Tumor cells tend to utilize glycolysis rather than aerobic respiration even under aerobic conditions. OVOL2, an inhibitory C2H2 zinc finger transcription factor, is a potential tumor suppressor in cancers. However, the association between OVOL2 and tumor energy metabolism is unknown. Western blotting was used to determine the expression of OVOL2 in different non-small cell lung cancer (NSCLC) cell lines and mouse models. The metabolic parameters in NSCLC cells following overexpression or knockdown OVOL2 were examined. To define the mechanism by which OVOL2 regulates aerobic glycolysis, interacting protein of OVOl2 and downstream molecular events were identified by luciferase assay and co-immunoprecipitation. We documented the regulatory mechanism in mouse xenograft models. Finally, clinical relevance of OVOL2, NF-κB signaling and GLUT1 was measured by immunostaining. OVOL2 is downregulated in NSCLC and overexpression of OVOL2 inhibits the survival of cancer cells. Moreover, OVOL2 directly binds to P65 and inhibits the recruitment of P300 but facilitates the binding of HDAC1 to P65, which in turn negatively regulates NF-κB signaling to suppress GLUT1 translocation and glucose import. In contrast, OVOL2 expression is negatively regulated by NF-κB signaling in NSCLC cells via the ubiquitin–proteasome pathway. Re-expression of OVOL2 significantly compromise NF-κB signaling-induced GLUT1 translocation, aerobic glycolysis in NSCLC cells and mouse models. Immunostaining revealed inverse correlations between the OVOL2 and phosphorylated P65 levels and between the OVOL2 and membrane GLUT1 levels, and a strong correlation between the phosphorylated P65 and membrane GLUT1 levels. These results suggest a regulatory circuit linking NF-κB and OVOL2, which highlights the role of NF-κB signaling and OVOL2 in the modulation of glucose metabolism in NSCLC.

Abstract Background A pathologically confirmed negative margin is required when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma. However, the optimal margin distance to ensure complete tumor resection while preserving healthy lung tissue remains unknown. We aimed to establish a reliable distance range for negative margins. Methods A total of 52 intraoperative para-cancer tissue specimens from patients with peripheral lung adenocarcinoma with pathological tumors ≤2 cm in size were examined. Depending on the distance from the tumor edge (D), the para-cancer tissues were divided into the following five groups: D < 0.5 cm (group I); 0.5 cm ≤ D < 1.0 cm (group II); 1.0 cm ≤ D < 1.5 cm (group III); 1.5 cm ≤ D < 2.0 cm (group IV); and D ≥ 2.0 cm (group V). During pathological examination of the specimens under a microscope, the presence of atypical adenomatous hyperplasia or more severe lesions was considered unsafe, whereas the presence of normal lung tissue or benign hyperplasia was considered safe. Results Group V, in which the margin was the farthest from the tumor edge, was the safest. There were significant safety differences in between groups I and V (χ2 = 26.217, P < 0.001). Significant safety differences also existed between groups II and V (χ2 = 9.420, P < 0.005). There were no significant safety differences between group III or IV and group V (P = 0.207; P = 0.610). Conclusions We suggest that when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma with pathological tumor sizes ≤2 cm, the resection margin distance should be ≥1 cm to ensure a negative margin.

目的 通过肺结节交互印证式诊断,提高术前影像诊断的准确率,选择合适的手术时机,指导肺小结节的随访时间.方法 回顾性分析单中心2016年7月至2019年10月厦门大学附属第一医院胸外科1 368例肺结节手术患者的临床资料,男531例、女837例,年龄44(21～67)岁.选择肺结节直径≤2 cm,术前行多学科会诊,详细阅读胸部CT,术中切开病灶剖面进行分析,快速病理诊断肺结节性质,术后常规行病理诊断.随后将肺结节影像特征、术中剖面特征与病理结果一一对照,通过两两对应,交互印证,把肺结节的影像病理及病变切面表现为一个动态变化的过程.结果 在1 368例肺小结节患者中,影像学表现为纯磨玻璃样结节的有376例(27.5％),混合性磨玻璃样结节共有729例(53.3％),实性结节共有263例(19.2％).在纯磨玻璃样结节患者中,原位腺癌(adenocarcinoma in situ,AIS)占比最高,为156例,微浸润性腺癌(microinvasive adenocarcinoma,MIA)和不典型腺瘤样增生(atypical adenomatous hyperplasia,AAH)比例相当,分别为90例和85例,其它良性肿瘤共20例.在混合性磨玻璃样结节中,浸润性腺癌(invasive adenocarcinoma,IA)共495例,其次是MIA 207例;且在实性结节中,病理结果主要为IA和其它良性肿瘤,分别为213例和50例,实性结节病理无AAH、AIS及MIA.结论 肺结节交互印证式诊断可以提高术前诊断的准确率,对选择手术时机、随访时间的判断具有重要意义.

The study aimed to retrospectively evaluate the success rate, utility, practicality and results of pre-operative CT (computed tomography)–guided semi-rigid single hook-wire placement and the pathology results of small pulmonary nodules (SPN). Seventy-four patients with 81 small pulmonary nodules underwent CT-guided semi-rigid single hook wire localization consecutively between 2016 and 2017 were reviewed. VATS (video-assisted thoracoscopic surgery) resection of lung tissue containing each pulmonary nodule and were performed in the direction of hook wire. The success rate and utility of the localization, hook wire related complications, the histopathology of SPN are analyzed. The semi-rigid hook wire was performed successfully in all 81 small pulmonary nodules within mean time of 10 min (8–13 min, SD: 1.58 min). Compared with solid nodules, GGOs (ground-glass opacity) were more frequently malignant (p < 0.05), with an OR (odds ratio) 8.59 (95%CI, 0.967, 412.845). Of the pure GGOs, 9 (25%) nodules were classified as AIS, 10 (27.8%) nodules were classified as MIA and 22 (57.9%) of the mGGOs were lung cancer. According to multivariate analysis, the malignant hazard was as high as 6.533-fold higher in nodules with a size larger than 10 mm compared with those smaller than 10 mm. GGOs with tiny blood vessels showed a statistically significant correlation with malignancy. Surprisingly, no statistically significant difference in the incidence of lung cancer in age. No major complication occurred. Preoperative localization of small pulmonary nodules using semi-rigid single hook wire was found to be practical and safe, which allows for proper diagnosis. Incidental small pulmonary nodule, especially GGO larger than 10 mm needs to be taken seriously.

髓外造血(extramedullary hematopoiesis ,EMH)是一种罕见疾病,为骨髓外出现造血成分,其中以腹部髓外造血最为常见,主要累及肝和脾,也可见于肾和肾上腺. 发生于纵隔脊髓旁的髓外造血极为少见.本文报道1例54岁男性,CT检查发现后纵隔肿物,影像学检查均考虑神经源性肿瘤或淋巴瘤,穿刺病理未能确定诊断,于2017年10月行胸腔镜手术完整切除,术后病理诊断为髓外造血,进一步查β-地中海贫血基因,检出β基因IVS-II-654 (C-T)突变杂合子,术后随访1年,无胸背部不适,贫血无加重.

BACKGROUND:The aim of this study was to compare the effects of currently available preoperative localization methods, including semi-rigid single hook-wire, double-thorn hook-wire, and microcoil, in localizing the pulmonary nodules, thus to select the best technology to assist video-assisted thoracoscopic surgery (VATS) for small ground glass opacities (GGO).METHODS:Preoperative CT-guided localizing techniques including semi-rigid single hook-wire, double-thorn hook-wire and microcoil were used in re-aerated fresh swine lung for location experiments. The advantages and drawbacks of the three positioning technologies were compared, and then the most optimal technique was used in patients with GGO. Technical success and post-operative complications were used as primary endpoints.RESULTS:All three localizing techniques were successfully performed in the re-aerated fresh swine lung. The median tractive force of semi-rigid single hook wire, double-thorn hook wire and microcoil were 6.5, 4.85 and 0.2 N, which measured by a spring dynamometer. The wound sizes in the superficial pleura, caused by unplugging the needles, were 2 mm in double-thorn hook wire, 1 mm in semi-rigid single hook and 1 mm in microcoil, respectively. In patients with GGOs, the semi-rigid hook wires localizations were successfully performed, without any complication that need to be intervened. Dislodgement was reported in one patient before VATS. No major complications related to the preoperative hook wire localization and VATS were observed.CONCLUSIONS:We found from our localization experiments in the swine lung that, among the commonly used three localization methods, semi-rigid hook wire showed the best operability and practicability than double-thorn hook wire and microcoil. Preoperative localization of small pulmonary nodules with single semi-rigid hook wire system shows a high success rate, acceptable utility and especially low dislodgement in VATS.