Film mammography has limited sensitivity for the detection of breast cancer in women with radiographically dense breasts. We assessed whether the use of digital mammography would avoid some of these ...limitations.
A total of 49,528 asymptomatic women presenting for screening mammography at 33 sites in the United States and Canada underwent both digital and film mammography. All relevant information was available for 42,760 of these women (86.3 percent). Mammograms were interpreted independently by two radiologists. Breast-cancer status was ascertained on the basis of a breast biopsy done within 15 months after study entry or a follow-up mammogram obtained at least 10 months after study entry. Receiver-operating-characteristic (ROC) analysis was used to evaluate the results.
In the entire population, the diagnostic accuracy of digital and film mammography was similar (difference between methods in the area under the ROC curve, 0.03; 95 percent confidence interval, -0.02 to 0.08; P=0.18). However, the accuracy of digital mammography was significantly higher than that of film mammography among women under the age of 50 years (difference in the area under the curve, 0.15; 95 percent confidence interval, 0.05 to 0.25; P=0.002), women with heterogeneously dense or extremely dense breasts on mammography (difference, 0.11; 95 percent confidence interval, 0.04 to 0.18; P=0.003), and premenopausal or perimenopausal women (difference, 0.15; 95 percent confidence interval, 0.05 to 0.24; P=0.002).
The overall diagnostic accuracy of digital and film mammography as a means of screening for breast cancer is similar, but digital mammography is more accurate in women under the age of 50 years, women with radiographically dense breasts, and premenopausal or perimenopausal women. (ClinicalTrials.gov number, NCT00008346.)
•Peak loads and failure modes of RC-beams are numerically predicted by limit analysis.•Upper and lower bounds to the peak load multiplier are evaluated.•Two well established numerical FE procedures ...are used simultaneously.•A Menétrey–Willam-type yield surface with cap in compression is adopted.•A classical benchmark on bending tests on large-scale real prototypes is addressed.
Steel-reinforced concrete beams are analyzed by a plasticity-based approach grounded on nonstandard limit analysis theory. Peak loads and failure modes are predicted by determination of upper and lower bound limits computed with two finite element based numerical procedures. A number of real beams prototypes, belonging to a standard benchmark, are studied and the obtained results are critically discussed outlining possible future developments, strengths and weaknesses of the proposed approach.
To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine-needle aspiration biopsy (FNAB) in the diagnosis of nonpalpable breast lesions.
At 18 institutions, ...442 women who underwent 22-25-gauge imaging-guided FNAB were enrolled. Definitive surgical, core-needle biopsy, and/or follow-up information was available for 423 (95.7%) of these women. The reference standard was established from additional clinical and imaging information for an additional six (1.4%) women who did not undergo further histopathologic evaluation. The FNAB protocol was standardized at all institutions, and all specimens were reread by one of two expert cytopathologists.
When insufficient samples were included in the analysis and classified as positive, the sensitivity and specificity of FNAB were 85%-88% and 55.6%-90.5%, respectively; accuracy ranged from 62.2% to 89.2%. The diagnostic accuracy of FNAB was significantly better for detection of masses than for detection of calcifications (67.3% vs. 53.8%, P =.006) and with US guidance than with stereotactic guidance (77.2% vs. 58.9%; P =.002).
FNAB of nonpalpable breast lesions has limited value given the high insufficient sample rate and greater diagnostic accuracy of other interventions, including core-needle biopsy and needle-localized open surgical biopsy.
The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the ...most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms.
Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed.
The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen’s κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen’s κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis.
Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation.
•Deficiency in homologous recombination repair of DNA generates genomic instability and permanent genomic changes.•HRD status is fundamental for identifying OC patients suitable for platinum and PARPi treatment.•HRD testing is considered a topic with urgent need for improvement, going beyond those available commercially.•Within this study, two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD.•Our tests compare favorably with the reference Myriad assay and correlate with the outcome of high-grade OC patients.
Abstract Objective Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients ...undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with three beneficial cardiovascular effects (inotropic, vasodilatory and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Design Double-blind, placebo-controlled, multicenter randomized trial. Setting Tertiary care hospitals. Interventions Cardiac surgery patients (n=1,000) with postoperative myocardial dysfunction(defined as: patients with intra-aortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/kg/min) or placebo for 24-48 hours. Measurements and main results The primary endpoint will be 30-day mortality. Secondary endpoints will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open label levosimendan, length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduce 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. Conclusions This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.
Assemblages composed of Heleobia parchappii and H. australis constitute the dominant elements in Quaternary deposits of the Pampean Region in the province of Buenos Aires. This study describes and ...analyzes the degree of preservation of shells of both species recovered from nine Holocene localities in order to describe and quantify taphonomic alterations, evaluate if preservation varied during the Holocene, and assess their utility as paleoenvironmental bioindicators. Heleobia parchappii displayed better overall preservation than H. australis, with little evidence of fragmentation, limited principally to levels with highest densities. On a temporal scale, no significant differences in fragmentation were found, whereas corrasion and luster displayed temporal differences.
Digital mammography Pisano, Etta D; Yaffe, Martin J
Radiology,
02/2005, Letnik:
234, Številka:
2
Journal Article
Recenzirano
In digital mammography, the processes of image acquisition, display, and storage are separated, which allows optimization of each. Radiation transmitted through the breast is absorbed by an ...electronic detector, the response of which is faithful over a wide range of intensities. Once this information is recorded, it can be displayed by using computer image-processing techniques to allow arbitrary settings of image brightness and contrast, without the need for further exposure to the patient. In this article, the current state of the art in technology for digital mammography and data from clinical trials that support the use of the technology will be reviewed. In addition, several potentially useful applications that are being developed with digital mammography will be described.
Seven breast cancer specimens were examined with diffraction-enhanced imaging at 18 keV with a silicon crystal with use of the silicon 333 reflection in Bragg mode. Images were compared with digital ...radiographs of the specimen, and regions of increased detail were identified. Six of the seven cases (86%) showed enhanced visibility of surface spiculation that correlated with histopathologic information, including extension of tumor into surrounding tissue.
Immunotherapy combined with chemotherapy significantly improves progression-free survival (PFS) compared to first-line chemotherapy alone in advanced endometrial cancer (EC), with a much larger ...effect size in microsatellite instability-high (MSI-H) cases. New biomarkers might help to select patients who may have benefit among those with a microsatellite-stable (MSS) tumor.
In a pre-planned translational analysis of the MITO END-3 trial, we assessed the significance of genomic abnormalities in patients randomized to standard carboplatin/paclitaxel without or with avelumab.
Out of 125 randomized patients, 109 had samples eligible for next-generation sequencing analysis, and 102 had MSI tested. According to The Cancer Genome Atlas (TCGA), there were 29 cases with MSI-H, 26 with MSS TP53 wild type (wt), 47 with MSS TP53 mutated (mut), and 1 case with POLE mutation. Four mutated genes were present in >30% of cases: TP53, PIK3CA, ARID1A, and PTEN. Eleven patients (10%) had a BRCA1/2 mutation (five in MSI-H and six in MSS). High tumor mutational burden (≥10 muts/Mb) was observed in all MSI-H patients, in 4 out of 47 MSS/TP53 mut, and no case in the MSS/TP53 wt category. The effect of avelumab on PFS significantly varied according to TCGA categories, being favorable in MSI-H and worst in MSS/TP53 mut (P interaction = 0.003); a similar non-significant trend was seen in survival analysis. ARID1A and PTEN also showed a statistically significant interaction with treatment effect, which was better in the presence of the mutation (ARID1A P interaction = 0.01; PTEN P interaction = 0.002).
The MITO END-3 trial results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced EC.
Diffraction-enhanced imaging (DEI) is a new x-ray imaging modality that has been shown to enhance contrast between normal and cancerous breast tissues. In this study, diffraction-enhanced imaging in ...computed tomography (DEI-CT) mode was used to quantitatively characterize the refraction contrasts of the organized structures associated with invasive human breast cancer. Using a high-sensitivity Si (3 3 3) reflection, the individual features of breast cancer, including masses, calcifications and spiculations, were observed. DEI-CT yields 14, 5 and 7 times higher CT numbers and 10, 9 and 6 times higher signal-to-noise ratios (SNR) for masses, calcifications and spiculations, respectively, as compared to conventional CT of the same specimen performed using the same detector, x-ray energy and dose. Furthermore, DEI-CT at ten times lower dose yields better SNR than conventional CT. In light of the recent development of a compact DEI prototype using an x-ray tube as its source, these results, acquired at a clinically relevant x-ray energy for which a pre-clinical DEI prototype currently exists, suggest the potential of clinical implementation of mammography with DEI-CT to provide high-contrast, high-resolution images of breast cancer (Parham 2006 PhD Dissertation University of North Carolina at Chapel Hill).
PDF
