Surgical outcomes of borderline breast lesions detected by needle biopsy in a breast screening program

<p>Abstract</p> <p>Background</p> <p>The Australian Capital Territory and South East New South Wales branch of BreastScreen Australia (BreastScreen ACT&SENSW) performs over 20,000 screening mammograms annually. This study describes the outcome of surgical biopsies of the breast performed as a result of a borderline lesion being identified after screening mammography and subsequent workup.</p> <p>A secondary aim was to identify any parameters, such as a family history of breast cancer, or radiological findings that may indicate which borderline lesions are likely to be upgraded to malignancy after surgery.</p> <p>Methods</p> <p>From a period of just over eight years, all patients of BreastScreen ACT&SENSW who were diagnosed with a borderline breast lesion were identified. These women had undergone needle biopsy in Breastscreen ACT&SENSW and either atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), atypical lobular hyperplasia (ALH), radial scar/complex sclerosing lesion, papillary lesion, mucocoele-like lesion (MLL) or lobular carcinoma in situ (LCIS) was found. Final outcomes for each type of borderline lesion after referral for surgical biopsy were recorded and analysed. Results of the surgical biopsy were compared to the type of needle biopsy and its result, radiological findings and family history status.</p> <p>Results</p> <p>Of the 94 surgical biopsies performed due to the presence of a borderline breast lesion, 20% showed benign pathology, 55% remained as borderline lesions, 17% showed non-invasive malignancy and 7% showed invasive malignancy. VALCS biopsy was the most common needle biopsy method used to identify the lesions in this study (76%). Malignant outcomes resulted from 24% of the surgical biopsies, with the most common malignant lesion being non-comedo ductal carcinoma <it>in situ </it>(DCIS). The most common borderline lesion for which women underwent surgical biopsy was ADH (38%). Of these women, 22% were confirmed as ADH on surgical biopsy and 47% with a malignancy.</p> <p>Conclusions</p> <p>Further research is required to determine whether characteristics of the mammographic lesion (particularly calcification patterns), the area targeted for biopsy and number of core samples retrieved, can indicate a closer correlation with eventual pathology. This study identified no findings in the diagnostic assessment that could exclude women with borderline lesions from surgical biopsy.</p

Gender influences health-related Quality of Life in IPF

Disclosure statements Dr. Han has received research support from the NIH. Dr. Bartholmai has received research support from the NIH and GlaxoSmithKline. Dr. Murray has received research support from the NIH. Dr. Giardino has received research support from the VAHS. Dr. Flaherty has received research support from Intermune and the NIH, consulting honorarium from GlaxoSmithKline and is a member of advisory boards for Boehringer Ingelheim and Gilead. Dr. Thompson has received research support from the NIH. Dr. Frederick has received research support from the NIH. Ms. Li has received research support from the NIH. Dr. Schwarz has received research support from the NIH. Dr. Limper received consulting fees and a research grant from Novartis and has received research support from the NIH. Dr. Martinez is a member of a steering committee for Actelion, Gilead, Centocor, and Genzyme and has received research support from Actelion and the NIH.Background HRQL in IPF patients is impaired. Data from other respiratory diseases led us to hypothesize that significant gender differences in HRQL in IPF also exist. Methods Data were drawn from the NIH-sponsored Lung Tissue Research Consortium (LTRC). Demographic and pulmonary physiology data along with MMRC, SF-12, and SGRQ scores from women vs. men were compared with two-sample t-tests. Multivariate linear regression was used to examine the association between SF-12 component scores and gender while adjusting for other relevant variables. Results The study sample consisted of 147 men and 74 women. Among several baseline variables, only DLCO% predicted differed between women and men, (43.7 vs. 38.0, p = 0.03). In general, men exhibited lower (better) MMRC scores (1.7 vs. 2.4, p = 0.02), particularly those with milder disease as measured by DLCO% predicted. In an adjusted analysis, SF-12 PCS scores in men were lower (worse) than women (p = 0.01), an effect that was more pronounced in men with greater dyspnea scores. In a similar analysis, SF-12 MCS scores in women were lower than men (worse) (48.3 vs. 54.4, p = 0.0004), an effect that was more pronounced in women with greater dyspnea scores. Conclusions Significant gender differences in HRQL exist in IPF. As compared to women, men reported less severe dyspnea, had worse SF-12 PCS scores, but better SF-12 MCS scores. Dyspnea appears to have a greater impact on the physical HRQL of men and the emotional HRQL of women. An improved understanding of the mechanism behind these differences is needed to better target interventions.This work is supported by the Lung Tissue Research Consortium (N01 HR46158 (Bartholmai), N01 HR46160 (Schwarz), N01 HR46161 (Limper), N01 HR46162 (Han, Martinez), N01 HR46164 (Li, Frederick, Thompson), KL2 RR024987 (Han), K24 HL04212 (Martinez).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91956/1/2010 Respiratory Medicine - Gender Influences health-related Quality of Life in IPF.pd

Sex differences in physiological progression of idiopathic pulmonary fibrosis

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for males versus females. Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences. Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity. These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.This work was supported by National Institutes of Health grants 5P50HL56402, U10HL080371, 2K24HL04212, K12RR024987 and K23HL68713, and the Alberta Heritage Medical Foundation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91966/1/2008 ERJ - Sex Differences in Physiologic Progression of Idiopathic Pulmonary Fibrosis.pd

Clinical Predictors of a Diagnosis of Idiopathic Pulmonary Fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonias (IIPs) have similar clinical and radiographic features, but their histopathology, response to therapy, and natural history differ. A surgical lung biopsy is often required to distinguish between these entities. Objectives: We sought to determine if clinical variables could predict a histopathologic diagnosis of IPF in patients without honeycomb change on high-resolution computed tomography (HRCT). Methods: Data from 97 patients with biopsy-proven IPF and 38 patients with other IIPs were examined. Logistic regression models were built to identify the clinical variables that predict histopathologic diagnosis of IPF. Measurements and Main Results: Increasing age and average total HRCT interstitial score on HRCT scan of the chest may predict a biopsy confirmation of IPF. Sex, pulmonary function, presence of desaturation, or distance walked during a 6-minute walk test did not help discriminate pulmonary fibrosis from other IIPs. Conclusions: Clinical data may be used to predict a diagnosis of IPF over other IIPs. Validation of these data with a prospective study is needed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91953/1/2010 AJRCCM Clinical Predictors of a Diagnosis of Idiopathic Pulmonary Fibrosis.pd

Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases.

BACKGROUND: Brain metastases are a significant cause of mortality and morbidity for patients with melanoma. We hypothesize that the development of brain metastases may be explained by molecular heterogeneity between primary cutaneous melanoma (PCM) or extracranial (ECM) and brain (MBM) melanoma metastases. MATERIALS AND METHODS: We compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM. RESULTS: The most common genetic alterations among MBM included: BRAF (52.4%), NRAS (26.6%), CDKN2A (23.3%), NF1 (18.9%), TP53 (18%), ARID2 (13.8%), SETD2 (11.9%), and PBRM1 (7.5%). Four genes were found with higher frequency among MBM compared to PCM or ECM: BRAF (52.4% v 40.4% v 40.9%), SETD2 (11.9% v 1.9% v 3.9%), PBRM1 (7.5% v 1.6% v 2.6%), and DICER1 (4.4% v 0.6% v 0.4%). MBM showed higher TMB ( CONCLUSIONS: Our findings suggest a unique molecular profile for MBM, including higher rates of BRAF mutations, higher TMB and higher PD-L1 expression, and also implicate chromatin remodeling in the pathogenesis of MBM

Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema

The composite physiologic index (CPI) was derived to represent the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF). We hypothesised that longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (DLCO) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema (CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n=321), 6 months (n=211) and 12 months (n=144). Presence of CPFE was determined by HRCT. A five-point increase in CPI over 12 months predicted subsequent mortality (HR 2.1, p=0.004). At 12 months, a 10% relative decline in FVC, a 15% relative decline in DLCO or an absolute increase in CPI of five points all discriminated median survival by 2.1 to 2.2 yrs versus patients with lesser change. Half our cohort had CPFE. In patients with moderate/severe emphysema, only a 10% decline in FEV1 predicted mortality (HR 3.7, p=0.046). In IPF, a five-point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in DLCO. For CPFE patients, change in FEV1 was the best predictor of mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91949/1/2011 ERJ - Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema.pd

Highly Variable Extinction and Accretion in the Jet-driving Class I Type Young Star PTF 10nvg (V2492 Cyg, IRAS 20496+4354)

We report extensive new photometry and spectroscopy of the highly variable young stellar object PTF 10nvg including optical and near-infrared time series data as well as mid-infrared and millimeter data. Following the previously reported 2010 rise, during 2011 and 2012 the source underwent additional episodes of brightening and dimming events including prolonged faint states. The observed high-amplitude variations are largely consistent with extinction changes having a 220 day quasi-periodic signal. Spectral evolution includes not only changes in the spectral slope but correlated variation in the prominence of TiO/VO/CO bands and atomic line emission, as well as anticorrelated variation in forbidden line emission which, along with H_2, dominates optical and infrared spectra at faint epochs. Neutral and singly-ionized atomic species are likely formed in an accretion flow and/or impact while the origin of zero-velocity atomic LiI 6707 in emission is unknown. Forbidden lines, including several rare species, exhibit blueshifted emission profiles and likely arise from an outflow/jet. Several of these lines are also seen spatially offset from the continuum source position, presumably in a shocked region of an extended jet. CARMA maps resolve on larger scales a spatially extended outflow in mm-wavelength CO. We attribute the observed photometric and spectroscopic behavior in terms of occultation of the central star as well as the bright inner disk and the accretion/outflow zones that renders shocked gas in the inner part of the jet amenable to observation at the faint epochs. We discuss PTF 10nvg as a source exhibiting both accretion-driven (perhaps analogous to V1647 Ori) and extinction-driven (perhaps analogous to UX Ori or GM Cep) high-amplitude variability phenomena.Comment: accepted to AJ - in press (74 pages

Melanoma staging: Evidence‐based changes in the American Joint Committee on Cancer eighth edition cancer staging manual

Answer questions and earn CME/CNETo update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8‐1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent”; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA‐IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in‐transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor‐involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence‐based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472‐492. © 2017 American Cancer Society.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139981/1/caac21409_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139981/2/caac21409-sup-0001-suppinfo01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139981/3/caac21409.pd