Breast reconstruction after therapeutic or prophylactic mastectomy for breast cancer: A comparison of guideline recommendations

BackgroundThe purpose of this article is to illuminate differences in published clinical practice guideline recommendations for breast reconstruction after prophylactic and therapeutic mastectomy.MethodsTen guidelines were identified through a systematic search of websites and databases of reputable oncology guideline developers, and key differences and gaps in recommendations were noted. Quality assessment of the guidelines was conducted by three reviewers using the AGREE II tool, focusing on breast reconstruction specific documents rather than the general breast cancer guidelines.ResultsThe most comprehensive guidelines were published by Alberta Health Services, Cancer Care Ontario, the American Society of Plastic Surgeons, and the Association of Breast Surgery/British Association of Plastic Reconstructive and Aesthetic Surgeons. AGREE II scores in the domains of “Scope and Purpose” and “Clarity and Presentation” were ranked relatively high for all four guidelines while “Applicability” and “Editorial Independence” were ranked relatively low. The Alberta and Ontario guidelines were the overall highest ranked guidelines across all domains.ConclusionOverall, these guidelines provide consistent recommendations on who should receive breast reconstruction education, who is a candidate for postmastectomy breast reconstruction, and the appropriate timing of reconstruction and extent of mastectomy. Future updates from all should focus on expanding to include alloplastic and autologous forms of reconstruction and should include a broad scope of relevant questions.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

不同抗血小板治疗策略对非透析慢性肾功能不全患者冠状动脉搭桥术后胸廓内动脉及大隐静脉桥血管通畅率的影响

目的 比较阿司匹林联合替格瑞洛或者氯吡格雷的双联抗血小板药物治疗(DAPT)，对慢性肾功能不全患者冠脉搭桥手术（CABG）术后早期桥血管通畅率的影响。方法 我科接受CABG手术患者77例，随机纳入A组（阿司匹林+替格瑞洛）与B组（阿司匹林+氯吡格雷）。A组35例，B组42例。术后1年行计算机断层扫描血管造影（CTA）检查，评估桥血管通畅性。并随访主要心血管事件、出血事件发生情况。结果 随访期间7例失访。70例完成CTA检查，A组32例，B组38例。静脉桥血管通畅率A组显著高于B组（46/51 90.2% vs 42/56 75.0%，P=0.024）。小型出血事件发生率A组高于B组（P=0.022）。Logistic回归分析提示替格瑞洛+阿司匹林双联抗血小板治疗可以降低桥血管狭窄风险（OR=0.193, 95%CI=0.043 0.861，P=0.031）。结论 在CKD患者接受冠状动脉搭桥术后，DAPT替格瑞洛联合阿司匹林可能更好地维护静脉桥血管的通畅率，并未增加主要出血事件的风险。     

小细胞肺癌关键基因及信号通路分析

目的 探究SCLC基因调控机制，为寻找SCLC早期诊断及靶向治疗潜在的生物标志物提供依据。方法 采用生物信息学方法从公共基因芯片数据库获取小细胞肺癌（SCLC）mRNA数据并筛选出差异表达基因（DEGs），对DEGs进行基因本体（GO）和基因组百科全书数据库（KEGG）富集分析，构建蛋白互作网络，筛选出核心基因并利用Kaplan-Meier在线工具进行生存分析。结果 17例SCLC组织样本和19例正常肺组织样本中筛选出248个DEGs，包括172个高表达基因和76个低表达基因（P<0.05）。GO和KEGG富集分析结果显示，DEGs的功能主要涉及细胞周期、DNA复制、错配修复、P53信号通路等，蛋白互作分析网络筛选出6个节点度最高的核心基因：TOP2A、PCNA、RFC4、 FEN1、CCNA2和MCM2，并与患者预后相关。结论 DEGs涉及的分子功能和信号通路可能是SCLC发生的分子机制，而核心基因可能是治疗SCLC的潜在靶点。     

Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC

IntroductionWe retrospectively analyzed the effects of crizotinib on serum creatinine and creatinine-based estimated glomerular filtration rate (eGFR) in patients with anaplastic lymphoma kinase–positive advanced NSCLC across four trials (NCT00585195, NCT00932451, NCT00932893, and NCT01154140).MethodsChanges from baseline data in serum creatinine and eGFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation, were assessed over time. eGFR was graded using standard chronic kidney disease criteria.ResultsMedian serum creatinine increased from 0.79 mg/dL at baseline to 0.93 mg/dL after 2 weeks of treatment (median percentage increase from baseline, 21.2%), was stable from week 12 (0.96 mg/dL) to week 104 (1.00 mg/dL), and decreased to 0.90 mg/dL at 28 days after last dose (median percentage increase from baseline, 13.1%). Median eGFR decreased over time (96.42, 80.23, 78.06 and 75.45 mL/min/1.73 m² at baseline, week 2, week 12, and week 104, respectively) and increased to 83.02 mL/min/1.73 m² at 28 days after the last dose. Median percentage decrease from baseline was 14.9%, 17.0%, and 10.4% at week 2, week 12, and 28 days after last dose of crizotinib, respectively. Overall, 12.6% of patients had a shift from eGFR grade less than or equal to 3a (≥45 mL/min/1.73 m²) at baseline to greater than or equal to 3b (<45 mL/min/1.73 m²) post-baseline.ConclusionsCrizotinib resulted in a decline in creatinine-based estimates of renal function mostly over the first 2 weeks of treatment. However, there was minimal evidence of cumulative effects with prolonged treatment and these changes were largely reversible following treatment discontinuation, consistent with previous reports suggesting this may be predominantly an effect on creatinine secretion as opposed to true nephrotoxicity.     

脑脊液ctDNA对非小细胞肺癌脑膜转移患者的临床价值

背景与目的肺癌脑膜转移病死率极高。循环肿瘤DNA（circulating tumor DNA, ctDNA）已被证实含有肿瘤的基因组改变信息，并已被用于监测肿瘤的进展和对治疗的响应。对于存在脑膜转移瘤的患者，由于血脑屏障等因素的存在，外周血ctDNA不能反映脑部病灶的信息，此时脑脊液ctDNA作为检测样本能更好地体现颅内肿瘤的基因状态，指导临床对颅内病灶的靶向治疗。本研究旨在探究脑脊液ctNDA用于监测非小细胞肺癌（non-small cell lung cancer, NSCLC）脑膜转移的可行性以及脑脊液ctDNA检测对NSCLC脑膜转移的临床价值。方法入组NSCLC脑膜转移患者21例，通过二代基因测序技术对患者的脑脊液及外周血样本进行基因检测，并进行脑脊液细胞学病理学检测和头颅核磁共振增强检查。结果入组21例患者脑脊液中均检测到ctDNA。脑脊液ctDNA检测的灵敏性在脑膜转移诊断方面优于细胞学（P < 0.001）。脑脊液的基因突变检出率及基因突变丰度均高于血浆（P < 0.001）。脑脊液具有独特的基因谱。6例动态检测的患者中，脑脊液中ctDNA丰度变化均同时或早于临床疾病变化出现，可及时揭示耐药机制和监测复发趋势。结论脑脊液ctDNA检出率高于细胞学及影像学；脑脊液ctDNA检测可展现脑膜转移病灶特有的突变图谱；脑脊液ctDNA动态监测对肺癌患者临床疗效具有提示意义。     

Self-assessed preoperative level of habitual physical activity predicted postoperative complications after colorectal cancer surgery: A prospective observational cohort study

IntroductionThere is a growing interest in physical activity in relation to recovery after surgery. One important aspect of measuring recovery after surgical procedures is postoperative complications. The aim of this study was to determine if there is an association between the preoperative level of habitual physical activity and postoperative complications in patients undergoing elective surgery for colorectal cancer.Materials and methods115 patients scheduled for elective surgery due to colorectal cancer between February 2014 and September 2015 answered a questionnaire regarding physical activity and other baseline variables. Physical activity was assessed using the Saltin-Grimby physical activity level scale. Complications within 30 days after surgery were classified according to Clavien-Dindo, and the Comprehensive Complications Index (CCI) was calculated. Primary outcome was difference in CCI and key secondary outcome was risk for CCI ≥20.ResultsPhysically inactive individuals had a CCI that was 12 points higher than individuals with light activity (p = 0.002) and 17 points higher than regularly active individuals (p = 0.0004). Inactive individuals had a relative risk for a CCI ≥20 that was 65% higher than for individuals reporting light activity (95% confidence interval (CI) for relative risk (RR) = 1.1–2.5) and 338% higher than for regularly active individuals (95% CI for RR = 2.1–9.4).ConclusionSelf-assessed level of habitual physical activity before colorectal cancer surgery was associated with fewer postoperative complications measured with CCI, in a dose-response relationship.     

SU11274抑制人子宫内膜癌细胞增殖的分子机制

目的:探索HGF/c-met传导通路抑制剂SU11274抑制子宫内膜癌细胞增殖的分子机制。方法:使用不同浓度SU11274（0.5 μmol/L、1.0 μmol/L、1.5 μmol/L）作用ishikawa 和HEC-1B 两种细胞株1小时后，加入40 ng/ml的HGF，继续培养48小时，然后使用RT-PCR检测c-met、Survivin、XIAP水平以及Western blot检测细胞中Survivin、XIAP蛋白表达水平。结果:ishikawa细胞c-met低表达，而HEC-1B细胞c-met明显高表达，HEC-1B细胞中c-met mRNA表达量为ishikawa中的2.5倍。SU11274可以使HEC-1B、ishikawa细胞的Survivin、XIAP蛋白表达下调，呈现剂量依赖性，并且在HEC-1B细胞中，该下调作用明显强于ishikawa细胞（P<0.05）。结论:SU11274可以通过下调HGF/c-met传导通路中Survivin、XIAP的表达来抑制人子宫内膜癌细胞增殖。