- 作者列表："Vieira A","Bourdages-Pageau E","Kennedy K","Ugalde PA
OBJECTIVES:Minimally invasive techniques for lung cancer surgery have revolutionized thoracic surgery, and single-port approaches are becoming increasingly used. We analyzed our experience with uniportal video-assisted thoracoscopic surgery for lobectomy to identify the number of procedures necessary to achieve proficiency according to clinical outcomes. METHODS:We queried our institutional prospective database for all single-port lobectomies in patients with early-stage lung cancer performed by a single surgeon from 2014 to 2017; 274 patients met the inclusion criteria. Using cubic splines, we derived 3 distinct learning phases based on the length of the procedure. Blood loss, additional port insertion, and conversion to thoracotomy were also compared according to these learning phases. RESULTS:The initial phase (procedures 1-60) had the longest procedure times and the most variability in procedure length (158.8 ± 52.2 minutes) compared with the transition phase (procedures 61-140; 145.9 ± 43.8 minutes) and the proficient phase (procedures 141-274; 117.9 ± 32.6 minutes, P < .001). Blood loss (156 mL vs 130.4 mL vs 64.9 mL, P = .003), conversion rate to thoracotomy (11.7% vs 3.8% vs 0.7%, P = .001), and need for a second incision (8.3% vs 5% vs 0.7%, P = .025) were all highest during the initial phase. In a multivariable model, there was a significant interaction between procedure number and learning phase (P = .003), indicating that the effect of each additional procedure on procedure length differed in each phase. CONCLUSIONS:In this analysis, a distinct learning curve for uniportal video-assisted thoracoscopic surgery lobectomy was observed. Procedure time decreased sharply at approximately the 60th procedure, but 80 additional lobectomies were required to master the approach.
目的: 肺癌手术的微创技术已经彻底改变了胸外科手术，单孔入路的应用日益增多。我们分析了我们的单孔胸腔镜肺叶切除术的经验，以根据临床结果确定达到熟练操作所需的手术数量。 方法: 我们在我们的机构前瞻性数据库中查询了 2014 年至 2017 年由单一外科医生进行的早期肺癌患者的所有单孔肺叶切除术; 274 例患者符合纳入标准。使用三次样条，我们基于程序的长度导出了 3 个不同的学习阶段。根据这些学习阶段，还比较了失血、额外的端口插入和向开胸的转化。 结果: 与过渡阶段 (程序 61-158.8) 相比，初始阶段 (程序 1-60) 具有最长的程序时间和最大的程序长度变异性 (52.2 ± 140 分钟); 145.9 ± 43.8 分钟) 和熟练阶段 (程序 141-274; 117.9 ± 32.6 分钟，P <.001)。出血量 (156 mL vs 130.4 mL vs 64.9 mL，P = .003)，中转开胸率 (11.7% vs 3.8% vs 0.7%，P = .001)，第二次切口的需求 (8.3% vs 5% vs 0.7%，P = .025) 在初始阶段都是最高的。在多变量模型中，程序数量和学习阶段之间存在显著的相互作用 (P = .003)，表明每个附加程序对程序长度的影响在每个阶段不同。 结论: 在这项分析中，我们观察到了单孔胸腔镜肺叶切除术的学习曲线。大约在第 60 次手术时，手术时间急剧减少，但需要另外 80 例肺叶切除术才能掌握该方法。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.