Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.     

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

CD44基因多态性与宫颈癌及非小细胞肺癌的相关性

背景与目的：CD44分子是众多肿瘤细胞的标志分子，其表达水平与肿瘤细胞的恶性程度有关。该研究探讨CD44基因中的单核苷酸多态性（single nucleotide polymorphism，SNP）位点与云南汉族人群宫颈癌和非小细胞肺癌（nonsmall cell lung cancer，NSCLC）易感性的相关性。方法：选取了CD44基因中的两个SNP位点rs13347和rs8193，采用TagMan基因分型的方法，分析这两个多态性位点在497例宫颈癌患者和500例健康对照个体以及483例NSCLC患者和471例健康对照个体中的分布特征，并分析CD44基因中的多态性位点与云南汉族人群宫颈癌和NSCLC的相关性。结果：rs13347和rs8193位点等位基因和基因型在宫颈癌组和对照组中的分布频率的差异无统计学意义（P>0.05）。而在NSCLC组和对照组的比较中：rs13347和rs8193位点等位基因在NSCLC组和对照组中的分布频率的差异有统计学意义（P=0.020和P=0.004）；这两个位点基因型在NSCLC组和对照组中分布频率的差异有统计学意义（P=0.027和P=0.020）；其中rs13347位点等位基因C在NSCLC组中的分布频率显著高于对照组，可能是NSCLC发生的风险因素（OR=1.250，95% CI：1.035～1.509），rs8193位点等位基因C在对照组中的分布频率显著高于NSCLC组，可能是NSCLC发生的保护性因素（OR=0.768，95%CI：0.641～0.921）。单倍型分析结果显示，rs13347C-rs8193T和rs13347T-rs8193C在NSCLC组和对照组中的分布频率差异有统计学意义（P=0.003和0.022）；该结果说明单倍型rs13347C-rs8193T可能是云南汉族人群NSCLC发生的风险性因素（OR=1.316，95%CI：1.096～1.579）。结论：CD44基因中的两个SNP位点rs13347和rs8193可能与云南汉族人群宫颈癌发病风险无关，而可能与云南汉族人群NSCLC具有相关性。     

Modern theatre design and usage: do joint replacements need laminar flow?

Since the introduction of laminar flow to theatre systems by Charnley, it has become a necessity in arthroplasty surgery. His initial work in the 1960s and 70s created improvements in terms of reducing overall rates of periprosthetic joint replacement, but it has been hard to ascertain if this stems from the laminar flow itself or improvements in asepsis and the utilization of perioperative antibiotics. The aim of this paper is therefore to establish if laminar flow is still a necessary addition to modern theatre design, particularly in joint replacement surgery, irrespective of other surgical factors. A wide variety of studies were utilized to form an objective analysis of whether laminar flow is essential to asepsis in theatre design. It explores a number of smaller earlier studies and ends with two large trials which provide evidence that laminar flow may in fact have a deleterious effect on the potential for peri-prosthetic joint infection (PJI). The article discusses potential reasons for these findings and seeks to explain them in context of overall asepsis during joint replacement surgery.     

氩氦冷冻消融在肺癌多学科综合治疗中的研究进展

肺癌是世界上发病率最高的恶性肿瘤之一,外科手术为首选治疗方式。近年来许多新兴微创技术治疗肺癌取得了良好效果。氩氦冷冻消融术因具有损伤小、恢复快、安全性高、并发症少等优点,已取得医患双方认可。冷冻消融适用于不能手术切除的早期肺癌及减少晚期肺癌负荷。肿瘤是一种全身性疾病,因此冷冻消融联合其他治疗方法将是未来肺癌治疗发展方向,从而改善患者临床症状,提高生活质量,延长生存时间,达到最佳治疗效果。该文就冷冻消融治疗及与其他方法综合治疗肺癌研究现状和进展作一综述。     

宣威地区与非宣威地区肺癌患者临床流行病学特征及病理类型特点分析

目的:分析宣威地区与非宣威地区的肺癌临床流行病学与病理特征。方法:以云南省肿瘤医院（昆明医科大学第三附属医院）2015年3月至2015年5月手术治疗的肺癌患者为研究对象，共295例，收集患者相关信息。将其分为宣威地区、非宣威地区进行统计。对患者的临床资料进行回顾性分析，包含病理类型、年龄、性别、吸烟史等。结果:宣威地区、非宣威地区肺癌患者男女比例为1.19∶1和1.69∶1。宣威地区患者平均年龄为［53.41±8.74(34~85)］岁，中位年龄53岁。非宣威地区肺癌患者平均年龄为［58.68±8.63(38~78)］岁，中位年龄59岁。宣威地区肺癌高发年龄为40~59岁段。宣威地区I期肺癌患者占比、T1期肺癌患者占比、N0期肺癌患者占比均高于非宣威地区。宣威地区男性腺癌鳞癌比远高于非宣威地区，差异有显著统计学意义。结论:宣威地区女性肺癌发病率更高，发病年龄更趋年轻化，腺癌比例高，吸烟与宣威地区男性腺癌高发关系不密切。     

基因间长链非编码RNA152靶向微小RNA?103a?3p对非小细胞肺癌细胞增殖和侵袭迁移的影响

目的探讨基因间长链非编码RNA 152(LINC00152)靶向调控微小RNA-103a-3p(miR-103a-3p)表达及对非小细胞肺癌(NSCLC)细胞增殖和侵袭迁移的影响。方法采用实时定量PCR(QPCR)检测正常肺上皮细胞BEAS-2B及NSCLC细胞(ANIP-973、NCI-H157、A549和NCI-H1975)的LINC00152水平。选取LINC00152水平最高的细胞分别转染LINC00152特异性小干扰RNA(si-LINC00152组)或无关序列(si-NC组),另设未转染细胞为对照组。QPCR检测LINC00152水平,活细胞计数CCK-8法、Transwell小室和划痕实验测定细胞增殖、侵袭和迁移能力,Western blotting检测基质金属蛋白酶(MMP)-2、MMP-9和第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)的水平;荧光素酶报告实验验证LINC00152靶向结合miR-103a-3p的能力。结果NSCLC细胞的LINC00152水平均高于BEAS-2B细胞(P<0.05),尤其是NCI-H1975细胞的最高。si-LINC00152组的LINC00152水平为0.352±0.087,低于对照组的1.058±0.219和si-NC组的1.126±0.139(P<0.05)。与si-NC组和对照组相比,si-LINC00152组NCI-H1975细胞转染48、72 h的增殖活力下降(P<0.05);si-LINC00152组的划痕愈合率和穿膜细胞数分别为(27.386±2.428)%和(78.840±5.031)个,低于si-NC组的(77.675±4.803)%和(179.208±13.264)个及对照组的(76.371±5.385)%和(174.003±15.678)个(P<0.05);与si-NC组和对照组相比,si-LINC00152组的MMP-2和MMP-9水平均降低,而PTEN水平升高(P<0.05)。对照组和si-NC组上述指标的差异无统计学意义(P>0.05)。双荧光素酶报告分析证实,miR-103a-3p模拟物降低了野生型LINC00152的荧光素酶活性(P<0.05),但对突变型无影响(P>0.05)。结论LINC00152在NSCLC细胞中高表达并发挥促癌作用,与NSCLC的迁移侵袭密切相关,LINC00152与miR-103a-3p间的相互作用在NSCLC靶向治疗中有一定潜能。