Nipple-Sparing Mastectomy in 99 Patients With a Mean Follow-up of 5 Years

Background. The safety and practicality of nipple-sparing mastectomy (NSM) are controversial. Methods. Review of a large breast center's experience identified 99 women who underwent intended NSM with subareolar biopsy and breast reconstruction for primary breast cancer. Outcome was assessed by biopsy status, postoperative nipple necrosis or removal, cancer recurrence, and cancer-specific death. Results. NSM was attempted for invasive cancer (64 breasts, 24 with positive lymph nodes), noninvasive cancer (35 breasts), and/or contralateral prophylaxis (50 breasts). Twenty-two nipples (14%) were removed because of positive subareolar biopsy results (frozen or permanent section). Seven patients underwent a pre-NSM surgical delay procedure because of increased risk for nipple necrosis. Reconstruction used transverse rectus abdominis myocutaneous flaps (56 breasts), latissimus flaps with expander (35 breasts), or expander alone (58 breasts). Of 127 retained nipples, 8 (6%) became necrotic and 2 others (2%) were removed at patient request. There was no nipple necrosis when NSM was performed after a surgical delay procedure. At a mean follow-up of 60.2 months, all 3 patients with recurrence had biopsy-proven subareolar disease and had undergone nipple removal at original mastectomy. There were no deaths. Conclusions. Five-year recurrence rate is low when NSM margins (frozen section and permanent) are negative. Nipple necrosis can be minimized by incisions that maximize perfusion of surrounding skin and by avoiding long flaps. A premastectomy surgical delay procedure improves nipple survival in high-risk patients. NSM can be performed safely with all types of breast reconstruction

Tamoxifen retards glycosphingolipid metabolism in human cancer cells

AbstractIn this study we provide evidence that tamoxifen, the widely used breast cancer drug, is a potent antagonist of glycolipid metabolism. When added to the medium of cultured multidrug resistant (MDR) KB-V-1 carcinoma cells, tamoxifen, at 5.0 μM, drastically lowered the levels of glucosylceramide (glc-cer), as evidenced by a reduction in glc-cer mass. In a similar fashion, in cultured human melanoma cells grown with [3H]galactose, tamoxifen inhibited formation of glc-cer by 44%, and retarded lactosylceramide and ganglioside formation by 50 and 35%, respectively. When glc-cer synthase of melanoma was assayed in cell-free incubations, the inclusion of tamoxifen, at a 1:10 molar ratio with ceramide, inhibited glc-cer synthesis by 50%. These results clearly reveal a new action of tamoxifen and thereby pose intriguing questions regarding mechanisms of action in the realm of estrogen receptor-independent modalities, including effects on MDR

hiPSC-Based Tissue Organoid Regeneration

Induced pluripotent stem cells (iPSCs) are generated from terminally differentiated cells and have the potential to differentiate to any organs originated from the embryonic germ layers. Extensive effort has been made to establish protocols for direct in vitro conversion of human iPSCs (hiPSCs) to different cell types/organs. Importantly, hiPSCs can be generated from patients with known genetic mutations that predispose to high-risks of specific disease development. Thus, the hiPSCs technology provides unlimited resources for creating patient-specific disease models. hiPSC-derived three-dimensional “organoid” models have recently emerged as a powerful tool to recapitulate the physiologically-relevant process of disease progression in vitro. In this chapter, we will discuss the current advancement of organoid regeneration from hiPSCs and the applications of hiPSCs-derived organoids. The limitations and challenges of this approach will also be discussed here

Translational Challenges and Therapeutic Opportunities in BRCA1-Related Breast Cancer

Although significant progress has been made in the management of the hereditary cancer syndrome related to mutations of BRCA1, two fundamental and clinically relevant questions regarding BRCA1-related cancer syndrome remain unresolved: (1) What factors account for the tissue specificity of the BRCA1-related cancer risk? (2) How does a mutation or loss of BRCA1 lead to the basal-like phenotype of breast cancer? This review focuses on recent studies in BRCA1-related pathways that lead to specific characteristics of the hereditary cancer syndrome and discusses the current translational evidence for exploiting these pathways in new therapeutic strategies. Mounting evidence suggests that estrogen signaling and metabolism, oxidative stress, specific secondary mutations, and regulation of specific progenitor cells and transcriptional programs are critical in BRCA1-associated breast cancer. Strategies geared toward estrogen reduction may play a role in treatment and prevention. Therapies aimed at mitigating oxidative stress may be a strategy for risk reduction, while cancer-cell-specific sensitivity to oxidative stress may also be an opportunity for specific targeting. BRCA1-related transcriptional regulation and signaling provide a number of therapeutic targets, including the PI3-AKT and Notch pathways. Thus, significant opportunities exist in translational and clinical research for developing the treatment strategies for the management of BRCA1-related breast cancer

Nearby Optical Galaxies: Selection of the Sample and Identification of Groups

In this paper we describe the Nearby Optical Galaxy (NOG) sample, which is a complete, distance-limited ($cz\leq$6000 km/s) and magnitude-limited (B$\leq$14) sample of $\sim$7000 optical galaxies. The sample covers 2/3 (8.27 sr) of the sky ($|b|>20^{\circ}$) and appears to have a good completeness in redshift (98%). We select the sample on the basis of homogenized corrected total blue magnitudes in order to minimize systematic effects in galaxy sampling. We identify the groups in this sample by means of both the hierarchical and the percolation {\it friends of friends} methods. The resulting catalogs of loose groups appear to be similar and are among the largest catalogs of groups presently available. Most of the NOG galaxies ($\sim$60%) are found to be members of galaxy pairs ($\sim$580 pairs for a total of $\sim$15% of objects) or groups with at least three members ($\sim$500 groups for a total of $\sim$45% of objects). About 40% of galaxies are left ungrouped (field galaxies). We illustrate the main features of the NOG galaxy distribution. Compared to previous optical and IRAS galaxy samples, the NOG provides a denser sampling of the galaxy distribution in the nearby universe. Given its large sky coverage, the identification of groups, and its high-density sampling, the NOG is suited for the analysis of the galaxy density field of the nearby universe, especially on small scales.Comment: 47 pages including 6 figures. Accepted for publication in Ap

Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial

The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor–positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology)

Preoperative Breast MRI in the Surgical Treatment of Ductal Carcinoma In Situ

n Abstract: Accurate determination of the size or extent of ductal carcinoma in situ (DCIS) by imaging is uncertain, and incomplete resection of tumor results in involved margins in up to 81% of cases. This study examined the accuracy of magnetic resonance imaging (MRI) for assessment of DCIS size, and evaluated the effect of preoperative breast MRI on achievement of tumor-free surgical margins after breast-conserving surgery (BCS). One-hundred and fifty-eight female patients with DCIS were identified from a prospective database: 60 patients (62 cases) had preoperative breast MRI, and 98 patients did not have MRI. The accuracy of tumor size assessed by MRI was determined by comparison with histopathologic size. All patients underwent BCS initially. The rate of involved margins after resection was compared in MRI and no-MRI groups. The overall correlation between MRI size and histopathologic size was high (p < 0.0001). MRI assessment of size was significantly more accurate when DCIS was high grade (p < 0.0001) or intermediate grade (p = 0.005) versus low grade (p = 0.187). The rate of tumor-involved margins was not significantly different in MRI and no-MRI groups (30.7% and 24.7%, respectively; p = 0.414). The rate of mastectomy was significantly higher in the MRI group than the no-MRI group (17.7% versus 4.1%; p = 0.004). These findings indicate that MRI can detect DCIS, especially when lesions are high or intermediate grade, but that MRI does not accurately predict the size of DCIS. In this study, MRI did not improve the surgeon's ability to achieve clear margins following BCS.

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Macrostructural Alterations of Subcortical Grey Matter in Psychogenic Erectile Dysfunction

Psychogenic erectile dysfunction (ED) has been defined as the persistent inability to attain and maintain an erection sufficient to permit sexual performance. It shows a high incidence and prevalence among men, with a significant impact on the quality of life. Few neuroimaging studies have investigated the cerebral basis of erectile dysfunctions observing the role played by prefrontal, cingulate, and parietal cortices during erotic stimulation. In spite of the well-known involvement of subcortical regions such as hypothalamus and caudate nucleus in male sexual response, and the key role of nucleus accumbens in pleasure and reward, poor attention was paid to their role in male sexual dysfunction. In this study, we determined the presence of grey matter (GM) atrophy patterns in subcortical structures such as amygdala, hippocampus, nucleus accumbens, caudate nucleus, putamen, pallidum, thalamus, and hypothalamus in patients with psychogenic ED and healthy men. After Rigiscan evaluation, urological, general medical, metabolic and hormonal, psychological and psychiatric assessment, 17 outpatients with psychogenic ED and 25 healthy controls were recruited for structural MRI session. Significant GM atrophy of nucleus accumbens was observed bilaterally in patients with respect to controls. Shape analysis showed that this atrophy was located in the left medial-anterior and posterior portion of accumbens. Left nucleus accumbens volumes in patients correlated with low erectile functioning as measured by IIEF-5 (International Index of Erectile Function). In addition, a GM atrophy of left hypothalamus was also observed. Our results suggest that atrophy of nucleus accumbens plays an important role in psychogenic erectile dysfunction. We believe that this change can influence the motivation-related component of sexual behavior. Our findings help to elucidate a neural basis of psychogenic erectile dysfunction