- 作者列表："Madariaga MLL","Troschel FM","Best TD","Knoll SJ","Gaissert HA","Fintelmann FJ
BACKGROUND:Sarcopenia represented by low psoas muscle area is associated with increased hospital length of stay (LOS), postoperative complications, and mortality. We studied whether thoracic skeletal muscle area (TSMA) derived from computed tomography (CT) predicts morbidity after pneumonectomy for lung cancer. METHODS:Consecutive patients who underwent pneumonectomy for lung cancer from 2005 to 2017 were retrospectively analyzed. TSMA was defined as the sum of muscle area at the level of the eighth and the 12th thoracic vertebral bodies on preoperative CT. Patients were stratified into sex-specific TSMA quartiles for univariate time-to-event analyses. The effect of continuous TSMA measurements on operative complications, hospital and intensive care unit (ICU) LOS, discharge disposition, and hospital readmission within 90 days was estimated using multivariable models adjusted for age, sex, body mass index, forced expiratory volume in 1 second, Zubrod score, and pneumonectomy type. RESULTS:Standard (n = 102, 78.5%) or high-risk (n = 28, 21.5%; extrapleural: n = 3, 2.3%; carinal: n = 9, 6.9%; completion: n = 16, 12.3%) pneumonectomy was performed in 130 patients (60.8 ± 10.6 years; 43.1% women). Major complications occurred in 33.1% (n = 43 of 130) and readmission in 17.7% (n = 23 of 130) of patients. In multivariable models, patients with high TSMA experienced fewer overall (odds ratio [OR], 0.87; P = .04) and cardiopulmonary (OR, 0.86; P = .04) complications, and fewer readmissions (OR, 0.78; P = .01). Associations with ICU LOS (hazard ratio, 1.08; P = .051) and hospital LOS (hazard ratio, 1.05; P = .18) did not reach significance. CONCLUSIONS:TSMA predicts adverse outcome after pneumonectomy for lung cancer. This marker, readily derived from standard chest CT, identifies patients at increased risk for postoperative complications and may help select patients appropriate for focused rehabilitation before pneumonectomy.
背景: 以腰大肌面积低为代表的肌肉减少症与住院时间 (LOS) 、术后并发症和死亡率增加相关。我们研究了来自计算机断层扫描 (CT) 的胸部骨骼肌面积 (TSMA) 是否预测肺癌全肺切除术后的发病率。 方法: 回顾性分析 2005 年至 2017 年因肺癌行全肺切除术的连续患者。TSMA定义为术前CT显示的第 8 和第 12 胸椎椎体水平肌肉面积的总和。将患者分为性别特异性TSMA四分位数进行单变量事件发生时间分析.使用根据年龄、性别调整的多变量模型估计连续TSMA测量对手术并发症、医院和重症监护病房 (ICU) LOS、出院处置和 90 天内再入院的影响，体重指数、 1 秒用力呼气量、Zubrod评分、全肺切除类型。 结果: 标准 (n = 102，78.5%) 或高风险 (n = 28，21.5%; 胸膜外: n = 3，2.3%; 隆突: n = 9，6.9%; 完成情况: n = 16，12.3%) 全肺切除术的 130 例患者 (60.8 ± 10.6 岁，43.1% 为女性).主要并发症发生率为 33.1% (130 例患者中n = 43 例)，再入院发生率为 17.7% (130 例患者中n = 23 例)。在多变量模型中，高TSMA患者经历较少的总体 (比值比 [OR]，0.87; P = .04) 和心肺 (OR，0.86; P = .04) 并发症，和更少的再入院 (OR，0.78; P = .01)。与ICU LOS (风险比，1.08; P = .051) 和医院LOS (风险比，1.05; P = .18) 的关联未达到显著性。 结论: TSMA可预测肺癌全肺切除术后的不良结局。该标记很容易从标准胸部CT获得，可识别术后并发症风险增加的患者，并可帮助选择适合肺切除术前集中康复的患者。
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.