The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics project since 2003. Its aim is to construct a toxicology database of 12 compounds administered to mice at initial phase. We chose 6-MP (6-mercaptopurine) which has been used in the treatment of childhood leukemia. It was administered at low (0.224 mg/kg) and at high (2.24 mg/kg) dose (5 mice per group) intraperitonealy to the postnatal 6 weeks mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after scarification. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to 6-MP induced toxicity, including lipid metabolism abnormality, inflammatory response, oxidative stress, ATP depletion and cell death. The potential toxic effects appearing as gene expression changes are dependent of the time of 6-MP but independent of the dosage of it. This study would contribute to establishment of international database as well as national one about hepatotoxicity.
Adenosine Triphosphate ; Animals ; Cell Death ; Gene Expression Profiling* ; Gene Expression* ; Genome ; Leukemia ; Lipid Metabolism ; Liver* ; Mice ; Microarray Analysis ; Oxidative Stress ; Toxicogenetics ; Toxicology ; Biomarkers

OBJECTIVE: To develop a scoring system stratifying the malignancy risk of mammographic microcalcifications using the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS).MATERIALS AND METHODS: One hundred ninety-four lesions with microcalcifications for which surgical excision was performed were independently reviewed by two radiologists according to the 5th edition of BI-RADS. Each category's positive predictive value (PPV) was calculated and a scoring system was developed using multivariate logistic regression. The scores for benign and malignant lesions or BI-RADS categories were compared using an independent t test or by ANOVA. The area under the receiver operating characteristic curve (AUROC) was assessed to determine the discriminatory ability of the scoring system. Our scoring system was validated using an external dataset.RESULTS: After excision, 69 lesions were malignant (36%). The PPV of BI-RADS descriptors and categories for calcification showed significant differences. Using the developed scoring system, mean scores for benign and malignant lesions or BI-RADS categories were significantly different (p < 0.001). The AUROC of our scoring system was 0.874 (95% confidence interval, 0.840–0.909) and the PPV of each BI-RADS category determined by the scoring system was as follows: category 3 (0%), 4A (6.8%), 4B (19.0%), 4C (68.2%), and 5 (100%). The validation set showed an AUROC of 0.905 and PPVs of 0%, 8.3%, 11.9%, 68.3%, and 94.7% for categories 3, 4A, 4B, 4C, and 5, respectively.CONCLUSION: A scoring system based on BI-RADS morphology and distribution descriptors could be used to stratify the malignancy risk of mammographic microcalcifications.
Breast Neoplasms ; Breast ; Dataset ; Information Systems ; Logistic Models ; Mammography ; ROC Curve ; Subject Headings

PURPOSE: Intramedullary spinal lesions in the conus medullaris (CM), including tumors and vascular lesion, are rarely reported. We reported various MR features of intramedullary spinal cord lesions involving the CM including ependymoma, hemangioblastomas, dermoid cyst, ventriculus terminalis and spinal AVF and tried to discuss them for differential diagnosis. MATERIALS AND METHODS: Six patients (male: female = 4:2, mean age = 44.3 year old) were enrolled from the clinical database of our institute from 2004 to 2010 and their radiological images and clinical symptoms were reviewed retrospectively. All patients had taken initial and postoperative MRI with contrast enhancement using gadopentate dimeglumine (Gd-DTPA). These images were analyzed by tumor size, location, signal intensity relative to the spinal cord, vascular flow voids, syrinx or cyst, edema and enhancement pattern. RESULTS: Contrast enhancement was seen in all intramedullary masses. An eccentric enhancing nodule was noted in two hemangioblastomas and unusual peripheral rim enhancement with septation was seen in ventriculus terminalis. Patchy enhancement of the CM was observed in spinal arteriovenous fistula (AVF). Extensive cord edema adjacent to the intramedullary lesions was seen in four cases and syrinx was noted in three cases. Vascular signal voids were found in two hemangioblastomas and one spinal AVF. CONCLUSION: In evaluation of intramedullary spinal lesions in the CM, it is necessary to consider these unusual MR findings and discriminate various pathologies with prudence and caution.
Arteriovenous Fistula ; Conus Snail* ; Dermoid Cyst ; Diagnosis, Differential* ; Edema ; Ependymoma ; Female ; Hemangioblastoma ; Humans ; Magnetic Resonance Imaging* ; Pathology ; Retrospective Studies ; Spinal Cord

PURPOSE: The goal of this study was to assess the clinicopathologic and ultrasonographic features of thyroid nodules with nondiagnostic results on repeat ultrasonography (US)-guided fineneedle aspiration biopsy (FNAB) according to size and the number of suspicious findings and to determine the proper management of nodules with consecutive nondiagnostic results. METHODS: This retrospective study included 297 nodules with nondiagnostic results on repeat FNAB that were evaluated by US over the course of at least 12 months of follow-up, a follow-up biopsy, or an operation. We compared clinical and US variables between benign and malignant nodules in thyroid nodules with repeat nondiagnostic results. RESULTS: The comparison of benign and malignant nodules with repeat nondiagnostic results revealed that age, marked hypoechogenicity, irregular or microlobulated margins, microcalcifications, and nonparallel shape were significantly associated with malignancy. Multivariate logistic regression analysis in malignant nodules revealed that microcalcifications and irregular or microlobulated margins were independently associated with malignancy. Among them, only irregular or microlobulated margins were independently significant as a predictor of malignancy in repeatedly nondiagnostic nodules measuring >10 mm. Using receiver operating characteristic analysis, the best cutoff value for the "number of suspicious findings" between benign and malignant nodules was three in nodules of all sizes, three in nodules measuring ≤10 mm, and two in nodules measuring >10 mm. CONCLUSION: Irregular or microlobulated margins may be the most frequent US features in repeatedly nondiagnostic nodules >10 mm. The presence of "two or more suspicious findings" can be used as the cutoff for distinguishing benign and malignant nodules.
Biopsy* ; Biopsy, Fine-Needle* ; Biopsy, Needle ; Follow-Up Studies* ; Logistic Models ; Retrospective Studies ; ROC Curve ; Thyroid Gland* ; Thyroid Nodule* ; Ultrasonography

OBJECTIVE: To determine which preoperative breast magnetic resonance imaging (MRI) findings and clinicopathologic features are associated with positive resection margins at the time of breast-conserving surgery (BCS) in patients with breast cancer. MATERIALS AND METHODS: We reviewed preoperative breast MRI and clinicopathologic features of 120 patients (mean age, 53.3 years; age range, 27–79 years) with breast cancer who had undergone BCS in 2015. Tumor size on MRI, multifocality, patterns of enhancing lesions (mass without non-mass enhancement [NME] vs. NME with or without mass), mass characteristics (shape, margin, internal enhancement characteristics), NME (distribution, internal enhancement patterns), and breast parenchymal enhancement (BPE; weak, strong) were analyzed. We also evaluated age, tumor size, histology, lymphovascular invasion, T stage, N stage, and hormonal receptors. Univariate and multivariate logistic regression analyses were used to determine the correlation between clinicopathological features, MRI findings, and positive resection margins. RESULTS: In univariate analysis, tumor size on MRI, multifocality, NME with or without mass, and segmental distribution of NME were correlated with positive resection margins. Among the clinicopathological factors, tumor size of the invasive breast cancer and in situ components were significantly correlated with a positive resection margin. Multivariate analysis revealed that NME with or without mass was an independent predictor of positive resection margins (odds ratio [OR] = 7.00; p < 0.001). Strong BPE was a weak predictor of positive resection margins (OR = 2.59; p = 0.076). CONCLUSION: Non-mass enhancement with or without mass is significantly associated with a positive resection margin in patients with breast cancer. In patients with NME, segmental distribution was significantly correlated with positive resection margins.
Breast Neoplasms* ; Breast* ; Humans ; Logistic Models ; Magnetic Resonance Imaging* ; Mastectomy, Segmental ; Multivariate Analysis ; Retrospective Studies*

Granular corneal dystrophy, type II (CGD2; Avellino corneal dystrophy) is the most common corneal dystrophy among Koreans, but its pathophysiology is still poorly understood. Many reports showed that even though the causative mutation is the same TGFBI R124H mutation, there are severe and mild phenotypes of the corneal dystrophy. We also observed the phenotype differences in our samples. For this reason, we focused our effort on the identification of unknown genetic factor related to phenotype variation. A total 551 individuals from 59 families were genotyped with SNP chip and used in genome-wide linkage analysis. From single-point linkage analyses, we confirmed the known 5q31 region for TGFBI gene, and selected novel nine candidate loci for CGD2. In simulation analysis, the only 3q26.3 region including neuroligin 1 gene (NLGN1) was supported by empirical statistic significance. To investigate the effect of genetic heterogeneity in linkage analysis, we classified CGD2 families into two subgroups. Although we could not find a significant evidence for correlation between the 3q26.3 region and CGD2 phenotypes, this first genome-wide analysis with CGD2 families in Korea has a very important value for offering insights in genetics of CGD2. In addition, the co-segregating loci with CGD2 including 3q26.3 would be a good target for further study to understand the pathophysiology of CGD2.
Cell Adhesion Molecules, Neuronal/genetics ; Chromosomes, Human, Pair 3/*genetics ; Chromosomes, Human, Pair 5/*genetics ; Computer Simulation ; Corneal Dystrophies, Hereditary/*genetics ; Female ; Genetic Linkage ; *Genetic Loci ; *Genome-Wide Association Study ; Genotype ; Humans ; Male ; Models, Genetic ; Polymorphism, Single Nucleotide ; Transforming Growth Factor beta1/genetics

A 62-year-old man was admitted, and thoracic endovascular aortic repair (TEVAR) procedure was performed to treat an accidentally detected aortic aneurysm, which was 63 mm in diameter. While performing TEVAR, the passage of the stent-graft introducer system was impossible due to the prolapse of the introducer system into a wide-necked aneurysm; this aneurysm was located at the greater curvature of the proximal descending thoracic aorta. In order to advance the introducer system, a compliant balloon was inflated. Thus, we created an artificial wall in the aneurysm with this inflated balloon. Finally, we were able to advance the introducer system into the target zone.
*Angioplasty, Balloon ; Angioplasty, Balloon, Coronary/*methods ; Aortic Aneurysm, Thoracic/radiography/*surgery ; Blood Vessel Prosthesis Implantation/*methods ; Endovascular Procedures/*methods ; Humans ; Male ; Middle Aged ; *Stents ; Tomography, X-Ray Computed

OBJECTIVE: To evaluate retrospectively the clinical effectiveness of FlightPlan for Liver (FPFL), an automated tumor-feeding artery detection software in cone-beam CT angiography (CBCTA), in identifying tumor-feeding arteries for the treatment of hepatocellular carcinoma (HCC) using three different segmentation sensitivities. MATERIALS AND METHODS: The study included 50 patients with 80 HCC nodules who received transarterial chemoembolization. Standard digital subtracted angiography (DSA) and CBCTA were systematically performed and analyzed. Three settings of the FPFL software for vascular tree segmentation were tested for each tumor: the default, Group D; adjusting the proportion of segmented tumor area between 30 to 50%, Group L; and between 50 to 80%, Group H. RESULTS: In total, 109 feeder vessels supplying 80 HCC nodules were identified. The negative predictive value of DSA, FPFL in groups D, L, and H was 56.8%, 87.7%, 94.2%, 98.5%, respectively. The accuracy of DSA, FPFL in groups D, L, and H was 62.6%, 86.8%, 93.4%, 95.6%, respectively. The sensitivity, negative predictive value (NPV), and accuracy of FPFL were higher in Group H than in Group D (p = 0.041, 0.034, 0.005). All three segmentation sensitivity groups showed higher specificity, positive predictive value, NPV, and accuracy of FPFL, as compared to DSA. CONCLUSION: FlightPlan for Liver is a valuable tool for increasing detection of HCC tumor feeding vessels, as compared to standard DSA analysis, particularly in small HCC. Manual adjustment of segmentation sensitivity improves the accuracy of FPFL.
Angiography ; Arteries ; Carcinoma, Hepatocellular* ; Cone-Beam Computed Tomography ; Humans ; Liver ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; Trees

A 66-year-old female who had undergone surgery for a herniated disc at the L5-S1 level at another hospital 3 months earlier was admitted with persistent back and leg pain. She was diagnosed with spondylodiscitis at the L5-S1 level by magnetic resonance imaging. A biopsy was performed, and Candida parapsilosis and Enterococcus faecium were isolated from the excised material. We report herein a case of successful treatment of polymicrobial spondylodiscitis in accordance with accurate microbiological diagnosis. Based on this case, we hope to encourage physicians to perform biopsies more aggressively or repeatedly to improve the diagnostic yield.
Aged ; Biopsy ; Candida ; Coinfection ; Diagnosis ; Discitis* ; Enterococcus faecium ; Female ; Hope ; Humans ; Intervertebral Disc Displacement ; Leg ; Magnetic Resonance Imaging

Here we present a rare case of pulmonary arterial thrombosis associated with a ductus arteriosus aneurysm that caused severe pulmonary stenosis. A 5-day-old newborn was admitted to our hospital for the evaluation of an intracardiac mass-like lesion found after the detection of a cardiac murmur. Echocardiography and heart computed tomography revealed a mass-like lesion measuring 8.1 mm in diameter across the distal main pulmonary artery to the proximal left pulmonary artery resulting in localized severe stenosis of the left pulmonary artery. Left pulmonary artery angioplasty for surgical resection of the thrombus revealed that the mass was adherent to the proximal part of the left pulmonary artery anterior wall and extended to the ductus arteriosus. Histological examination of the mass showed an old thrombus with dystrophic calcification. Five months after surgery, follow-up echocardiography showed that the left pulmonary artery peak pressure gradient had decreased but the proximal left pulmonary artery stenosis remained. Cardiac catheterization and balloon angioplasty suc cessfully relieved the pulmonary stenosis.