Radiological features of screening-detected and interval breast cancers and subsequent survival in Eastern Finnish women.

Interval breast cancers are diagnosed between scheduled screenings and differ in many respects from screening-detected cancers. Studies comparing the survival of patients with interval and screening-detected cancers have reported differing results. The aim of this study was to investigate the radiological and histopathological features and growth rates of screening-detected and interval breast cancers and subsequent survival. This retrospective study included 942 female patients aged 50-69 years with breast cancers treated and followed-up at Kuopio University Hospital between January 2010 and December 2016. The screening-detected and interval cancers were classified as true, minimal-signs, missed, or occult. The radiological features were assessed on mammograms by one of two specialist breast radiologists with over 15 years of experience. A χ2 test was used to examine the association between radiological and pathological variables; an unpaired t test was used to compare the growth rates of missed and minimal-signs cancers; and the Kaplan-Meier estimator was used to examine survival after screening-detected and interval cancers. Sixty occult cancers were excluded, so a total of 882 women (mean age 60.4 ± 5.5 years) were included, in whom 581 had screening-detected cancers and 301 interval cancers. Disease-specific survival, overall survival and disease-free survival were all worse after interval cancer than after screening-detected cancer (p < 0.001), with a mean follow-up period of 8.2 years. There were no statistically significant differences in survival between the subgroups of screening-detected or interval cancers. Missed interval cancers had faster growth rates (0.47% ± 0.77%/day) than missed screening-detected cancers (0.21% ± 0.11%/day). Most cancers (77.2%) occurred in low-density breasts (< 25%). The most common lesion types were masses (73.9%) and calcifications (13.4%), whereas distortions (1.8%) and asymmetries (1.7%) were the least common. Survival was worse after interval cancers than after screening-detected cancers, attributed to their more-aggressive histopathological characteristics, more nodal and distant metastases, and faster growth rates.

Specimen tomosynthesis provides no additional value to specimen ultrasound in ultrasound-visible malignant breast lesions.

BACKGROUND: The aim of this study was to evaluate the accuracy and added value of specimen tomosynthesis (ST) to specimen ultrasound (SUS) in margin assessment of excised breast specimens in breast-conserving therapy for non-palpable US-visible breast lesions. MATERIALS: Between January 2018 and August 2019, all consecutive patients diagnosed with non-palpable breast cancer visible by ultrasound (US), treated with breast-conserving surgery (BCS) and requiring radiological intraoperative breast specimen assessment, were included in this study. Excised breast specimens were examined with SUS by radiologists blinded to the ST results, and margins smaller than 10 mm were recorded. STs were evaluated retrospectively by experienced radiologists. RESULTS: A total of 120 specimens were included. SUS showed a statistically significant correlation with pathological margin measurements, while ST did not and provided no additional information. The odds ratios (ORs) for SUS to predict a positive margin was 3.429 (confidence interval (CI) = 0.548-21.432) using a 10-mm cut-off point and 14.182 (CI = 2.134-94.254) using a 5-mm cut-off point, while the OR for ST were 2.528 (CI = 0.400-15.994) and 3.188 (CI = 0.318-31.998), respectively. CONCLUSIONS: SUS was superior in evaluating intraoperative resection margins of US-visible breast resection specimens when compared to ST. Therefore, ST could be considered redundant in applicable situations.

Diagnostic performance of tomosynthesis, digital mammography and a dedicated digital specimen radiography system versus pathological assessment of excised breast lesions.

BACKGROUND: The aim of the study was to compare the performance of full-field digital mammography (FFDM), digital breast tomosynthesis and a dedicated digital specimen radiography system (SRS) in consecutive patients, and to compare the margin status of resected lesions versus pathological assessment. PATIENTS AND METHODS: Resected tissue specimens from consecutive patients who underwent intraoperative breast specimen assessment following wide local excision or oncoplastic breast conservative surgery were examined by FFDM, tomosynthesis and SRS. Two independent observers retrospectively evaluated the visibility of lesions, size, margins, spiculations, calcifications and diagnostic certainty, and chose the best performing method in a blinded manner. RESULTS: We evaluated 216 specimens from 204 patients. All target malignant lesions were removed with no tumouron-ink. One papilloma had positive microscopic margins and one patient underwent reoperation owing to extensive in situ components. There were no significant differences in measured lesion size among the three methods. However, tomosynthesis was the most accurate modality when compared with the final pathological report. Both observers reported that tomosynthesis had significantly better lesion visibility than SRS and FFDM, which translated into a significantly greater diagnostic certainty. Tomosynthesis was superior to the other two methods in identifying spiculations and calcifications. Both observers reported that tomosynthesis was the best performing method in 76.9% of cases. The interobserver reproducibilities of lesion visibility and diagnostic certainty were high for all three methods. CONCLUSIONS: Tomosynthesis was superior to SRS and FFDM for detecting and evaluating the target lesions, spiculations and calcifications, and was therefore more reliable for assessing complete excision of breast lesions.

Can supine breast magnetic resonance imaging help hit the target in extreme oncoplastic surgery?

OBJECTIVES: To evaluate the clinical value of supine magnetic resonance imaging (MRI) for tumor localization in breast cancer patients with large or multifocal tumors detected by prone MRI, scheduled for oncoplastic breast conserving surgery (OBCS). Outcomes were compared with those of patients who underwent wide local excision (WLE) or OBCS without MRI guidance. METHODS: Over a 2-year period, consecutive patients with large or multifocal disease scheduled for OBCS with MRI-only findings were invited to participate (Group-1). Supplementary supine MRI was performed, and tumor margins were marked in the surgical position. Consecutive patients with early, non-palpable breast cancer who underwent WLE (Group-2) or OBCS (Group-3) were included for comparisons. The primary outcome was reoperation due to an insufficient margin. Secondary outcomes included surgical complications and delayed adjuvant treatment. RESULTS: Altogether, 102 breasts (98 patients) were analyzed. All preoperative demographic data were comparable among the three groups. Multifocality, tumor-to-breast volume ratio, and the volume of excised breast tissue were significantly greater in Group-1 than in Groups-2 and 3. Operation time was longer and the need for axillary clearance or surgery for both breasts was more common in Groups-1 and 3 than in Group-2. Adequate margins were achieved in all patients in Groups-1 and 2, and one patient underwent re-excision in Group-3. CONCLUSIONS: Supine MRI in the surgical position is a new, promising method to localize multifocal, large tumors visible on MRI. Its short-term outcomes were comparable with those of conventional WLE and OBCS.

Diagnostic performance of the Kaiser score for characterizing lesions on breast MRI with comparison to a multiparametric classification system.

PURPOSE: To determine the diagnostic performance of the Kaiser score and to compare it with the BI-RADS-based multiparametric classification system (MCS). METHOD: Two breast radiologists, blinded to the clinical and pathological information, separately evaluated a database of 499 consecutive patients with structural 3.0 T breast MRI and 697 histopathologically verified lesions. The Kaiser scores and corresponding MCS categories were recorded. The sensitivity and specificity of the Kaiser score and the MCS categories to differentiate benign from malignant lesions were calculated. The interobserver reproducibility and receiver operating characteristic (ROC) parameters were analysed. RESULTS: The sensitivity and specificity of the MCS were 100 % and 12 %, respectively, and those of the Kaiser score were 98.5 % and 34.8 % for reader 1 and 98.7 % and 47.5 % for reader 2. The area under the ROC-curve was 85.9 and 87.6 for readers 1 and 2. The interobserver intraclass correlation coefficient was excellent at 0.882. Reader 1 upgraded six lesions from BI-RADS 3 to a Kaiser score of >4, and reader 2 upgraded seven lesions. When applying the Kaiser score to 158 benign lesions readers 1 and 2 would have reduced the biopsy rate by 22.8 % and 35.4 %, respectively. CONCLUSIONS: The Kaiser score showed high diagnostic accuracy with excellent interobserver reproducibility. The MCS had perfect sensitivity but low specificity. Although the Kaiser score had slightly lower sensitivity, its specificity was 3-4 times greater than that of the MCS. Thus, the Kaiser score has the potential to considerably reduce the biopsy rate for true negative lesions.

The mammographic breast density distribution of Finnish women with breast cancer and comparison of breast density reporting using the 4th and 5th editions of the Breast Imaging-Reporting and Data System.

PURPOSE: To examine the breast density distribution in patients diagnosed with breast cancer in an eastern Finnish population and to examine the changes in breast density reporting patterns between the 4th and 5th editions of the Breast Imaging-Reporting and Data System (BI-RADS). METHOD: 821 women (mean age 62.8 ± 12.2 years, range 28-94 years) with breast cancer were included in this retrospective study and their digital mammographic examinations were assessed semi-automatically and then visually by two radiologists in accordance with the 4th and 5th editions of the BI-RADS. Intraclass correlation coefficients (ICCs) were used to evaluate interobserver reproducibility. Chi-square tests were used to examine the associations between the breast density distribution and age or body mass index (BMI). RESULTS: Interobserver reproducibility of the visual assessment was excellent, with an ICCr = 0.93. The majority of breast cancers occurred in fatty breasts (93.8 %) when density was assessed according to the 4th edition of the BI-RADS. The distributions remained constant after correction for age and BMI. Using the 5th edition, there was an overall 50.2 % decrease in almost entirely fatty (p < 0.001), 19.4 % increase in scattered fibroglandular (p < 0.001), 28.7 % increase in heterogeneously dense (p < 0.001), and 2.1 % increase in extremely dense (p < 0.001) categories. CONCLUSIONS: Most breast cancers in eastern Finland occur in fatty breasts with an area density of < 50 %. Assessing breast density using the 5th edition of the BI-RADS greatly increased denser assessments.

Peritumor to tumor apparent diffusion coefficient ratio is associated with biologically more aggressive breast cancer features and correlates with the prognostication tools.

PURPOSE: The apparent diffusion coefficient (ADC) is increasingly used to characterize breast cancer. The peritumor/tumor ADC ratio is suggested to be a reliable and generally applicable index. However, its overall prognostication value remains unclear. We aimed to evaluate the associations between the peritumor/tumor ADC ratio and histopathological biomarkers and published prognostic tools in patients with invasive breast cancer. MATERIALS AND METHODS: This prospective study included 88 lesions (five bilateral) in 83 patients with primary invasive breast cancer who underwent preoperative 3.0-T magnetic resonance imaging. The lowest intratumoral mean ADC value on the slice with the largest tumor cross-sectional area was designated the tumor ADC, and the highest mean ADC value on the peritumoral breast parenchymal tissue adjacent to the tumor border was designated the peritumor ADC. The peritumor/tumor ADC ratio was then calculated. The tumor and peritumor ADC values and peritumor/tumor ADC ratios were compared with histopathological parameters using an unpaired t test, and their correlations with published prognostic tools were evaluated with Pearson's correlation coefficient. RESULTS: The peritumor/tumor ADC ratio was significantly associated with tumor size (p<0.001), histological grade (p = 0.005), Ki-67 index (p = 0.006), axillary-lymph-node metastasis (p = 0.001), and lymphovascular invasion (p = 0.006), but was not associated with estrogen receptor status (p = 0.931), progesterone receptor status (p = 0.160), or human epidermal growth factor receptor 2 status (p = 0.259). The peritumor/tumor ADC ratio showed moderate positive correlations with the Nottingham Prognostic Index (r = 0.498, p<0.001) and mortality predicted using PREDICT (r = 0.436, p<0.001). CONCLUSION: The peritumor/tumor ADC ratio was correlated with histopathological biomarkers in patients with invasive breast cancer, showed significant correlations with published prognostic indexes, and may provide an easily applicable imaging index for the preoperative prognostic evaluation of breast cancer.

The feasibility of ultrasound-guided vacuum-assisted evacuation of large breast hematomas.

Background Breast hematoma is an often underrated and disregarded post-procedural complication in the literature. Current treatment modalities are comprised of either surgical or expectant therapy, while percutaneous procedures play a smaller role in their treatment. We aimed to examine the efficacy of vacuum-assisted evacuation (VAE) in the treatment of clinically significant large breast hematomas as an alternative to surgery. Patients and methods We retrospectively analysed patients that underwent breast interventions (surgical and percutaneous), who later developed clinically significant large hematomas and underwent a trial of VAE of hematoma in our hospital within the period of four years. Patient and procedure characteristics were acquired before and after VAE. Success of intervention was based on ≥ 50% clearance of hematoma volume and patients' subjective resolution of symptoms. All patients were followed clinically and by ultrasound if needed at different intervals depending on the severity of presenting symptoms. Results Eleven patients were included in the study. The mean largest diameter of hematomas was 7.9 cm and mean surface area was 32.4 cm2. The mean duration of the procedure was 40.5 min. In all patients VAE of hematoma was implemented successfully with no complications. Control visits showed no major residual hematoma or seroma formation. Conclusions Our results show that VAE of hematoma can be implemented as a safe alternative to surgery in large, clinically significant hematomas, regardless of aetiology or duration. The procedure carries less risk, stress and cost with the added benefit of outpatient treatment when compared to surgical treatment.

Peritumoral ADC values in breast cancer: region of interest selection, associations with hyaluronan intensity, and prognostic significance.

OBJECTIVES: We aimed to evaluate the differences in peritumoral apparent diffusion coefficient (ADC) values by four different ROI selection methods and to validate the optimal method. Furthermore, we aimed to evaluate if the peritumor-tumor ADC ratios are correlated with axillary lymph node positivity and hyaluronan accumulation. METHODS: Altogether, 22 breast cancer patients underwent 3.0-T breast MRI, histopathological evaluation, and hyaluronan assay. Paired t and Friedman tests were used to compare minimum, mean, and maximum values of tumoral and peritumoral ADC by four methods: (M1) band ROI, (M2) whole tumor surrounding ROI, (M3) clockwise multiple ROI, and (M4) visual assessment of ROI selection. Subsequently, peritumor/tumor ADC ratios were compared with hyaluronan levels and axillary lymph node status by the Mann-Whitney U test. RESULTS: No statistically significant differences were found among the four ROI selection methods regarding minimum, mean, or maximum values of tumoral and peritumoral ADC. Visual assessment ROI measurements represented the less time-consuming evaluation method for the peritumoral area, and with sufficient accuracy. Peritumor/tumor ADC ratios obtained by all methods except the clockwise ROI (M3) showed a positive correlation with hyaluronan content (M1, p = 0.004; M2, p = 0.012; M3, p = 0.20; M4, p = 0.025) and lymph node metastasis (M1, p = 0.001; M2, p = 0.007; M3, p = 0.22; M4, p = 0.015), which are established factors for unfavorable prognosis. CONCLUSIONS: Our results suggest that the peritumor/tumor ADC ratio could be a readily applicable imaging index associated with axillary lymph node metastasis and extensive hyaluronan accumulation. It could be related to the biological aggressiveness of breast cancer and therefore might serve as an additional prognostic factor. KEY POINTS: • Out of four different ROI selection methods for peritumoral ADC evaluation, measurements based on visual assessment provided sufficient accuracy and were the less time-consuming method. • The peritumor/tumor ADC ratio can provide an easily applicable supplementary imaging index for breast cancer assessment. • A higher peritumor/tumor ADC ratio was associated with axillary lymph node metastasis and extensive hyaluronan accumulation and might serve as an additional prognostic factor.

Tumor microenvironment and breast cancer survival: combined effects of breast fat, M2 macrophages and hyaluronan create a dismal prognosis.

PURPOSE: Tumor microenvironment, including inflammatory cells, adipocytes and extracellular matrix constituents such as hyaluronan (HA), impacts on cancer progression. Systemic metabolism also influences tumor growth e.g. obesity and type 2 diabetes (T2D) are risk factors for breast cancer. Here, in 262 breast cancer cases, we explored the combined impacts on survival of M2-like tumor associated macrophages (TAMs), the abundance of breast fat visualized as low density in mammograms, and tumor HA, and their associations with T2D. METHODS: Mammographic densities were assessed visually from the diagnostic images and dichotomized into very low density (VLD, density ≤ 10%, "fatty breast") and mixed density (MID, density > 10%). The amounts of TAMs (CD163+ and CD68+) and tumor HA were determined by immunohistochemistry. The data of T2D was collected from the patient records. Statistical differences between the parameters were calculated with Chi square or Mann-Whitney test and survival analyses with Cox's model. RESULTS: A combination of fatty breasts (VLD), abundance of M2-like TAMs (CD163+) and tumor HA associated with poor survival, as survival was 88-89% in the absence of these factors but only 40-47% when all three factors were present (p < 0.001). Also, an association between T2D and fatty breasts was found (p < 0.01). Furthermore, tumors in fatty breasts contained more frequently high levels of M2-like TAMs than tumors in MID breasts (p = 0.01). CONCLUSIONS: Our results demonstrate a dramatic effect of the tumor microenvironment on breast cancer progression. We hypothesize that T2D as well as obesity increase the fat content of the breasts, subsequently enhancing local pro-tumoral inflammation.

Galactography is not an obsolete investigation in the evaluation of pathological nipple discharge.

PURPOSE: To evaluate the malignancy rate and diagnostic performance of galactography in patients with pathological nipple discharge (PND) after negative clinical breast examination, mammography and ultrasound. MATERIALS AND METHODS: We retrospectively evaluated all galactograms obtained between January 2006 and December 2014 in women with PND. Galactographic findings were classified into 6 groups according to a modified Galactogram Image Classification system (GICS) to comply with the breast imaging reporting and data system classification. Observers were blinded to the final histology and clinical outcome at the time of analysis. MRI was performed as a problem solving ancillary examination. Imaging findings, pathological diagnosis and follow-up data were evaluated. The diagnostic performance of MRI and technically successful galactography in the detection of neoplastic or risk lesions were separately calculated. RESULTS: A total of 146 patients with PND (mean age, 51.5 years; range, 17-93) were examined. Malignant lesions were detected in only 4 patients (2.7%) and risk-lesions in 5 patients (3.4%). Only one low-grade ductal carcinoma in situ was missed by galactography (GICS 1) and MRI. MRI examinations were performed in 21 (14.4%) patients; one of these patients (4.8%) had a malignant finding (GICS 0), two (9.5%) had risk-lesions (GICS 2 and 5). In the detection of neoplastic or risk lesions the sensitivity and specificity of galactography were 77.4% and 75.7% and of MRI 85.7% and 71.4%, consecutively. CONCLUSION: The malignancy rate is negligible if clinical, mammography, ultrasound and galactography examinations are negative. Galactography remains a practical, valuable and cost-effective examination procedure. If galactography is technically unsuccessful, MRI should be considered as an additional ancillary tool to evaluate the possible etiology of symptoms, but the routine use of MRI in all patients cannot be justified.

UDP-sugar accumulation drives hyaluronan synthesis in breast cancer.

Increased uptake of glucose, a general hallmark of malignant tumors, leads to an accumulation of intermediate metabolites of glycolysis. We investigated whether the high supply of these intermediates promotes their flow into UDP-sugars, and consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human breast cancer biopsies, the levels of enzymes contributing to their synthesis, and their association with the hyaluronan accumulation in the tumor. The content of UDP-GlcUA was 4 times, and that of UDP-GlcNAc 12 times higher in the tumors as compared to normal glandular tissue obtained from breast reductions. The surge of UDP-GlcNAc correlated with an elevated mRNA expression of glutamine-fructose-6-phosphate aminotransferase 2 (GFAT2), one of the key enzymes in the biosynthesis of UDP-GlcNAc, and the expression of GFAT1 was also elevated. The contents of both UDP-sugars strongly correlated with tumor hyaluronan levels. Interestingly, hyaluronan content did not correlate with the mRNA levels of the hyaluronan synthases (HAS1-3), thus emphasizing the role of the UDP-sugar substrates of these enzymes. The UDP-sugars showed a trend to higher levels in ductal vs. lobular cancer subtypes. The results reveal for the first time a dramatic increase of UDP-sugars in breast cancer, and suggest that their high supply drives the accumulation of hyaluronan, a known promoter of breast cancer and other malignancies. In general, the study shows how the disturbed glucose metabolism typical for malignant tumors can influence cancer microenvironment through UDP-sugars and hyaluronan.

Gadoterate meglumine decreases ADC values of breast lesions depending on the b value combination.

To retrospectively evaluated the influence of administration of the gadolinium based intravenous contrast agent (G-CA) on apparent diffusion coefficient (ADC) values in ADC maps generated using multiple b value combinations. A total of 106 women underwent bilateral 3.0 T breast MRI. As an internal validation, diffusion-weighted imaging (b values of 0, 200, 400, 600, 800 s/mm2) was performed before and after the G-CA (gadoterate meglumine (0.2 ml/kg, 3 ml/s)). Whole lesion and fibroglandular tissue (FGT) covering region-of-interests (ROIs) were drawn on the b = 800 s/mm2 images; ROIs were then propagated to multiple retrospectively generated ADC maps. Twenty-seven patients (mean age 55.8 ± 10.8 years) with 32 mass-like enhancing breast lesions including 25 (78.1 %) histopathologically malignant lesions were enrolled. Lesion ADC values were statistically significantly higher in pre-G-CA than post-G-CA ADC maps (ADC0,200,400,600,800: 1.05 ± 0.35 × 10-3 mm2/s vs. 1.02 ± 0.36 × 10-3 mm2/s (P < 0.05); ADC0,200,400: 1.25 ± 0.42 × 10-3 mm2/s vs. 1.20 ± 0.35 × 10-3 mm2/s (P < 0.05)). ADC values between pre- and post-contrast maps were not statistically different when the maps were generated using other b value combinations. Contrast agent administration did not affect the FGT ADC values. G-CA statistically significantly reduced the ADC values of breast lesions on ADC maps generated using the clinically widely utilized b values.

Quantitative Volumetric K-Means Cluster Segmentation of Fibroglandular Tissue and Skin in Breast MRI.

Mammographic breast density (MBD) is the most commonly used method to assess the volume of fibroglandular tissue (FGT). However, MRI could provide a clinically feasible and more accurate alternative. There were three aims in this study: (1) to evaluate a clinically feasible method to quantify FGT with MRI, (2) to assess the inter-rater agreement of MRI-based volumetric measurements and (3) to compare them to measurements acquired using digital mammography and 3D tomosynthesis. This retrospective study examined 72 women (mean age 52.4 ± 12.3 years) with 105 disease-free breasts undergoing diagnostic 3.0-T breast MRI and either digital mammography or tomosynthesis. Two observers analyzed MRI images for breast and FGT volumes and FGT-% from T1-weighted images (0.7-, 2.0-, and 4.0-mm-thick slices) using K-means clustering, data from histogram, and active contour algorithms. Reference values were obtained with Quantra software. Inter-rater agreement for MRI measurements made with 2-mm-thick slices was excellent: for FGT-%, r = 0.994 (95% CI 0.990-0.997); for breast volume, r = 0.985 (95% CI 0.934-0.994); and for FGT volume, r = 0.979 (95% CI 0.958-0.989). MRI-based FGT-% correlated strongly with MBD in mammography (r = 0.819-0.904, P < 0.001) and moderately to high with MBD in tomosynthesis (r = 0.630-0.738, P < 0.001). K-means clustering-based assessments of the proportion of the fibroglandular tissue in the breast at MRI are highly reproducible. In the future, quantitative assessment of FGT-% to complement visual estimation of FGT should be performed on a more regular basis as it provides a component which can be incorporated into the individual's breast cancer risk stratification.

Prognostic contribution of mammographic breast density and HER2 overexpression to the Nottingham Prognostic Index in patients with invasive breast cancer.

BACKGROUND: To investigate whether very low mammographic breast density (VLD), HER2, and hormone receptor status holds any prognostic significance within the different prognostic categories of the widely used Nottingham Prognostic Index (NPI). We also aimed to see whether these factors could be incorporated into the NPI in an effort to enhance its performance. METHODS: This study included 270 patients with newly diagnosed invasive breast cancer. Patients with mammographic breast density of <10 % were considered as VLD. In this study, we compared the performance of NPI with and without VLD, HER2, ER and PR. Cox multivariate analysis, time-dependent receiver operating characteristic curve (tdROC), concordance index (c-index) and prediction error (0.632+ bootstrap estimator) were used to derive an updated version of NPI. RESULTS: Both mammographic breast density (VLD) (p < 0.001) and HER2 status (p = 0.049) had a clinically significant effect on the disease free survival of patients in the intermediate and high risk groups of the original NPI classification. The incorporation of both factors (VLD and HER2 status) into the NPI provided improved patient outcome stratification by decreasing the percentage of patients in the intermediate prognostic groups, moving a substantial percentage towards the low and high risk prognostic groups. CONCLUSIONS: Very low density (VLD) and HER2 positivity were prognostically significant factors independent of the NPI. Furthermore, the incorporation of VLD and HER2 to the NPI served to enhance its accuracy, thus offering a readily available and more accurate method for the evaluation of patient prognosis.

Comprehensive MR Urography Protocol: Equally Good Diagnostic Performance and Enhanced Visibility of the Upper Urinary Tract Compared to Triple-Phase CT Urography.

OBJECTIVES: To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT) using a comprehensive 3.0T- magnetic resonance urography (MRU) protocol versus triple-phase computed tomography urography (CTU). METHODS: During the study period (January-2014 through December-2015), all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test. RESULTS: Twenty patients (39 UUT excreting units) were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU) and 87.2% (with CTU) and >75% visualization in 100% (3.0T-MRU) and 93.6% (CTU). Mean CTU effective radiation dose was 9.2 mSv. CONCLUSIONS: Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02606513.

Incidentally detected enhancing lesions found in breast MRI: analysis of apparent diffusion coefficient and T2 signal intensity significantly improves specificity.

OBJECTIVES: To evaluate the value of adding T2- and diffusion-weighted imaging (DWI) to the BI-RADS® classification in MRI-detected lesions. METHODS: This retrospective study included 112 consecutive patients who underwent 3.0T structural breast MRI with T2- and DWI on the basis of EUSOMA recommendations. Morphological and kinetic features, T2 signal intensity (T2 SI) and apparent diffusion coefficient (ADC) findings were assessed. RESULTS: Thirty-three (29.5 %) patients (mean age 57.0 ± 12.7 years) had 36 primarily MRI-detected incidental lesions of which 16 (44.4 %) proved to be malignant. No single morphological or kinetic feature was associated with malignancy. Both low T2 SI (P = 0.009) and low ADC values (≤0.87 × 10-3 mm2s-1, P < 0.001) yielded high specificity (80.0 %/80.0 %). The BI-RADS classification supplemented with information from DWI and T2-WI improved the diagnostic performance of the BI-RADS classification as sensitivity remained 100 % and specificity improved from 30 % to 65.0 %. The numbers of false positive lesions declined from 39 % (N = 14) to 19 % (N = 7). CONCLUSION: MRI-detected incidental lesions may be challenging to characterize as they have few specific malignancy indicating features. The specificity of MRI can be improved by incorporating T2 SI and ADC values into the BI-RADS assessment. KEY POINTS: • MRI-detected incidental lesions have few specific malignancy indicating features. • ≥ 1 suspicious morphologic or kinetic feature may warrant biopsy. • T2 signal intensity and DWI assessment are feasible in primarily MRI-detected lesions. • T2 SI and DWI assessment improve the BI-RADS specificity in MRI-detected lesions.

Diffusion-Weighted Imaging in 3.0 Tesla Breast MRI: Diagnostic Performance and Tumor Characterization Using Small Subregions vs. Whole Tumor Regions of Interest.

INTRODUCTION: Apparent diffusion coefficient (ADC) values are increasingly reported in breast MRI. As there is no standardized method for ADC measurements, we evaluated the effect of the size of region of interest (ROI) to diagnostic utility and correlation to prognostic markers of breast cancer. METHODS: This prospective study was approved by the Institutional Ethics Board; the need for written informed consent for the retrospective analyses of the breast MRIs was waived by the Chair of the Hospital District. We compared diagnostic accuracy of ADC measurements from whole-lesion ROIs (WL-ROIs) to small subregions (S-ROIs) showing the most restricted diffusion and evaluated correlations with prognostic factors in 112 consecutive patients (mean age 56.2±11.6 years, 137 lesions) who underwent 3.0-T breast MRI. RESULTS: Intra- and interobserver reproducibility were substantial (κ = 0.616-0.784; Intra-Class Correlation 0.589-0.831). In receiver operating characteristics analysis, differentiation between malignant and benign lesions was excellent (area under curve 0.957-0.962, cut-off ADC values for WL-ROIs: 0.87×10-3 mm2s-1; S-ROIs: 0.69×10-3 mm2s-1, P<0.001). WL-ROIs/S-ROIs achieved sensitivities of 95.7%/91.3%, specificities of 89.5%/94.7%, and overall accuracies of 89.8%/94.2%. In S-ROIs, lower ADC values correlated with presence of axillary metastases (P = 0.03), high histological grade (P = 0.006), and worsened Nottingham Prognostic Index Score (P<0.05). In both ROIs, ADC values correlated with progesterone receptors and advanced stage (P<0.01), but not with HER2, estrogen receptors, or Ki-67. CONCLUSIONS: ADC values assist in breast tumor characterization. Small ROIs were more accurate than whole-lesion ROIs and more frequently associated with prognostic factors. Cut-off values differed significantly depending on measurement procedure, which should be recognized when comparing results from the literature. Instead of using a whole lesion covering ROI, a small ROI could be advocated in diffusion-weighted imaging.

The reciprocal association between mammographic breast density, hyaluronan synthesis and patient outcome.

Low mammographic breast density (MBD) and increased hyaluronan (HA) synthesis have been shown to have adverse effects on breast cancer prognosis. We aimed at elucidating the background of risk associated with mammographic characteristics, MBD and HA and its synthesizing isoforms in an attempt to uncover potential underlying biological mechanisms. MBD and mammographic characteristics of 270 patients were classified according to percentile density (very low density VLD, ≤25 %; mixed density MID, >25 %) and the BI-RADS 5th edition lexicon. Breast density and mammographic features were correlated with the localization and expression of HA, CD44, and HAS1-3 isoforms, and their combined effect on patients' survivals was explored. VLD showed an increased level of HA-positive carcinoma cells and stromal HA, HAS2, and HAS3. Tumors presenting as masses had more HA-positive carcinoma cells and more stromal HAS2 and HAS3. Indistinct margin tumors showed more stromal HA and HAS3. Patients who combined both VLD breasts with either high HA in carcinoma cells or stroma showed a worse prognosis compared to low levels (carcinoma cells 58.0 vs. 80.5 %, p = 0.001; stroma 64.2 vs. 79.6 %, p = 0.017), while no similar HA-related effect was observed in MID breasts. Our findings suggest a strong reciprocal relationship between low MBD and HA expression and synthesis. The expression of both factors simultaneously leads to an especially adverse prognostic effect which might have an impact on treatment decision in the future. Moreover, HA around cancer cells may inhibit chemotherapy agents and antibody treatments from reaching cancer cells.

Preoperative axillary staging with 3.0-T breast MRI: clinical value of diffusion imaging and apparent diffusion coefficient.

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p<0.001). Mean ADCs were 0.663-0.676 x 10(-3) mm2/s for the histologically confirmed metastatic LNs and 1.100-1.225 x 10(-3) mm2/s for the benign. The sensitivity, specificity, and accuracy of DWI were 72.4%, 79.6%, and 75.9%, respectively with threshold ADC 0.812 x 10(-3) mm2/s. Region of interest with information on the minimum value increased the diagnostic performance (area under the curve 0.794 vs. 0.619). Even though ADCs are significantly associated with histopathologically confirmed axillary metastases the diagnostic performance of axillary DWI remains moderate and ultrasound-guided core biopsies or sentinel lymph node biopsies cannot be omitted.