Clinical Outcomes With Recurrence After Pleurectomy/Decortication for Malignant Pleural Mesothelioma.
- 作者列表："Nakamura A","Takuwa T","Hashimoto M","Kuroda A","Nakamichi T","Matsumoto S","Kondo N","Kijima T","Yamakado K","Hasegawa S
BACKGROUND:Most patients with malignant pleural mesothelioma experience recurrence after treatment. However no clinical studies have evaluated postrecurrence survival after pleurectomy/decortication for malignant pleural mesothelioma. This study aimed to clarify postrecurrence survival, treatment, prognostic factors, and recurrence pattern after pleurectomy/decortication. METHODS:We conducted a retrospective cohort study of 90 patients who underwent neoadjuvant chemotherapy followed by pleurectomy/decortication at our hospital between September 2012 and December 2017. Survival and recurrence were calculated using the Kaplan-Meier method with the log-rank test. Clinical factors related to postrecurrence survival were assessed using multivariate analysis with the Cox proportional hazards model. RESULTS:Of 90 patients, 57 (63.3%) developed recurrence. The 1- and 3-year recurrence-free survival rates were 69.7% and 34.0%, respectively (median recurrence-free survival time, 19.0 months). With regard to initial recurrence, 39 patients (68.4%) developed local recurrence, 6 (10.5%) developed distant recurrence, and 12 (21.1%) developed both local and distant recurrences. The 1-year postrecurrence survival rate was 59.5% (median post-recurrence survival time, 14.4 months). Forty-three patients (75.4%) underwent a postrecurrence treatment. Multivariate analysis revealed that postrecurrence treatment (hazard ratio, 0.2; 95% confidence interval, 0.07-0.55; P = .002), performance status 0 to 1 (hazard ratio, 0.24; 95% confidence interval, 0.08-0.76; P = .01), and disease-free interval more than 12 months (hazard ratio, 0.4; 95% confidence interval, 0.16-0.99; P = .04) were the independent, favorable, and significant prognostic factors of postrecurrence survival. CONCLUSIONS:Postrecurrence survival after pleurectomy/decortication is acceptable, and postrecurrence treatment, performance status, and disease-free interval are important prognostic factors of postrecurrence survival.
背景: 大多数恶性胸膜间皮瘤患者在治疗后复发。然而，没有临床研究评估恶性胸膜间皮瘤胸膜切除术/胸膜剥脱术后复发后的生存。本研究旨在阐明术后复发生存率、治疗、预后因素和术后复发模式。 方法: 我们对 2012 年 9 月至 2017 年 12 月在我院接受新辅助化疗后行胸膜切除术/剥脱术的 90 例患者进行了回顾性队列研究。使用Kaplan-Meier方法和时序检验计算生存和复发。使用Cox比例风险模型的多变量分析评估与复发后生存相关的临床因素。 结果: 90 例患者中，57 例 (63.3%) 复发。1 年和 3 年无复发生存率分别为 69.7% 和 34.0% (中位无复发生存时间，19.0 个月)。关于初次复发，39 例患者 (68.4%) 出现局部复发，6 例 (10.5%) 出现远处复发，12 例 (21.1%) 出现局部和远处复发。复发后 1 年生存率为 59.5% (中位复发后生存时间 14.4 个月)。43 例患者 (75.4%) 接受了复发后治疗。多变量分析显示复发后治疗 (风险比，0.2; 95% 置信区间，0.07-0.55; P = .002)，体能状态 0 比 1 (风险比，0.24; 95% 置信区间，0.08-0.76; P = .01)，且无病间期超过 12 个月 (风险比，0.4; 95% 置信区间，0.16-0.99; P = .04) 是复发后生存的独立、有利和显著的预后因素。 结论: 胸膜切除术/胸膜剥脱术后复发生存是可以接受的，复发后治疗、体能状态和无病间隔是复发后生存的重要预后因素。
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.