Objectives In this study, we aimed to develop a multiparameter prediction model to improve the diagnostic accuracy of invasive adenocarcinoma in pulmonary pure glass nodules. Method We included patients with pulmonary pure glass nodules who underwent lung resection and had a clear pathology between January 2020 and January 2022 at the Qilu Hospital of Shandong University. We collected data on the clinical characteristics of the patients as well as their preoperative biomarker results and computed tomography features. Thereafter, we performed univariate and multivariate logistic regression analyses to identify independent risk factors, which were then used to develop a prediction model and nomogram. We then evaluated the recognition ability of the model via receiver operating characteristic (ROC) curve analysis and assessed its calibration ability using the Hosmer-Lemeshow test and calibration curves. Further, to assess the clinical utility of the nomogram, we performed decision curve analysis. Result We included 563 patients, comprising 174 and 389 cases of invasive and non-invasive adenocarcinoma, respectively, and identified seven independent risk factors, namely, maximum tumor diameter, age, serum amyloid level, pleural effusion sign, bronchial sign, tumor location, and lobulation. The area under the ROC curve was 0.839 (95% CI: 0.798–0.879) for the training cohort and 0.782 (95% CI: 0.706–0.858) for the validation cohort, indicating a relatively high predictive accuracy for the nomogram. Calibration curves for the prediction model also showed good calibration for both cohorts, and decision curve analysis showed that the clinical prediction model has clinical utility. Conclusion The novel nomogram thus constructed for identifying invasive adenocarcinoma in patients with isolated pulmonary pure glass nodules exhibited excellent discriminatory power, calibration capacity, and clinical utility.

BACKGROUND:Circular RNA (circRNA) has become a new focus in the field of tumor biology research in recent years. Many circRNAs have been showed to play an important role in the progression of lung adenocarcinoma (LUAD). In this work, we studied the oncological role of hsa-circ-000881 in LUAD and attempted to explore the related mechanism.METHODS:The relative expressions of hsa-circ-000881, miR-665, and PRICKLE2 were detected by RT-qPCR or western blot. Functional assays were conducted to analyze the role of hsa-circ-000881 in the proliferation, migration, and invasion of LUAD cells. A luciferase reporter assay was performed to verify whether hsa-circ-000881, miR-665, and PRICKLE2 interact with each other.RESULTS:Circ-000881 was remarkably downregulated in LUAD. Overexpression of circ-000881 attenuated cell growth, migration, and invasion, whereas its knockdown enhanced the malignancy of LUAD cells. The results of luciferase reporter assay and bioinformatics analysis confirmed that circ-000881 served as a sponge for miR-665, and PRICKLE2 was a direct target of miR-665.Overexpression of miR-665 or silencing of PRICKLE2 abolished circ-000881-mediated inhibition of malignant tumor behavior in LUAD cells.CONCLUSIONS:Circ-000881 has inhibitory effects on LUAD via a miR-665/PRICKLE2 axis, suggesting that circ-000881 may be an underlying therapeutic target for LUAD.

目的 在倾向性评分匹配配对良好的情况下,比较机器人与胸腔镜在肺癌手术治疗中的围手术期安全性与短期疗效.方法 回顾性分析2020年8月至2020年10月期间,山东大学齐鲁医院胸外科田辉教授肺外科团队因原发性肺癌行肺叶或亚肺叶切除+肺门纵隔淋巴结清扫或采样术的286例患者的临床资料.其中,130例行达芬奇机器人辅助胸外科(RATS)肺切除术,为RATS组;156例行电视胸腔镜辅助胸外科(VATS)肺切除术,为VATS组.采用倾向性评分匹配方法进行混杂因素校正,比较匹配后两组病例的围手术期结果.结果 倾向性评分匹配分析后,每组88例配对成功.对两组病例的围手术期临床资料行统计学分析,发现RATS组手术时间略长于VATS组,但差异无统计学意义(P=0.625).RATS组术中出血量较VATS组更少(P<0.001).RATS组淋巴结清扫站数(P<0.001)及清扫个数(P=0.031)均高于VATS组;RATS组住院费用较VATS组高,差异有统计学意义(P<0.001).术后第1～3天疼痛数字评分(NRS评分)差异有统计学意义(P<0.001),RATS组术后第1～3天NRS评分更高.两组淋巴结升期率、术后第1～3天引流量、术后全部拔管时间、术后住院天数、术后并发症差异无统计学意义(P>0.05).结论 在可切除肺癌手术治疗上,RATS与VATS的围手术期安全性及短期疗效相似.此外,RATS在术中出血量、淋巴结清扫彻底性上存在优势,缺点是增加了住院总费用,潜在增加了术后疼痛.

加速康复外科(enhanced recovery after surgery,ERAS)理念由丹麦哥本哈根大学的Kehlet[1-2]首次提出.2007年,由黎介寿院士将ERAS理念引入我国[3].目前已被广泛的应用于临床外科各个专业.在2018年世界十大医疗创新成果中,ERAS位居第8位.ERAS是以患者为中心,在外科、麻醉、护理、营养等多学科团队协作的基础上,通过一系列具有循证医学证据的围手术期优化措施的综合应用,以减少手术患者的生理及心理的创伤应激反应,达到加速康复的目的[4].

在全世界范围内,肺癌的发病率及病死率均位居所有恶性肿瘤的第一位[1].虽然近年化疗、放疗、靶向治疗或免疫治疗等取得了长足的进展,但其仅能够一定程度改善肺癌患者的预后,目前外科手术治疗仍是公认的治疗早中期肺癌的最有效方法[2].随着电视胸腔镜手术(video-assisted thoracic surgery,VATS)在肺癌外科治疗领域的广泛应用及不断发展,研究表明VATS相比传统开放手术,患者的术后疼痛更轻、住院时间更短、生活质量更高,但其并不能有效改善肺癌患者的长期预后(包括无病生存期及总生存期等);与此同时,研究发现规范化及标准化的手术质量控制尤为重要,其可显著提高患者的围手术期疗效并明显改善肺癌患者的预后[3-5].

Based on previous findings regarding the angiogenic activities and prognostic roles of metastasis-associated protein 1 (MTA1) in early-stage non-small cell lung cancer, the clinicopathological and prognostic significance of MTA1 protein expression, and its correlation with angiogenesis in lung invasive adenocarcinoma, were further assessed in the present study, according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. High protein expression levels of MTA1 were commonly observed in patients with lung invasive adenocarcinoma, and were significantly correlated with tumor size (P=0.030), lymph node metastasis (P=0.021) and microvessel density (P=0.015). Survival analysis demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those patients whose protein expression levels of MTA1 were low (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). In addition, Cox regression multivariate analysis demonstrated that high protein expression levels of MTA1 significantly correlated with unfavorable five-year disease-free survival (P=0.024). These findings indicate that MTA1 protein expression may possess clinical potential as an indicator of progressive phenotype. Therefore, MTA1 is a promising prognostic predictor to identify subgroups of patients with high risk of relapse, and a potentially novel therapeutic target for antiangiogenesis in patients with lung invasive adenocarcinoma.

Background. The aim of this study was to detect the expression of heat shock factor 1 (HSF1) and microvessel density (MVD) in patients with non-small cell lung cancer (NSCLC) and to examine the relevance between HSF1 and angiogenesis, clinicopathologic factors, and prognosis.Methods. Immunohistochemical staining was used to examine the level of expression of HSF1 and CD34. MVD was used to detect the number of microvessels by counting CD34D endothelial cells. Their relationship with clinicopathologic factors and prognosis in patients with NSCLC was determined using IBM SPSS Statistics, version 19 (SPSS Inc, Chicago, IL).Results. The level of expression of HSF1 was increased significantly in NSCLC. HSF1 overexpression was observed in 45 patients and was significantly associated with MVD (p = 0.005). The overexpression of HSF1 was not associated with patient sex, age, tumor size, histologic type, or differentiation, but it was significantly associated with node metastasis (p = 0.005) and clinical stage (p = 0.006). HSF1 overexpression and high MVD were significantly associated with poor 5-year disease-free survival (p = 0.001 and p[0.006, respectively). Patients with HSF1 overexpression and high MVD had a significantly poor overall survival (p = 0.006 and p = 0.019, respectively) and disease-specific survival (p = 0.005 and p = 0.016, respectively). Multivariate analysis showed that HSF1 overexpression was an independent prognosticator for poor overall, disease-specific, and disease-free survival (p = 0.040, p = 0.046, and p = 0.004, respectively).Conclusions. Overexpression of HSF1 is common and significantly correlated with tumor angiogenesis in NSCLC. Patients with high HSF1 expression had poorer overall, disease-free, and disease-specific survival. These current findings suggest that HSF1 may serve as a novel prognostic marker and potential therapeutic target molecule for anti-angiogenic therapy in patients with NSCLC. (C) 2015 by The Society of Thoracic Surgeons

The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) is believed to be a promising candidate for cancer gene therapy, yet gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumor tissue. Mesenchymal stem cells (MSCs) have been shown to home to tumor sites and could potentially act as a shield and vehicle for an antitumor gene therapy vector. Here, we used an adenoviral vector expressing TRAIL to transduce MSCs and studied the apoptosis-inducing activity of these TRAIL-carrying MSCs on esophageal cancer cell Eca-109. Our results showed that, in vitro, TRAIL-expressing MSCs were able to inhibit proliferation and induce apoptosis in Eca-109 cells by an MTT assay, co-culture experiments and flow cytometry analysis. In vivo, TRAIL-expressing MSCs also displayed an ability to inhibit tumor growth in an Eca-109 xenograft mouse model. Together, our findings indicated that the gene therapy strategy of MSCs-based TRAIL gene delivery has a wide potential value for improving the treatment of esophageal cancer.

Background: Sirtuin1 (SIRT1) is an NAD(+)-dependent type III histone deacetylase (HDAC). This research investigated the prevalence of SIRT1 protein expression and its prognostic influence with the aim of validating its potential role in lymphangiogenesis and lymphovascular invasion (LVI) in pN0 esophageal squamous cell carcinoma (ESCC).Methods: A total of 206 patients were enrolled in this retrospective study. SIRT1 and VEGF-C protein expression was detected by immunohistochemical staining. Peritumoral lymphatic microvessel density (LVD) and LVI were evaluated by immunostaining for D2-40. Statistical analysis was then preformed to investigate the relevance of SIRT1 expression and various clinicopathologic features and to examine the effect of SIRT1 on tumor-induced lymphangiogenesis, LVI and prognosis.Results: SIRT1 positive expression was identified in 95 cases in the nucleus and was significantly correlated with T status (P < 0.001), disease stage (P = 0.001), VEGF-C positive expression (P = 0.015), high LVD (P = 0.013) and positive LVI (P = 0.015). Patients with SIRT1 positive expression, high LVD and positive LVI had a significantly unfavorable 5-year disease free survival (P < 0.001, P = 0.030, and P < 0.001, respectively) and overall survival (P < 0.001, P = 0.017, and P < 0.001, respectively). However, based on multivariate Cox regression analysis, only SIRT1 positive expression and positive LVI were significant independent prognosticators of poor disease-free survival (P = 0.029 and 0.018, respectively) and overall survival (P = 0.045 and 0.031, respectively).Conclusions: SIRT1 positive expression was significantly associated with tumor progression, lymphangiogenesis, LVI and poor survival in pN0 ESCC patients. Our research shows a utilization of SIRT1 in prognosing poor survival and providing possible target for ESCC patients through inhibiting its lymphangiogenesis activity.

The nuclear receptor coactivator 5 (NCOA5) was a unique coactivator independent of AF2 that can modulate ERα-mediated transcription. Recent researches have indicated that its downregulation may participate in cancer development and progression. The aims of the present study were to investigate NCOA5 expression in esophageal squamous cell carcinoma (ESCC) and validate its possible influence on patients’ prognosis. NCOA5 expression was examined by immunohistochemical staining in 119 ESCC patients’ tissues. Ten paired tumor and adjacent normal specimens were examined by Western blot analysis. Statistical analysis was performed to assess its relevance with various clinicopathologic features and its influence on patients’ survival. By immunohistochemistry analysis, NCOA5 expression was found to be significantly correlated with differentiation ( P = 0.039), T status ( P = 0.047) and stage ( P = 0.036). Furthermore, we found NCOA5 higher expression in normal tissues than in tumor tissues by Western blot analysis. Univariate analysis showed that poor differentiation ( P = 0.035, P = 0.027), lymph node metastasis ( P < 0.001, P < 0.001), high T status ( P = 0.010, P = 0.012), advanced stage ( P < 0.001, P < 0.001) and NCOA5 low expression ( P < 0.001, P < 0.001) were significantly correlated with poor prognosis of both disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that NCOA5 low expression ( P = 0.019, P = 0.047), high T status ( P = 0.015, P = 0.012), lymph node metastasis ( P = 0.040, P = 0.021) and advanced stage ( P = 0.017, P = 0.046) were independent prognostic factors of poor DFS and OS. Our findings suggest that NCOA5 low expression is associated with ESCC progression and is a potential biomarker in predicting poor prognosis. Further studies of NCOA5 may help develop new therapeutic strategies against ESCC.