Bmi1和METTL3在胆管癌中的临床意义及与肿瘤转移的关系

目的探究B淋巴瘤Mo-MLV插入蛋白1(B lymphoma Mo-MLV insertion region 1,Bmi1)和甲基转移酶3(methyltransferase 3,METTL3)在胆管癌(cholangiocarcinoma,CCA)中的临床意义及与肿瘤转移的关系。方法通过生物信息学方法分析Bmi1和METTL3在CCA中的表达特点。随机选择2013年1月至2015年1月间的CCA患者45例,收集CCA组织和癌旁组织。通过免疫组化染色检测Bmi1和METTL3蛋白水平。分析Bmi1和METTL3与CCA病理特点和转移的关系。结果在TCGA数据库中,CCA组织中Bmi1和METTL3的水平显著高于正常组织。Bmi1在CCA组织中的阳性率(80.00%)显著高于癌旁组织(17.78%)(P<0.05)。METTL3在CCA组织中的阳性率(82.22%)显著高于癌旁组织(22.22%)。性别、年龄、肿瘤大小、神经累犯和分化程度对CCA组织中Bim1的影响不大(P>0.05),出现转移的患者的CCA组织中Bim1水平显著高于未出现转移的患者(P<0.05)。性别、年龄、肿瘤大小对CCA组织中METTL3的影响不大(P>0.05),神经累犯、低分化程度和出现转移的患者的CCA组织中METTL3水平显著升高(P<0.05)。结论Bmi1和METTL3在CCA中过表达,METTL3可能参与CCA的分期、分化和神经累犯有关,并且高水平的Bmi1和METTL3均与CCA的转移有关。     

Chronic subdural hematoma associated with dural metastasis leads to early recurrence and death: A single-institute,retrospective cohort study

The prevalence of chronic subdural hematoma (CSDH) associated with dural metastasis is uncertain, and appropriate treatment strategies have not been established. This study aimed to investigate the characteristics of and appropriate treatment strategies for CSDH associated with dural metastasis. We retrospectively reviewed the charts of 214 patients who underwent surgery for CSDH. The patients were divided into the dural metastasis group (DMG; n = 5, 2.3%) and no dural metastasis group (No-DMG; n = 209, 97.3%). Patient characteristics, treatment, and outcomes were compared between the two groups. Active cancer was detected in 31 out of 214 patients, 5 of whom (16.1%) had dural metastasis. In-hospital death (80.0% vs. 0%; p < 0.001) and recurrence within 14 days (80.0% vs. 2.9%; p < 0.001) and 60 days (80.0% vs. 13.9%; p = 0.002) were significantly prevalent in the DMG. All patients in the DMG developed subdural hematoma re-accumulation requiring emergent surgery because of brain herniation, and patients in the DMG had significantly worse recurrence-free survival (p < 0.001). This relationship remained significant (p < 0.001) even when the analysis was limited to the active cancer cohort (n = 31). CSDH associated with dural metastasis leads to early recurrence and death because of the difficulty in controlling subdural hematoma re-accumulation by common drainage procedures. Depending on the primary cancer status, withdrawal of active treatment and change to palliative care should be discussed after diagnosing CSDH associated with dural metastasis.     

CLCA1在结肠癌组织中的表达及临床意义

目的:探讨CLCA1在结肠癌组织中的表达水平及其与肿瘤进展和预后的关系。方法:随机选取西安交通大学第一附属医院及第四军医大学西京医院行手术切除的临床结肠癌病例239例，应用免疫组织化学方法检测结肠癌组织及癌旁组织中CLCA1的表达情况，使用统计学方法分析CLCA1在结肠癌中的表达与肿瘤临床病理特征及预后的相关性。结果:CLCA1 在肿瘤中的表达较癌旁组织显著降低（P＜0.05），CLCA1在结肠癌中表达与原发肿瘤浸润深度、淋巴转移和肿瘤TNM分期显著相关（P＜0.05），而且CLCA1低表达组患者总体生存期较高表达组显著缩短（P＜0.001），多因素分析显示CLCA1的表达可作为结肠癌的独立预后因素。结论:CLCA1在结肠癌中表达下调，CLCA1的低表达与肿瘤的侵袭转移和临床预后密切相关，有望作为结肠癌个体化治疗靶点。     

Relation Between Tumor Size and Lymph Node Metastasis According to Subtypes of Breast Cancer

PurposeTumor size and lymph node metastasis are important factors that contribute to the progression of breast cancer. We aimed to analyze the relationship between tumor size and lymph node metastasis molecular subtype and examine the effects of nodal metastasis on overall survival (OS).MethodsWe retrospectively reviewed the data of 16,552 patients who underwent breast surgery in Samsung Medical Center between 2000 and 2015. Information on tumor size (largest diameter of the invasive component), number of positive lymph nodes, and molecular subtype were obtained. We constructed a linear regression model to evaluate the relationship between tumor size and lymph node metastasis. To determine the effect of nodal metastasis on OS, we performed a Cox proportional regression analysis with Np/T (number of metastatic lymph nodes [n]/tumor size [cm]).ResultsThis study included 12,007 patients with a median follow-up of 62 months. The linear regression coefficients were 1.043 for luminal A, 1.024 for luminal B, 0.656 for HER2, and 0.435 for triple-negative breast cancer (TNBC) subtypes. No significant difference was observed in the coefficients between the luminal A and B subtypes (p = 0.797), while all other coefficients showed significant difference. After adjusting for other risk factors, the hazard ratio (HR) of Np/T for each subtype was significant for OS: luminal A (HR, 1.134; 95% confidence interval [CI], 1.097–1.171; p < 0.001), luminal B (HR, 1.049; 95% CI, 1.013–1.086; p = 0.007), HER2 (HR, 1.069; 95% CI, 1.014–1.126; p = 0.013), and TNBC (HR, 1.038; 95% CI, 1.01–1.067; p = 0.008).ConclusionThe incidence of lymph node metastasis differed according to molecular subtype. Luminal types have higher incidence of nodal metastasis than HER2 and TNBC. The HR of Np/T was highest in luminal A subtypes and lowest in TNBC subtypes.     

胃癌腹膜转移病人腹腔化疗港并发症发生及危险因素分析

目的:分析腹腔化疗港并发症发生及相关危险因素。方法:回顾性分析我院323例放置腹腔化疗港病人的临床资料,纳入261例胃癌腹膜转移病人。分析腹腔化疗港在胃癌腹膜转移病人腹腔化疗时发生的并发症及其危险因素。结果:261例中59例(22.6%)发生化疗港相关并发症。其中,皮下积液(25例,42.4%)和化疗港感染(16例,27.1%)是发生较多的并发症。其他是港体倾斜翻转(9例,15.3%),化疗港局部切口裂开(7例,11.9%),导管堵塞(1例,1.7%),和皮下转移(1例,1.7%)。化疗港并发症发生的中位时间为化疗港放置后3.0个月。结合Clavien-Dindo分级方法,将化疗港发生的并发症分为1~4个等级。ECOG评分、血清白蛋白水平、置港流程优化及专业团队放置为化疗港并发症发生的独立危险因素(P<0.05)。ECOG评分为唯一影响并发症分级的关联因素(P<0.05)。结论:腹腔化疗港在胃癌腹膜转移病人腹腔化疗中的应用安全可行,发生并发症可控。ECOG评分、血清白蛋白水平、置港方式是否优化及是否专业团队放置为化疗港并发症发生的独立危险因素。     

循环肿瘤细胞数量变化在预测局限性肾癌术后复发转移中的作用CSCD

目的探讨局限性肾癌患者行部分切除术后循环肿瘤细胞数量的变化在预测肿瘤复发转移中的作用。方法收集41例局限性肾癌患者,依据术前及术后3月循环肿瘤细胞数量变化分为阳性组(n=23)和阴性组(n=18)。对两组患者进行随访,终点事件为肿瘤复发转移。对所得数据进行统计学分析。结果阳性组复发转移率为43.5%,明显高于阴性组11.1%,差异有统计学意义(P=0.024);阳性组5年生存率为58.0%,阴性组为88.9%,差异有统计学意义(P=0.048)。结论术后3月循环肿瘤细胞计数较术前增加的局限性肾癌患者易出现复发转移。循环肿瘤细胞数量变化可作为较好的术后监测指标。     

Anatomic extent of lymph node metastases as an independent prognosticator in node-positive major salivary gland carcinoma: A study of the US SEER database and a Chinese multicenter cohort

BackgroundWe aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC).MethodsA total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort).ResultsUsing the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort.ConclusionAE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.     

“莪黄灌肠液”对人大肠癌SW480细胞HIF-1α通路uPA、uPAR基因表达的影响

目的:通过莪黄灌肠液对SW480细胞HIF-1α通路uPA、uPAR基因表达的影响，探讨莪黄灌肠液对SW480细胞侵袭与迁移的影响。方法:根据随机数学分组的原则，将50只健康SD雄性大鼠分成随机5组并逐个编号，体重控制在（200±20）g。通过预实验得出的药物分组量分别灌胃给药:莪黄灌肠液（莪黄汤）每毫升药液中含生药2 g，莪黄灌肠液（莪黄汤）组由低、中、高（6.075 g/kg，12.15 g/kg，24.3 g/kg）剂量组（灌胃剂量2 ml）组成，空白组为生理盐水组(灌胃剂量2 ml，pH 7.2)，阳性对照组由腹腔注射氟尿嘧啶0.025 g/(kg·d)，调整注射剂量1 ml构成。标准化灌胃1周，无菌条件下提取各组含药血清。在体外使用含药血清体培养SW480细胞，划痕实验观察莪黄灌肠液含药血清在体外对SW480细胞迁移能力的影响；Transwell实验检测肿瘤细胞侵袭能力；Western-blot实验检测各组细胞中HIF-1α、uPA、uPAR蛋白表达。结果:预实验提示莪黄灌肠液对大鼠无明显副作用。SW480细胞具有明显的迁移及侵袭能力。各组莪黄灌肠液含药血清能抑制SW480细胞的侵袭与迁移特性，其中莪黄灌肠液各组（24.3 g/kg，12.15 g/kg，6.075 g/kg）和氟尿嘧啶组较空白组均能够有效抑制肿瘤细胞的侵袭与迁移作用，且氟尿嘧啶组作用最强，中药24.3 g/kg组表现出的抑制侵袭作用较12.15 g/kg，6.075 g/kg组均强（P<0.05）。莪黄灌肠液含药血清作用于肿瘤细胞24 h后，其细胞内HIF-1α、uPA、uPAR蛋白含量均有明显的下降，HIF-1α、uPA、uPAR蛋白表现出浓度依赖性（P<0.05)。结论:“莪黄灌肠液”可能通过作用于HIF-1α通路抑制SW480细胞的侵袭与转移。