- 作者列表："Nelson DB","Niu J","Mitchell KG","Sepesi B","Hofstetter WL","Antonoff MB","Giordano SH","Mehran RJ","Rice DC
BACKGROUND:Opioids represent the mainstay for treating postsurgical pain but can cause significant morbidity in addition to dependency. The aim of the study was to determine the incidence of persistent opioid use after lung surgery. METHODS:Patients who underwent lung resection from 2008 to 2013 for non-small cell lung cancer were identified in the Surveillance, Epidemiology and End Results-Medicare database. Patients were categorized as being chronic, intermittent, or naïve preoperative opioid users using information obtained from part D records. Persistent opioid use was defined as having a filled opioid prescription between 3 and 6 months after lung resection. RESULTS:A total of 6948 patients were identified, among whom 3946 (56.8%) were opioid naïve, 2017 (29.0%) were intermittent opioid users, and 985 (14.2%) were chronic opioid users preoperatively. Persistent opioid use (3-6 months) after lung resection was high (31%), even among opioid-naïve patients (17%). Among those who were previously opioid naïve, independent predictors of persistent opioid use were receipt of adjuvant radiation or chemotherapy, less than 70 years of age, Charlson comorbidity score of 1 or 2, and residence in zip codes associated with lower education. Conversely, patients who underwent minimally invasive surgery were less likely to have persistent opioid use. Those with persistent opioid use after surgery did not show any trend toward returning to preoperative opioid utilization for at least the first postoperative year. CONCLUSIONS:Opioid dependence after lung resection in the population over 65 years of age is high but was significantly lower among those who received minimally invasive surgery, in addition to other factors.
背景: 阿片类药物是治疗术后疼痛的主要药物，但除了依赖性外，还可能导致显著的发病率。该研究的目的是确定肺部手术后持续使用阿片类药物的发生率。 方法: 在监测流行病学学和最终结果-医疗保险数据库中确定 2008 年至 2013 年因非小细胞肺癌接受肺切除术的患者。使用从D部分记录中获得的信息，将患者归类为慢性、间歇性或幼稚的术前阿片类药物使用者。持续使用阿片类药物被定义为在肺切除术后 3 至 6 个月之间具有填充的阿片类药物处方。 结果: 共确定了 6948 例患者，其中 3946 例 (56.8%) 为未使用阿片类药物，2017 例 (29.0%) 为间歇性阿片类药物使用者，985 例 (14.2%) 为术前慢性阿片类药物使用者。肺切除术后持续使用阿片类药物 (3-6 个月) 较高 (31%)，即使在未使用阿片类药物的患者中 (17%)。在那些以前没有阿片类药物的人中，持续使用阿片类药物的独立预测因素是接受辅助放疗或化疗，年龄小于 70 岁，Charlson合并症评分为 1 或 2，和居住在与教育程度较低相关的邮政编码。相反，接受微创手术的患者不太可能持续使用阿片类药物。术后持续使用阿片类药物的患者至少在术后第一年没有出现恢复术前阿片类药物使用的趋势. 结论: 除其他因素外，65 岁以上人群肺切除术后阿片类药物依赖较高，但在接受微创手术的人群中明显较低。
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.