Comparison of outcomes following segmentectomy or lobectomy for patients with clinical N0 invasive lung adenocarcinoma of 2 cm or less in diameter.
直径 ≤ 2厘米的临床N0 浸润性肺腺癌患者行肺段切除术或肺叶切除术后的结果比较。
- 作者列表："Wen Z","Zhao Y","Fu F","Hu H","Sun Y","Zhang Y","Chen H
PURPOSE:Previous studies have reported similar survival between segmentectomy and lobectomy for patients with small-sized non-small cell lung cancer. However, part of those patients were with adenocarcinoma in situ or minimally invasive adenocarcinoma, which were considered to have a favorable prognosis. We compared survival outcomes of patients with clinical N0 invasive lung adenocarcinomas of no more than 2 cm who underwent segmentectomy or lobectomy. METHODS:Between June 1, 2008, and May 31, 2018, 1018 patients with clinical N0 invasive lung adenocarcinomas of no more than 2 cm in diameter on thin-section chest CT scans were retrospectively included in this study. Of them, 214 underwent segmentectomy and 804 underwent lobectomy. Propensity-score matching of preoperative factors, such as gender, age, smoking status, forced expiratory volume in 1 s predicted%, tumor's CT appearance, tumor size on CT scan and tumor location was used to compare survival outcomes of those patients receiving different surgical treatments. Cox proportional hazard regression model was used to identify independent prognostic factors. This study was approved by the Committee for Ethical Review of Research (Fudan University Shanghai Cancer Center IRB# 090977-1). Informed consent was waived because of the retrospective nature of this study. RESULTS:Average follow-up time was 42.5 months. Before matching, the lobectomy group had a shorter recurrence-free survival (P = 0.02), but similar overall survival (P = 0.60). After matching, no significant difference of overall survival or recurrence-free survival was found between the two groups (P = 0.70 and P = 0.40, respectively). CONCLUSIONS:Our results suggest that segmentectomy achieved similar recurrence-free and overall survival compared with lobectomy for patients with clinical N0 invasive lung adenocarcinomas of no more than 2 cm. Therefore, segmentectomy could be an alternative approach. These results need to be further validated by randomized trials.
目的: 以前的研究已经报道了肺段切除术和肺叶切除术治疗小尺寸非小细胞肺癌患者的相似生存率。但部分患者为原位腺癌或微浸润腺癌，预后良好。我们比较了接受肺段切除术或肺叶切除术的临床N0 浸润性肺腺癌患者 (不超过 2厘米) 的生存结局。 方法: 2008 年 6 月 1 日至 20 18 年 5 月 31 日，回顾性纳入 1018 例临床N0 浸润性肺腺癌患者，胸部薄层ct扫描直径不超过 2厘米cm。其中 214 例行肺段切除术，804 例行肺叶切除术。术前因素的倾向评分匹配，如性别、年龄、吸烟状况、 1 s用力呼气容积预测 % 、肿瘤的CT外观、使用ct扫描的肿瘤大小和肿瘤位置来比较接受不同手术治疗的患者的生存结果。Cox比例风险回归模型用于确定独立的预后因素。本研究获得了研究伦理审查委员会 (复旦大学上海肿瘤中心IRB #090977-1) 的批准。由于本研究的回顾性性质，放弃了知情同意。 结果: 平均随访时间 42.5 个月。匹配前，肺叶切除组无复发生存期较短 (p = 0.02)，但总生存期相似 (p = 0.60)。匹配后，两组患者的总生存期和无复发生存期差异无统计学意义 (p = 0.70 和p = 0.40)。 结论: 我们的结果表明，对于不超过 2厘米的临床N0 浸润性肺腺癌患者，与肺叶切除术相比，肺段切除术获得了相似的无复发和总生存率。因此，肺段切除术可能是一种替代方法。这些结果需要通过随机试验进一步验证。
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.