CFD measured using a simple fluorometric assay has shown good correlation to stage and enhanced sensitivity to locally advanced disease. A large prospective study is warranted to evaluate if inclusion of this method as a decisive marker before mammography is advantageous.
Mammography has a crucial role in the detection of breast cancer (Bc), yet it is not limitation-free. We hypothesized that the combination of mammography and cell-free DnA (cfDnA) levels may better discriminate patients with cancer. This prospective study included 259 participants suspected with Bc before biopsy. Blood samples were taken before biopsy and from some patients during and at the end of treatment. cfDNA blood levels were measured using our simple fluorescent assay. The primary outcome was the pathologic diagnosis of Bc, and the secondary aims were to correlate cfDnA to severity, response to treatments, and outcome. Median cfDnA blood levels were similar in patients with positive and negative biopsy: 577 vs. 564 ng/ml (p = 0.98). A significant decrease in cfDnA blood level was noted after the following treatments: surgery, surgery and radiation, neoadjuvant chemotherapy and surgery, and at the end of all treatments. to conclude, the cfDnA level could not be used in suspected patients to discriminate Bc. Reduction of tumor burden by surgery and chemotherapy is associated with reduction of cfDnA levels. in a minority of patients, an increase in post-treatment cfDnA blood level may indicate the presence of a residual tumor and higher risk. further outcome assessment for a longer period is suggested. Breast cancer (BC) is the most common form of cancer diagnosed in women worldwide, and is a leading cause of death among women in the United States and Israel 1. Mortality rates in developed countries have been declining in the last decade due to mammographic screening and improved adjuvant/neo-adjuvant therapy. Conversely, the mortality rate in undeveloped countries has been increasing due to the lack of screening and the westernization of reproductive and nutritional patterns 2. Mammography is the only screening tool proven effective for detecting early breast cancer and reducing mortality. Yet mammography and ultrasound-assisted core needle biopsy (US-CNB) limitations have been raised. In a meta-analysis of eight eligible trials of 600,000 women, Gøtzsche and Nielsen found no effect of screening on BC mortality after 10 years. These authors concluded that screening led to 30% over-diagnosis and over-treatment, or an absolute increase of 0.5% in the risk of death. In fact, nearly 20% of women without BC underwent biopsy after ten mammograms 3. As for US-CNB, the overall false-negative rate may reach 6.1% and a diagnosis underestimation rate of 31.4%. While US-CNB is useful in confirming invasive carcinomas, it has much lower efficacy when only ductal carcinoma in-situ (DCIS) is detected. Among lesions yielding DCIS at US-CNB, surgery revealed an infiltrating carcinoma in 16-55.5% of patients 4 .
Diffusion‐weighted imaging (DWI) can improve breast cancer characterizations, but often suffers from low image quality –particularly at informative b > 1000 s/mm2 values. The aim of this study was to evaluate multishot approaches characterizing Gaussian and non‐Gaussian diffusivities in breast cancer. This was a prospective study, in which 15 subjects, including 13 patients with biopsy‐confirmed breast cancers, were enrolled. DWI was acquired at 3 T using echo planar imaging (EPI) with and without zoomed excitations, readout‐segmented EPI (RESOLVE), and spatiotemporal encoding (SPEN); dynamic contrast‐enhanced (DCE) data were collected using three‐dimensional gradient‐echo T1 weighting; anatomies were evaluated with T2‐weighted two‐dimensional turbo spin‐echo. Congruence between malignancies delineated by DCE was assessed against high‐resolution DWI scans with b‐values in the 0–1800 s/mm2 range, as well as against apparent diffusion coefficient (ADC) and kurtosis maps. Data were evaluated by independent magnetic resonance scientists with 3–20 years of experience, and radiologists with 6 and 20 years of experience in breast MRI. Malignancies were assessed from ADC and kurtosis maps, using paired t tests after confirming that these values had a Gaussian distribution. Agreements between DWI and DCE datasets were also evaluated using Sorensen–Dice similarity coefficients. Cancerous and normal tissues were clearly separable by ADCs: by SPEN their average values were (1.03 ± 0.17) × 10−3 and (1.69 ± 0.19) × 10−3 mm2/s (p < 0.0001); by RESOLVE these values were (1.16 ± 0.16) × 10−3 and (1.52 ± 0.14) × 10−3 (p = 0.00026). Kurtosis also distinguished lesions (K = 0.64 ± 0.15) from normal tissues (K = 0.45 ± 0.05), but only when measured by SPEN (p = 0.0008). The best statistical agreement with DCE‐highlighted regions arose for SPEN‐based DWIs recorded with b = 1800 s/mm2 (Sorensen–Dice coefficient = 0.67); DWI data recorded with b = 850 and 1200 s/mm2, led to lower coefficients. Both ADC and kurtosis maps highlighted the breast malignancies, with ADCs providing a more significant separation. The most promising alternative for contrast‐free delineations of the cancerous lesions arose from b = 1800 s/mm2 DWI. Level of Evidence 2. Technical Efficacy Stage 3.
Adding furosemide (F) to mannitol causes a greater decrease of brain volume, intracranial pressure, and brain water content (BW) as compared with mannitol alone. We examined whether adding F to hypertonic saline (HS) causes less increase of BW early after closed head trauma (CHT) as compared with HS alone. With institutional approval, 125 rats underwent sham surgery or CHT and then immediately received no treatment, HS (1.2 g/kg, 3% solution), or HS + F (2 mg/kg). In groups 1-10 (n = 8/group), the percent BW content was determined at 30, 60, or 120 minutes. In groups 11-14 (n = 8/group), physiologic values were determined at 0, 30, 60, and 120 minutes. At 120 minutes, the increase of BW caused by CHT (sham = 78.9 +/- 0.6% and CHT = 81.5 +/- 2.2%, mean +/- SD) was prevented by HS + F (78.0 +/- 0.8%) but not by HS (80.7 +/- 2.2%). Both HS and HS + F similarly increased plasma osmolality and sodium concentration. Post-CHT hypotension and acidosis (30 and 60 minutes) and decrease of hemoglobin concentration (120 minutes) were less with HS + F than with HS. We conclude that adding F to HS decreases BW without causing more increase of osmolality and Na than that caused by HS alone.
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