肝细胞性肝癌骨转移的诊疗进展与预后因素研究

随着临床诊治水平的不断进步，肝细胞性肝癌（hepatocellular carcinoma，HCC）患者的总生存时间获得延长，但是HCC骨转移发生率则显著升高，HCC骨转移的筛查与诊治已成为全球性热点与难点问题。明确HCC骨转移的致病机制有助于临床肿瘤筛查及诊疗手段的提高，血管形成和上皮-间质转化（epithelial mesenchymal transition，EMT）是HCC骨转移的主要致病机制，骨微环境使得HCC骨转移持续发生。明确HCC骨转移的预后因素有利于对此类患者进行早期干预以延长患者总生存期，但目前尚未就HCC骨转移患者的治疗策略达成共识。本文就HCC骨转移分子病理学致病机制的研究进展进行综述，为早期筛查、精准诊断和个体化治疗提供依据。      

基于剂量组学预测肺癌患者放射性肺炎发生的研究

目的 探讨剂量组学在预测肺癌根治性放疗患者放射性肺炎发生中的应用潜能。方法 回顾性收集行根治性放疗的314例肺癌患者的临床资料、放疗剂量文件、定位及随访CT图像,根据临床资料及影像学随访资料对放射性肺炎进行分级,提取全肺的剂量组学特征,构建机器学习模型。应用1000次自助抽样法（bootstrap）的最小绝对值收敛和选择算子嵌套逻辑回归（LASSO‐LR）及1000次bootstrap的赤池信息量准则（AIC）向后法筛选与放射性肺炎相关的剂量组学特征,随机按照7∶3划分为训练集及验证集,应用逻辑回归建立预测模型,并应用ROC曲线及校正曲线评价模型的性能。结果 共提取120个剂量组学特征,经LASSO‐LR降维筛选得到12个特征进入“特征池”,再经过AIC向后法筛选,最终筛选出6个剂量组学特征进行模型构建,训练集AUC为0.77（95%CI为0.65~0.87）,独立验证集AUC为0.72（95%CI为0.64~0.81）。结论 利用剂量组学建立的预测模型具有预测放射性肺炎发生的潜力,但仍需继续纳入多中心数据及前瞻性数据进一步挖掘剂量组学的应用潜能。     

MicroRNA expression profiling of Chinese follicular lymphoma by microarray: A preliminary study

BackgroundMicroRNAs (miRNAs) have been widely regarded as crucial regulators in various biological processes involved in carcinogenesis. However, the comprehensive miRNA profiles of Chinese follicular lymphoma (FL) remains completely unknown.MethodsThe Exiqon miRCURY LNA™ microRNA Array (v.18.0) was used to detect the miRNA expression profiles of three Chinese FL samples, and compared to three reactive lymphatic nodes (RLN). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the selected miRNAs in different series. Three databases (miRAnda, miRBase and TargetScan) were used to predict the putative target genes. Bioinformatic analysis (gene ontology analysis and pathway analysis) was performed for further evaluation.ResultsThe microarray assay demonstrated that 1643 miRNAs were expressed; in which 103 miRNAs were upregulated and 68 miRNAs were downregulated, according to P-value (< 0.05) and fold change (FC > 2-fold). Furthermore, qRT-PCR was used to confirm that miR-17-5p, miR-20a-5p and miR-19a-3p were upregulated, and miR-3615 was downregulated (P < 0.05). Bioinformatic analysis (gene ontology analysis and pathway analysis) was used for further evaluation. Pathway analysis indicated that 25 pathways corresponded to differentially expressed miRNAs (P-value cut-off is 0.05). Furthermore, miR-17-5p, miR-20a-5p and miR-19a-3p were validated by qRT-PCR in an independent series including five FL3a and five RLN cases. Data analysis revealed that the changing trend of miR-19a-3p and miR-17-5p expression in the independent series was basically identical with that of the microarray data.ConclusionsOur results are the first to reveal the miRNA expression profiling of Chinese FL and three upregulated miRNAs. Furthermore, the expression of miR-19a-3p and miR-17-5p were found to be significantly upregulated in FL3a. Further study needs to be urgently performed to reveal its potential role in the pathogenesis of FL in the near future.     

Using arterial spin labeling blood flow and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma from lymphoid hyperplasia

To investigate the feasibility of arterial spin labeling (ASL) blood flow (BF) and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPLH).Sixty-three stage T1 NPC patients and benign NPLH patients underwent ASL on a 3.0-T magnetic resonance imaging system. BF histogram parameters were derived automatically, including the mean, median, maximum, minimum, kurtosis, skewness, and variance. Absolute values were obtained for skewness and kurtosis (absolute value of skewness [AVS] and absolute value of kurtosis [AVK], respectively). The Mann–Whitney U test, receiver operating characteristic curve, and multiple logistic regression models were used for statistical analysis.The mean, maximum, and variance of ASL BF values were significantly higher in early-stage NPC than in NPLH (all P < 0.0001), while the median and AVK values of early-stage NPC were also significantly higher than those of NPLH (all P < 0.001). No significant difference was found between the minimum and AVS values in early-stage NPC compared with NPLH (P = 0.125 and P = 0.084, respectively). The area under the curve (AUC) of the maximum was significantly higher than those of the mean and median (P < 0.05). The AUC of variance was significantly higher than those of the other parameters (all P < 0.05). Multivariate analysis showed that variance was the only independent predictor of outcome (P < 0.05).ASL BF and its histogram analysis could distinguish early-stage NPC from NPLH, and the variance value was a unique independent predictor.     

Anti-neutrophil antibodies (anti-MPO-ANCAs) are associated with poor prognosis in breast cancer patients

Anti-neutrophil antibodies are capable of activating neutrophils in sterile environments, releasing extracellular traps containing myeloperoxidase (MPO) and anti-MPO antibodies (MPO-ANCAs or anti-MPO-ANCAs), which have been implicated in the pathogenesis of several diseases. The present study evaluated systemic and tumor tissue levels of anti-MPO-ANCAs breast cancer patients, and its relation to clinicopathological characteristics. Anti-MPO-ANCAs were measured in serum and tissue samples of 150 patients by enzyme-linked immunoassay. Samples were pooled according to clinicopathological characteristics of patients. Higher anti-MPO-ANCAs levels were detected in groups presenting negative clinicopathological characteristics, such as high histological grade tumors and risk factors such as body mass index, menopausal status and early onset at diagnosis. The present data highlights anti-MPO-ANCAs as associated to poor prognosis in breast cancer, a role beyond its actually discussed role in autoimmunity and vasculitis.     

Durability of humoral immune responses to rubella following MMR vaccination

BackgroundWhile administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults.MethodsIn this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot.ResultsRubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women.ConclusionsCollectively, rubella-specific humoral immunity declines following vaccination, although subjects’ antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.     

阿来替尼治疗ALK基因融合重排NSCLC脑转移瘤的临床疗效分析

  目的  探讨阿来替尼治疗ALK融合重排非小细胞肺癌（non-small cell lung cance，NSCLC）脑转移患者的疗效及不良反应。  方法  回顾性分析2016年8月至2019年10月天津医科大学肿瘤医院34例以脑转移为首发的ALK基因融合重排NSCLC患者的临床资料，其中13例（38.2%）患者接受阿来替尼单药一线治疗。男性7例（53.8%），女性6例（46.2%），中位年龄51（35~72）岁。应用Kaplan-Meier分析其生存情况。  结果  阿来替尼治疗ALK基因融合重排肺癌脑转移瘤，颅内中位无进展生存期（median progression-free survival，mPFS）为24.5个月。药物不良反应较轻。  结论  在颅内可测量病灶得到局部治疗的基础上，阿来替尼作为ALK基因融合重排NSCLC脑转移患者的一线治疗方案，显著延长患者无进展生存期（progression-free survival，PFS）。      

Risk of lymph node metastasis and prognostic outcome in early gastric cancer patients with mixed histologic type

BackgroundWhether early gastric cancer with mixed histologic type should be considered for endoscopic submucosal dissection (ESD) remains controversial. The objective of this study was to evaluate the risk of lymph node metastasis (LNM) and prognostic significance for early gastric cancer with mixed histologic type.MethodsWe retrospectively reviewed clinicopathologic and survival data of 302 patients who underwent surgical resection for early gastric cancer. Based on the histologic components, all patients were classified as pure differentiated type, pure undifferentiated type and mixed histologic type. The prognostic differences between different types were compared and predictive factors for LNM were evaluated.ResultsHistopathologically, the proportion of mixed histologic type was 12.3% in early gastric cancer. In terms of LNM, mixed histologic type had a more frequent incidence than pure differentiated type (32.4% vs 11.1%, P < 0.01). However, there was no significant difference between mixed type and pure undifferentiated type for LNM (32.4% vs 21.1%, P = 0.139). Multivariate analysis revealed that tumor size >2 cm (odds ratio [OR]: 2.153, 95% confidence interval [CI]: 1.113-4.164, P < 0.05), submucosal invasion (OR: 3.881, 95%CI: 1.832-8.222, P < 0.001), lymphovascular invasion (OR: 8.797, 95% CI: 2.643-29.277, P < 0.001), undifferentiated type (OR: 3.146, 95% CI: 1.352-7.320, P < 0.01), and mixed histologic type (OR: 3.635, 95% CI: 1.272-10.390, P < 0.05) were independent risk factors for LNM in early gastric cancer patients. However, mixed histologic type did not affect the survival outcome of these patients (hazard ratio: 0.629, 95% CI: 0.074-5.311, P > 0.05).ConclusionMixed histologic type was an independent risk factor for lymph node metastasis in early gastric cancer patients. The decisions regarding endoscopic submucosal dissection for mixed histologic type should be carefully considered.     

应用放射组学和剂量学特征预测食管癌放射治疗后的两年生存情况

  目的  使用放射组学与剂量学特征参数，建立机器学习预测模型，预测食管癌患者放射治疗后两年的生存情况。  方法  回顾性分析2013年1月至2017年12月在天津医科大学肿瘤医院接受放射治疗的食管癌患者共579例。从食管癌患者的放射治疗计划中提取GTV的放射组学和剂量学的特征，使用最大相关最小冗余与人工方法对特征参数进行筛选，分别选取14项放射组学和14项剂量学特征，并将特征变量进行标准化归一至[0, 1]范围。建立支持向量机、逻辑回归和随机森林等机器学习模型，先使用14项放射组学特征，再使用28项放射组学和剂量学混合特征参数进行训练和测试，来预测食管癌放射治疗患者的两年生存情况。  结果  仅使用放射组学特征预测放射治疗后两年生存情况时，支持向量机、逻辑回归和随机森林模型的准确率分别为84.98%、85.92%和84.51%。使用放射组学和剂量学的混合特征参数进行预测时，支持向量机、逻辑回归和随机森林模型的准确率分别为86.32%、83.02%和90.01%。在放射组学特征参数基础上，增加剂量学特征，支持向量机和随机森林模型的预测准确性得到有效提高。  结论  针对支持向量机和随机森林模型，使用放射组学和放射治疗剂量学特征参数放射治疗，可有效提高对食管癌患者放射治疗后两年生存情况预测评估的准确性。      

食管癌根治性放疗剂量研究进展

同步放化疗是不可手术局部晚期食管癌的标准治疗模式,国际推荐根治性放疗剂量为50.0~50.4Gy,但中国食管癌与西方国家在病理类型、生物学行为等方面大有不同,行根治性放疗剂量仍倾向于60Gy。增加放疗剂量能否带来生存获益成为临床亟待解决的问题。有研究认为高剂量放疗可提高局控率、改善生存,但也有研究认为提高剂量未能带来生存获益,且可增加不良反应事件发生率。因此,本文就食管癌根治性放疗剂量对预后的影响进行探讨,并通过放化疗后疗效评估对放疗剂量做出适当调整,以期达个体化放疗。