HCC patients with bile duct invasion at initial diagnosis is generally poor. However, aggressive treatments for HCC such as resection or biliary drainage may be beneficial therapeutic options for patients with preserved liver function.
Bile Ducts* ; Bile* ; Carcinoma, Hepatocellular* ; Diagnosis ; Drainage ; Drug Therapy ; Humans ; Jaundice, Obstructive ; Liver ; Liver Neoplasms ; Portal Vein ; Prognosis ; Retrospective Studies ; Survival Rate ; Thrombosis

BACKGROUND/AIMS: The presence of invasion is a diagnostic criterion of early gastric cancer (EGC) in Korea, whereas diagnosis in Japan is based on enlarged nuclei and prominent nucleoli. Moreover, the depth of invasion is the location of cancer cell infiltration in Korea, whereas it is the location of lymphovascular invasion (LVI) or cancer cell infiltration in Japan. We evaluated the characteristics of EGC with LVI to uncover the effects of different diagnostic criteria. METHODS: Consecutive T1-stage EGC patients who underwent complete resection were included after endoscopic or surgical resection. The presence of LVI was evaluated. RESULTS: LVI was present in 112 of 1,089 T1-stage EGC patients. LVI was associated with depth of invasion (p<0.001) and age (p=0.017). The prevalence of LVI in mucosal cancer was significantly higher in Korea (p<0.001), whereas that of submucosal cancer was higher in Japan (p=0.024). For mucosal EGC types, LVI was positively correlated with diagnostic criteria applied in Korea (p=0.017). For submucosal EGC types, LVI was positively correlated with Japanese criteria (p=0.001) and old age (p=0.045). CONCLUSIONS: The higher prevalence of LVI for mucosal EGC in Korea and for submucosal EGC in Japan indicates that different diagnostic criteria should be considered when reading publications from other countries.
Asian Continental Ancestry Group ; Diagnosis ; Humans ; Japan* ; Korea* ; Prevalence* ; Stomach Neoplasms*

Aurora kinase A plays an essential role in mitosis including chromosome separation and cytokinesis. Aberrant expression and activity of Aurora kinase A is associated with numerous malignancies including colorectal cancer followed by poor prognosis. The aim of this study is to determine the inhibitory effects of LDD970, an indirubin derivative, on Aurora kinase A in HT29 colorectal cancer cells. In vitro kinase assay revealed that, LDD970 inhibited levels of activated Aurora kinase A (IC₅₀=0.37 mM). The inhibitory effects of LDD970 on Aurora kinase A, autophosphorylation and phosphorylation of histone H3 (Ser10), were confirmed by immunoblot analysis. Moreover, LDD970 inhibited migration of HT29 cells and upregulated apoptosis-related protein cleaved PARP. In cell viability assay, LDD970 was observed to suppress HT29 cell growth (GI₅₀=4.22 µM). Although further studies are required, results of the present study suggest that LDD970 provide a valuable insight into small molecule indirubin derivative for therapeutic potential in human colorectal cancer.
Aurora Kinase A* ; Cell Survival ; Colorectal Neoplasms* ; Cytokinesis ; Histones ; HT29 Cells ; Humans* ; In Vitro Techniques ; Mitosis ; Phosphorylation ; Phosphotransferases ; Prognosis

OBJECTIVE: To introduce the Korean Database of Cerebral Palsy (KDCP) and to provide the first report on characteristics of subjects with cerebral palsy (CP). METHODS: The KDCP is a nationwide database of subjects with CP, which includes a total of 773 subjects. Characteristics such as demography, birth history, onset and type of CP, brain magnetic resonance imaging (MRI) findings, functional ability and accompanying impairments, were extracted and analyzed. RESULTS: Preterm delivery and low birth weight were found in 59.51% and 60.28% of subjects, respectively. Postnatally acquired CP was 15.3%. The distribution of CP was 87.32%, 5.17%, and 1.81% for spastic, dyskinetic, and ataxic types, respectively. Functional ability was the worst in dyskinetic CP, as compared to other types of CP. Speech-language disorder (43.9%), ophthalmologic impairment (32.9%), and intellectual disability (30.3%) were the three most common accompanying impairments. The number of accompanying impairments was elevated in subjects with preterm birth and low birth weight. Brain MRI showed normal findings, malformations, and non-malformations in 10.62%, 9.56%, and 77.35% of subjects, respectively. Subjects with normal MRI findings had better functional ability than subjects with other MRI findings. MRI findings of a non-malformation origin, such as periventricular leukomalacia, were more common in subjects with preterm birth and low birth weight. CONCLUSION: The KDCP and its first report are introduced in this report, wherein the KDCP established agreement on terminologies of CP. This study added information on the characteristics of subjects with CP in South Korea, which can now be compared to those of other countries and ethnicities.
Brain ; Cerebral Palsy* ; Classification ; Demography ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Intellectual Disability ; Korea* ; Leukomalacia, Periventricular ; Magnetic Resonance Imaging ; Muscle Spasticity ; Premature Birth ; Reproductive History

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.
Anoxia ; Brain Neoplasms ; Cell Death* ; Cell Line ; Dichloroacetic Acid ; Glioblastoma* ; Glucose ; Glycolysis ; Metabolism ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphotransferases ; Pyruvic Acid

PURPOSE: This study examined 2-year outcome of consecutive therapy using entecavir (ETV) followed by telbivudine (LdT) in subjects with undetectable hepatitis B virus (HBV) DNA level and normal alanine aminotransferase level after the initial 6 months of ETV treatment. MATERIALS AND METHODS: Sixty subjects were randomized to continue with ETV or switch to LdT. Significant difference in baseline characteristics was not found between the two groups. Persistent HBV DNA level of 20–60 IU/mL in three consecutive samples collected three months apart or singly measured HBV DNA level of >60 IU/mL was defined as virological rebound. RESULTS: During 96 weeks of follow-up, all subjects of the ETV-only group (n=30) resulted in undetectable HBV DNA level. On the other hand, 83.3% (n=25) of the LdT-switched group showed treatment success. Virological rebound time varied from week 24 to 84 after switching to LdT. HBV DNA level was 180 to 2940 IU/mL at rebound time. All subjects with virological rebound (n=5) showed drug-resistant mutation: three had mutation rtM204I, and two had mutation rtM204V. Consecutive treatment using ETV followed by LdT showed virological rebound in 16.7% of subjects during 96 weeks of follow-up. HBV DNA negativity during initial ETV therapy could not be achieved in patients who switched to LdT. CONCLUSION: Consecutive treatment using ETV followed by lamivudine was ineffective for treating chronic hepatitis B. LdT was found as a more potent antiviral agent than lamivudine. However, this conclusion requires larger-scale, long-term prospective reviews of the treatment effects of ETV-LdT switch therapy.
Alanine Transaminase ; DNA ; DNA, Viral* ; Follow-Up Studies ; Hand ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Lamivudine ; Prospective Studies

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor widely used to treat several types of solid tumor. Although bevacizumab has fewer adverse effects than conventional chemotherapy agents, several serious events have been reported. Gastrointestinal perforation is an infrequent but potentially fatal side-effect of bevacizumab. The major mechanism of bevacizumab-associated gastrointestinal perforation is damage to the intestinal vasculature. However, preceding ischemic colitis is difficult to diagnose due to its non-specific symptoms. We report a case of a 56-year-old male with bevacizumab-associated ischemic colitis proven by colonoscopy and pathologic findings. The patient's condition improved after general supportive care including bowel rest, intravenous fluids, and intravenous antibiotics. No similar event has been reported since he resumed chemotherapy without bevacizumab.
Anti-Bacterial Agents ; Bevacizumab ; Colitis, Ischemic* ; Colonoscopy* ; Drug Therapy ; Humans ; Intestinal Perforation ; Male ; Middle Aged ; Vascular Endothelial Growth Factor A

OBJECTIVE: To evaluate the frequency and adequacy of statistical analyses in a general radiology journal when reporting a reliability analysis for a diagnostic test. MATERIALS AND METHODS: Sixty-three studies of diagnostic test accuracy (DTA) and 36 studies reporting reliability analyses published in the Korean Journal of Radiology between 2012 and 2016 were analyzed. Studies were judged using the methodological guidelines of the Radiological Society of North America-Quantitative Imaging Biomarkers Alliance (RSNA-QIBA), and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative. DTA studies were evaluated by nine editorial board members of the journal. Reliability studies were evaluated by study reviewers experienced with reliability analysis. RESULTS: Thirty-one (49.2%) of the 63 DTA studies did not include a reliability analysis when deemed necessary. Among the 36 reliability studies, proper statistical methods were used in all (5/5) studies dealing with dichotomous/nominal data, 46.7% (7/15) of studies dealing with ordinal data, and 95.2% (20/21) of studies dealing with continuous data. Statistical methods were described in sufficient detail regarding weighted kappa in 28.6% (2/7) of studies and regarding the model and assumptions of intraclass correlation coefficient in 35.3% (6/17) and 29.4% (5/17) of studies, respectively. Reliability parameters were used as if they were agreement parameters in 23.1% (3/13) of studies. Reproducibility and repeatability were used incorrectly in 20% (3/15) of studies. CONCLUSION: Greater attention to the importance of reporting reliability, thorough description of the related statistical methods, efforts not to neglect agreement parameters, and better use of relevant terminology is necessary.
Biomarkers ; Diagnostic Tests, Routine* ; Methods*