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BACKGROUND Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features. OBJECTIVE To perform a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as healthy controls. METHODS Induced sputum supernatant was collected from 211 asthmatic adults and 41 healthy individuals enrolled in the U-BIOPRED study. Sputum lipidomes were characterised by semi-quantitative shotgun mass spectrometry, and clustered using topological data analysis to identify lipid phenotypes. RESULTS Shotgun lipidomics of induced sputum supernatant revealed a spectrum of nine molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthmatics and healthy controls, but within the asthmatic population as well. Matching clinical, pathobiological, proteomic and transcriptomic data informed on the underlying disease processes. Sputum lipid phenotypes with higher levels of non-endogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts. CONCLUSION We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthmatics, resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator. CLINICAL IMPLICATION Immunomodulation of extracellular vesicle secretion in the lungs may provide a novel therapeutic target for severe asthma.

BACKGROUND: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project.METHODS: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate.RESULTS: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05).CONCLUSIONS: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.

Rationale: Asthma phenotyping requires novel biomarker discovery. Objectives: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterized cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, chronic obstructive pulmonary disease (COPD) subjects and healthy controls (HC). Methods: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HC in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a two-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results: In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HC. Ten proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, RANK, TGF-?1, and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, hsCRP, and BMI, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions: The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers, and validated several proteins with established involvement in the pathophysiology of severe asthma.

The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project has described phenotypic differences of severe asthma using a systems biology approach. We obtained three molecular phenotypes termed transcription-associated clusters (TACs) using hierarchical clustering of differentially expressed transcripts between T2-high and T2-low [1]. TAC1 was characterised by receptors IL33R, CCR3 and TSLPR, with the highest enrichment of gene signatures for IL-13/type-2 (T2) inflammation with sputum eosinophilia; TAC2 by inflammasome-associated genes, interferon-α (IFN-α) and tumour necrosis factor-α (TNF-α)-associated genes with sputum neutrophilia; and TAC3 by metabolic and mitochondrial function genes with pauci-granulocytic inflammation. Given that sputum eosinophilia may vary with time in many asthmatic subjects [2, 3], we hypothesised that TAC status may also change with time., At 1 year, 45% of severe asthma change molecular phenotype as determined by sputum transcriptomic analysis. Together with concomitant shift in sputum granulocytic markers, this may indicate variability of driving mechanisms in this unstable group. https://bit.ly/35aj489

RATIONALE: New approaches are needed to guide personalized treatment of asthma. OBJECTIVE: To test if urinary eicosanoid metabolites can direct asthma phenotyping. METHODS: Urinary metabolites of prostaglandins (PGs), cysteinyl-leukotrienes (LTs) and isoprostanes were quantified in the Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy controls (HC). Validation was performed internally in 302 SA subjects followed-up after 12-18 months, and externally in 95 adolescents with asthma. MEASUREMENT AND MAIN RESULTS: Metabolite levels in HC were unrelated to age, BMI and sex, except for the PGE2-pathway. Eicosanoid levels were generally greater in MMA relative to HC, with further elevations in SA. However, PGE2-metabolite levels were either the same or lower in male non-smoking asthmatics as in HC. Metabolite levels were unchanged in asthmatics adherent to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas SA treated with omalizumab had lower levels of LTE4 and the PGD2 metabolite 2,3-dinor-11β-PGF2α. High levels of LTE4 and PGD2-metabolites were associated with lower lung-function, and increased levels of exhaled nitric oxide and eosinophil markers in blood, sputum and urine in U-BIOPRED and in adolescents with asthma. These type-2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study, and found to be as sensitive to detect T2 inflammation as the established biomarkers. CONCLUSIONS: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new non-invasive approach for molecular phenotyping of adult and adolescent asthma. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Gastro-oesophageal reflux disease (GORD) and obesity are associated with frequent exacerbations and poor quality of life in asthmatics. Multiple mechanisms have been proposed for the effect of obesity, including modification of inflammation affecting epithelial cell proliferation and wound repair, while the role of GORD is poorly understood and proton pump inhibitor (PPI) are of variable efficacy. GORD might exert a deleterious effect by inducing vagal reflex, neuroinflammation and directly ( via microaspiration) triggering airway inflammation. Studies of reflux in animal models and human bronchial epithelial cell culture show varying impact on inflammation and airway remodelling. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr PEROTIN has nothing to disclose. Conflict of interest: Dr Schofield has nothing to disclose. Conflict of interest: Dr Wilson has nothing to disclose. Conflict of interest: Dr Ward has nothing to disclose. Conflict of interest: Dr Brandsma has nothing to disclose. Conflict of interest: Dr Strazzeri has nothing to disclose. Conflict of interest: Dr Bansal has nothing to disclose. Conflict of interest: Dr Yang has nothing to disclose. Conflict of interest: Dr Rowe reports and a full time employee and shareholder of Janssen Pharmaceutical Companies of Johnson and Johnson. Conflict of interest: Miss Corfield has nothing to disclose. Conflict of interest: Dr Lutter has nothing to disclose. Conflict of interest: Prof. Shaw reports personal fees and non-financial support from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, personal fees from Circassia, and a grant from GSK, outside the submitted work. Conflict of interest: Dr Bakke reports personal fees from GSK, AZ, Novartis andTeva, outside the submitted work. Conflict of interest: MC have no conflict of interest to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Fowler reports personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, outside the submitted work. Conflict of interest: Dr Horvath reports personal fees from Astra Zeneca, Boehringer Ingelheim, Novartis, CSL, Chiesi, Roche, GSK, Berlin-Chemie and Sandoz, outside the submitted work. Conflict of interest: Dr Howarth reports personal fees from GSK, outside the submitted work. Conflict of interest: Dr Krug has nothing to disclose. Conflict of interest: Dr Montuschi has nothing to disclose. Conflict of interest: Dr Sanak has nothing to disclose. Conflict of interest: Dr Sandstrom reports other monetary support from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr Sun has nothing to disclose. Conflict of interest: Dr Pandis has nothing to disclose. Conflict of interest: Dr Auffray reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr De Meulder reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Ms. Lefaudeux reports grants from Innovative Medicine Initiative, grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr Riley reports and I have shares in and I am employed by GSK. Conflict of interest: Dr Sousa has nothing to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Adcock reports grants from EU-IMI, during the conduct of the study. Conflict of interest: KFC has received honoraria for participating in Advisory Board meetings of GSK, AZ, BI, Teva, Novartis and Merck regarding treatments for asthma and chronic obstructive pulmonary disease and has also been renumerated for speaking engagements. Conflict of interest: Dr Sterk reports grants from Innovative Medicines Initiative, during the conduct of the study. Conflict of interest: Dr Skipp has nothing to disclose. Conflict of interest: Dr Collins reports a patent application for use of a genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease and uses to screen the impact of such genes. Conflict of interest: Dr Davies has nothing to disclose. Conflict of interest: Dr Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline. He is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company.

Rationale: A proportion of severe asthma patients suffers fro m persistent airflow limitation, often associated with more symptoms and exacerbations . Little is known about the underlying mechanisms. Aiming for discovery of unexplored potential mechanisms, we used Gene Set Variation Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous samples. Methods: Severe asthma patients from the U -BIOPRED cohort with persistent airflow limitation (post -bronchodilator FEV 1 /FVC ratio < lower limit of normal) were compared to those without persistent airflow limitation. Gene expression was assessed on the total RNA of sputum cells, nasal brushin gs and endobronchial brushings and biopsies. GSVA was applied to identify differentially - enriched pre -defined gene signatures based on all available gene expression publications and data on airways disease. Results: Differentially -enriched gene signatures were identified in nasal brushings (1), sputum (9), bronchial brushings (1) and bronchial biopsies (4), that were associated with response to inhaled steroids, eosinophils, IL -13, IFN -alpha, specific CD4+ T -cells and airway remodeling. Conclusion: Persiste nt airflow limitation in severe asthma has distinguishable underlying gene networks that are associated with treatment, inflammatory pathways and airway remodeling. These results point towards targets for the therapy of persistent airflow limitation in sev ere asthma.

INTRODUCTION: Matrix metalloproteinase-1 and mast cells are present in the airways of people with asthma. We hypothesised that matrix metalloproteinase-1 could be activated by mast cells and increase asthma severity. METHODS: Patients with stable asthma and healthy controls underwent spirometry, methacholine challenge, bronchoscopy and their airway smooth muscle cells were grown in culture. A second asthma group and controls had symptom scores, spirometry and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extra-cellular matrix was prepared from decellularised airway smooth muscle cultures. Matrix metalloproteinase-1 protein and activity were assessed. RESULTS: Airway smooth muscle cells generated pro-matrix metalloproteinase-1 which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extra-cellular matrix which enhanced subsequent airway smooth muscle growth by 1.5 fold (p

Background Patients with difficult-to-control asthma consume 50–60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called ‘T2-low asthma’ and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and optimized corticosteroid dose. However, it has been challenging to move induced sputum into the clinical setting. There is therefore a need to examine novel algorithms to target appropriate levels of corticosteroid treatment in difficult asthma, particularly in T2-low asthmatics. This study examines whether a composite non-invasive biomarker algorithm predicts exacerbation risk in patients with asthma on high-dose inhaled corticosteroids (ICS) (± long-acting beta agonist) treatment, and evaluates the utility of this composite score to facilitate personalized biomarker-specific titration of corticosteroid therapy. Methods/design Patients recruited to this pragmatic, multi-centre, single-blinded randomised controlled trial are randomly allocated into either a biomarker controlled treatment advisory algorithm or usual care group in a ratio of 4:1. The primary outcome measure is the proportion of patients with any reduction in ICS or oral corticosteroid dose from baseline to week 48. Secondary outcomes include the rate of protocol-defined severe exacerbations per patient per year, time to first severe exacerbation from randomisation, dose of inhaled steroid at the end of the study, cumulative dose of inhaled corticosteroid during the study, proportion of patients on oral corticosteroids at the end of the study, proportion of patients who decline to progress to oral corticosteroids despite composite biomarker score of 2, frequency of hospital admission for asthma, change in the 7-item Asthma Control Questionnaire (ACQ-7), Asthma Quality of Life Questionnaire (AQLQ), forced expiratory volume in 1 s (FEV1), exhaled nitric oxide, blood eosinophil count, and periostin levels from baseline to week 48. Blood will also be taken for whole blood gene expression; serum, plasma, and urine will be stored for validation of additional biomarkers. Discussion Multi-centre trials present numerous logistical issues that have been addressed to ensure minimal bias and robustness of study conduct. Trial registration ClinicalTrials.gov, NCT02717689. Registered on 16 March 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2384-7) contains supplementary material, which is available to authorized users.

Many people with asthma do not achieve disease control, despite bronchodilators and inhaled corticosteroid therapy. People with uncontrolled asthma are at higher risk of an asthma attack and death, with mortality rates estimated at 1000 deaths/year in England and Wales. The recent National Review of Asthma Deaths (NRAD) report, ‘Why asthma still kills’, recommended that patients at step 4 or 5 of the British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) guidance must be referred to a specialist asthma service. This article reviews the 2014 evidence base for therapy of asthma patients at BTS/SIGN step 4 of the treatment cascade, in response to key findings of the NRAD report and lack of preferred treatment option at this step.

379 páginas incluye diagramas y fotografías. El estudio y análisis de las dinámicas de la cultura ambiental escolar, toma relevancia debido al inminente deterioro del medio ambiente a nivel local, nacional y global, y a la responsabilidad formativa que la sociedad delega a la escuela. Teniendo en cuenta la política en Colombia, que establece planes y programas académicos para los diferentes niveles educativos, en materia de educación ambiental se hace relevante generar propuestas socio educativas en esta línea, que permitan fortalecer en niños, niñas, jóvenes, docentes y comunidad educativa general, las actitudes y comportamientos proambientales necesarios para cuidar el ambiente. Considerando está situación se genera este proyecto de investigación que plantea como objetivo la implementación de estrategias socio educativas en cinco instituciones educativas distritales de Bogotá para fortalecer la cultura ambiental escolar, a través de un proceso de investigación acción participativa, con enfoque cualitativo, de carácter longitudinal y con técnicas de recolección de datos a partir de la observación, registros en diarios de campo y rejillas observacionales, sobre los comportamientos ambientales frente al manejo de residuos sólidos, el recurso hídrico y la energía eléctrica presentados por los estudiantes de cuatro instituciones educativas distritales (I.E.D) y los docentes de una I.E.D. La información obtenida permitió establecer la necesidad de generar un plan de acción que potencie el Proyecto Ambiental Escolar, PRAE, con acciones pedagógicas concretas que redunden en una cultura escolar proambiental, y en la formación de ciudadanos con un alto grado de compromiso y posturas críticas que les permita comprender las dinámicas de las problemáticas ambientales propias de su contexto y proponer alternativas de solución.

To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy.Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. Mammographic database review (1994-2003) revealed core biopsy diagnoses of benign papilloma (n=38), atypical papilloma (n=15), sclerotic papilloma (n=6), and micropapilloma (n=4) in 57 women (mean age, 57 years). Excisional or mammographic follow-up (or=2 years) findings were available. Patients with in situ or invasive cancer in the same breast or patients without follow-up were excluded. Findings were collected from mammography, ultrasonography, core technique, core biopsy, excision, and subsequent mammography. Reference standard was excisional findings or follow-up mammogram with no change at 2 years. Associations were examined with regression methods.In 38 of 63 lesions, surgical excision was performed; in 25 additional lesions (considered benign), follow-up mammography (24-month minimum) was performed, with no interval change. In 15 lesions, 14-gauge core needle was used; in 48, vacuum assistance (mean cores per lesion, 8.7). Carcinoma was found at excision in 14 of 38 lesions. Core pathologic findings associated with malignancy were benign papilloma (n=1), sclerotic papilloma (n=1), micropapilloma (n=2), and atypical papilloma (n=10). Frequency of malignancy was one (3%) of 38 benign papillomas, 10 (67%) of 15 atypical papillomas, two (50%) of four micropapillomas, and one (17%) of six sclerotic papillomas. Excisional findings included lobular carcinoma in situ (n=2), ductal carcinoma in situ (n=7), papillary carcinoma (n=2), and invasive ductal carcinoma (n=3). Low-risk group (micropapillomas and sclerotic and benign papillomas) was compared with high-risk atypical papilloma group. Core findings were associated with malignancy at excision for atypical papilloma (P=.006). Lesion location, mammographic finding, core number, or needle type were not associated (P.05) with underestimation of malignancy at excision.Benign papilloma diagnosed at core biopsy is infrequently (3%) associated with malignancy; mammographic follow-up is reasonable. Because of the high association with malignancy (67%), diagnosis of atypical papilloma at core biopsy should prompt excision for definitive diagnosis.

Purpose: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by utilizing an ex vivo small animal ovalbumin (OVA) model of human asthma. Methods: Hyperpolarized (hp) 129Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp 129Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol. Results: Significant differences were demonstrated between control and OVA challenged animals on global lung hp 129Xe gas inhalation with p < 0.05 at MCh dosages above 460 μg. Spatial mapping of the regional hp gas distribution revealed an approximately 3 fold increase in heterogeneity for the asthma model organs. Conclusion: The experimental results from this proof of concept work suggest that the ex vivo hp noble gas imaging arrangement and the applied image analysis methodology may be useful as an adjunct to current diagnostic techniques.

The lactiferous duct system of the breast is the site of development of various benign and malignant lesions. Asymptomatic patients may have incidental diagnosis of ductal dilation on mammography. A mass or area of calcifications identified on mammography as suspicious and subsequently biopsied may represent a lesion of a primary lactiferous duct. The smaller terminal ducts are the site of development of most cancers and hyperplasias. In patients who present with the symptom of nipple discharge, a clinical assessment is made to determine the potential significance of the finding. In patients with uniorificial, spontaneous and suspicious discharge, further evaluation with galactography is recommended. In this article we will review the benign and malignant lesions of the main lactiferous ducts, the assessment of asymptomatic patients with ductal dilation on mammography, and the assessment of patients with abnormal nipple discharge.

The American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) defines four different types of asymmetric breast findings: asymmetric breast tissue, densities seen in one projection, architectural distortion, and focal asymmetric densities. These lesions are frequently encountered at screening and diagnostic mammography and are significant because they may indicate a neoplasm, especially if an associated palpable mass is present. Once these lesions are detected at standard mammography, supplementary breast imaging with additional mammographic views and ultrasonography (US) can be a key aspect of work-up. The role of US in this setting has not been clearly defined. However, a positive US finding such as a solid mass or an area of focal shadowing increases the level of suspicion for malignancy. A thorough knowledge of the patient's clinical history, along with a fundamental understanding of the ACR BI-RADS lexicon and the role and limitations of supplementary breast imaging, will allow more accurate interpretation of these potentially perplexing soft-tissue findings.

We report on some extensions and further developments of a well-known microcalcification detection algorithm based on adaptive noise equalization. Tissue equivalent phantom images with and without labeled microcalcifications were subjected to this algorithm, and analyses of results revealed some shortcomings in the approach. Particularly, it was observed that the method of estimating the width of distributions in the feature space was based on assumptions which resulted in the loss of similarity preservation characteristics. A modification involving a change of estimator statistic was made, and the modified approach was tested on the same phantom images. Other modifications for improving detectability such as downsampling and use of alternate local contrast filters were also tested. The results indicate that these modifications yield improvements in detectability, while extending the generality of the approach. Extensions to real mammograms and further directions of research are discussed.

Stereotactic core needle biopsy (SCNB) has become a popular method for diagnosis of occult breast abnormalities. There are few large series of SCNB from a single institution. Data on patients undergoing SCNB for mammographic abnormalities were collected prospectively over 43 months at a university hospital. Mammographic findings were categorized as benign, probably benign, indeterminate, suspicious or malignant. For lesions with SCNB pathology that were non-diagnostic, showed atypical hyperplasia or malignancy (in situ or invasive), or were discordant with the pre-biopsy mammogram findings, surgical excision was recommended. Subsequent surgical pathology was reviewed. All remaining lesions were followed mammographically after SCNB. SCNB was performed on 692 lesions in 607 patients. There were 79 malignancies, for a positive SCNB rate of 11.4%. The 349 SCNB performed for benign, probably benign and indeterminate lesions on mammography had a positive SCNB rate of only 4%. Surgery was recommended for 127 (18.3%) lesions, while 565 (81.6%) were followed mammographically after SCNB. A compliance rate of 61 % for at least one follow-up mammogram was obtained, with a median follow-up of 17.2 months and with no cancers found. The sensitivity for malignancy with SCNB was 93%. SCNB provides a minimally invasive method to assess mammographic abnormalities. Abnormalities considered radiographically to be other than malignant or suspicious yielded few cancers. In this series a low positive SCNB rate resulted in no false negatives on mammographic follow-up. The optimal positive biopsy rate for SCNB is debatable.

1From the Department of Radiology, University of Arkansas for Medical Sciences, Slot 581, 4301 W Markham, Little Rock, AR 72205-7199 (T.L.A.); the Department of Radiology, Medical College of Virginia, Richmond (E.S.P.); private practice, Women’s Imaging Center, Denver, Colo (K.A.M.); and the Department of Radiology, University of California, San Francisco (H.H.). Presented as a refresher course at the 1998 RSNA scientific assembly. Received and accepted May 3, 1999. Address reprint requests to T.L.A.

Detection and management of breast abnormalities that develop during pregnancy and lactation is difficult for both the clinician and the radiologist. This article reviews the hormonal and physiologic effects on the breast during pregnancy and lactation. Breast masses that occur in pregnant or lactating patients, including pregnancy-associated breast cancer, are discussed and the corresponding ultrasound and mammographic findings are presented. Finally, a rationale for the imaging evaluation and management of the pregnant or lactating patient with a breast mass are presented.

The capability to provide histologic diagnoses of nonpalpable lesions by performance of percutaneous needle biopsy has revolutionized breast imaging in the past decade. The radiologist who performs percutaneous breast biopsies assumes an increased level of responsibility for the patient regarding patient selection, lesion selection, performance of the biopsy procedure, interpretation of results, and patient follow-up. With variable and increasingly numerous options for the biopsy of breast lesions, careful attention must be paid to the selection of patients and types of lesions for different procedures. Critical technical considerations affect whether biopsy of a lesion can be optimally performed percutaneously, and these considerations must be factored into the recommendations for patient treatment. In addition, a limited preprocedural clinical assessment of the patient will allow a safer procedure to be performed expeditiously. Most breast abnormalities classified by using the ACR Lexicon as 4 (suggestive) or 5 (highly suggestive, likely malignant) are suitable for either percutaneous breast needle biopsy or needle localization and excisional biopsy. In general, those lesions classified as 3 (probably benign) carry a recommendation for early follow-up and not biopsy, because the likelihood of malignancy is small. A particular advantage of percutaneous biopsy is in the diagnosis of multicentric breast cancer. Core biopsy is less invasive and less costly than surgical biopsy, and it can be used to demonstrate multicentric disease, saving the patient a two-step surgery. However, several lesions are better treated by excision than by percutaneous biopsy. Among these are architectural distortion or loosely arranged, segmental or regional microcalcifications. For nonpalpable breast lesions visualized on mammography, sonography, or both, imaging-guided localization is required for precise needle placement either for wire localization or for percutaneous breast biopsy. The selection of which modality to use for guidance depends on (1) the adequacy of visualization of the lesion by the modality used, (2) the position of the lesion, (3) the ease of positioning the patient, (4) the skill of the operator, (5) the need to reduce radiation exposure, (6) the overall patient condition, and (7) size of the lesion. Fine-needle aspiration biopsy (FNAB) has a high sensitivity and specificity in the diagnosis of palpable breast lesions when the procedure is properly performed and interpreted. Variable results have been achieved with FNAB of nonpalpable breast lesions under imaging guidance. Three critical components are necessary to achieve reliable results by using FNAB. These include the following: (1) accuracy in needle placement, (2) skill in performance of FNAB, and (3) expert cytopathologic analysis. Accurate preoperative needle localization of nonpalpable breast lesions allows the radiologist to guide the surgeon performing an open biopsy and helps to ensure that the surgical procedure can be performed quickly and can be accomplished with the best possible cosmetic result for the patient. Lesions selected for needle localization and biopsy should undergo a complete tailored imaging evaluation before the needle localization is scheduled. Specimen radiography should be performed for all nonpalpable lesions. Once the lesion has been identified on specimen radiography, the radiologist can assist the pathologist in identifying the lesion microscopically by marking the lesion within the surgical specimen. We cover the technical and interpretative aspects of percutaneous breast biopsy and needle localization for surgical biopsy.