The Tomosynthesis Broken Halo Sign: Diagnostic Utility for the Classification of Newly Diagnosed Breast Tumors.

BACKGROUND: Compared to conventional 2D mammography, digital breast tomosynthesis (DBT) offers greater breast lesion detection rates. Ring-like hypodense artifacts surrounding dense lesions are a common byproduct of DBT. This study's purpose was to assess whether minuscule changes spanning this halo-termed the "broken halo sign"-could improve lesion classification. METHODS: This retrospective study was approved by the local ethics review board. After screening 288 consecutive patients, DBT studies of 191 female participants referred for routine mammography with a subsequent histologically verified finding of the breast were assessed. Examined variables included patient age, histological diagnosis, architectural distortion, maximum size, maximum halo depth, conspicuous margins, irregular shape and broken halo sign. RESULTS: While a higher halo strength was indicative of malignancy in general (p = 0.031), the broken halo sign was strongly associated with malignancy (p < 0.0001, odds ratio (OR) 6.33), alongside architectural distortion (p = 0.012, OR 3.49) and a diffuse margin (p = 0.006, OR 5.49). This was especially true for denser breasts (ACR C/D), where the broken halo sign was the only factor predicting malignancy (p = 0.03, 5.22 OR). CONCLUSION: DBT-associated halo artifacts warrant thorough investigation in newly found breast lesions as they are associated with malignant tumors. The "broken halo sign"-the presence of small lines of variable diameter spanning the peritumoral areas of hypodensity-is a strong indicator of malignancy, especially in dense breasts, where architectural distortion may be obfuscated due to the surrounding tissue.

Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH.

Peritumoural Strain Elastography of Newly Diagnosed Breast Tumours: Does Maximum Peritumoural Halo Depth Correlate with Tumour Differentiation and Grade?

To evaluate the diagnostic utility of the maximum ultrasound strain elastography (SE) halo depth in newly diagnosed and histologically confirmed breast lesions, a retrospective study approval was granted by the local Ethical Review Board. Overall, the maximum strain elastography peritumoural halos (SEPHmax)-the maximum distance between the SE stiffening area and the B-mode lesion size-in 428 cases with newly diagnosed breast lesions were retrospectively analysed alongside patient age, affected quadrant, tumour echogenicity, size, acoustic shadowing, and vascularity. Statistical analysis included an ordinary one-way ANOVA to compare the SEPHmax between BI-RADS 2, 3, and 5 groups and between tumour grades 1, 2, and 3. A binary regression analysis was used to determine the correlation between tumour malignancy and the above-mentioned demographic and imaging factors. SEPHmax was significantly higher in BI-RADS 5 tumours (5.5 ± 3.9 mm) compared to BI-RADS 3 (0.9 ± 1.7 mm, p < 0.0001) and 2 (0.6 ± 1.4 mm, p < 0.0001). The receiver operating characteristic area under the curve was 0.933 for the detection of BI-RADS 5 lesions. Furthermore, tumour grades 2 (5.6 ± 3.6 mm, p = 0.001) and 3 (6.8 ± 4.2 mm, p < 0.0001) exhibited significantly higher SEPHmax than grade 1 tumours (4.0 ± 3.9 mm). Similarly, St. Gallen Ki67-stratified low-risk (p = 0.005) and intermediate-risk (p = 0.013) tumours showed smaller SEPHmax than high-risk tumours. Multivariate analysis revealed a significant correlation between malignant differentiation and SEPHmax (standardized regression coefficient 3.17 [95% confidence interval (CI) 2.42-3.92], p < 0.0001), low tumour echogenicity (1.68 [95% CI 0.41-3.00], p = 0.03), and higher patient age (0.89 [95% CI 0.52-1.26], p < 0.0001). High SEPHmax is a strong predictor for tumour malignancy and a higher tumour grade and can be used to improve tumour characterisation before histopathological evaluation. It may also enable radiologists to identify lesions warranting observation rather than immediate biopsy.

Preoperative staging by multimodal imaging in newly diagnosed breast cancer: Diagnostic performance of contrast-enhanced spectral mammography compared to conventional mammography, ultrasound, and MRI.

PURPOSE: To compare contrast-enhanced spectral mammography (CESM) with mammography (Mx), ultrasound (US), and magnetic resonance imaging (MRI) regarding breast cancer detection rate and preoperative local staging. MATERIAL AND METHODS: This prospective observational, single-centre study included 128 female patients (mean age 55.8 ± 11.5 years) with a newly diagnosed malignant breast tumour during routine US and Mx were prospectively enrolled. CESM and MRI examinations were performed within the study. Analysis included interreader agreement, tumour type and grade distribution, detection rates (DR), imaging morphology, contrast-enhancement and was performed by two independent readers blinded to patient history and histopathological diagnosis. Assessment of local disease extent was compared between modalities via Bland-Altman plots. RESULTS: One-hundred-and-ten tumours were classified as NST (85.9%), 4 as ILC (3.1%) and 10 as DCIS (7.8%). DR was highest for MRI (128/128, 100.0%), followed by US (124/128, 96.9%) and CESM (123/128, 96.1%) and lowest for conventional Mx (106/128, 82.8%) (p = 0.0002). Higher breast density did not negatively affect DR of US, CESM or MRI. Local tumour extent measurements based on CESM (Bland-Altman bias 6.6, standard deviation 30.2) showed comparable estimation results to MRI, surpassing Mx (23.4/43.7) and US (35.4/40.5). Even though detection of multifocality and multicentricity was highest for CESM and MRI (p < 0.0001), second-look rates, i.e., targeted US examinations after MRI or CESM, were significantly lower for CESM (10.2% of cases) compared to MRI (16.2%) with a significantly higher true positive rate for CESM (72.0%) vs. MRI (42.5%). CONCLUSION: CESM is a viable alternative to MRI for lesion detection and local staging in newly diagnosed malignant breast cancer and provides higher specificity in regard to second-look examinations.

Female sexual dysfunction in multiple system atrophy: a prospective cohort study.

PURPOSE: The diagnosis of probable multiple system atrophy relies on the presence of severe cardiovascular or urogenital autonomic failure. Erectile dysfunction is required to fulfil the latter criterion in men, whereas no corresponding item is established for women. In this study, we aimed to investigate sexual dysfunction in women with multiple system atrophy. METHODS: We administered the Female Sexual Function Index questionnaire and interviewed women with multiple system atrophy and age-matched controls regarding the presence of "genital hyposensitivity." RESULTS: We recruited 25 women with multiple system atrophy and 42 controls. Female Sexual Function Index scores in sexually active women with multiple system atrophy were significantly lower (multiple system atrophy = 10; 15.4, 95% CI [10.1, 22.1], controls = 37; 26.1 [24.1, 28.1], p = 0.0004). The lowest scores concerned the domains of desire, arousal and lubrication. Genital hyposensitivity was reported by 56% of the patients with multiple system atrophy and 9% controls (p < 0.0001). CONCLUSIONS: Sexual dysfunction is highly prevalent in women with multiple system atrophy. Screening for disturbances in specific sexual domains should be implemented in the clinical evaluation of women with suggestive motor symptoms.

Interval breast cancer: Analysis of occurrence, subtypes and implications for breast cancer screening in a model region.

PURPOSE: Interval breast carcinomas (IBC) constitute a subgroup of malignancies in women participating in a breast cancer screening programme, yet diagnosed outside of a screening appointment. Tyrol is an Austrian screening model region with a dedicated IBC board. We analysed IBC subtype distribution, demographic and biological parameters and implications for screening programmes. METHOD: 161 patients with an IBC diagnosed from 2014 to 2017 were retrospectively analysed and grouped into true, occult, minimal-signs, and false negative (due to reading or technical error) IBCs cases by three independent readers. The influence of demographic and disease-related covariates were assessed. RESULTS: The median interval from screening to diagnostic diagnosis was 12.8 months (range 1.1 to 23.9 months). Most cases were true (36.02%), occult (31.06%) and false-negative IBCs due to reading errors (29.81%). Interobserver agreement was rated as 'high' between all readers. Higher breast density was associated with true and occult IBCs. The rate of invasive subtypes was highest in true IBCs. Regardless of smaller tumour size in true and occult IBCs, doubling time was lower and ki-67 index higher in true and occult compared to false-negative IBCs. CONCLUSIONS: True and occult IBCs present with a more aggressive biological phenotype and are associated with younger age and higher breast density. Additional yearly ultrasound examinations in women at risk may aid in the earlier detection.

Disorders of eating and body image during the menopausal transition: associations with menopausal stage and with menopausal symptomatology.

OBJECTIVE: Recent reports from our laboratory and others suggest that the menopausal transition may represent a window of vulnerability for eating disorders in women. Here, we present new findings regarding this issue. METHODS: We surveyed 230 women aged 40-60 years using an anonymous questionnaire focused on eating-disorder and body-image symptomatology. We then compared groups of respondents based on (a) menopausal stage as assessed by World Health Organization (WHO) criteria and (b) menopausal symptomatology as assessed by the Menopause Rating Scale (MRS). RESULTS: WHO-defined menopausal stage (premenopausal, perimenopausal, and postmenopausal) showed no significant associations with eating and body-image measures. However, MRS scores showed strong associations with most measures of the Eating Disorder Examination Questionnaire, as well as with questions regarding satisfaction with body image. These associations remained little changed even when removing the four psychological items from the MRS score and examining only the association of the MRS somato-vegetative and urogenital items with these outcome variables. DISCUSSION: Our data augment existing evidence that the menopausal transition may be associated with eating and body-image disturbances. However, reported menopausal stage, which is difficult to define reliably, may be less informative than menopausal symptoms as a predictor of disordered eating and associated symptoms. LEVEL OF EVIDENCE: V-descriptive survey study.

Performance of 4 years of population-based mammography screening for breast cancer combined with ultrasound in Tyrol / Austria.

BACKGROUND: Systems for the delivery of screening mammography vary among countries and these differences can influence screening effectiveness. We evaluated the performance of organized mammography screening for breast cancer combined with ultrasound in Tyrol / Austria, an approach that differs from many other population-based screening programs. METHODS: Data on women aged 40-69 years screened in the period from June 2008 to May 2012 were collected within the framework of an organized screening program. A total of 272,555 invitations were sent to the target population living in Tyrol and 176,957 screening examinations were performed. We analyzed the main performance indicators as defined by European Union (EU) guidelines and some important estimates of harms. RESULTS: The estimated 2­year participation rate was 56.9%. As ultrasound is implemented as second-line screening procedure, 76.2% of all women screened underwent supplementary ultrasound. In total 2322 women were recalled for further assessment (13.1 per 1000 screens) and 1351 biopsies were performed (7.6 per 1000 screens). The positive predictive value was 28.2% for assessment and 48.5% for biopsies. The cancer detection rate was 3.7 per 1000 screens and the proportion of all stage II+ screen-detected cancers was 35.5%. The interval cancer rate was 0.33 and 0.47 per 1000 screens in the first and second years, respectively. The estimated cumulative risk for a false positive screening result and an unnecessary biopsy for women following the invitation approach was 21.1% and 9.4%, respectively. CONCLUSION: The performance of our population-based screening approach combining mammography and ultrasound is very favorable and potential harm is kept very low compared to other European mammography screening programs for breast cancer.

Self-reported sexual health: Breast cancer survivors compared to women from the general population - an observational study.

BACKGROUND: Cancer survivorship is of increasing importance in post-treatment care. Sexual health (SH) and femininity can be crucial issues for women surviving cancer. We aimed to determine a more complete understanding of the contribution that a breast cancer (BC) diagnosis and its treatment exert on patients' follow-up SH. For this purpose, self-reported levels and predictors of SH in breast cancer survivors (BCS) were compared with those of women with no previous or current BC (WNBC). METHODS: BCS and WNBC underwent a comprehensive, cross-sectional patient-reported outcome (PRO) assessment. Validated PRO instruments were used to measure SH, body image, anxiety and depression and menopausal symptoms. Assessments were performed within the routine clinical setting. Instruments used were the Sexual Interest and Desire Inventory - Female, Sexual Activity Questionnaire, Body Image Scale, Hospital Anxiety and Depression Scale and the Menopause-Specific Quality of Life Questionnaire. RESULTS: One hundred five BCS (average time since diagnosis of 3 years) and 97 WNBC with a mean age of 49 years completed the assessment. SH was significantly worse in BCS compared to WNBC (p = 0.005; BCS SIDI-F mean = 24.9 vs. WNBC mean = 29.8). 68.8% of BCS and 58.8% of WNBC met criteria of a hypo-active sexual desire disorder. Higher depressive symptoms, higher age and lower partnership satisfaction were predictive for poorer SH in BCS. CONCLUSION: SH problems are apparent in BCS and differ significantly from those seen in the general population. Consequently, BC survivorship care should include interventions to ameliorate sexual dysfunction and provide help with depressive symptoms and partnership problems, which are associated with poor BCS SH.

Dual-energy contrast-enhanced spectral mammography (CESM).

Dual-energy contrast-enhanced mammography is one of the latest developments in breast care. Imaging with contrast agents in breast cancer was already known from previous magnetic resonance imaging and computed tomography studies. However, high costs, limited availability-or high radiation dose-led to the development of contrast-enhanced spectral mammography (CESM). We reviewed the current literature, present our experience, discuss the advantages and drawbacks of CESM and look at the future of this innovative technique.

Introduction of organised mammography screening in Tyrol: results following first year of complete rollout.

BACKGROUND: In Tyrol, Austria, the existing system of spontaneous mammography screening was switched in 2007 to an organised program by smoothly changing the established framework. This process followed most EU recommendations for organised mammography screening with the following exceptions: women aged 40-49 are part of the target population, screening is offered annually to the age group 40-59, breast ultrasound is available as an additional diagnostic tool, and double reading has not yet been implemented. After a pilot phase the program was rolled out to all of Tyrol in June 2008. The aim of this study was to analyse the performance of the organised screening system by comparing quality indices and recommended levels given in the well-established EU guidelines. METHODS: Working from the results of the pilot phase, we extended the organised mammography system to all counties in Tyrol. All women living in Tyrol and covered by compulsory social insurance were invited for a mammography, in the age group 40-59 annually and in the age group 60-69 biennially. Screening mammography was offered mainly by radiologists in private practice, with further assessment performed at hospitals. Using the screening database, all well-established performance indicators were analysed and compared with accepted/desired levels as per the EU guidelines. RESULTS: From June 2008 to May 2009, 120,440 women were invited. Per 1000 mammograms, 14 women were recalled for further assessment, nine underwent biopsy and four cancer cases were detected. Of invasive breast cancer cases, 32.3% and 68.4% were ≤ 10 mm and ≤ 15 mm in size, respectively, and 79.2% were node-negative. The positive predictive value for further assessment and for biopsy was 25.9% and 39.9%, respectively. Estimated two-year participation rate was 57.0%. In total, 14 interval cancer cases were detected during one year of follow-up; this is 18.4% of the background incidence rate. CONCLUSIONS: In Tyrol, Austria, an organised mammography screening program was implemented in a smooth transition from an existing spontaneous screening system and was completely rolled out within a short time. The high level of performance already seen in the pilot phase was maintained after rollout, and improvements resulting from the pilot phase were affirmed after one year of complete rollout.

Introduction of organised mammography screening in Tyrol: results of a one-year pilot phase.

BACKGROUND: Efficiency and efficacy of organised mammography screening programs have been proven in large randomised trials. But every local implementation of mammography screening has to check whether the well established quality standards are met. Therefore it was the aim of this study to analyse the most common quality indices after introducing organised mammography screening in Tyrol, Austria, in a smooth transition from the existing system of opportunistic screening. METHODS: In June 2007, the system of opportunistic mammography screening in Tyrol was changed to an organised system by introducing a personal invitation system, a training program, a quality assurance program and by setting up a screening database. All procedures are noted in a written protocol. Most EU recommendations for organised mammography screening were followed, except double reading. All women living in Tyrol and covered by social insurance are now invited for a mammography, in age group 40-59 annually and in age group 60-69 biannually. Screening mammography is offered mainly by radiologists in private practice. We report on the results of the first year of piloting organised mammography screening in two counties in Tyrol. RESULTS: 56,432 women were invited. Estimated participation rate was 34.5% at one year of follow-up (and 55.5% at the second year of follow-up); 3.4% of screened women were recalled for further assessment or intermediate screening within six months. Per 1000 mammograms nine biopsies were performed and four breast cancer cases detected (N = 68). Of invasive breast cancer cases 34.4% were ≤ 10 mm in size and 65.6% were node-negative. In total, six interval cancer cases were detected during one year of follow-up; this is 19% of the background incidence rate. CONCLUSIONS: In the Tyrolean breast cancer screening program, a smooth transition from a spontaneous to an organised mammography screening system was achieved in a short time and with minimal additional resources. One year after introduction of the screening program, most of the quality indicators recommended by the European guidelines had been reached.However, it will be necessary to introduce double reading, to change the rule for BI-RADS 3, and to concentrate on actions toward improving the participation rate.

Sequencing strategy for the whole mitochondrial genome resulting in high quality sequences.

BACKGROUND: It has been demonstrated that a reliable and fail-safe sequencing strategy is mandatory for high-quality analysis of mitochondrial (mt) DNA, as the sequencing and base-calling process is prone to error. Here, we present a high quality, reliable and easy handling manual procedure for the sequencing of full mt genomes that is also appropriate for laboratories where fully automated processes are not available. RESULTS: We amplified whole mitochondrial genomes as two overlapping PCR-fragments comprising each about 8500 bases in length. We developed a set of 96 primers that can be applied to a (manual) 96 well-based technology, which resulted in at least double strand sequence coverage of the entire coding region (codR). CONCLUSION: This elaborated sequencing strategy is straightforward and allows for an unambiguous sequence analysis and interpretation including sometimes challenging phenomena such as point and length heteroplasmy that are relevant for the investigation of forensic and clinical samples.

Ultrasound-guided core needle biopsy of the breast: does frozen section give an accurate diagnosis?

Reducing the period of uncertainty between the discovery of a breast tumor and histological diagnosis alleviates the psychological impact of breast cancer to an important degree. We aimed to verify whether histological results obtained with frozen sections of core needle biopsies (CNBs) offer an accurate and reliable tool for minimising this period. In 2619 cases we compared histological diagnosis on frozen sections with those on paraffin sections of CNB and finally with the results of open biopsies. Of the cases 49% were proved malignant and 51% benign. In 99.3% of the malignant lesions preceding CNB was correctly classified as B5 (n = 1185, 92.9%) or at least B4 (n = 82, 6.4%) in frozen and in paraffin sections. There were seven false-negative cases in frozen (false-negative rate = 0.5%) and five false-negative cases (false-negative rate = 0.4%) in paraffin sections of CNB. On frozen sections complete sensitivity was 99.5% and the positive predictive value of B5 was 99.9%. There was one false-positive case in frozen sections and one in paraffin sections. False-positive rate = 0.08%, negative predictive value for B2 = 99.4% for frozen and 99.6% for paraffin sections; full specificity was 85.9 for frozen and 85.8 for paraffin sections of CNBs. Immediate investigation of CNB in frozen sections is an accurate diagnostic method and an important step in reducing psychological strain on patients with breast tumors and may be offered by specialised Breast Assessment Units.

Ovoid shape of the vermiform appendix: a criterion to exclude acute appendicitis--evaluation with US.

PURPOSE: To investigate whether the shape of the appendix in transverse section may be considered an ultrasonographic (US) criterion to exclude or confirm acute appendicitis. MATERIALS AND METHODS: The shapes of appendices of 100 control subjects, of 174 patients with clinical suspicion of acute appendicitis but without acute appendicitis, and of 108 patients with acute appendicitis were prospectively evaluated with US. Definite diagnoses in patients with clinical suspicion of acute appendicitis were established and confirmed either with surgery and histologic examination in 161 patients or with clinical follow-up in 121 patients. Statistical measures such as sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for the appendiceal shape as a diagnostic US criterion for acute appendicitis. RESULTS: An at least partly round appendix indicated acute appendicitis with a sensitivity of 100%; specificity of 37%; positive and negative predictive values of 50% and 100%, respectively; and accuracy of 61%. In 67 of 174 patients with clinical suspicion of acute appendicitis but without acute appendicitis, the partly ovoid appendiceal shape aided in the exclusion of acute appendicitis, since it indicated a normal appendix with a probability of 86%. In 65 of 174 patients with clinical suspicion of acute appendicitis but without acute appendicitis, the ovoid shape over the entire appendiceal length excluded acute appendicitis with confidence. CONCLUSION: The shape of the appendix in transverse section is a useful US criterion, since an ovoid shape over the entire appendiceal length reliably rules out acute appendicitis.