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

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*

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

Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

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

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