Early disc degeneration in radiotherapy-treated childhood brain tumor survivors.

BACKGROUND: Childhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls. METHODS: In this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5-33.1), 67 survivors (mean age 28.4, range 16.2-43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration. RESULTS: Childhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05). CONCLUSIONS: Signs of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.

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.

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.

Prevalence of C9ORF72 Expansion in a Large Series of Patients with Idiopathic Normal-Pressure Hydrocephalus.

BACKGROUND/AIMS: The C9ORF72 expansion is known to cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We aim to identify the prevalence of the C9ORF72 expansion in idiopathic normal pressure hydrocephalus (iNPH). METHODS: We analysed the C9ORF72 expansion in a large cohort of patients with possible iNPH (n = 487) and cognitively intact elderly controls (n = 432; age > 65 years). RESULTS: While the C9ORF72 expansion was detected in 1.6% (n = 8/487) of cases with possible iNPH, no control subject was found to carry the mutation. The mean age at onset of symptoms of C9ORF72 expansion carriers was 59 years (range: 52-67 years), 11 years less than non-carriers (p = 0.0002). The most frequent initial/main symptom pertained to gait difficulties. Despite identified mutation, only 3 of the patients fulfilled the criteria for the FTLD-ALS spectrum. Clinically significant shunt response was detected in 6 out of 7 shunted C9ORF72 expansion carriers. CONCLUSION: This is the first study cohort identifying the underlying C9ORF72 expansion in patients with iNPH providing evidence for the potential comorbidity between iNPH and the FTLD-ALS spectrum. Analysis of the C9ORF72 expansion should be considered for patients with probable iNPH presenting with frontal atrophy and personality changes or other severe psychiatric symptoms.

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.

Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus.

BACKGROUND: It remains unclear how intracranial pressure (ICP) measures are associated with brain biopsies and radiological markers. Here, we aim to investigate associations between ICP and radiological findings, brain biopsies, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus (iNPH). METHOD: In this study, we retrospectively analyzed data from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of these patients, 71% underwent shunt surgery. The NPH registry included data on clinical and radiological examinations, 24-h intraventricular pressure monitoring, and frontal cortical biopsy. RESULTS: The mean ICP and mean ICP pulse wave amplitude were not associated with the shunt response. Aggregations of Alzheimer's disease (AD)-related proteins (amyloid-ß, hyperphosphorylated tau) in frontal cortical biopsies were associated with a poor shunt response (P = 0.014). High mean ICP was associated with Evans' index (EI; P = 0.025), disproportional sylvian and suprasylvian subarachnoid spaces (P = 0.014), and focally dilated sulci (P = 0.047). Interestingly, a high pulse wave amplitude was associated with AD-related biopsy findings (P = 0.032), but the mean ICP was not associated with the brain biopsy. The ICP was not associated with medial temporal lobe atrophy, temporal horn widths, or white matter changes. ICP B waves were associated with less atrophy of the medial temporal lobe (P = 0.018) and more severe disproportionality between the sylvian and suprasylvian subarachnoid spaces (P = 0.001). CONCLUSIONS: The EI and disproportional sylvian and suprasylvian subarachnoid spaces were associated with mean ICP. Disproportionality was also associated with ICP B waves. These associations, although rather weak, with elevated ICP in 24-h measurements, support their value in iNPH diagnostics and suggest that these radiological markers are potentially related to the pathogenesis of iNPH. Interestingly, our results suggested that elevated pulse wave amplitude might be associated with brain amyloid accumulation.

Is there a Role for Contrast-enhanced Ultrasound in the Detection and Biopsy of MRI Only Visible Breast Lesions?

BACKGROUND: This study aimed to evaluate the feasibility of contrast-enhanced ultrasound (CEUS) and CEUS-guided interventions in the diagnostics of MRI visible targeted US occult breast lesions. PATIENTS AND METHODS: This retrospective study examined 10 females with 10 occult, MRI only detected breast lesions between July 2014 and April 2017. Targeted second look US followed by CEUS with 2.4 ml of SonoVue® were performed for all of the lesions. After positive CEUS localization the same dose was repeated for confirmation and CEUS-guided interventions were performed. RESULTS: MRI revealed 8 mass lesions with a mean size of 9 mm (range 5-16 mm) and 2 non-mass enhancing lesions of 10 and 20 mm in largest diameters. Targeted US revealed no morphological correlate for the lesions. Five out of 10 lesions (50%) were visible on CEUS. CEUS-guided core biopsy was performed on 4 lesions and 1 was marked with a clip for later surgical removal. Histopathological analysis confirmed 4 of them to be malignant. Three out of 5 nonvisible lesions on CEUS underwent MRI-guided interventions, 1 lesion was scheduled for follow-up as it was non-amenable for MRI biopsy, and 1 lesion was biopsied under US-guidance. Three of these nonvisible lesions on CEUS were confirmed to be malignant. CONCLUSIONS: Based on our preliminary results, CEUS is a feasible tool for detecting many MRI only visible breast lesions, resulting in a more cost effective and less time-consuming practice. It is a more convenient alternative than MRI guided biopsy and has the potential to be included in the diagnostic algorithm which evaluates MRI only visible breast lesions.

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.

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.

Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus.

OBJECTIVES: Optimal selection of idiopathic normal pressure hydrocephalus (iNPH) patients for shunt surgery is challenging. Disease State Index (DSI) is a statistical method that merges multimodal data to assist clinical decision-making. It has previously been shown to be useful in predicting progression in mild cognitive impairment and differentiating Alzheimer's disease (AD) and frontotemporal dementia. In this study, we use the DSI method to predict shunt surgery response for patients with iNPH. METHODS: In this retrospective cohort study, a total of 284 patients (230 shunt responders and 54 non-responders) from the Kuopio NPH registry were analyzed with the DSI. Analysis included data from patients' memory disorder assessments, age, clinical symptoms, comorbidities, medications, frontal cortical biopsy, CT/MRI imaging (visual scoring of disproportion between Sylvian and suprasylvian subarachnoid spaces, atrophy of medial temporal lobe, superior medial subarachnoid spaces), APOE genotyping, CSF AD biomarkers, and intracranial pressure. RESULTS: Our analysis showed that shunt responders cannot be differentiated from non-responders reliably even with the large dataset available (AUC = 0.58). CONCLUSIONS: Prediction of the treatment response in iNPH is challenging even with our extensive dataset and refined analysis. Further research of biomarkers and indicators predicting shunt responsiveness is still needed.

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.

Very low mammographic breast density predicts poorer outcome in patients with invasive breast cancer.

OBJECTIVES: To examine the prognostic value of mammographic breast density (MBD) and mammographic features and their relationship with established prognostic factors in patients with invasive breast cancer. METHODS: Mammographic characteristics of 270 patients were analyzed. MBD was classified according to percentile density (<5%, 5-10%, 10-25%, 25-50%, 50-75%, >75%) and further categorized into very low density (VLD; <10%), low density (LOD; <25%) and mixed density (MID; >25%). Mammographic features were compared with established prognostic factors and patient outcomes while correcting for possible confounders. RESULTS: MBD was inversely associated with tumour grade (p = 0.019). Patients with LOD breasts had worse prognoses compared to those with MID breasts (disease-free survival 74.7% vs. 84.8%, p = 0.048; overall survival 75.3% vs. 90.2%, p = 0.003). Patients with VLD breasts showed the strongest significance compared to the remaining patients, even after adjusting for age, body mass index, and menopausal status. No other mammographic feature was prognostically significant. In Cox regression analysis, VLD proved to be an independent, poor prognostic feature (hazard ratio = 3.275; p < 0.001). CONCLUSION: In patients with newly diagnosed breast cancer, very low MBD proved to be an independent prognostic feature, associated with higher tumour grade and predicted worse survival even after correcting for possible confounders. KEY POINTS: • Percentile mammographic breast density was associated with patient prognosis. • Very low density proved to be an independent poor prognostic factor. • Only patients with densities <10% displayed this difference in survival. • Mammographic breast density was inversely associated with histological tumour grade.

Feasibility of radiological markers in idiopathic normal pressure hydrocephalus.

BACKGROUND: Various radiological markers have been proposed for diagnostics in idiopathic normal pressure hydrocephalus (iNPH). We examined the usefulness of radiological markers in the diagnostics and prediction of shunt response in iNPH. METHOD: In this retrospective cohort study, we evaluated brain CT or MRI scans of 390 patients with suspected iNPH. Based on a 24-h intraventricular pressure monitoring session, patients were classified into a non-NPH (n = 161) or probable iNPH (n = 229) group. Volumes of cerebrospinal fluid compartments (lateral ventricles, sylvian and suprasylvian subarachnoid spaces and basal cisterns) were visually assessed. Disproportionally enlarged subarachnoid spaces, flow void, white matter changes, medial temporal lobe atrophy and focally dilated sulci were evaluated. Moreover, we measured quantitative markers: Evans' index (EI), the modified cella media index, mean width of the temporal horns and callosal angle. RESULTS: iNPH was more likely in patients with severe volumetric disproportion between the suprasylvian and sylvian subarachnoid spaces than in those without disproportion (OR 7.5, CI 95 % 4.0-14.1, P < 0.0001). Mild disproportion (OR 2.6, CI 95 % 1.4-4.6, P = 0.001) and narrow temporal horns (OR per 1 mm 0.91, CI 95 % 0.84-0.98, P = 0.014) were also associated with an iNPH diagnosis. Other radiological markers had little association with the iNPH diagnosis in the final combined multivariate model. Interestingly, EI was higher in non-NPH than iNPH patients (0.40 vs. 0.38, P = 0.039). Preoperative radiological markers were not associated with shunt response. CONCLUSIONS: Visually evaluated disproportion was the most useful radiological marker in iNPH diagnostics. Narrower temporal horns also supported an iNPH diagnosis, possibly since atrophy was more pronounced in the non-NPH than iNPH group.

[Axillary ultrasound for a breast cancer patient and changing international treatment practices]. / Rintasyöpäpotilaan kainalon kaikukuvaus ja muuttuvat kansainväliset hoitokäytännöt.

INTRODUCTION: We explored the effects of novel treatment practices on radiological examinations of the axilla in Finland. PATIENTS AND METHODS: Axillary ultrasound was performed for 178 new breast cancer patients preoperatively. A core biopsy was taken from the suspected lymph nodes, and the finding was compared with the postoperative results. RESULTS: Ultrasound in combination with the core biopsy detects 61.6% of the macrometastases. Ultrasound detected almost all axilla having a high tumor burden. CONLUSIONS: Preoperative axillary ultrasound and core biopsy for suspected lymph nodes before the operation is still recommended for all breast cancer patients. Frozen section examination of the sentinel lymph node can be omitted if preoperatively the primary tumour is unifocal, less than 15mm and the axillary ultrasound finding negative.

Radiotherapy-induced vascular cognitive impairment 20 years after childhood brain tumor.

BACKGROUND: Studies have established that radiotherapy for childhood brain tumors (BTs) increases the risk of cerebrovascular disease (CVD); however, it is unclear how this will affect cognitive function. This study aimed to investigate the associations between radiotherapy-induced CVD, white matter hyperintensities (WMHs), and neurocognitive outcomes in adult survivors of childhood BTs. METHODS: In a cross-sectional setting, we conducted a national cohort that included 68 radiotherapy-treated survivors of childhood BTs after a median follow-up of 20 years. Markers of CVD and WMHs were evaluated using brain MRI, and the sum of CVD-related findings was calculated. Additionally, the associations among CVD findings, WMHs, and neuropsychological test results were analyzed. RESULTS: Of the 68 childhood BT survivors, 54 (79%) were diagnosed with CVD and/or WMHs at a median age of 27 years. CVD and/or WMHs were associated with lower scores for verbal intelligence quotient, performance intelligence quotient (PIQ), executive function, memory, and visuospatial ability (P < .05). Additionally, survivors with microbleeds had greater impairments in the PIQ, processing speed, executive function, and visuospatial ability (P < .05). WMHs and CVD burden were associated with greater difficulties in memory function and visuospatial ability (P < .05). Small-vessel disease burden was associated with PIQ scores, processing speed, working memory, and visuospatial ability. CONCLUSIONS: The study results suggest that markers of radiotherapy-induced CVD, the additive effect of CVD markers, and risk factors of dementia are associated with cognitive impairment, which may suggest that the survivors are at a high risk of developing early-onset dementia.

Axillary lymph node biopsy in newly diagnosed invasive breast cancer: comparative accuracy of fine-needle aspiration biopsy versus core-needle biopsy.

PURPOSE: To compare the diagnostic accuracy of ultrasonographically (US)-guided fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) of the axillary lymph nodes (LNs) of patients with newly diagnosed invasive breast cancer. MATERIALS AND METHODS: This prospective single-center study had institutional review board approval, and written informed consent was obtained. Between April 2011 and March 2012, 178 consecutive patients (182 axillae) were evaluated by using axillary US. Sixty-six axillae fulfilled the inclusion criteria (cortical thickness greater than 2 mm or abnormal morphologic characteristics), and patients with these axillae underwent US-guided axillary LN biopsy. Both FNAB and CNB were obtained from the same suspicious LN. Patients with biopsy-proved metastasis underwent axillary clearance, and those with a negative biopsy underwent sentinel LN biopsy with completion axillary clearance if needed. Diagnostic performance was calculated separately for US, FNAB, and CNB. Statistical differences in sensitivities were evaluated by using the McNemar test. RESULTS: From the total study population, 45.6% (83 of 182 axillae) had metastases. A total of 66 axillae underwent both FNAB and CNB. The sensitivity for US was 61.4% (51 of 83 axillae), and specificity was 84.8% (84 of 88 axillae). The sensitivities for FNAB and CNB were 72.5% (37 of 51 axillae) and 88.2% (45 of 51 axillae), respectively (P = .008). Specificity for both was 100% (15 of 15 axillae). The negative predictive value for FNAB was 81.7%, and that for CNB was 91.2%. The positive predictive value was 100% for both methods. CONCLUSION: When accurate preoperative staging of the axilla is needed in patients with newly diagnosed invasive breast cancer, CNB is more sensitive than FNAB.

Association between breast cancer's prognostic factors and 3D textural features of non-contrast-enhanced T1 weighted breast MRI.

OBJECTIVES: The aim of this exploratory study was to evaluate whether three-dimensional texture analysis (3D-TA) features of non-contrast-enhanced T1 weighted MRI associate with traditional prognostic factors and disease-free survival (DFS) of breast cancer. METHODS: 3D-T1 weighted images from 78 patients with 81 malignant histopathologically verified breast lesions were retrospectively analysed using standard-size volumes of interest. Grey-level co-occurrence matrix (GLCM)-based features were selected for statistical analysis. In statistics the Mann-Whitney U and the Kruskal-Wallis tests, the Cox proportional hazards model and the Kaplan-Meier method were used. RESULTS: Tumours with higher histological grade were significantly associated with higher contrast (1 voxel: p = 0.033, 2 voxels: p = 0.036). All the entropy parameters showed significant correlation with tumour grade (p = 0.015-0.050) but there were no statistically significant associations between other TA parameters and tumour grade. The Nottingham Prognostic Index (NPI) was correlated with contrast and sum entropy parameters. A higher sum variance TA parameter was a significant predictor of shorter DFS. CONCLUSION: Texture parameters, assessed by 3D-TA from non-enhanced T1 weighted images, indicate tumour heterogeneity but have limited independent prognostic value. However, they are associated with tumour grade, NPI, and DFS. These parameters could be used as an adjunct to contrast-enhanced TA parameters. ADVANCES IN KNOWLEDGE: 3D-TA of non-contrast enhanced T1 weighted breast MRI associates with tumour grade, NPI, and DFS. The use of non-contrast 3D-TA parameters in adjunct with contrast-enhanced 3D-TA parameters warrants further research.

Neuropathological findings in possible normal pressure hydro-cephalus: A post-mortem study of 29 cases with lifelines.

Aims: There are very few detailed post-mortem studies on idiopathic normal-pressure hydrocephalus (iNPH) and there is a lack of proper neuropathological criteria for iNPH. This study aims to update the knowledge on the neuropathology of iNPH and to develop the neuropathological diagnostic criteria of iNPH. Methods: We evaluated the clinical lifelines and post-mortem findings of 29 patients with possible NPH. Pre-mortem cortical brain biopsies were taken from all patients during an intracranial pressure measurement or a cerebrospinal fluid (CSF) shunt surgery. Results: The mean age at the time of the biopsy was 70±8 SD years and 74±7 SD years at the time of death. At the time of death, 11/29 patients (38%) displayed normal cognition or mild cognitive impairment (MCI), 9/29 (31%) moderate dementia and 9/29 (31%) severe dementia. Two of the demented patients had only scarce neuropathological findings indicating a probable hydrocephalic origin for the dementia. Amyloid-ß (Aß) and hyperphosphorylated τ (HPτ) in the biopsies predicted the neurodegenerative diseases so that there were 4 Aß positive/low Alzheimer's disease neuropathological change (ADNC) cases, 4 Aß positive/intermediate ADNC cases, 1 Aß positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HPτ/PSP and primary age-related tauopathy (PART) case, 1 Aß/HPτ and low ADNC/synucleinopathy case and 1 case with Aß/HPτ and high ADNC. The most common cause of death was due to cardiovascular diseases (10/29, 34%), followed by cerebrovascular diseases or subdural hematoma (SDH) (8/29, 28%). Three patients died of a postoperative intracerebral hematoma (ICH). Vascular lesions were common (19/29, 65%). Conclusions: We update the suggested neuropathological diagnostic criteria of iNPH, which emphasize the rigorous exclusion of all other known possible neuropathological causes of dementia. Despite the first 2 probable cases reported here, the issue of "hydrocephalic dementia" as an independent entity still requires further confirmation. Extensive sampling (with fresh frozen tissue including meninges) with age-matched neurologically healthy controls is highly encouraged.

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.