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Objective: The purpose of this study was to analyse the lesion characteristics and the patterns of dilated ducts on ultrasonography (US) to determine the appropriateness of the Breast Imaging Reporting and Data System (BI-RADS) categories.Materials and Methods: From July 2001 to June 2006, 172 consecutive pathologically proved lesions with dilated ducts on US were reviewed retrospectively. All the lesions were classified into four types according to their US features, and in combination with the size, location, margins and number of lesions, the corresponding positive predictive values (PPVs) were obtained.Results: Of the 172 lesions, 55 (32%) were classified as type I, 68 (40%) as type II, 14 (8%) as type III and 35 (20%) as type IV. The PPVs for malignancy were 9% for type I, 13% for type II, 43% for type III and 17% for type IV. There was a significantly higher frequency of malignancy among type III lesions than among type I (43% vs 9%, respectively, P = 0.002; chi (2) test) or type II lesions (43% vs 13%, respectively, P = 0.009; chi (2) test). Lesions with a nonsubareolar location and noncircumscribed margins had a high probability of malignancy (P < 0.001 and P = 0.03, respectively).Conclusion: The four types of US classifications used in our study establish reliable references for the dilated duct patterns when stratified according to BI-RADS categories, and they clarify the indications for biopsy of these lesions. [ABSTRACT FROM AUTHOR]

Small vertebrate carcasses represent critical resources for many terrestrial organisms, including burying beetles, which rely on carcasses for survival and breeding. Carcass attributes can influence the reproduction of burying beetles, yet most studies on their breeding ecology have used laboratory-reared carcasses of limited sizes. We conducted breeding and feeding experiments using a wide size range of lab (laboratory mice) and wild carcasses (wild mammals, birds and reptiles) to investigate how carcass size, source and taxon affect various breeding outcomes (e.g. clutch size, brood size and brood mass) of the burying beetle Nicrophorus nepalensis . Our results reveal a hump-shaped relationship between carcass size and breeding performance, with optimal breeding outcomes occurring on medium-sized carcasses. Furthermore, despite the variation in carcass tissue nutritional composition, breeding outcomes and larval growth did not differ between the two carcass sources or among the three wild carcass taxa. Finally, we found a larval quality-quantity trade-off across the range of carcasses examined, with carcass size shaping the larval life-history traits. Overall, these results elucidate how carcass resources may influence the breeding performance of burying beetles. Importantly, our study provides solid evidence validating decades of research using lab carcasses to study the reproductive ecology of burying beetles., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Background: Eliciting host plant resistance using plant hormones such as jasmonates has the potential to protect seeds and seedlings against insect pests; however, several hurdles exist for adapting it for pest management. This includes determining a dose that promotes resistance without limiting plant growth, an application method that growers could use, and ensuring the plants are responsive in the abiotic conditions when the pest occurs. In laboratory and field assays, we tested if treating corn seeds with multiple concentrations of methyl jasmonate would reduce the preference of ovipositing seed corn maggot adults and the performance of larvae feeding on seeds., Results: We found that corn seeds soaked in aqueous 0.2 mM methyl jasmonate solution showed marginally lower seedling growth, but the adult oviposition preference was ~60% lower on these seeds compared to control water-soaked seeds. Seeds that were treated with methyl jasmonate using a conventional polymer-based seed coating showed no effect on seedling growth but reduced adult oviposition preference. In no-choice bioassays with adult flies, we found reduced oviposition on seeds soaked with aqueous methyl jasmonate compared to controls. Larval survival to pupation was also lower in methyl jasmonate-treated seeds. Lastly, the methyl jasmonate-induced resistance also occurred at the lower temperatures typical of the spring soil conditions when this fly is most damaging., Conclusion: Methyl jasmonate seed treatment in aqueous solution or using conventional polymer-based technology, has the potential to deter adult oviposition and reduce maggot performance in spring temperature conditions with minor effects on seed germination and growth. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for ∼60% of CPVT patients which is inherited in an autosomal dominant pattern., Objective: This study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide., Methods: Clinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included., Results: This is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002)., Conclusion: The discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan., Methods: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO., Results: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort., Conclusion: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups., Trail Registration: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019., (© 2024. The Author(s).)

Background: The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan's Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50-69 years since 2004 and for those aged 45-69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004-2009) and latter (2010-2020) periods., Methods: A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs., Results: Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004-2009) and latter (2010-2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83-9.97%) in the early period and decreased to 8.15% (95%CI, 8.13-8.17%) in the latter period., Conclusions: The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs., (© 2023. The Author(s).)

Background: Vascular anomalies and tumors are common in the head, neck, and craniofacial areas and are associated with abnormalities in the angiomatous architecture. However, the etiology and molecular basis for the pathogenesis of most vascular lesions are still unknown. Pericytes are mural cells that surround endothelial cells. Besides angiogenesis and other physiological functions, pericytes play an important role in vascularized tissue repair and as resident mesenchymal stem/progenitor cells. Perivascular cells demonstrate a distinct immunohistochemical profile, including expression of alpha-smooth muscle actin (α-SMA), CD146, CD105, and PDGFRβ, without endothelial differentiation (absence of CD31 and CD34 immunoreactivity). These pericyte markers have been shown to be expressed in soft tissue hemangiomas. However, they have not been fully examined in intraosseous hemangiomas., Methods: In this study, we compared mesenchymal stem cell (MSC) expression of CD146 and α-SMA markers in pericytes from hemangiomas from different tissues and malignant vascular tumors., Results: The results demonstrated an increased expression of pericyte markers in perivascular cells of benign hemangiomas, especially intraosseous hemangiomas and a significantly reduced expression of pericyte markers in malignant angiosarcomas., Conclusion: The evidence provides insight into the function of pericytes in vascular tumors and suggests their role in vascular tumor disease types., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue- and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue-derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.

Heterotopic ossification (HO) is a pathologic process characterized by the formation of bone tissue in extraskeletal locations. The hip is a common location of HO, especially as a complication of arthroplasty. Here, we devise a first-of-its-kind mouse model of post-surgical hip HO and validate expected cell sources of HO using several HO progenitor cell reporter lines. To induce HO, an anterolateral surgical approach to the hip was used, followed by disclocation and acetabular reaming. Animals were analyzed with high-resolution roentgenograms and micro-computed tomography, conventional histology, immunohistochemistry, and assessments of fluorescent reporter activity. All the treated animals' developed periarticular HO with an anatomical distribution similar to human patients after arthroplasty. Heterotopic bone was found in periosteal, inter/intramuscular, and intracapsular locations. Further, the use of either PDGFRα or scleraxis (Scx) reporter mice demonstrated that both cell types gave rise to periarticular HO in this model. In summary, acetabular reaming reproducibly induces periarticular HO in the mouse reproducing human disease, and with defined mesenchymal cellular contributors similar to other experimental HO models. This protocol may be used in the future for further detailing of the cellular and molecular mediators of post-surgical HO, as well as the screening of new therapies., (© The Author(s) 2022. Published by Oxford University Press.)

Intra-articular injection of mesenchymal stem cells has shown benefit for the treatment of osteoarthritis (OA). However, mesenchymal stem/stromal cells at the origin of these clinical results are heterogenous cell populations with limited cellular characterization. Here, two transgenic reporter mice were used to examine the differential effects of two precisely defined perivascular cell populations (Pdgfrα +  and Pdgfrβ +  cells) from white adipose tissue for alleviation of OA. Perivascular mesenchymal cells were isolated from transgenic Pdgfrα-and Pdgfrβ-CreER T2 reporter animals and delivered as a one-time intra-articular dose to C57BL/6J mice after destabilization of the medial meniscus (DMM). Both Pdgfrα +  and Pdgfrβ +  cell preparations improved metrics of cartilage degradation and reduced markers of chondrocyte hypertrophy. While some similarities in cell distribution were identified within the synovial and perivascular spaces, injected Pdgfrα +  cells remained in the superficial layers of articular cartilage, while Pdgfrβ +  cells were more widely dispersed. Pdgfrβ +  cell therapy prevented subchondral sclerosis induced by DMM, while Pdgfrα +  cell therapy had no effect. In summary, while both cell therapies showed beneficial effects in the DMM model, important differences in cell incorporation, persistence, and subchondral sclerosis were identified., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Mesenchymal progenitor cells are broadly distributed across perivascular niches-an observation conserved between species. One common histologic zone with a high frequency of mesenchymal progenitor cells within mammalian tissues is the tunica adventitia, the outer layer of blood vessel walls populated by cells with a fibroblastic morphology. The diversity and functions of (re)generative cells present in this outermost perivascular niche are under intense investigation; we have reviewed herein our current knowledge of adventitial cell potential with a somewhat narrow focus on bone formation. Antigens of interest to functionally segregate adventicytes are discussed, including CD10, CD107a, aldehyde dehydrogenase isoforms, and CD140a, among others. Purified adventicytes (such as CD10 + , CD107a low , and CD140a + cells) have stronger osteogenic potential and promote bone formation in vivo. Recent bone tissue engineering applications of adventitial cells are also presented. A better understanding of perivascular progenitor cell subsets may represent a beneficial advance for future efforts in tissue repair and bioengineering., (© 2021 The Authors. STEM CELLS published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Bone repair requires the tightly regulated control of multiple intrinsic and extrinsic cell types and signaling pathways. One of the positive regulatory signaling pathways in membranous and endochondral bone healing is the Hedgehog (Hh) signaling family. Here, a novel therapeutic liposomal delivery vector was developed by self-assembly of an Hh-activating cholesterol analog with an emulsifier, along with the addition of Smoothened agonist (SAG) as a drug cargo, for the enhancement of Hh signaling in bone regeneration. The drug-loaded nanoparticulate agonists of Hh signaling were immobilized onto trabecular bone-mimetic apatite-coated 3D scaffolds using bioinspired polydopamine adhesives to ensure favorable microenvironments for cell growth and local therapeutic delivery. Results showed that SAG-loaded liposomes induced a significant and dose-dependent increase in Hh-mediated osteogenic differentiation, as evidenced by in vitro analysis of bone marrow stromal cells, and in vivo calvarial bone healing, as evidenced using all radiographic parameters and histomorphometric analyses. Moreover, favorable outcomes were achieved in comparison to standards of care, including collagen sponge-delivered rBMP2 or allograft bone. In summary, this study demonstrates using a nanoparticle packaged Hh small molecule as a widely applicable bone graft substitute for robust bone repair.

Progenitor cells from adipose tissue are able to induce bone repair; however, inconsistent or unreliable efficacy has been reported across preclinical and clinical studies. Soluble inhibitory factors, such as the secreted Wnt signaling antagonists Dickkopf-1 (DKK1), are expressed to variable degrees in human adipose-derived stem cells (ASCs), and may represent a targetable "molecular brake" on ASC mediated bone repair. Here, anti-DKK1 neutralizing antibodies were observed to increase the osteogenic differentiation of human ASCs in vitro, accompanied by increased canonical Wnt signaling. Human ASCs were next engrafted into a femoral segmental bone defect in NOD-Scid mice, with animals subsequently treated with systemic anti-DKK1 or isotype control during the repair process. Human ASCs alone induced significant but modest bone repair. However, systemic anti-DKK1 induced an increase in human ASC engraftment and survival, an increase in vascular ingrowth, and ultimately improved bone repair outcomes. In summary, anti-DKK1 can be used as a method to augment cell-mediated bone regeneration, and could be particularly valuable in the contexts of impaired bone healing such as osteoporotic bone repair., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

The vascular wall stores mesenchymal progenitor cells which are able to induce bone regeneration, via direct and paracrine mechanisms. Although much is known regarding perivascular cell regulation of osteoblasts, their regulation of osteoclasts, and by extension utility in states of high bone resorption, is not known. Here, human perivascular stem cells (PSCs) were used as a means to prevent autograft resorption in a gonadectomy-induced osteoporotic spine fusion model. Furthermore, the paracrine regulation by PSCs of osteoclast formation was evaluated, using coculture, conditioned medium, and purified extracellular vesicles. Results showed that PSCs when mixed with autograft bone induce an increase in osteoblast:osteoclast ratio, promote bone matrix formation, and prevent bone graft resorption. The confluence of these factors resulted in high rates of fusion in an ovariectomized rat lumbar spine fusion model. Application of PSCs was superior across metrics to either the use of unpurified, culture-defined adipose-derived stromal cells or autograft bone alone. Under coculture conditions, PSCs negatively regulated osteoclast formation and did so via secreted, nonvesicular paracrine factors. Total RNA sequencing identified secreted factors overexpressed by PSCs which may explain their negative regulation of graft resorption. In summary, PSCs reduce osteoclast formation and prevent bone graft resorption in high turnover states such as gonadectomy-induced osteoporosis., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO.

Heterotopic ossification (HO) is defined as abnormal differentiation of local stromal cells of mesenchymal origin, resulting in pathologic cartilage and bone matrix deposition. Cyr61, CTGF, Nov (CCN) family members are matricellular proteins that have diverse regulatory functions on cell proliferation and differentiation, including the regulation of chondrogenesis. However, little is known regarding CCN family member expression or function in HO. Here, a combination of bulk and single-cell RNA sequencing defined the dynamic temporospatial pattern of CCN family member induction within a mouse model of trauma-induced HO. Among CCN family proteins, Wisp1 (also known as Ccn4) was most upregulated during the evolution of HO, and Wisp1 expression corresponded with chondrogenic gene profile. Immunohistochemistry confirmed WISP1 expression across traumatic and genetic HO mouse models as well as in human HO samples. Transgenic Wisp1LacZ/LacZ knockin animals showed an increase in endochondral ossification in HO after trauma. Finally, the transcriptome of Wisp1-null tenocytes revealed enrichment in signaling pathways, such as the STAT3 and PCP signaling pathways, that may explain increased HO in the context of Wisp1 deficiency. In sum, CCN family members, and in particular Wisp1, are spatiotemporally associated with and negatively regulate trauma-induced HO formation.

Background: To determine if mammography combined with digital breast tomosynthesis (DBT), leads to superior performance in screening for breast cancer compared to digital mammography (DM) alone., Methods: We retrospectively collected data from A) the results of population-based mammography-screening provided by the National Cancer Registry in Taiwan, and B) the results from all screening mammography performed with DBT from 2012 through 2015 at Kaohsiung Veterans General Hospital (VGHKS) since the institution of DBT at the end of 2011. This was compared data from 3 years with DM performed prior to DBT implementation. We calculated the results of medical audit of VGHKS and compared this with national data. Fisher's exact test is applied., Results: VGHKS data demonstrated a higher cancer detection rate (CDR) and positive predictive value 1 (PPV 1) than the national average. Most prominently in the year 2014, our CDR was 120% better than that of the national average. CDR ranged from 6.3 to 8.1‰ prior to the introduction of DBT, and following DBT implementation this improved to 8.5-11.4‰, reflecting a mean increase of 32.2%. Early cancer detection was 50% higher and node negative rate was 25% higher than the national average of latest year. A 17.8% reduction in recall rate (RR) was achieved due to a decrease in unnecessary recall., Conclusion: There was a 32.2% increase in CDR and a 17.8% decrease in RR when DBT was used as an adjunct to DM, as compared to DM alone. CDRs were approximately twofold better than national average data. DBT was more effective at detecting cancer in ductal carcinoma in situ and stage 1., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background and Objectives: The Breast Imaging Reporting and Data System (BI-RADS) of Mammography (MG) and Ultrasonography (US) were equivalent to the "5-point score" and applied for combined and sub-stratified imaging assessments. This study evaluated the value of combined and sub-stratified imaging assessments with MG and US over breast cancer subtypes (BCS)., Materials and Methods: Medical records of 5,037 cases having imaging-guided core biopsy, performed from 2009 to 2012, were retrospectively reviewed. This study selected 1,995 cases (1,457 benign and 538 invasive cancer) having both MG and US before biopsy. These cases were categorized with the "5-point score" for their MG and US, and applied for combined and sub-stratified imaging assessments. Invasive cancers were classified on the basis of BCS, and correlated with combined and sub-stratified imaging assessments., Results: These selected cases were evaluated by the "5-point score." MG, US, and combined and sub-stratified imaging assessments all revealed statistically significant (P < 0.001) incidence of malignancy. The sensitivity was increased in the combined imaging score (99.8%), and the specificity was increased in the sub-stratified combined score (75.4%). In the sub-stratified combined imaging assessment, all BCS can be classified with higher scores (abnormality hierarchy), and luminal B subtype showed the most salient result (hierarchy: higher, 95%; lower, 5%)., Conclusions: Combined and sub-stratified imaging assessments can increase sensitivity and specificity of breast cancer diagnosis, respectively, and Luminal B subtype shows the best identification by sub-stratified combined imaging scoring.

The purpose of this study was to verify the utility of second-look ultrasonography (US) in evaluating nonmass enhancement (NME) lesions detected on breast magnetic resonance imaging (MRI) by analysing its correlation and imaging features. From July 2008 to June 2012, 102 consecutive MRI-detected NME lesions were subsequently evaluated with US. Lesions were evaluated according to the established Breast Imaging Reporting and Data System (BI-RADS) lexicon. The correlation between MRI-detected NME lesion characteristics, lesion size, histopathological findings and features at second-look US were analysed. Second-look US identified 44/102 (43%) of the NME lesions revealed by MRI. A US correlate was seen in 34/45 (76%) malignant lesions compared with 10/57 (18%) benign lesions (p < 0.0001). The likelihood of malignancy was significantly higher for NME lesions with a US correlate than lesions without: 34/44 (77%) versus 11/58 (19%) (p < 0.0001). The malignancy of the 44 (43%) MRI-detected NME lesions with a US correlate was significantly associated with US lesion margins and BI-RADS categories (p = 0.001 and 0.002 respectively). Second-look US of MRI-detected NME lesions is useful for decision-making as part of the diagnostic workup. Familiarity with the US features associated with malignancy improves the utility of US in the workup of these NME abnormalities., (© 2015 Wiley Periodicals, Inc.)

Aims: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress., Results: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1(-/-) mice, a mouse strain lacking the expression of the NCF1/p47(phox) component of NOX2. The levels of interleukin-1β (IL-1β) and IL-6 in inflamed joints were higher in Ncf1(-/-) than in controls. Antagonists of tumor necrosis factor-α (TNFα) and IL-1β were equally effective in suppressing arthritis in wild-type mice, while IL-1β blockade was more effective than TNFα blockade in Ncf1(-/-) mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1(-/-) mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1β to its active form and this activity was suppressed by ROS., Innovation: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS., Conclusion: Our results suggest that ROS act as a negative feedback to constrain IL-1β-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2.

Arterial and venous thrombosis are among the most common causes of death and hospitalization worldwide. Nanotechnology approaches hold great promise for molecular imaging and diagnosis as well as tissue-targeted delivery of therapeutics. In this study, we developed and investigated bioengineered nanoprobes for identifying thrombus formation; the design parameters of nanoparticle shape and surface chemistry, i.e. incorporation of fibrin-binding peptides CREKA and GPRPP, were investigated. Two nanoparticle platforms based on plant viruses were studied - icosahedral cowpea mosaic virus (CPMV) and elongated rod-shaped tobacco mosaic virus (TMV). These particles were loaded to carry contrast agents for dual-modality magnetic resonance (MR) and optical imaging, and both modalities demonstrated specificity of fibrin binding in vitro with the presence of targeting peptides. Preclinical studies in a carotid artery photochemical injury model of thrombosis confirmed thrombus homing of the nanoprobes, with the elongated TMV rods exhibiting significantly greater attachment to thrombi than icosahedral (sphere-like) CPMV. While in vitro studies confirmed fibrin-specificity conferred by the peptide ligands, in vivo studies indicated the nanoparticle shape had the greatest contribution toward thrombus targeting, with no significant contribution from either targeting ligand. These results demonstrate that nanoparticle shape plays a critical role in particle deposition at the site of vascular injury. Shaping nanotechnologies opens the door for the development of novel targeted diagnostic and therapeutic strategies (i.e., theranostics) for arterial and venous thrombosis.

Objective: To analyze the features of non-mass-like (NML) breast lesions on ultrasound (US) and determine their corresponding malignancy rate and to stratify these lesion patterns according to US BI-RADS categories., Materials and Methods: One hundred sixty-four consecutive lesions were retrospectively classified into four types according to the US features, the corresponding positive predictive values (PPVs) were obtained. Clinical, imaging, and histopathological findings were reviewed., Results: Among the 164 lesions, 39 (24%) were classified as type Ia, 14 (8%) as type Ib, 39 (24%) as type IIa, 19 (12%) as type IIb, 19 (12%) as type III, and 34 (21%) as type IV. The PPVs for malignancy were 21% for type Ia, 79% for type Ib, 10% for type IIa, 58% for type IIb, 16% for type III, and 21% for type IV. All NML lesions were classified as BI-RADS category 4a (type IIa), 4b (type Ia, III and IV) and 4c (type Ib and IIb) according to their PPVs. There was a significantly higher frequency of malignancy among lesions of type Ib and type IIb compared with the other types (P<0.01 for each). Lesions with associated calcifications, presence of abnormal axillary nodes, or a mammographic finding of suspected malignancy had a higher probability of malignancy (P<0.05 for each)., Conclusion: US is useful in clarifying the indication for biopsy of NML lesions. The types of US classifications used in our study establish reliable references for the NML patterns when stratified according to the BI-RADS categories., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: A greater policy of emphasis on the early detection and treatment of breast cancer is prevalent among developed countries. To raise the screening performance with a potentially decreased mortality rate, it is crucial to evaluate and analyze the screening outcome after implementation. We report the clinical outcome of an 8-year nationwide mammography screening in Taiwan to help share our statistical information on breast screening worldwide, especially in Asia., Methods: Taiwan has provided nationwide, free, biennial mammographic screening since 2004. A total of 2,392,789 consecutive screening mammography examinations were performed during this study period for women aged 50-69 years (2006-2009) and 45-69 years (from December 2009 onwards). The screening covers 33.2% of the target population in the most recent 2 years. The workload of every screening radiologist, the overall recall rate, positive predictive value (PPV1), cancer detection rate (CDR), cancer incidence rate (CIR) from the screening, 1-year interval cancer, sensitivity, and specificity of the screening mammography are calculated, and compared with the American College of Radiology (ACR) recommendation level and/or those of other screening mammographic series., Results: The CDRs (%) and CIRs (%) increased from 3.94-4.08 and 4.80-5.04 to 4.71-5.04 and 5.71 after 2009, implying a high occurrence of breast cancer in the younger age group of 45-49 years. The recall rates (9.3-10.0%) in this review are within the ACR recommendation range (<10%) and the PPV1 has also reached the ACR recommended level (>5%) in the most recent 2 years. The improvement of the screening performance may be attributed to our peer auditing review and education program. The sensitivity of our screening mammography is slightly lower than that of the ACR recommended level (>85%), which is still comparable to the results of the Vermont area in the USA. Although the workload (screenees/screeners) for every radiologist each year has increased from 150 in 2004 to 1360 in 2012, it does not seem to worsen the quality outcome of this screening program., Conclusion: From the outcome review of this national mammography screening, there is still room to ameliorate our performance through comprehensive and continued education, to improve the competence of cancer detection and decrease false negative (FN) cases., (Copyright © 2014. Published by Elsevier B.V.)

Purpose: To determine the rate of underestimation of ductal carcinoma in situ (DCIS) diagnosed at imaging-guided biopsy and to analyze its association with HER2/neu oncogene, an important biomarker in assessing the tumour aggressiveness and guiding hormone therapy for breast cancer., Methods: We retrospectively reviewed 162 patients with DCIS diagnosed by imaging-guided core needle biopsy between January 2008 and March 2013. All of these patients received surgical excision, and in 25, the diagnosis was upgraded to invasive breast cancer. In this study, we examined the ultrasound, mammographic features and histopathological results for each patient, and compared these parameters between those with and without HER2/neu overexpression., Results: Of the 162 DCIS lesions, 110 (67.9%) overexpressed HER2/neu. Nineteen patients with HER2/neu overexpressing DCIS (n=19/110, 17.3%) were upgraded after surgery to a diagnosis of invasive breast cancer. In this group, the upgrade rate was highest in patients with a dilated mammary duct pattern (42.1%, n=8/19, p=0.02) and the presence of abnormal axillary nodes (40.0%, n=12/30, p<0.01) at ultrasound and was significantly associated with comedo tumour type on pathology., Conclusions: Biopsy may underestimate the invasive component in DCIS patients. Sonographic findings of dilated mammary ducts and presence of abnormal axillary lymph nodes may help predicting the invasive components and possibly driving more targeted biopsy procedures., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

In the title compound, C9H13NO2S, the dihedral angle between the thiophene ring and the carbamate group is 15.79 (14)°. In the crystal structure, intra-molecular C-H⋯O inter-actions in tandem with the tert-butyl groups render the packing of adjacent mol-ecules in the [001] direction nearly perpendicular [the angle between adjacent thio-phene rings is 74.83 (7)°]. An inter-molecular N-H⋯O hydrogen bond gives rise to a chain extending along [001]. The crystal studied was found to be a racemic twin.

Objective: The Standards for Medical Exposure Quality Assurance in mammography systems were enacted on July 1, 2008, in Taiwan. This study aimed to evaluate the trends in performance of mammography units before and after the regulation started on the basis of annual on-site surveys from 2008 to 2010., Materials and Methods: On-site measurements were conducted on 215, 205, and 209 mammography units in 2008, 2009, and 2010, respectively, which accounted for more than 95% of all units in Taiwan. Phantom image quality, average glandular dose (AGD), and half-value layer were evaluated on all systems. Processor conditions, compression conditions, radiation output, and computed radiography exposure indicators were assessed on units participating in mammography screening in 2008 and on all units in the later years. Evaluations of maximum compression force and automatic exposure control reproducibility were added into the protocol from 2009 onward., Results: Mean phantom scores were improved significantly from 2008 to 2009 (11.63 ± 1.30 vs 12.31 ± 0.94, p < 0.05) and remained stable for 2010 (12.35 ± 0.87). Mean AGDs were 1.48 ± 0.47, 1.38 ± 0.41, and 1.37 ± 0.42 mGy over the 3 years, with a significant reduction from 2008 to 2009 (p < 0.05). For film-screen mammography systems, variations of sensitometric curves were greatly reduced in 2009 and 2010 when compared with 2008. Passing rates were increased after the regulation took effect in almost all aspects., Conclusion: Results from large-scale on-site surveys showed an overall improvement in performance after quality assurance in mammography was enforced in Taiwan.

The title compound, C5H3N3OS, is almost planar (r.m.s. deviation for the ten non-H atoms = 0.018 Å) and forms an extended layer structure in the (100) plane, held together via hydrogen-bonding inter-actions between adjacent mol-ecules. Of particular note is the occurrence of RC-H⋯N(-)=N(+)=NR inter-actions between an aromatic C-H group and an azide moiety which, in conjunction with a complementary C-H⋯O=C inter-action, forms a nine-membered ring.

Background: Early detection with screening mammography can potentially reduce breast cancer mortality rates. To achieve an efficient screening, a peer review system provides a compensatory double-check reviewing, will hopefully to prevent the omission of detectable lesions and reduce unnecessary recall., Methods: In 2009, 4643 initial mammographic screenings reported by 74 screening radiologists had negative results with a recall rate of less than 5%. In the same year, 2538 initial positives screened by 18 screening radiologists had a recall rate higher than 15%. Those 7181 randomized screenings were evenly distributed for reassessment by 39 reviewing radiologists. The disagreement of assessments between the reviewers and screening radiologists was recorded. The differential rate was defined as the number of the disagreements divided by the number of audited films reviewed by a screening radiologist. The equality of the differential rates for each screening radiologists with negative and positive assessments was compared by a Chi-square test. The performance of the 39 auditors was measured by the Kendall's tau statistic. P values less than 0.05 were considered statistically significant., Results: The mean differential rate for screening radiologists of negative assessments was 6.7% (P = 0.588), while 35.0% for positive assessments were significant (P < 0.001). The result indicated that most of the initial negative assessments reported by the screening radiologists were generally accepted by the reviewers but not the positive assessments. With respect to the 39 reviewers, there was no significant evidence for the association of the difference rates between negative and positive assessments. Nine reviewers were found to have their differential rate for negative and positive assessments larger than the average of the population. Eleven reviewers were found to have their differential rates smaller than the average for both. Thirteen reviewers had their differential rates smaller than the average for negative assessments but larger than the average for positive assessments. The opposite condition was found for six reviewers. The Kendall's tau statistic was 0.038 (P = 0.735)., Conclusions: Reviewers usually agreed with the opinion of the initial screening doctors who reported negative findings. Therefore, a 5% recall rate as the lower range of reviewing negatives may be still too high. The recall rate of more than 15% was significantly related to improper interpretation, especially when the differential rate is 25% or higher, a warning to the underperforming screening radiologist is recommended. An ideal reviewer should interpret films independently. Reviewers with tendencies to be followers or contrarians should not be enrolled in the reviewing system.

Purpose: We analysed the ultrasonographic (US) features of atypical ductal hyperplasia (ADH) of the breast diagnosed by US-guided core needle biopsy (CNB) with the aim of identifying factors that affect the underestimation of ADH., Materials and Methods: A total of 134 ADH lesions sampled by US-guided CNB were reviewed retrospectively. All lesions were evaluated for pattern, size, lesion characteristics and margins, and the corresponding surgical outcome or imaging follow-up was obtained. Each patient's clinical and radiological features were analysed to identify factors involved in ADH underestimation., Results: The prevalence of malignancy in each pattern of lesions following surgical excision was 32/81 (40%) for solid masses, 14/31 (45%) for ductal patterns, 5/17 (29%) for complex cystic lesions and 2/5 (40%) for architectural distortions. Based on the results of surgical and US follow-up, none of the category 3 lesions was proven to be a malignancy. Malignancy was found in 17 (21%) of the 80 BI-RADS (Breast Imaging Reporting and Data System) category 4a lesions, 20 (74%) of the 27 category 4b lesions, 12 (92%) of the 13 category 4c lesions, and four (100%) of the four category 5 lesions. Lesions with a higher US assessment category, lacking circumscribed margins, or a mammographic finding of suspected malignancy were all significantly associated with underestimation (p < 0.05 for each)., Conclusion: US is useful in evaluating ADH lesions and in clarifying the indication for biopsy of these lesions. Familiarity with the frequency associated with malignancy for each feature will improve the utility of US in the work-up of these breast abnormalities., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: This study was conducted to investigate whether detectable missed breast cancers could be distinguished from truly false negative images in a mammographic screening by a regular peer auditing., Methods: Between 2004 and 2007, a total of 311,193 free nationwide biennial mammographic screenings were performed for 50- to 69-year-old women in Taiwan. Retrospectively comparing the records in Taiwan's Cancer registry, 1283 cancers were detected (4.1 per 1000). Of the total, 176 (0.6 per 1000) initial mammographic negative assessments were reported to have cancers (128 traditional films and 48 laser-printed digital images). We selected 186 true negative films (138 traditional films and 48 laser-printed ones) as control group. These were seeded into 4815 films of 2008 images to be audited in 2009. Thirty-four auditors interpreted all the films in a single-blind, randomized, pair-control study. The performance of 34 auditors was analyzed by chi-square test. A p value of < 0.05 was considered significant., Results: Eight (6 traditional and 2 digital films) of the 176 false negative films were not reported by the auditors (missing rate of 4.5%). Of this total, 87 false negatives were reassessed as positive, while 29 of the 186 true negatives were reassessed as positive, making the overall performance of the 34 auditors in interpreting the false negatives and true negatives a specificity of 84.4% and sensitivity of 51.8%. The specificity and sensitivity in traditional films and laser-printed films were 98.6% versus 43.8% and 41.8% versus 78.3%, respectively. Almost 42% of the traditional false negative films had positive reassessment by the auditors, showing a significant difference from the initial screeners (p < 0.001). The specificity of their reinterpretation of laser-printed films was obviously low., Conclusion: Almost 42% of the false negative traditional films were judged as missed cancers in this study. A peer auditing should reduce the probability of missed cancers., (2012 Published by Elsevier B.V)

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10(-18)), rs3803662 (16q12) (P = 3.7 × 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10(-6) and P = 4.1 × 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.

Purpose: To analyze the features of breast complex cystic lesions at ultrasonography (US) and to determine appropriate Breast Imaging Reporting and Data System (BI-RADS) categories and management recommendations for these lesions based on US findings with pathologic correlation., Materials and Methods: From July 2001 to June 2007, 152 consecutive pathologically proven complex cystic lesions on US were retrospectively reviewed. All lesions at US were evaluated for size, lesion characteristics, margins, and presence of abnormal axillary nodes. US features of lesions were classified into four types, and positive predictive values (PPVs) were calculated for each type. Clinical, imaging, and histopathological findings were reviewed., Results: Of the 152 lesions based on US appearance, 36 (24%) were classified as type I, 49 (32%) as type II, 28 (18%) as type III, and 39 (26%) as type IV. The PPVs for malignancy in each type were 14% for type I, 16% for type II, 14% for type III, and 41% for type IV. There was a significantly higher frequency of malignancy among lesions of type IV compared with the other three types (16/39=41% vs 5/36=14%, p=0.0089; 16/39=41% vs 8/49=16%, p=0.0098; and 16/39=41% vs 4/28=14%, p=0.018 [Chi-squared test]). Lesions with maximum diameter equal to or larger than 20mm, not circumscribed margins, or a mammographic finding of suspected malignancy had a high probability of malignancy (p<0.05 for each)., Conclusion: US is useful in evaluating the complex cystic lesions and in clarifying the indication for biopsy of these lesions. The four types of US classifications used in our study establish accepted benchmarks for these breast abnormalities when stratified according to BI-RADS categories., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Tumours metastasising to the breast are very infrequent, with an incidence of 0.4-6.6% of all breast tumours. Occasionally a breast mass is the first indicator of a tumour arising elsewhere. Development of metastases to the breast from a lung cancer is very rare and the prognosis for such patients is poor. We present three patients who had metastases to the breast presenting clinically as the primary origin. It is important to distinguish a primary breast cancer from a metastasis, as different therapies are offered with considerably different outcomes.

Peroxisome proliferator-activated receptor γ (PPARγ) has been linked with possible antineoplastic effects in colorectal carcinogenesis. However, data for the possible link between PPARγ and breast cancer risk are sparse. We assessed the association of three polymorphisms in PPARγ (rs10865710 [C-681T], rs1805192 [Pro12Ala], and rs3856806 [C1431T]) with the risk of breast cancer in an ethnic Chinese female population in Taiwan. In addition, interactions with estrogen exposures were also explored. Genotypes for the PPARγ polymorphisms were determined on 291 incident breast cancer cases and 589 matched controls by fluorogenic 5'-nuclease assay. The at-risk haplotypes were defined according to the three polymorphisms in the following order: C-681T, Pro12Ala, and C1431T, which include CCT, GGT, and GGC. In addition, a critical period of estrogen exposure was estimated by the interval between age at menarche and age at first full-term pregnancy. Overall, there was no evidence of a significant impact of individual polymorphisms of PPARγ on breast cancer risk. However, the haplotype analysis revealed that women harboring at-risk haplotypes showed a significant 67% increase in breast cancer risk [adjusted odds ratio (OR) 1.67; 95% confidence interval (CI) 1.11-2.52]. Furthermore, there was a significant joint effect of estrogen exposure-related factors and at-risk haplotypes of PPARγ on breast cancer risk (adjusted OR 4.04; 95% CI 1.89-8.65), particularly in premenopausal women. The present study implicates a role for PPARγ in breast cancer risk. Mechanistic studies to fully elucidate the mechanisms underlying PPARγ's effects should be pursued in future investigations.

We report a rare case of breast cancer concomitant with progesterone-receptor-positive renal cell carcinoma. A 48-year-old woman was diagnosed as having infiltrating ductal carcinoma of the breast and underwent modified radical mastectomy. A synchronous retroperitoneal tumour was detected by sonography of the abdomen in a routine cancer staging. Initially, the tumour was diagnosed as a synchronous retroperitoneal metastasis by needle biopsy; further tests revealed that it was progesterone receptor-positive. The retroperitoneal tumour showed poor response to full courses of adjuvant chemotherapy for breast cancer. Subsequently, the patient underwent a radical operation that included nephrectomy. The final pathology confirmed a sarcomatoid renal cell carcinoma. The post-operative course was uneventful. The patient had no recurrence at the 1-year follow-up. In this report, accurate diagnosis and adequate treatment were discussed. An intra-abdominal tumour with progesterone receptor- (PR) positive features is usually considered to be metastatic in breast cancer patients. For breast cancer patients with a PR-positive retroperitoneal tumour, renal cell carcinoma should be differentiated from a metastatic lesion of breast cancer, even if PR-expression is rare in renal cell carcinoma. To the best of our knowledge, this is the first case of PR-positive expression in breast cancer concomitant with renal carcinoma. In clinical settings, it is challenging for the surgeon to make an accurate diagnosis and to provide prompt treatment in such cases.

Background: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors., Methods: We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided., Results: In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors., Conclusions: This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Introduction: Estrogen forms a complex with the estrogen receptor (ER) that binds to estrogen response elements (EREs) in the promoter region of estrogen-responsive genes, regulates their transcription, and consequently mediates physiological or tumorigenic effects. Thus, sequence variants in EREs have the potential to affect the estrogen-ER-ERE interaction. In this study, we examined the hypothesis that genetic variations of EREs are associated with breast cancer development., Methods: This case-control study involved 815 patients of Asian descent with incident breast cancer and 821 healthy female controls. A total of 13,737 ERE sites in the whole genome predicted by a genome-wide computational algorithm were blasted with single-nucleotide polymorphism (SNP) sequences. Twenty-one SNPs located within 2,000 bp upstream or within introns 1 and 2 of putative genes and with a minor allele frequency greater than 5% were identified and genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility., Results: A significant combined effect of rs12539530, an ERE SNP in intron 2 of NRCAM which codes for a cell adhesion molecule, and SNPs of ESR1, the gene coding for ER, on breast cancer risk was found. Interestingly, this combined effect was more significant in women who had experienced a longer period of lifetime estrogen exposure, supporting a hormonal etiology of this SNP in breast tumorigenesis., Conclusions: Our findings provide support for a role of genetic variation in ERE-ESR1 in determining susceptibility of breast cancer development.

Background: B vitamins, including vitamin B(6), are coenzymes that are important for DNA integrity and stability. Deficiencies in B vitamins may promote tumor carcinogenesis., Methods: We examined the association of dietary vitamin B(6) intake with overall breast cancer risk and breast cancers stratified by hormone receptor status. This case-control study included 391 breast cancer cases and 782 control subjects enrolled at the Tri-Service General Hospital in Taipei, Taiwan. Energy-adjusted intake of vitamin B(6) was derived from a food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression., Results: As compared with women in the lowest tertile, the multivariate-adjusted ORs for breast cancer among women in the second and highest tertiles of vitamin B(6) intake were 0.78 (95% CI, 0.64-2.52) and 0.64 (0.26-0.92), respectively. In addition, higher vitamin B(6) intake was associated with a significantly lower risk of developing ER-negative breast tumors., Conclusions: Our findings suggest that higher intake of vitamin B(6) is associated with a reduction in breast cancer risk, particularly ER-negative tumors.

Objective: To evaluate the nature and imaging appearance of incidental enhancing breast lesions detected on a routine contrast-enhanced chest CT., Materials and Methods: Twenty-three patients with incidental enhancing breast lesions on contrast-enhanced chest CT were retrospectively reviewed. The breast lesions were reviewed by unenhanced and enhanced CT, and evaluated by observing the shapes, margins, enhancement patterns and backgrounds of breast lesions. A histopathologic diagnosis or long-term follow-up served as reference standard., Results: Sixteen (70%) patients had malignant breast lesions and seven (30%) had benign lesions. In 10 patients, the breast lesions were exclusively detected on contrast-enhanced CT. Using unenhanced CT, breast lesions with fibroglandular backgrounds were prone to be obscured (p < 0.001). Incidental primary breast cancer showed an non-significant trend of a higher percentage irregular margin (p = 0.056). All of the four incidental breast lesions with non-mass-like enhancement were proven to be malignant., Conclusion: Routine contrast-enhanced chest CT can reveal sufficient details to allow for the detection of unsuspected breast lesions, in which some cases may be proven as malignant. An irregular margin of incidental enhancing breast lesion can be considered a suggestive sign of malignancy.

Purpose: The purpose of this retrospective study was to calculate the positive predictive value (PPV) of sonographic Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 in different age groups to investigate whether age influences the PPV of the BI-RADS category in breast ultrasound., Materials and Methods: From our sonography-guided core biopsy database of breasts between 2006 and 2008, we identified 2817 BI-RADS category 3, 4, and 5 lesions with known pathological diagnosis in 2587 women, all of whom underwent the earlier breast assessment via ultrasound with a sonographic BI-RADS lexicon and later sonography-guided core biopsy. All lesions were classified into three age groups (< 45, 45 - 59, and > 59 years). The age-related PPVs of each BI-RADS category among three age groups were calculated on the basis of pathological diagnoses and were compared using a χ(2)-test., Results: The overall PPV of each BI-RADS category was 2.2 % in category 3, 6.5 % in category 4a, 35.2 % in category 4b, 79.6 % in category 4c, and 99.6 % in category 5. The age-related PPVs of category 3 varied significantly among the three age groups (0.9 % versus 3.9 % versus 2.0 % p = 0.048), and notably, the age-related PPV in group 2 was higher than the others. Additionally, there was a significant positive association between the age-related PPVs and increasing age in categories 4a and 4b (4a, p < 0.0001 and 4b, p = 0.0139), but not in categories 4c and 5 (4c, p = 0.1853 and 5, p = 0.2871)., Conclusion: The incidence of female breast cancer differs not only in different sonographic BI-RADS categories, but also in different age groups. Therefore, more attention should be paid to the special age group that we found for sonographic BI-RADS categories 3, 4a, and 4b., (© Georg Thieme Verlag KG Stuttgart · New York.)

Adipocytokine resistin is a member of the newly discovered family of cysteine-rich protein. Recent data suggest that macrophages are a major source of human resistin. Given the obesity-breast cancer link and convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and breast cancer risk in humans. We conducted a hospital-based case-control study to evaluate whether plasma resistin levels were associated with breast cancer risk in women. We also examined the modification effect of estrogen exposures on the resistin-breast cancer link. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 380 incident cases with breast cancer and 760 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2008. Plasma levels of resistin were measured by enzyme immunoassay. Cumulative exposure to estrogens were estimated according to the age at menarche and age at enrollment for premenopausal women and age at menarche and age at menopause for postmenopausal women. Cases with breast cancer had significantly elevated resistin concentrations as compared with control subjects. Compared with those in the lowest quartile, the adjusted odds ratios of breast cancer for women in the second, third, and highest quartiles were 1.48 [95% confidence interval (CI) = 0.65-3.38], 1.76 (95% CI = 1.00-4.73), and 2.08 (95% CI = 1.04-3.85), respectively. Furthermore, the biological gradient of breast cancer risk by plasma resistin levels remained after adjustment for measures of adiposity. The dose-dependent relationship of resistin levels with breast cancer risk was notably pronounced among women with excess exposure to estrogens. Adipocytokine resistin may have an adiposity-independent role in breast carcinogenesis. Mechanistic studies to fully elucidate the mechanisms underlying resistin's effects should be pursued in future investigations.

Purpose: To test the hypothesis that polymorphisms of ESR1, the gene encoding estrogen receptor alpha (ERalpha), are associated with susceptibility, clinical phenotype, and progression of breast cancer., Patients and Methods: A case-control study was done on 940 patients with incident breast cancer and 1,547 healthy female controls. Fifteen single-nucleotide polymorphisms (SNP) selected from chr6:152,170,379-152,466,100 (exons 1-8 of the ESR1 gene, excluding flanking sequences), reflecting major polymorphisms of this gene, were genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility and between cases with different clinical phenotypes to determine the role of ESR1 polymorphism in cancer progression., Results: SNPs located in one cluster in intron 1 and one haplotype, based on these SNPs, showed a significant association with breast cancer susceptibility. The tumorigenic contribution of these intron 1 SNPs was more obvious in combination with reproductive risk factors (P for interaction <0.05). One of these intron 1 SNPs was also significantly associated with low ERalpha expression in tumors. Interestingly, the same intron 1 SNPs showed a correlation with worse clinical phenotypes, including poor differentiation of tumor cells and a late stage. These intron 1 SNPs also showed a significant association with the 5-year breast cancer-specific survival rate of patients, but had opposite effects in ERalpha-negative and ERalpha-positive early-stage patients., Conclusions: Our findings provide support for diverse roles of ESR1 polymorphism in determining susceptibility in different stages of breast cancer. The differences between the important ESR1 SNPs identified in Chinese women in this study and those identified in studies on Western women with breast cancer suggest different roles of ERalpha in these two populations.

Epidemiological observations suggest that insulin-like growth factor-I (IGF-I), a potent mitogenic and anti-apoptotic peptide, plays a role in the etiology of breast cancer. Estrogen, which is crucial in breast carcinogenesis, both regulates and is influenced by IGF-I family. A case-control study was conducted to assess the role of IGF-I as a biomarker for breast cancer and to evaluate the potential joint effect of circulating IGF-I and critical period of estrogen exposure, as estimated by the interval between age at menarche and age at first full-term pregnancy on the risk of breast cancer. Questionnaire information and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2006. Plasma levels of IGF-I and IGFBP-3 were measured by immunoradiometric assay. Conditional logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our case-control data indicate that breast cancer risk related to IGF-I differs according to menopausal status. High circulating levels of IGF-I increased risk of pre- but not postmenopausal breast cancer (top vs. bottom tertile, adjusted OR, 1.86; 95% CI, 1.01-3.44). Furthermore, elevated IGF-I concentrations in conjunction with prolonged interval of critical period of estrogen exposure were associated with significantly increased risk of breast cancer, particularly among estrogen-positive cases (adjusted OR, 2.42, 95% CI, 1.33-4.38). These results suggest that the joint effect of IGF-I and estrogens may provide novel methods of breast cancer risk reduction among women.

In breast cancer patients, pulmonary nodules are frequently considered a metastatic disease or primary lung tumor. We report the case of a 53-year-old woman with early-stage breast cancer (T1micN0M0) presenting with asymptomatic pulmonary nodules in the left upper lobe at follow-up 6 years after she underwent a mastectomy. A presumptive diagnosis of pulmonary metastasis was made, and the patient underwent a video-assisted thoracoscopic lung biopsy. Pathology showed granulomatous inflammation with Cryptococcus infection. Subsequently, antifungal therapy was prescribed, and full recovery followed. We demonstrate the importance of differentiating between pulmonary Cryptococcus infection and metastasis in breast cancer patients for correct management. The relationship between pulmonary Cryptococcus infection and breast cancer is also discussed., (Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)