- 作者列表："Yamada K","Ozawa D","Onozato R","Suzuki M","Fujita A","Ojima H
:This study aims to clarify the surgical treatment time of pulmonary metastasis in patients with colorectal cancer.Early relapse after resection of pulmonary metastasis is often encountered when the interval from the detection of pulmonary metastasis to pulmonary metastasectomy was short.In this retrospective analysis, data of patients with colorectal cancer who underwent surgical treatment of pulmonary metastasis at the Gunma Prefectural Cancer Center, Gunma, from April 2001 through September 2018 were evaluated. The patients were divided into 2 groups. We examined the interval period from the diagnosis of pulmonary metastasis to pulmonary metastasectomy. This period was divided into every 3 months, and the prognosis of each group was compared with clarify the appropriate timing of pulmonary metastasectomy.The primary endpoints were 5-year overall survival and recurrence-free survival rates.The most significant difference was observed when the cutoff value was 9 months (5-year recurrence-free survival 45.8% vs 85.6%, P < .01). No significant difference was found in any background factors between the 2 groups. Twenty-five patients (34.7%) experienced recurrence after pulmonary metastasectomy. The most common site of recurrence was the lung (48%). Among the 12 cases of recurrence of pulmonary metastasis, 11 cases belonged to the <9 months group. A multivariable survival analysis found that the interval period of <9 months was a significant predictor of recurrence.Our study suggests that clinical follow-up for 9 months prior pulmonary metastasectomy in colorectal patients would improve the prognosis.
: 本研究旨在阐明结直肠癌患者肺转移的手术治疗时间。当从发现肺转移到肺转移切除术的间隔时间较短时，经常遇到肺转移切除术后的早期复发。在这项回顾性分析中，对 2001 年 4 月至 2018 年 9 月在Gunma县癌症中心接受肺转移手术治疗的结直肠癌患者的数据进行了评估。将患者分为 2 组。我们检查了从肺转移诊断到肺转移切除术的间隔时间。每 3 个月一次，比较各组的预后，明确肺转移瘤切除的合适时机。主要终点为 5 年总生存率和无复发生存率。当截断值为 9 个月时，观察到最显著的差异 (5 年无复发生存率为 45.8% vs 85.6%，p <.01)。两组之间的任何背景因素没有发现显著差异。25 例 (34.7%) 肺转移瘤切除术后复发。最常见的复发部位是肺 (48%)。12 例肺转移复发病例中，<9 个月组 11 例。多变量生存分析发现，<9 个月的间隔时间是复发的显著预测因素。我们的研究表明，结直肠患者肺转移切除术前 9 个月的临床随访将改善预后。
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.