Women's preferences for contralateral prophylactic mastectomy following unilateral breast cancer: What risk-reduction makes it worthwhile?

ObjectivesContralateral prophylactic mastectomy (CPM) reduces the risk of contralateral breast cancer (BC) following unilateral BC, but may not increase survival in BRCA1/2 mutation negative women. Despite this, and the risk for adverse physical and psychological impact, uptake is increasing in BRCA1/2 mutation negative women. We aimed to quantify the degree of reduction in lifetime contralateral BC risk women required to justify CPM, and to explore demographic, disease and psychosocial predictors of preferences using Protection Motivation Theory (PMT) as a theoretical framework. Reasoning behind preferences was also examined.Materials and methods388 women previously diagnosed with unilateral BC, of negative or unknown BRCA1/2 status, were recruited from an advocacy group research database. Two hypothetical risk trade-off scenarios were used to quantify the reduction in lifetime contralateral BC risk that women judged necessary to justify CPM, using a 5% and 20% baseline. Demographic, disease and PMT measures were assessed using a questionnaire.ResultsMost women required their risk to be more than halved from a 5% or 20% baseline to justify CPM. Polarised preferences were also common, with some women consistently accepting or refusing CPM independent of risk/benefit trade-offs. Preferences were associated with coping self-efficacy and having a prior CPM. Explanations for judging CPM worthwhile included reducing or eliminating contralateral BC risk, attaining breast symmetry and reducing worry.ConclusionRisk-reduction preferences were highly variable. Decisive factors in women's preferences for CPM related to clinical, psychological and cosmetic outcomes, but not to demographic or disease characteristics.     

X-ray structure of an AdoMet radical activase reveals an anaerobic solution for formylglycine posttranslational modification

Arylsulfatases require a maturating enzyme to perform a co- or posttranslational modification to form a catalytically essential formylglycine (FGly) residue. In organisms that live aerobically, molecular oxygen is used enzymatically to oxidize cysteine to FGly. Under anaerobic conditions, S-adenosylmethionine (AdoMet) radical chemistry is used. Here we present the structures of an anaerobic sulfatase maturating enzyme (anSME), both with and without peptidyl-substrates, at 1.6–1.8 Å resolution. We find that anSMEs differ from their aerobic counterparts in using backbone-based hydrogen-bonding patterns to interact with their peptidyl-substrates, leading to decreased sequence specificity. These anSME structures from Clostridium perfringens are also the first of an AdoMet radical enzyme that performs dehydrogenase chemistry. Together with accompanying mutagenesis data, a mechanistic proposal is put forth for how AdoMet radical chemistry is coopted to perform a dehydrogenation reaction. In the oxidation of cysteine or serine to FGly by anSME, we identify D277 and an auxiliary [4Fe-4S] cluster as the likely acceptor of the final proton and electron, respectively. D277 and both auxiliary clusters are housed in a cysteine-rich C-terminal domain, termed SPASM domain, that contains homology to ∼1,400 other unique AdoMet radical enzymes proposed to use [4Fe-4S] clusters to ligate peptidyl-substrates for subsequent modification. In contrast to this proposal, we find that neither auxiliary cluster in anSME bind substrate, and both are fully ligated by cysteine residues. Instead, our structural data suggest that the placement of these auxiliary clusters creates a conduit for electrons to travel from the buried substrate to the protein surface.     

Fast gated EPR imaging of the beating heart: Spatiotemporally resolved 3D imaging of free‐radical distribution during the cardiac cycle

In vivo or ex vivo electron paramagnetic resonance imaging (EPRI) is a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. However, applications of EPRI have been limited by long projection acquisition times and the consequent fact that rapid gated EPRI was not possible. Hence in vivo EPRI typically provided only time‐averaged information. In order to achieve direct gated EPRI, a fast EPR acquisition scheme was developed to decrease EPR projection acquisition time down to 10–20 ms, along with corresponding software and instrumentation to achieve fast gated EPRI of the isolated beating heart with submillimeter spatial resolution in as little as 2–3 min. Reconstructed images display temporal and spatial variations of the free‐radical distribution, anatomical structure, and contractile function within the rat heart during the cardiac cycle. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

The role of fibrin glue instillation under skin flaps in the prevention of seroma formation and related morbidities following breast and axillary surgery for breast cancer: A meta‐analysis

A systematic review of randomised, controlled trials investigating the effectiveness of fibrin glue (FG) in reducing the postoperative seroma and seroma related morbidities following breast and axillary surgery was conducted. FG failed to influence the incidence of postoperative seroma, average volume of seroma, wound infection, complications and length of hospital stay in patients undergoing breast cancer surgery. However, a major multicentre and high quality randomised, controlled trial is required to validate these findings. J. Surg. Oncol. 2012; 106:783–795. © 2012 Wiley Periodicals, Inc.     

Apheresis Induces Oxidative Stress in Blood Cells

Oxidative stress mediates damage to various cells and is thought to be involved in various pathologies, including hereditary and acquired hemolytic anemias. It is induced by a multitude of physiological and environmental factors, including extracorporeal manipulation of blood. As a result, hemodialysis induces oxidative damage to red blood cells, thereby increasing their susceptibility to hemolysis and shortening their life span. We studied the effect of apheresis on the oxidative status of blood components. Using flow cytometric measurements, we showed that red blood cells, lymphocytes, monocytes, and polymorphonuclear cells undergo oxidative stress induced by the procedure. Their reactive oxygen species and externalization of phosphatidylserine increased, while their levels of reduced glutathione decreased. This oxidative stress, which may be caused by a direct interaction with the membranous system, may lead to cellular abnormalities with clinical consequences such as hemolysis and platelet hyperactivation.     

T1G3期膀胱癌诊治策略

膀胱癌是我国泌尿系统最常见的恶性肿瘤，新发病例中75％的病变局限于黏膜和固有层，临床分期属于T1期。其中10％的肿瘤病理分级属于G3级。把临床分期T1、病理分级G3的膀胱移行上皮癌统称为T1G3期膀胱癌。研究发现，T1G3期膀胱癌患者疾病进展和死亡的风险比其他T1期肿瘤患者高出10倍，其生物学行为复杂、临床预后较差，临床诊治相对较为棘手。目前国际上对于这类疾病多采取经尿道膀胱肿瘤电切联合膀胱灌注BCG保留膀胱、或根治性膀胱切除术的方式进行治疗。但何时选择保留膀胱的治疗方案、何时选择根治性膀胱切除术，还需要根据患者的具体临床风险因素进行综合分析，并制定最佳的治疗方案。作者在认真学习并总结国际上关于T1G3期膀胱癌最新治疗指南的基础上，对这类疾病的诊断与治疗的最新理念及方法进行综合分析，供广大泌尿外科同道参考。     

The Effect of Electric Properties of Liposomes on SOD-like Activity ofCopper Salicylate

The SOD-like activities of copper salicylate encapsulated in neutral positively and negativelycharged liposomes were studied with cytochrome c method. The results showed that the SOD-like activity of coppersalicylate encapsulated in neutral liposomes was enhanced over 3 times more than that of copper salicylate in aqueoussolution. However, the activity decreased for copper salicylate encapsulated in positively and negatively chargedliposomes. It was also found that at experimental concentrations there was no regularity for the change of activity ofcopper salicylate encapsulated in negatively charged liposomes, and copper salicylate encapsulated in liposomes withmore negative charges could promote the dismutation of superoxide anion free radicals, however, so could coppersalicylate encapsulated in liposomes with fewer negative charges only in lower concentrations.     

脂质过氧化与食管癌发病关系的研究

本文用硫代巴比妥酸荧光法测定了122例食管癌前各期人群及食管癌宿主血清中的过氧化脂质(Lipoperoxide,Lpo)含量。结果显示,随食管上皮细胞病变的进展,机体Lpo水平明显升高。癌症组与癌前增生组和正常组比较,差异非常显著,但癌前增生组与正常组间差异无显著性,提示脂质过氧化水平的升高可能是食管癌发生后的伴行改变,其机制尚待探讨。     

Efficacy of internal mammary node dissection in the treatment of breast cancer.

The present study compares clinical and pathological findings and survival data from 410 patients who have undergone extended radical mastectomies in our hospital during the 20 years from 1967 with those derived from 261 who underwent mastectomies without dissections of the internal mammary nodes, in order to determine the value of additional internal mammary node dissection following standard radical mastectomy. Extended radical mastectomy was used in 289 of 361 (80.1%) patients with medial tumors, and in 121 of 310 (39.0%) with lateral tumors. Metastases to the internal mammary nodes were found in 18.5% (76) of all patients, in 20.4% (59) of the patients with medial tumors and in 14.0% (17) of those with lateral tumors. Of the patients with medial tumors, internal mammary node metastases were found in seven of 44 (15.9%) at TNM Stage I, and the rate of metastases rose with advances in stage. Internal mammary node metastases alone, without those to the axillary nodes, were found in 14 patients (4.8%) with medial tumors and in two with lateral tumors. The 10-year survival rate in patients with medial tumors and metastases to the internal mammary nodes only was 67.0%, which was as good as that in patients with metastases to the axillary nodes only. In conclusion, extended radical mastectomy was valuable in the treatment of relatively early medial breast cancer at TNM Stages I and II.     

煤烟对大鼠肺细胞氧化性损伤作用途径的探讨

目的：探讨煤烟导致肺Ⅱ型细胞氧化性损伤的途径，方法：通过对加入抗氧化剂N－乙酰半胱氨酸、维生素E、维生素C和甘露醇作为实验干预手段，采用MTT法观察其对煤烟所致大鼠肺Ⅱ型细胞毒性的影响，结果：与对照组相比，加入10mmol/L N-乙酰半胱氨酸，维生素E，维生素C后的实验组细胞毒性有所下降，而甘露醇没有观察到类似的作用。结论：煤烟可以通过产生氧自由基或脂质过氧化物等多种途径对机体造成氧化性损伤。