Oncological considerations of skin-sparing mastectomy

AIM: To review evidence concerning the oncological safety of performing skin-sparing mastectomy (SSM) for invasive breast cancer and ductal carcinoma in situ (DCIS). Furthermore, the evidence concerning RT in relation to SSM and the possibility of nipple preservation was considered. METHODS: Literature review facilitated by Medline and PubMed databases. FINDINGS: Despite the lack of randomised controlled trials, SSM has become an accepted procedure in women undergoing mastectomy and immediate reconstruction for early breast cancer. Compared to non-skin-sparing mastectomy (NSSM), SSM seems to be oncologically safe in patients undergoing mastectomy for invasive tumours smaller than 5 cm, multicentric tumours, DCIS or risk-reduction. However, the technique should be avoided in patients with inflammatory breast cancer or in those with extensive tumour involvement of the skin in view of the high risk of local recurrence. SSM with nipple areola complex (NAC) preservation appears to be oncologically safe, provided the tumour is not close to the nipple and a frozen section protocol for the retro-areolar tissue is followed. Although radiotherapy (RT) does not represent a contraindication to SSM, the latter should be used with caution if postoperative RT is likely, since it detracts from the final cosmetic outcome

Oncological outcome and patient satisfaction with skin-sparing mastectomy and immediate breast reconstruction: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>The management of early breast cancer (BC) with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) is not based on level-1 evidence. In this study, the oncological outcome, post-operative morbidity and patients' satisfaction with SSM and IBR using the latissimus dorsi (LD) myocutaneous flap and/or breast prosthesis is evaluated.</p> <p>Methods</p> <p>137 SSMs with IBR (10 bilateral) were undertaken in 127 consecutive women, using the LD flap plus implant (n = 85), LD flap alone (n = 1) or implant alone (n = 51), for early BC (n = 130) or prophylaxis (n = 7). Nipple reconstruction was performed in 69 patients, using the trefoil local flap technique (n = 61), nipple sharing (n = 6), skin graft (n = 1) and Monocryl mesh (n = 1). Thirty patients underwent contra-lateral procedures to enhance symmetry, including 19 augmentations and 11 mastopexy/reduction mammoplasties. A linear visual analogue scale was used to assess patient satisfaction with surgical outcome, ranging from 0 (not satisfied) to 10 (most satisfied).</p> <p>Results</p> <p>After a median follow-up of 36 months (range = 6-101 months) there were no local recurrences. Overall breast cancer specific survival was 99.2%, 8 patients developed distant disease and 1 died of metastatic BC. There were no cases of partial or total LD flap loss. Morbidities included infection, requiring implant removal in 2 patients and 1 patient developed marginal ischaemia of the skin envelope. Chemotherapy was delayed in 1 patient due to infection. Significant capsule formation, requiring capsulotomy, was observed in 85% of patients who had either post-mastectomy radiotherapy (PMR) or prior radiotherapy (RT) compared with 13% for those who had not received RT. The outcome questionnaire was completed by 82 (64.6%) of 127 patients with a median satisfaction score of 9 (range = 5-10).</p> <p>Conclusion</p> <p>SSM with IBR is associated with low morbidity, high levels of patient satisfaction and is oncologically safe for T(is), T1 and T2 tumours without extensive skin involvement.</p

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study

Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD

Temporal and Individual Variation in Offspring Provisioning by Tree Swallows: A New Method of Automated Nest Attendance Monitoring

Studies of the ecology and evolution of avian nesting behavior have been limited by the difficulty and expense of sampling nest attendance behavior across entire days or throughout a substantial portion of the nestling period. Direct observation of nesting birds using human observers and most automated devices requires sub-sampling of the nestling period, which does not allow for the quantification of the duration of chick-feeding by parents within a day, and may also inadequately capture temporal variation in the rate at which chicks are fed. Here I describe an inexpensive device, the Automated Perch Recorder (APR) system, which collects accurate, long-term data on hourly rates of nest visitation, the duration of a pair's workday, and the total number of visits the pair makes to their nest across the entire period for which it is deployed. I also describe methods for verifying the accuracy of the system in the field, and several examples of how these data can be used to explore the causes of variation in and tradeoffs between the rate at which birds feed their chicks and the total length of time birds spend feeding chicks in a day

Introduction: Rethinking the Impact of the Inter-American Human Rights System

This chapter introduces the central themes of the book and argues that the Inter-American Human Rights System (IAHRS) is activated by political actors and institutions in ways that transcend traditional compliance perspectives and that have the potential to meaningfully alter politics and provoke positive domestic human rights change. The chapter identifies key gaps in existing human rights scholarship, particularly in relation to the IAHRS, and outlines three core perspectives on the System’s impact on human rights. It offers a synthesis of the key findings of the volume, and provides reflections on the future prospects of the System by locating it in its broader global context

Salivary Glucose Oxidase from Caterpillars Mediates the Induction of Rapid and Delayed-Induced Defenses in the Tomato Plant

Caterpillars produce oral secretions that may serve as cues to elicit plant defenses, but in other cases these secretions have been shown to suppress plant defenses. Ongoing work in our laboratory has focused on the salivary secretions of the tomato fruitworm, Helicoverpa zea. In previous studies we have shown that saliva and its principal component glucose oxidase acts as an effector by suppressing defenses in tobacco. In this current study, we report that saliva elicits a burst of jasmonic acid (JA) and the induction of late responding defense genes such as proteinase inhibitor 2 (Pin2). Transcripts encoding early response genes associated with the JA pathway were not affected by saliva. We also observed a delayed response to saliva with increased densities of Type VI glandular trichomes in newly emerged leaves. Proteomic analysis of saliva revealed glucose oxidase (GOX) was the most abundant protein identified and we confirmed that it plays a primary role in the induction of defenses in tomato. These results suggest that the recognition of GOX in tomato may represent a case for effector-triggered immunity. Examination of saliva from other caterpillar species indicates that saliva from the noctuids Spodoptera exigua and Heliothis virescens also induced Pin2 transcripts

The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation.

In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought

Variation in Vector Competence for Dengue Viruses Does Not Depend on Mosquito Midgut Binding Affinity

Several factors, such as mosquito and virus genetics and environmental variables, determine the ability of mosquitoes to transmit dengue viruses. In this report, we describe new and important information that in some ways contradicts what is in the literature. Midgut infection barriers have been described as important determinants of virus transmission in mosquitoes but we found that virus binding to these midgut cells does not vary. When we compared binding of 8 different, low passage dengue viruses to mosquito midguts that were dissected out of Aedes aegypti mosquitoes (the main vectors of dengue) from Mexico and Texas, we found that there were no differences. Previously, we (and others) had shown that these same viruses differed significantly in replication and dissemination throughout the rest of the mosquito body, including the salivary glands, and therefore they differed greatly in their potential to be transmitted to humans. Thus, the data presented here are important considerations for future studies of vector competence and in determining strategies for control of dengue viruses in the vector

Identification of Tuberculosis Susceptibility Genes with Human Macrophage Gene Expression Profiles

Although host genetics influences susceptibility to tuberculosis (TB), few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of Mycobacterium tuberculosis (Mtb) infection would have distinct gene expression profiles and that polymorphisms in these genes may also be associated with susceptibility to TB. We measured gene expression levels of >38,500 genes from ex vivo Mtb-stimulated macrophages in 12 subjects with 3 clinical phenotypes: latent, pulmonary, and meningeal TB (n = 4 per group). After identifying differentially expressed genes, we confirmed these results in 34 additional subjects by real-time PCR. We also used a case-control study design to examine whether polymorphisms in differentially regulated genes were associated with susceptibility to these different clinical forms of TB. We compared gene expression profiles in Mtb-stimulated and unstimulated macrophages and identified 1,608 and 199 genes that were differentially expressed by >2- and >5-fold, respectively. In an independent sample set of 34 individuals and a subset of highly regulated genes, 90% of the microarray results were confirmed by RT-PCR, including expression levels of CCL1, which distinguished the 3 clinical groups. Furthermore, 6 single nucleotide polymorphisms (SNPs) in CCL1 were found to be associated with TB in a case-control genetic association study with 273 TB cases and 188 controls. To our knowledge, this is the first identification of CCL1 as a gene involved in host susceptibility to TB and the first study to combine microarray and DNA polymorphism studies to identify genes associated with TB susceptibility. These results suggest that genome-wide studies can provide an unbiased method to identify critical macrophage response genes that are associated with different clinical outcomes and that variation in innate immune response genes regulate susceptibility to TB