Radiomics Based on Adapted Diffusion Kurtosis Imaging Helps to Clarify Most Mammographic Findings Suspicious for Cancer.

Purpose To evaluate a radiomics model of Breast Imaging Reporting and Data System (BI-RADS) 4 and 5 breast lesions extracted from breast-tissue-optimized kurtosis magnetic resonance (MR) imaging for lesion characterization by using a sensitivity threshold similar to that of biopsy. Materials and Methods This institutional study included 222 women at two independent study sites (site 1: training set of 95 patients; mean age ± standard deviation, 58.6 years ± 6.6; 61 malignant and 34 benign lesions; site 2: independent test set of 127 patients; mean age, 58.2 years ± 6.8; 61 malignant and 66 benign lesions). All women presented with a finding suspicious for cancer at x-ray mammography (BI-RADS 4 or 5) and an indication for biopsy. Before biopsy, diffusion-weighted MR imaging (b values, 0-1500 sec/mm2) was performed by using 1.5-T imagers from different MR imaging vendors. Lesions were segmented and voxel-based kurtosis fitting adapted to account for fat signal contamination was performed. A radiomics feature model was developed by using a random forest regressor. The fixed model was tested on an independent test set. Conventional interpretations of MR imaging were also assessed for comparison. Results The radiomics feature model reduced false-positive results from 66 to 20 (specificity 70.0% [46 of 66]) at the predefined sensitivity of greater than 98.0% [60 of 61] in the independent test set, with BI-RADS 4a and 4b lesions benefiting from the analysis (specificity 74.0%, [37 of 50]; 60.0% [nine of 15]) and BI-RADS 5 lesions showing no added benefit. The model significantly improved specificity compared with the median apparent diffusion coefficient (P < .001) and apparent kurtosis coefficient (P = .02) alone. Conventional reading of dynamic contrast material-enhanced MR imaging provided sensitivity of 91.8% (56 of 61) and a specificity of 74.2% (49 of 66). Accounting for fat signal intensity during fitting significantly improved the area under the curve of the model (P = .001). Conclusion A radiomics model based on kurtosis diffusion-weighted imaging performed by using MR imaging machines from different vendors allowed for reliable differentiation between malignant and benign breast lesions in both a training and an independent test data set. © RSNA, 2018 Online supplemental material is available for this article.

Bile acid-induced inflammatory signaling in mice lacking Foxa2 in the liver leads to activation of mTOR and age-onset obesity.

Cytokine signaling has been connected to regulation of metabolism and energy balance. Numerous cytokine gene expression changes are stimulated by accumulation of bile acids in livers of young Foxa2 liver-conditional null mice. We hypothesized that bile acid-induced inflammation in young Foxa2 mutants, once chronic, affects metabolic homeostasis. We found that loss of Foxa2 in the liver results in a premature aging phenotype, including significant weight gain, reduced food intake, and decreased energy expenditure. We show that Foxa2 antagonizes the mammalian target of rapamycin (mTOR) pathway, resulting in increased hepatic lipogenesis and adiposity. While much prior work has focused on adipose tissue in obesity, we discovered a novel age-onset obesity phenotype in a model where gene deletion occurs only in the liver, underscoring the importance of the role hepatic lipogenesis plays in the development of obesity.

Revision rates after total ankle arthroplasty in sample-based clinical studies and national registries.

BACKGROUND: The aim of this study was to evaluate the outcome of specific implants in total ankle arthroplasty as reported in clinical studies and determined by national registries. MATERIALS AND METHODS: A structured literature review was conducted regarding sample-based clinical studies and national registry data. To allow for comparative analyses, registry data had to be available for the implants included. These were STAR Ankle, Büchel-Pappas, Hintegra, Mobility, Agility, and Ramses Total Ankle Arthroplasty. The revision rate was used as the main outcome parameter. RESULTS: On average, the revision rates published in sample-based clinical studies were about half the value found in registries. Implant developers represent a share of almost 50% of the published content and are therefore over-represented in scientific publications. The inventors of STAR Ankle and BP total ankle implants published data which was statistically significantly superior to the outcome achieved in average patients as documented in registries. Irrespective of the implant, the average revision rate to be expected according to the registry data available is 21.8% after 5 years, and 43.5% after 10 years. CONCLUSION: The average revision rate published in peer-reviewed scientific articles was significantly lower than the outcome achieved according to national arthroplasty registry data, which reflect actual average patient care in the respective countries. Publications by some research groups, particularly by implant inventors, show a deviation from the outcome published by other users and those shown in registry data.

Prognostic value of cyclin D1 overexpression in correlation with pRb and p53 status in non-small cell lung cancer (NSCLC).

PURPOSE: The aim of this study was to assess the impact of cyclin D1 overexpression (considered separately or jointly with previously assessed p53 and pRb statuses) on survival in a group of 111 surgically treated non-small cell lung cancer patients (NSCLC). METHODS: Cyclin D1 accumulation was assessed immunohistochemically, with the use of monoclonal antibody (DCS-6, DakoCytomation) and the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. RESULTS: Overexpression of cyclin D1 was found in 55 samples (49%), whereas the altered phenotypes cyclin D1+/p53+ or cyclin D1+/pRb- were found in 23 (22%) and 9 samples (9%), respectively. Statistical analysis was performed for different cut-off values and the only significant differences were found if samples with some expression of each protein were considered positive. There was no relationship between cyclin D1 overexpression and major clinicopathological factors, including p53 expression; however, there was a direct correlation between cyclin D1 and pRb protein expression (p=0.007). Cyclin D1 accumulation did not influence patients' survival. Of all possible cyclin D1/p53, cyclin D1/pRb and cyclin D1/p53/pRb phenotypes, patients with cyclin D1-/p53+ phenotype had shortened overall survival compared to other patients (p=0.027, HR=1.8). In the multivariate analysis, the only variable associated with shortened overall and disease-free survival was the stage of disease (p<0.001). CONCLUSIONS: These results suggest the lack of prognostic value of cyclin D1 overexpression in NSCLC patients.

Absence of prognostic significance of p21(WAF1/CIP1) protein expression in non-small cell lung cancer.

Prognostic value of p21WAF1/CIP1 expression in non-small-cell lung cancer patients (NSCLC) remains unclear. In this study the authors investigated the clinical significance of p21WAF1/CIP1 expression in a group of 117 NSCLC patients, who underwent curative pulmonary resection. Expression of p21WAF1/CIP1 protein was assessed immunohistochemically and samples showing>5% of positive tumor cells were considered positive. Seventy-six samples (65%) showed positive nuclear p21WAF1/CIP1 protein expression. There was no relationship between the expression of p21WAF1/CIP1 protein and major clinico-pathological factors, and neither there was an impact of p21WAF1/CIP1 protein expression on disease-free and overall survival. p21WAF1/CIP1 protein occurrence was not correlated with previously determined p53 protein expression and there was also no relationship between all possible p21WAF1/CIP1/p53 phenotypes and survival. In uni- and multivariate analysis only stage of disease was independent prognostic factors. These results suggest the lack of prognostic relevance of p21WAF1/CIP1 expression (analyzed separately or jointly with p53 protein) in surgically treated NSCLC patients.

Prognostic relevance of altered pRb and p53 protein expression in surgically treated non-small cell lung cancer patients.

OBJECTIVE: The prognostic value of pRb and p53 altered expression in non-small cell lung cancer (NSCLC) remains debatable. We assessed the occurrence of altered pRb and p53 protein expression, and the prognostic value of these assays considered as separate and combined variables in operable NSCLC. The study group included 195 NSCLC consecutive patients from one institution who underwent curative pulmonary resection between 1994 and 1999. METHODS: Expression of pRb and p53 was assessed immunohistochemically with the use of monoclonal antibodies (LM95.1 and Pab 1801, Oncogene Science, respectively). RESULTS: A lack of pRb and abnormal p53 protein expression were found in 57 (29%) and 92 samples (47%), respectively, whereas both abnormalities (pRb-/p53+) occurred in 24 samples (12%). There was no relationship between altered pRb/p53 expression and major clinico-pathological characteristics, neither was there a significant difference in disease-free and overall survival between particular groups of patients with tumors carrying four possible pRb/p53 phenotypes. In uni- and multivariate analysis, the only variable associated with shortened disease-free and overall survival was stage of disease (p < 0.001) and degree of tumor differentiation (p = 0.005). CONCLUSION: These results suggest that altered pRb and p53 expression does not provide prognostic information in operable NSCLC patients.

HOPE--a new fixing technique enables preservation and extraction of high molecular weight DNA and RNA of > 20 kb from paraffin-embedded tissues. Hepes-Glutamic acid buffer mediated Organic solvent Protection Effect.

The growing number of molecular pathologic tools that are currently available require material with good long term preservation of morphology, nucleic acids, and antigenic structures. However, pathologic investigations of tissues done at a molecular level are often hampered by the fixatives in use. We thus endeavored to design a new fixing system, including subsequent paraffin-embedding and sectioning, that makes complete pathologic analyses possible, with special consideration of immunohistochemistry (IHC), in situ hybridization (ISH), and molecular pathology. The optimized HOPE (Hepes-Glutamic acid buffer mediated Organic solvent Protection Effect) fixing technique allows us to preserve and extract high molecular weight DNA and RNA of > 20 kbp suitable for downstream applications, such as PCR and RT-PCR from HOPE-fixed, paraffin-embedded tissues that are up to 5 years old. This technique will most probably lead to new impacts on molecular pathology.

Synthesis and Crystal Structure Determination of Bifunctional Phosphine-Linked Triplatinum Double-Cluster Complexes.

Reactions of [Pt(3)(&mgr;-CO)(3)(PCy(3))(3)] (1) and [Pt(3)(&mgr;-CNXyl)(2)(&mgr;-CO)(CNXyl)(PCy(3))(2)] (2) (Cy = C(6)H(11), Xyl = C(8)H(9)) with (1)/(2) equiv of a bifunctional metal phosphine cation [(MPR'(2))(2)(R)](2+) (M = Cu, Ag, Au; R = C(6)H(4), (CH(2))(2)C(6)H(4), Fe(C(5)H(5)); R' = C(6)H(5), C(6)H(11)) yielded quantitatively [{Pt(3)(&mgr;-CO)(3)(PCy(3))(3)}(2){(MPR'(2))(2) (R)}](2+) and [{Pt(3)(&mgr;-CNXyl)(2)(&mgr;-CO)(CNXyl)(PCy(3))(2)}(2){(MPR'(2))(2)(R)}](2+), respectively. The compounds were characterized by IR-, MS-, and (31)P-NMR spectroscopy. The X-ray structure is given for [{Pt(3)(&mgr;-CO)(3)(PCy(3))(3)}(2){(AuPPh(2))(2)(CH(2))(2)C(6)H(4))}][PF(6)](2) (14), which crystallizes in the triclinic space group P&onemacr; with Z = 1, a = 15.350 Å, b = 17.150 Å, c = 20.446 Å, alpha = 84.54 degrees, beta = 84.84 degrees, and gamma = 64.56 degrees. The structure was refined to R = 0.0435 for the 8430 observed reflections (I > 3sigma(I)).