Breast Elastography: How to Perform and Integrate Into a “Best-Practice” Patient Treatment Algorithm

Breast elastography has been available for more than 15 years but is not widely incorporated into clinical practice. Many publications report extremely high accuracy for various breast elastographic techniques. However, results in the literature are extremely variable. This variability is most likely due to variations in technique, a relatively steep learning curve, and variability in methods between vendors. This article describes our protocol for performing breast elastography using both strain elastography and shear wave elastography, which produces high sensitivity and specificity. Additionally, we will describe the most commonly known false-positive and false-negative lesions as well as how to detect them.     

经自然腔道取标本手术在结直肠外科手术中的应用进展

随着腔镜技术的进一步发展以及微创理念应用于结直肠外科疾病的诊治中,结直肠相关疾病的诊治发生了翻天覆地的变化。由传统的经腹手术到腹腔镜手术、经自然腔道手术,再到经自然腔道取标本手术(NOSES),结直肠疾病的外科诊治在微创领域取得了巨大成果。NOSES技术是目前结直肠外科在微创领域前沿的手术方式之一,它通过经直肠、阴道取标本来避免了腹壁的辅助取标本切口,从而将结直肠外科手术进一步微创化。NOSES技术集传统腹腔镜手术的优势与现代微创外科的理念于一体,它在确保手术效果的基础上集中体现了微创、加速康复外科、功能外科、"无疤"等理念的特点。本文主要就国内外各中心开展NOSES技术在结直肠外科诊治开展中的相关经验、心得和体会进行综述。     

Cost-effectiveness of breast cancer screening programme for women in rural China

In low and middle-income countries mammographic breast cancer screening is prohibitively expensive and a cheaper alternative option is to use ultrasound as the primary screening test. In 2009, China launched a breast cancer screening programme for rural women aged 35–64 years with clinical breast examination coupled with ultrasound as the primary tool. Our study aimed to analyse the cost-effectiveness of breast screening compared to no screening among Chinese rural women. We developed a Markov model to estimate the lifetime costs and effects for rural women aged 35 years from a societal perspective. Asymptomatic women in the intervention arm were screened every 3 years before age 64 years. Breast cancer in the non-screening arm can only be diagnosed on presentation of symptoms. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses. Compared to no screening, breast cancer screening cost $186.7 more and led to a loss of 0.20 quality-adjusted life years (QALYs). Breast screening was more expensive and did harm to health among rural women with an incremental cost-effectiveness ratio (ICER) of $-916/QALY. The sensitivity analysis identified utility loss from false positives as the factor that most influenced the results, but this did not affect the conclusions. In a rural setting with such low breast cancer incidence, screening for asymptomatic disease is not cost-effective with current screening tools. Priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms.     

Clinicopathologic factors associated with malignant transformation of oral leukoplakias: a retrospective cohort study

It is clinically challenging to identify oral leukoplakias that have a high risk of undergoing malignant transformation. The aim of this retrospective study was to elucidate the associations between malignant transformation of oral leukoplakias and various clinicopathologic factors. Patients with a diagnosis of clinical oral leukoplakia, verified through histopathologic examination and with access to digital images of the lesion, were retrospectively included for the period 2003–2013. Using the clinical images, all lesions were re-evaluated regarding diagnosis and clinical subtype. Of the 234 included patients, with a median follow-up of 9 years, 27 (11.5%) developed oral squamous cell carcinoma. Among the clinicopathologic factors investigated, non-homogeneous oral leukoplakia (OL), OL with dysplasia, and OL localized to the tongue showed statistically significant increased rates of malignant transformation in the multivariate Cox regression analysis. Non-homogeneous OL showed a 15.2-times higher transformation rate than homogenous OL (P < 0.001). Dysplastic leukoplakias developed into carcinomas 2.4-times more often than did non-dysplastic leukoplakias (P = 0.048). OL located on the tongue showed a 2.8-times higher malignant transformation rate than OLs at other oral locations (P = 0.018), when other locations were combined into one group. Non-homogeneous OL, OL with dysplasia, and OL localized to the tongue have higher transformation rates.     

Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

转录调节因子c-Myb通过炎症因子Ccl2抑制乳腺癌肺转移的实验研究

目的:研究乳腺癌细胞中转录调节因子c-Myb的表达对肺转移的影响及其分子机制。方法:构建c-Myb高表达的4T1乳腺癌细胞株，种植小鼠构建乳腺癌动物模型，检测实验动物肺转移情况，通过荷瘤抑制试验检测肺转移抑制效果。提取组织进行荧光PCR检测相关炎症因子的表达。利用Medisapiens数据库的生物信息学资源，对c-Myb和Ccl2的表达与乳腺癌患者的预后进行分析。结果:高表达c-Myb的荷瘤小鼠肺部转移灶明显减少，其中炎症相关因子表达受限。由数据库分析得出，c-Myb高表达患者生存期得以延长。结论:乳腺癌中c-Myb的表达能够通过炎症因子Ccl2抑制肺转移从而延长患者生存期。     

基于生物信息学筛选早发性乳腺癌差异表达基因

目的筛选并分析与早发性乳腺癌发生、发展相关的靶基因。 方法(1)在美国国立生物技术信息中心的公共基因芯片数据库(GEO)中检索早发性乳腺癌样本及非早发性乳腺癌样本相关基因芯片数据。对上述数据使用GEO2R、R4.1.2及Venn软件筛选出相关差异表达基因(DEGs)，并运用在线分析工具(Web Gestalt)对DEGs，进行相关功能和信号通路富集分析。(2)同时，通过String在线数据库构建DEGs编码的蛋白质-蛋白质相互作用(PPI)网络，并利用Cytohubba插件对该网络中的基因进行评分，筛选出枢纽基因。将枢纽基因导入Kaplan-Meier生存分析工具(Kaplan-Meier Plotter)，评估枢纽基因在早发性乳腺癌的预后价值。(3)将肿瘤基因组图谱(TCGA)数据库中的肿瘤组织以年龄为标准进行分组，分析枢纽基因在各年龄组中的表达，并与正常组织中的表达进行比较，对得到的枢纽基因进行验证。DEGs表达量的多组间比较使用Kruskal-Wallis H检验，使用Bonferroni法进行两两比较。 结果(1)筛选出编号为GSE89116、GSE109169、GSE36295的基因芯片数据集，共得到80个差异表达基因，其中上调差异表达基因17个，下调差异表达基因63个。富集分析显示：DEGs主要富集在脂质代谢和氧化还原过程以及PPAR信号通路、AMPK信号通路上。(2)在PPI中发现主要的关键基因为PPARG、ADIPOQ、LIPE、PCK1、PDK4、ACACB、PLIN1、CAV1、CD36、ANGPTL4。ACACB、ADIPOQ、CAV1、LIPE、PLIN1、PPARG基因的低表达与乳腺癌患者的不良OS相关(HR＝0.69、0.84、0.76、0.88、0.78、0.82；95%CI：0.59~0.80、0.76~0.93、0.67~0.83、0.79~0.97、0.70~0.86、0.73~0.90；P均<0.050)。(3)ACACB、ADIPOQ、LIPE、PLIN1、CAV1及PPARG这6个与预后相关的基因在正常组织中的表达量均远高于各年龄组肿瘤组织中的表达量(χ²＝104.03、179.57、161.85、189.87、118.56、103.62，P均<0.001)，早发性乳腺癌组(21~40岁)的LIPE、PLIN1表达量低于41~60岁、61~80岁年龄组，差异具有统计学意义(LIPE: Z＝21.07、23.12, P均<0.050; PLIN1：Z＝16.89、18.76, P均<0.050)。 结论早发性乳腺癌与非早发性乳腺癌存在差异基因表达谱，LIPE、PLIN1可能是早发性乳腺癌发生、发展的关键基因。     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.