Comparative analysis of human Wharton's jelly mesenchymal stem cells derived from different parts of the same umbilical cord.

Easy isolation, lack of ethical issues, high proliferation, multi-lineage differentiation potential and immunomodulatory properties of umbilical cord (UC)-derived mesenchymal stem cells (MSCs) make them a valuable tool in stem cell research. Recently, Wharton's jelly (WJ) was proven as the best MSC source among various compartments of UC. However, it is still unclear whether or not Wharton's jelly-derived MSCs (WJMSCs) from different parts of the whole cord exhibit the same characteristics. There may be varied MSCs present in different parts of WJ throughout the length of the UC. For this purpose, using an explant attachment method, WJMSCs were isolated from three different parts of the UC, mainly present towards the placenta (mother part), the center of the whole cord (central part) and the part attached to the fetus (baby part). WJMSCs from all three parts were maintained in normal growth conditions (10% ADMEM) and analyzed for mesenchymal markers, pluripotent genes, proliferation rate and tri-lineage differentiation potential. All WJMSCs were highly proliferative, positively expressed CD90, CD105, CD73 and vimentin, while not expressing CD34, CD45, CD14, CD19 or HLA-DR, differentiated into adipocytes, osteocytes and chondrocytes and expressed pluripotency markers OCT-4, SOX-2 and NANOG at gene and protein levels. Furthermore, MSCs derived from all the parts were shown to have potency towards hepatocyte-like cell differentiation. Human bone marrow-derived MSCs were used as a positive control. Finally, we conclude that WJMSCs derived from all the parts are valuable sources and can be efficiently used in various fields of regenerative medicine.

Multivalent ion-based in situ gelling polysaccharide hydrogel as an injectable bone graft.

We prepared in situ gelling alginate (ALG)/hyaluronic acid (HA) hydrogels with a controllable gelation rate using CaSO4 as a crosslinking agent and Na2HPO4 as a crosslinking retardation agent. The ALG/HA hydrogels provided sustained release of bone morphogenetic protein-2 (BMP-2) immobilized in the hydrogels over 5 weeks. The BMP-2-immobilized ALG/HA hydrogels with different ALG/HA ratios were investigated for their in vitro osteogenic differentiation behavior of human bone marrow stem cells (hBMSCs) and in vivo bone regeneration behavior using an animal model (mandibular defect model of miniature pigs). Our findings from cell culture and animal study demonstrated that the osteogenic differentiation of hBMSCs was improved with increasing HA composition in the hydrogel. The hBMSCs/BMP-2-immobilized ALG/HA hydrogel allowed greatly enhanced osteogenic differentiation of hBMSCs (in vitro) and bone regeneration (in vivo) compared with the ALG/HA hydrogel itself and single hBMSCs- or BMP-2-immobilized hydrogel groups.

The involvement of histone methylation in osteoblastic differentiation of human periosteum-derived cells cultured in vitro under hypoxic conditions.

Although oxygen concentrations affect the growth and function of mesenchymal stem cells (MSCs), the impact of hypoxia on osteoblastic differentiation is not understood. Likewise, the effect of hypoxia-induced epigenetic changes on osteoblastic differentiation of MSCs is unknown. The aim of this study was to examine the in vitro hypoxic response of human periosteum-derived cells (hPDCs). Hypoxia resulted in greater proliferation of hPDCs as compared with those cultured in normoxia. Further, hypoxic conditions yielded decreased expression of apoptosis- and senescence-associated genes by hPDCs. Osteoblast phenotypes of hPDCS were suppressed by hypoxia, as suggested by alkaline phosphatase activity, alizarin red-S-positive mineralization, and mRNA expression of osteoblast-related genes. Chromatin immunoprecipitation assays showed an increased presence of H3K27me3, trimethylation of lysine 27 on histone H3, on the promoter region of bone morphogenetic protein-2. In addition, mRNA expression of histone lysine demethylase 6B (KDM6B) by hPDCs was significantly decreased in hypoxic conditions. Our results suggest that an increased level of H3K27me3 on the promoter region of bone morphogenetic protein-2, in combination with downregulation of KDM6B activity, is involved in the suppression of osteogenic phenotypes of hPDCs cultured in hypoxic conditions. Although oxygen tension plays an important role in the viability and maintenance of MSCs in an undifferentiated state, the effect of hypoxia on osteoblastic differentiation of MSCs remains controversial. In addition, evidence regarding the importance of epigenetics in regulating MSCs has been limited. This study was to examine the role hypoxia on osteoblastic differentiation of hPDCs, and we examined whether histone methylation is involved in the observed effect of hypoxia on osteogenic differentiation of hPDCs.

In vitro and long-term (2-year follow-up) in vivo osteogenic activities of human periosteum-derived osteoblasts seeded into growth factor-releasing polycaprolactone/pluronic F127 beads scaffolds.

Polycaprolactone (PCL) is a biodegradable polyester that is bioresorbable and biocompatible, and is widely used in medical fields. This study examines in vitro and in vivo osteogenic activities of cultured human periosteum-derived osteoblasts (POs) seeded into growth factor (bone morphogenic protein 2 [BMP-2] or vascular endothelial growth factor [VEGF])-releasing scaffolds of PCL beads coated with Pluronic F127. Each growth factor immobilized in the PCL/F127 is cumulatively released from the beads for more than 40 days (up to 3.04 ± 0.08 ng mg-1 BMP-2 and 3.41 ± 0.18 ng mg-1 VEGF in 42 days). Long-term (∼2 years) experimental results obtained in a miniature pig model suggest that POs seeded into BMP-2 + VEGF-releasing PCL/P-F127 beads are the most effective for bone repair. In in vitro assays, osteogenic activities were higher in POs seeded into BMP-2-releasing PCL/Pluronic F127 beads at earlier time points and in POs seeded into BMP-2 + VEGF-releasing PCL/Pluronic F127 beads at later time points. These results suggest that the combination of BMP-2 and VEGF more sufficiently stimulates (in particular at late time points) osteoblast differentiation of POs seeded in the PCL/F127 in vitro and in vivo, and thus allows effective bone regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 363-376, 2017.

Isolation and Cellular Phenotyping of Mesenchymal Stem Cells Derived from Synovial Fluid and Bone Marrow of Minipigs.

Mesenchymal stem cells (MSCs) have been established after isolation from various tissue sources, including bone marrow and synovial fluid. Recently, synovial-fluid-derived MSCs were reported to have multi-lineage differentiation potential and immunomodulatory features, which indicates that these cells can be used for tissue engineering and systemic treatments. This study presents a protocol for simple and non-invasive isolation of MSCs derived from the bone marrow and synovial fluid of minipigs to analyze cell surface markers for cell phenotyping and in vitro culturing. Using sexually mature six-month-old minipigs, bone marrow was extracted from the iliac crest bone using a bone marrow extractor, and the synovial fluid was aspirated from the femorotibial joint. Procedures for the collection of samples from both sources were non-invasive. The protocols for effective isolation of MSCs from harvested cell sources and for creating in vitro culture conditions to expand stable MSCs from minipigs and the application of systemic autologous treatments are provided. For cell phenotyping, the cell surface markers of both cells were analyzed using flow cytometry. In the results, the MSCs were isolated from the synovial fluid of the minipigs and showed that synovial-fluid-derived MSCs have a similar morphology and cell phenotype to bone-marrow-derived MSCs. Therefore, non-invasively obtained synovial fluid is a valuable source of MSCs.

DMSO- and Serum-Free Cryopreservation of Wharton's Jelly Tissue Isolated From Human Umbilical Cord.

The facile nature of mesenchymal stem cell (MSC) acquisition in relatively large numbers has made Wharton's jelly (WJ) tissue an alternative source of MSCs for regenerative medicine. However, freezing of such tissue using dimethyl sulfoxide (DMSO) for future use impedes its clinical utility. In this study, we compared the effect of two different cryoprotectants (DMSO and cocktail solution) on post-thaw cell behavior upon freezing of WJ tissue following two different freezing protocols (Conventional [-1°C/min] and programmed). The programmed method showed higher cell survival rate compared to conventional method of freezing. Further, cocktail solution showed better cryoprotection than DMSO. Post-thaw growth characteristics and stem cell behavior of Wharton's jelly mesenchymal stem cells (WJMSCs) from WJ tissue cryopreserved with a cocktail solution in conjunction with programmed method (Prog-Cock) were comparable with WJMSCs from fresh WJ tissue. They preserved their expression of surface markers, pluripotent factors, and successfully differentiated in vitro into osteocytes, adipocytes, chondrocytes, and hepatocytes. They also produced lesser annexin-V-positive cells compared to cells from WJ tissue stored using cocktail solution in conjunction with the conventional method (Conv-Cock). Real-time PCR and Western blot analysis of post-thaw WJMSCs from Conv-Cock group showed significantly increased expression of pro-apoptotic factors (BAX, p53, and p21) and reduced expression of anti-apoptotic factor (BCL2) compared to WJMSCs from the fresh and Prog-Cock group. Therefore, we conclude that freezing of fresh WJ tissue using cocktail solution in conjunction with programmed freezing method allows for an efficient WJ tissue banking for future MSC-based regenerative therapies. J. Cell. Biochem. 117: 2397-2412, 2016. © 2016 Wiley Periodicals, Inc.

In vitro comparative analysis of human dental stem cells from a single donor and its neuronal differentiation potential evaluated by electrophysiology.

AIMS: The aim of this study was to find out a mesenchymal stem cells (MSCs) source from human dental tissues of the same donor (follicle, papilla and pulp), which exhibits higher neurogenic differentiation potential in vitro. MAIN METHODS: MSCs were isolated from dental tissues (follicle, papilla and pulp) by digestion method. All MSCs were analyzed for pluripotent makers by western blot, cell surface markers by flow cytometry, adipo- and osteocytes markers by RT-qPCR. The neuronal differentiated MSCs were characterized for neuronal specific markers by RT-qPCR and immunofluorescence. Functional neuronal properties were analyzed by electrophysiology and synaptic markers expression. KEY FINDINGS: All MSCs expressed pluripotent markers (Oct4, Sox2 and Nanog) and were found positive for mesenymal markers (CD44, CD90, CD105) while negative for hematopoietic markers (CD34 and CD45). Furthermore, MSCs were successfully differentiated into adipocytes, osteocytes and trans-differentiated into neuronal cells. Among them, dental pulp derived MSCs exhibits higher neurogenic differentiation potential, in term of expression of neuronal specific markers at both gene and protein level, and having higher Na(+) and K(+) current with the expression of synaptic markers. SIGNIFICANCE: The three types of dental MSCs from a single donor broadly possessed similar cellular properties and can differentiate into neuronal cells; however, pulp derived MSCs showed higher neurogenic potential than the follicle and papilla, suggesting their use in future stem cells therapy for the treatment of neurodegenerative disorders.

Disarming an Electrophilic Warhead: Retaining Potency in Tyrosine Kinase Inhibitor (TKI)-Resistant CML Lines While Circumventing Pharmacokinetic Liabilities.

Pharmacologic blockade of the activation of signal transducer and activator of transcription 3 (STAT3) in tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML) cell lines characterized by kinase-independent resistance was shown to re-sensitize CML cells to TKI therapy, suggesting that STAT3 inhibitors in combination with TKIs are an effective combinatorial therapeutic for the treatment of CML. Benzoic acid- and hydroxamic acid-based STAT3 inhibitors SH-4-054 and SH-5-007, developed previously in our laboratory, demonstrated promising activity against these resistant CML cell lines. However, pharmacokinetic studies in murine models (CD-1 mice) revealed that both SH-4-054 and SH-5-007 are susceptible to glutathione conjugation at the para position of the pentafluorophenyl group via nucleophilic aromatic substitution (SN Ar). To determine whether the electrophilicity of the pentafluorophenyl sulfonamide could be tempered, an in-depth structure-activity relationship (SAR) study of the SH-4-054 scaffold was conducted. These studies revealed that AM-1-124, possessing a 2,3,5,6-tetrafluorophenylsulfonamide group, retained STAT3 protein affinity (Ki =15 µm), as well as selectivity over STAT1 (Ki >250 µm). Moreover, in both hepatocytes and in in vivo pharmacokinetic studies (CD-1 mice), AM-1-124 was found to be dramatically more stable than SH-4-054 (t1/2 =1.42 h cf. 10 min, respectively). AM-1-124 is a promising STAT3-targeting inhibitor with demonstrated bioavailability, suitable for evaluation in preclinical cancer models.

Evaluation of phenotypic, functional and molecular characteristics of porcine mesenchymal stromal/stem cells depending on donor age, gender and tissue source.

The biological properties of mesenchymal stem cells (MSCs) are influenced by donor age, gender and/or tissue sources. The present study investigated the cellular and molecular properties of porcine mesenchymal stromal/stem cells (MSCs) isolated from different tissues (adipose & dermal skin) and sex at different ages (1 week & 8 months after birth) with similar genetic and environmental backgrounds. MSCs were analyzed for alkaline phosphatase (AP) activity, CD90 and Oct3/4 expression, in vitro differentiation ability, senescence-associated ß-galactosidase (SA-ß-Gal) activity, telomeric properties, cell cycle status and expression of senescence (IL6, c-myc, TGFß, p53 and p21)- and apoptosis (Bak and Bcl2)-related proteins. An age-dependent decline in AP activity and adipogenesis was observed in all MSCs, except for male A-MSCs. CD90 expression did not change, but SA-ß-Gal activity increased with advancement in age, except in A-MSCs. Telomeric properties were similar in all MSCs, whereas expression levels of Oct3/4 protein declined with the advancement in age. p21 expression was increased with increase in donor age. Male derived cells have shown higher IL6 expression. The expression of p53 was slightly lower in MSCs of dermal tissue than in adipose tissue. Bak was expressed in all MSCs regardless of age, but up regulation of Bcl2 was observed in DS-MSCs derived at 1 week after birth. In conclusion, adipose tissue-derived MSCs from young female individuals were found to be more resistant to senescence under in vitro culture conditions.

Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs.

The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1ß and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1ß levels in CIA mice.

Imaging features of benign adenomyoepithelioma of the breast.

PURPOSE: The purpose of our study was to evaluate the imaging features of benign adenomyoepithelioma of the breast with a focus on sonographic (US) appearances. METHODS: Ten benign adenomyoepitheliomas in 9 patients were included in this study. Mammographic and US findings were analyzed retrospectively by 2 radiologists according to the Breast Imaging-Reporting and Data System (BI-RADS) lexicon. The BI-RADS final assessment category was also recorded. RESULTS: Of the 8 lesions for which mammography was available, 4 lesions presented with abnormal findings. Two lesions presented with an indistinct, irregular, isodense mass and a circumscribed, oval, isodense mass. The other 2 lesions presented with areas of focal asymmetry and asymmetry, respectively. On US, all of 10 lesions presented as a mass. The masses measured 0.5-1.2 cm (mean, 0.8 cm), were irregular (n = 8) or oval (n = 2) with microlobulated (n = 5), indistinct (n = 3), or angular (n = 2) margins. They were all hypoechoic, had non parallel orientation in 6 cases, and increased peripheral vascularity in 7 cases. The BI-RADS final assessment category was 4B in 6, and 4A in 4. CONCLUSIONS: Mammographic findings of benign adenomyoepithelioma were nonspecific. An irregular, non parallel orientation, microlobulated or indistinct margin, hypoechogenicity, and increased peripheral vascularity were the most frequent US features.

Imaging-pathologic correlation of diseases in the axilla.

OBJECTIVE: This article reviews the imaging and histopathologic findings of various axillary diseases and suggests management guidelines for radiologists based on imaging findings with clinical correlation. CONCLUSION: Although axillary diseases may reveal nonspecific imaging findings, a knowledge of the characteristic radiologic manifestations of specific diseases according to anatomic origin (nodal, accessory breast, adipocytic, fibrous, nerve, vascular, stromal, and dermal) and postsurgical lesions aids in establishing an appropriate differential diagnosis and determining whether intervention is necessary.

Periductal mastitis mimicking breast cancer in a male breast.

Periductal mastitis in a male patient rarely has been reported in the English literature. Herein, we now present a rare case of periductal mastitis mimicking breast cancer, both clinically and radiologically, in a 37-year-old man. Mammogram and sonogram showed a mass with irregular shape, spiculated margin and a nipple retraction, mimicking a male breast cancer. Radiologic and pathologic correlation is provided.

Can symptomatic acromioclavicular joints be differentiated from asymptomatic acromioclavicular joints on 3-T MR imaging?

OBJECTIVE: To evaluate retrospectively whether symptomatic acromioclavicular joints can be differentiated from asymptomatic acromioclavicular joints on 3-T MR imaging. METHODS: This study included 146 patients who underwent physical examination of acromioclavicular joints and 3-T MR imaging of the shoulder. Among them, 67 patients showing positive results on physical examination were assigned to the symptomatic group, whereas 79 showing negative results were assigned to the asymptomatic group. The following MR findings were compared between the symptomatic and asymptomatic groups: presence of osteophytes, articular surface irregularity, subchondral cysts, acromioclavicular joint fluid, subacromial fluid, subacromial bony spurs, joint capsular distension, bone edema, intraarticular enhancement, periarticular enhancement, superior and inferior joint capsular distension degree, and joint capsular thickness. The patients were subsequently divided into groups based on age (younger, older) and the method of MR arthrography (direct MR arthrography, indirect MR arthrography), and all the MR findings in each subgroup were reanalyzed. The meaningful cutoff value of each significant continuous variable was calculated using receiver operating characteristic analysis. RESULTS: The degree of superior capsular distension was the only significant MR finding of symptomatic acromioclavicular joints and its meaningful cutoff value was 2.1mm. After subgroup analyses, this variable was significant in the older age group and indirect MR arthrography group. CONCLUSION: On 3-T MR imaging, the degree of superior joint capsular distension might be a predictable MR finding in the diagnosis of symptomatic acromioclavicular joints.

Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation.

We previously reported that MSTO-211H cells have a higher capacity to regulate Nrf2 activation in response to changes in the cellular redox environment. To further characterize its biological significance, the response of Nrf2, a transcription factor that regulates ARE-containing genes, on the synergistic cytotoxic effect of clofarabine and resveratrol was investigated in mesothelioma cells. The combination treatment showed a marked growth-inhibitory effect, which was accompanied by suppression of Nrf2 activation and decreased expression of heme oxygenase-1 (HO-1). While transient overexpression of Nrf2 conferred protection against the cytotoxicity caused by their combination, knockdown of Nrf2 expression using siRNA enhanced their cytotoxic effect. Pretreatment with Ly294002, a PI3K inhibitor, augmented the decrease in HO-1 level by their combination, whereas no obvious changes were observed in Nrf2 levels. Altogether, these results suggest that the synergistic cytotoxic effect of clofarabine and resveratrol was mediated, at least in part, through suppression of Nrf2 signaling.

The prevalence and features of thyroid pyramidal lobes as assessed by computed tomography.

BACKGROUND: The pyramidal lobe is an accessory lobe of the thyroid gland. The prevalence of the pyramidal lobe in thyroid glands and its features have been studied in autopsy series but there is little information regarding its parameters in patients or normal subjects. The purpose of the current study was to assess the frequency, location, and size of the pyramidal lobe using computed tomography (CT) of the neck. METHODS: From January to December 2010, 327 patients who underwent neck CT for trauma, thyroid cancer, pharyngolaryngeal malignancy, a palpable neck mass, cervical lymphadenopathy, and vocal cord paralysis were enrolled in the study. Their neck CTs were retrospectively analyzed by a single radiologist. Small pyramidal lobes (<9 mm) were not included in the study. RESULTS: A pyramidal lobe was present in 41.3% (135/327) of the patients; some pyramidal lobes showed complete separation from the thyroid gland (12.6%, 17/135). There was no difference in the frequency of pyramidal lobe detection by gender (p>0.05, Fisher's exact test). The pyramidal lobe predominantly originated from the left thyroid gland in 54.1% (73/135) of patients. There were two patients in whom the pyramidal lobe was located bilaterally (one case from both the right and left sides of the thyroid gland and one case from the left side and midline of the thyroid gland). The average length and volume of the pyramidal lobes were 25.0 mm and 129.4 mm(3), respectively. The upper margin of the pyramidal lobe was most commonly located at the level of the thyroid cartilage. CONCLUSION: The prevalence of the pyramidal lobe in the left lobe of the thyroid gland is somewhat greater than 50% using the criteria employed in this study. Neck CT is useful for detecting the presence, size, configuration, and location of the pyramidal lobe.

Ultrasonography-guided fine-needle aspiration cytology for thyroid nodules: an emphasis on one-sampling and biopsy techniques.

The aim of this study was to assess the adequacy and efficacy of ultrasonography (US)-guided fine-needle aspiration cytology (US-FNAC) with one-sampling technique (only one specimen through a single needle pass was obtained during the procedure on each thyroid nodule in each study patient) for the cytological diagnosis of thyroid nodules. In this study, US-FNAC techniques, including "free two-hand," "mixed sampling," "flipping-extraction," and "single-needle-pass" procedures were used to collect thyroid cells from July 2007 to June 2009. The cytopathology results and patients' complications were reviewed retrospectively. Of the 1456 thyroid-nodule samples obtained from 977 patients (1.49 per patient), the incidence of adequate and inadequate samplings was 88.5% (1289/1456) and 11.5% (167/1456), respectively. After thyroid surgery in 396 patients, 568 nodules were confirmed as 353 papillary thyroid carcinomas including one diffuse sclerosing variant, five follicular thyroid carcinomas, three medullary thyroid carcinomas, one anaplastic thyroid carcinoma, one metastatic renal cell carcinoma, two poorly differentiated carcinomas, 17 follicular adenomas, two nodular thyroiditis, two pseudonodules related to thyroiditis, and 182 cases of nodular hyperplasia. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false-negative rate, and false-positive rate for the US-FNAC were 94.3%, 91.9%, 96.2%, 88.3%, 93.6%, 3.9%, and 2.6%, respectively. There were no significant patients' complications, but 87 patients (8.9%) reported mild pain during or after the procedure. This study showed a good adequacy and efficacy of US-FNAC for thyroid nodules despite one-sampling.

Thyroid cysts treated with ethanol ablation can mimic malignancy during sonographic follow-up.

PURPOSE: We aimed to assess long-term ultrasound (US) findings after US-guided percutaneous ethanol ablation (EA) in benign thyroid cysts and predominantly cystic thyroid nodules. METHODS: Forty patients with thyroid cysts (n = 14) and predominantly cystic thyroid nodules (n = 26) underwent long-term US follow-up (range, 12-36 months; mean, 18.2 months) after EA. US images of 40 post-EA nodules were retrospectively investigated to study the reduction in nodule volume and detailed US appearance. RESULTS: On follow-up US, post-EA nodules showed the following features: Marked hypoechogenicity (n = 28), spiculated margin (n = 7), microcalcifications (n = 6), taller-than-wide shape (n = 2), centrally predominant vascularity (n = 3), no vascularity (n = 31), mixed vascularity (n = 3), and peripheral vascularity (n = 3). Post-EA nodules were diagnosed by US as benign (n = 3), probably benign (n = 2), borderline (n = 5), possibly malignant (n = 20), and malignant (n = 10). No statistical difference in the incidence of malignant US findings was observed between thyroid cysts and predominantly cystic thyroid nodules (p > 0.05, Fisher's exact test). CONCLUSIONS: Long-term follow-up US after successful EA of benign thyroid cysts and predominantly cystic thyroid nodules revealed a high incidence of findings that are usually associated with malignancy. Recognizing these consequences of the procedure would help avoid unnecessary FNA on post-EA nodules.

Differentiation between benign and malignant solid thyroid nodules using an US classification system.

OBJECTIVE: To evaluate the diagnostic accuracy of a new ultrasound (US) classification system for differentiating between benign and malignant solid thyroid nodules. MATERIALS AND METHODS: In this study, we enrolled 191 consecutive patients who received real-time US and subsequent US diagnoses for solid thyroid nodules, and underwent US-guided fine-needle aspiration. Each thyroid nodule was prospectively classified into 1 of 5 diagnostic categories by real-time US: "malignant," "suspicious for malignancy," "borderline," "probably benign," and "benign". We evaluated the diagnostic accuracy of thyroid US and the cut-off US criteria by comparing the US diagnoses of thyroid nodules with cytopathologic results. RESULTS: Of the 191 solid nodules, 103 were subjected to thyroid surgery. US categories for these 191 nodules were malignant (n = 52), suspicious for malignancy (n = 16), borderline (n = 23), probably benign (n = 18), and benign (n = 82). A receiver-operating characteristic curve analysis revealed that the US diagnosis for solid thyroid nodules using the 5-category US classification system was very good. The sensitivity, specificity, positive and negative predictive values, and accuracy of US diagnosis were 86%, 95%, 91%, 92%, and 92%, respectively, when benign, probably benign, and borderline categories were collectively classified as benign (negative). CONCLUSION: The diagnostic accuracy of thyroid US for solid thyroid nodules is high when the above-mentioned US classification system is applied.

Sonographic findings of high-grade and non-high-grade ductal carcinoma in situ of the breast.

OBJECTIVE: The purpose of this study was to differentiate between high-grade and non-high-grade ductal carcinoma in situ (DCIS) of the breast on sonography. METHODS: From October 2003 to August 2009, 76 DCIS lesions in 73 women who underwent sonography and mammography were included in this study. Lesions were confirmed by mastectomy, breast-conserving surgery, or surgical biopsy. Images were analyzed by 2 radiologists with consensus and were correlated with histologic grades. RESULTS: Of the 76 lesions, 44 were classified as high--grade and 32 as non-high-grade DCIS. Fifty-seven lesions (75.0%) were identified on sonography, which revealed a mass in 30 cases, microcalcifications in 20, ductal changes in 4, and architectural distortion in 3. All cases with false-negative findings on sonography (n = 19) showed microcalcifications on mammography. On sonography, masses were more frequently found in non-high-grade (62.5%) than high-grade DCIS (22.7%; P < .01). No significant difference was seen in the sonographic features of masses between high-grade and non-high-grade DCIS. Microcalcifications were more common in high-grade (43.2%) than non-high-grade (3.1%) DCIS (P = .02). Most sonographically visible microcalcifications had associated findings such as ductal changes (n = 11), a mass (n = 7), or a hypoechoic area (n = 5). The detection rate of microcalcifications on sonography was higher in high-grade (62.9%) than non-high-grade DCIS (25.0%; P = .023). CONCLUSIONS: Microcalcifications with associated ductal changes (11 of 31 [35.5%]) were the most common sonographic findings in high-grade DCIS. An irregular hypoechoic mass with an indistinct and microlobulated margin (13 of 26 [50.0%]) was the most frequent finding in non-high-grade DCIS.