基于多参数MR的影像组学融合模型术前预测宫颈鳞癌脉管浸润的应用价值

目的 探讨基于多参数MR的影像组学融合模型术前预测宫颈鳞癌脉管间隙浸润（LVSI）的应用价值。方法 回顾性研究。纳入2016年6月—2019年3月山西省肿瘤医院宫颈鳞癌患者168例。患者年龄22~76（52.0±10.1）岁,临床分期为国际妇产联盟（FIGO）ⅠB期127例、ⅡA期41例。所有患者术前行多参数盆腔MR扫描,均接受根治性子宫切除术联合盆腔淋巴结清扫术治疗。收集其临床病理资料和多参数MRI数据,以7∶3的比例按照随机抽样法分为训练集117例和验证集51例。在T₂加权像（T₂WI）、表观弥散系数[ADC,由2个b值的弥散加权成像数据自动生成]及增强T₁加权像（cT₁WI）3个序列的MRI上,对病灶进行手动分割勾画肿瘤轮廓感兴趣区（ROI）,得到三维感兴趣区（VOI）并提取特征,通过以最大相关最小冗余和最小绝对收缩与选择算子回归为主的三步降维法筛选特征并构建影像组学模型。多因素logistic回归分析筛选临床特征并联合影像组学模型建立融合模型,制作列线图。受试者操作特征曲线（ROC 曲线）、校正曲线、决策分析曲线评估列线图的效能及临床效益。结果 术后病理检查确诊LVSI阳性42例,阴性126例。训练集与验证集患者的年龄、FIGO分期、肿瘤最大径、肿瘤分化程度、LVSI状态等临床病理特征比较,差异均无统计学意义（P值均>0.05）。基于T₂WI、ADC及cT₁WI多参数MRI提取的影像组学特征,经特征筛选后得到7个关键特征,均与宫颈癌LVSI相关（P值均<0.05）,并构建影像组学模型。训练集T₂WI、ADC及cT₁WI 3个序列独立构建的影像组学模型预测宫颈癌LVSI的ROC曲线下面积（AUC）分别为0.630[95%可信区间（CI）0.557~0.698]、0.686（95%CI 0.563~0.694）、0.761（95%CI 0.702~0.818）,3个序列共同构建的联合影像组学模型对应的AUC为0.887（95%CI 0.842~0.925）,诊断效能最优,并在验证集中得到验证。联合影像组学模型与肿瘤分化程度构建的融合模型列线图预测宫颈癌LVSI,在训练集与验证集中的AUC分别为0.893（95%CI 0.851~0.929）、0.854（95%CI 0.749~0.943）,校正曲线显示出列线图有良好的校正性能;决策曲线表明当风险阈值概率范围在0.50~0.96时,采用影像组学融合模型预测宫颈癌LVSI的净收益优于“将所有患者视为宫颈癌LVSI阳性或阴性”。结论 基于多参数MRI影像组学特征与临床特征的融合模型对宫颈癌LVSI状态有良好的预测价值。     

睾丸小叶内的淋巴间隙

目的　探讨睾丸小叶内淋巴间隙的结构特点。方法　灌流固定半薄、超薄切片 ,光镜和电镜下观察。结果　淋巴间隙宽窄不一、相互交通 ,呈多形性及迷路状。结论　淋巴间隙分为管周淋巴间隙及被膜下淋巴间隙 ,淋巴间隙之间是通过间质组织内大、小不一的孔隙相互交通     

胃癌NK细胞浸润与预后的关系

目的：探讨NK细胞浸润与胃癌患者预后的关系。方法：应用免疫组化S－P法对159例有详细随访资料的胃癌组织进行CD57染色分析，通过NK细胞计数，将NK细胞浸润程度分为3组：NK细胞少量浸润组（NK细胞浸润＜50个）；NK细胞中量浸润组（NK细胞数在50－150个）和NK细胞多量浸润组（NK细胞数＞150个），使用Cox风险模型进行多因素分析。结果：随着TNM分期的进展胃癌患者5年生存率明显降低（P＜0．05）。NK细胞多量浸润者5年生存率高于NK细胞少量浸润者和中量浸润者（P＜0．05），同时对TNM分期后发现TNMⅢ-Ⅳ期的胃癌患者中，NK细胞多量浸润得的5年生存率高于NK细胞少量浸润者和中量浸润者。多因素Cox风险模型分析发现影响胃癌患者总体生存率的因素有：TNM分期，NK细胞浸润数量，肿瘤分化程度和肿瘤大小。结论：胃癌患者肿瘤细胞间NK细胞多量浸润与较好的预后有关，并且肿瘤细胞间NK细胞浸润烽量可作为判定胃癌预后的一个指标，特别是TNMⅢ-Ⅳ期的胃癌患者。     

嗜酸性白细胞浸润与胃癌预后的研究

肿瘤组织中嗜酸性白细胞浸润的现象虽然早有人注意到,但其意义尚不太清楚。我们观察了88例胃癌间质中嗜酸性白细胞以及淋巴细胞浸润与病人预后的关系,现将结果报道如下。 1 材料和方法 材料选自本教研室1978～1988年胃癌胃次全切除标本88例,均经10％福尔马林溶液固定,在肿瘤部位取材2～4块,石蜡包     

乳腺癌肿瘤出芽与肿瘤浸润淋巴细胞及患者预后的关系研究

目的:研究肿瘤出芽与乳腺癌临床病理特征、肿瘤浸润淋巴细胞(TILs)以及患者预后的关系。方法:收集2012年1月～2016年12月于暨南大学附属第一医院行手术治疗的178例乳腺癌患者资料及肿瘤组织切片,显微镜下观察乳腺癌组织病理切片中肿瘤出芽和肿瘤浸润淋巴细胞水平,X~2检验分析肿瘤出芽水平与乳腺癌患者临床病理特征和TILs的关系,Log-rank检验分析肿瘤出芽水平与乳腺癌患者无病生存期和总生存期的关系。结果:高肿瘤出芽组患者淋巴结阳性数目多、组织性分级高、脉管癌栓更多;肿瘤出芽数较多的患者TILs的水平较低,而肿瘤出芽数较少的患者TILs水平较高;高肿瘤出芽患者比低肿瘤出芽患者预后较差。结论:乳腺癌肿瘤出芽水平与恶性程度高的临床病理指标密切相关,肿瘤出芽水平与TILs水平呈负相关,是影响乳腺癌预后的重要因素。     

miRNA在宫颈癌早期诊断及预后中的研究进展

微小RNA(miRNA)在宫颈癌的发生、侵袭、转移和复发等过程中扮演重要角色,与其预后密切相关.宫颈癌患者血清中异常表达的miRNA可作为其无创诊断和预后判断的生物标志物,通过研究血清miRNA可以早期诊断宫颈癌,减少肿瘤的转移和复发,寻找治疗靶点,为宫颈癌的诊疗提供突破点.     

贲门腺癌侵犯脉管意义的研究

用石蜡大切片法观察根治术后转归截然不同的102例贲门腺癌标本,分析癌侵犯脉管情况及宿主间质反应的表现。生存5年以上与2年内死于癌的两组间淋巴管与血管阳性例数均有显著差异。癌侵犯脉管以淋巴管最多,且常为多数性。受侵脉管越多、管径越大、预后越差。观察到癌前缘间质中血管周围淋巴细胞套状浸润及血管壁纤维组织增生,认为均是宿主对癌侵犯脉管的抵抗反应表现。     

N6-甲基腺嘌呤调控因子对宫颈癌预后及免疫浸润的作用

目的：探究N6-甲基腺嘌呤（m6A）RNA甲基化调控因子对宫颈癌预后及肿瘤免疫微环境的潜在作用及机制。方法：从TCGA和GEO数据库下载宫颈癌转录组表达数据和相应临床数据，通过生物信息学方法和组织验证实验分析m6A调控因子表达及相关性，LASSO Cox回归分析建立m6A预后相关风险预测模型，一致性聚类分析确定2种m6A修饰模式，ssGSEA分析两组间免疫细胞浸润相对丰度。结果：与正常组织相比，宫颈癌组织RBM15、IGF2BP2、IGF2BP3、FMR1、YTHDF1、METTL3和YTHDF2表达显著上调，而ZC3H13、METTL14、YTHDC1、FTO和ALKBH3表达显著下调。选择5个m6A调控因子HNRNPC、LRPPRC、METTL3、ELAVL1和FMR1建立风险预后模型，HPA数据库和qRT-PCR验证其在宫颈癌组织中的表达，该模型具有较好的预测价值，可作为独立的预后指标（AUC=0.734）。基于25个m6A调控因子表达确定了2种m6A修饰模式，即m6Acluster A和m6Acluster B，两组生物学功能及信号通路和肿瘤微环境中免疫细胞浸润水平存在差异。结...     

早产儿早期干预的预后影响研究分析

目的探讨对早产儿早期干预的预后影响。方法根据《0～3岁早期干预大纲》进行干预和指导，对105例早产儿随机分为干预组55例，对照组50例，观察早产儿生后2周内呼吸、心率、吸吮能力的影响及其婴儿2岁时智力和精神运动发育情况、心理卫生及行为问题调查、后遗症发生率的影响。结果干预组出生2周内呼吸、心率、吸吮能力较对照组强（P〈0．01），2岁时智力和精神运动发育指数、心理卫生及行为问题均高于对照组，后遗症发生率低于对照组（P〈0．05）。结论早产儿通过早期干预，可有效提高生命质量，促进智能和神经、心理、体格发育。     

DPH2在前列腺癌中的免疫浸润及预后预测的研究

目的 白磺酰胺生物合成蛋白2(DPH2)基因是白喉毒素靶标白硫胺生物合成的关键酶，它对前列腺癌患者的预后和免疫浸润的影响尚不清楚，探讨其在前列腺癌中的免疫浸润及预后预测中作用。方法 从癌症基因组图谱(TCGA)数据库中获得的前列腺癌患者的表达谱和临床信息。使用Wilcoxon秩和检验，比较前列腺癌和正常前列腺组织之间的DPH2表达水平。进行功能富集分析以探索所涉及的潜在信号通路和生物学功能。使用单样本基因集富集分析评估免疫细胞浸润。UALCAN数据库用于分析DPH2的甲基化状态。采用Kaplan-Meier方法和Cox回归分析确定DPH2的预后价值。构建列线图以预测癌症诊断后1年、3年和5年的复发转移率。结果 DPH2在前列腺癌中过表达，与T分期(P=0.013)、N分期(P=0.025)、PFI事件(P=0.023)和OS(P<0.001)显著相关。DPH2过表达导致OS和疾病特异性生存率显著下降。多变量Cox分析将DPH2确定为OS的独立预后标志物。同样，DPH2的低甲基化状态也与预后不良有关。功能富集分析表明，富集途径包括葡萄糖醛酸盐代谢过程、脱氧核糖核酸-结合转录激活物R...     

STC-1在宫颈癌中的表达及其在预后判断中的价值

目的:研究宫颈癌中分泌蛋白斯坦尼钙调节蛋白1(stanniocalcin 1,STC-1)的表达情况及其与预后的关系.方法:Western印迹分析STC-1在宫颈癌细胞系的表达,免疫组织化学染色(immunochemistry,IHC)检测STC-1在宫颈癌和正常组织的表达,分析STC-1表达水平与宫颈患者临床病理特征之间关系,通过网上数据库初步探索STC-1表达与预后的关系.结果:宫颈正常上皮细胞Ect1/E6E7细胞株中几乎检测不到STC-1,宫颈癌细胞株中STC-1呈不同程度表达;IHC结果显示:STC-1主要在宫颈细胞的胞质和胞膜中表达,与匹配的癌旁正常组织相比,STC-1蛋白水平在宫颈癌组织中更高(P<0.05),并且与患者淋巴结转移正相关(P=0.038);另外,通过对数据库中宫颈癌患者的样本分析发现:高表达STC-1的宫颈癌患者预后更差(P<0.01).结论:STC-1表达与宫颈患者的总体存活负相关,STC-1可能具有预测宫颈癌患者预后生存时间的潜在价值.     

Prediction of lymphovascular space invasion in patients with endometrial cancer

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC).Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients'' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis.Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the “LVSI index” as “TD×%MMI×tumor grade×cervical stromal involvement.” The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200.Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.     

Peritumoural,but not intratumoural,lymphatic vessel density and invasion correlate with colorectal carcinoma poor-outcome markers

To evaluate whether lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) are useful markers of worse outcome in colorectal carcinoma and if LVD and LVI correlate to the classical clinical-pathological parameters, we analysed 120 cases of colorectal carcinomas selected from the files of Division of Pathology, Hospital das Clinicas, São Paulo University, Brazil. Assessment of LVD and LVI was performed by immunohistochemical detection of lymphatic vessels, using the monoclonal antibody D2-40. Higher LVD was found in the intratumoural area, when comparing with normal and peritumoural areas (p?p?=?0.037) and liver metastasis (p?=?0.012). Remarkably, LVI was found associated with local invasion (p?=?0.016), nodal metastasis (p?=?0.022) and hepatic metastasis (p?相似文献   

MicroRNA-101 regulates the viability and invasion of cervical cancer cells

Background: Cervical cancer has the second highest morbidity and mortality rates of any malignancy in women worldwide, and it is one of the leading causes of death in Uygur women in Xinjiang China. MicroRNAs are involved in cancer development and progression. Previously, we found that miR-101 is significantly down-regulated in cervical cancer tissues from Uyghur women. The underlying pathophysiology and relevance to tumorigenesis of miR-101 is still largely unknown. The purpose of this study was to elucidate the molecular mechanisms of miR-101 regulation of cervical cancer cell viability and invasion. Materials and methods: The expression of miR-101 in cervical cancer cell line (SiHa) was detected by real-time PCR. A miR-101 mimic was overexpressed in SiHa cells, and MTT assays were performed to determine the impact on cell proliferation. Cell would heal assays and flow cytometry were used to detect migratory ability and cellular apoptosis, respectively. Immunohistochemistry was performed to assess protein expression of the miR-101 target gene COX-2. Results: MiR-101 was endogenously expressed in SiHa cells, and alterations in its expression had profound effects on cellular migration and invasion efficiency. Overexpression of miR-101 decreased proliferation in the MTT assay (the mimics at 490 nm absorbance is lower 60% than normal, and decreased cellular motility in the cell would healing assay (transfected: 37 ± 2 m, pre-transfected 184 ± 2 m). Apoptosis rate was significantly higher with overexpression of miR-101 relative to control (transfected: 76.6%, pre-transfected: 3.5%) (P < 0.05). The expression of Cox-2 was decreased in transfected cells. Conclusions: MiR-101 likely acts as a tumor suppressor in cervical cancer. Overexpression of miR-101 decreased expression of its target gene Cox-2 and inhibited proliferation and invasion, and promoted apoptosis to suppress tumorigenicity. MiR-101 is a promising new target for the development of therapeutic strategies for the clinical treatment of cervical cancer.     

Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40

Lymphatic invasion is known as an independent predictor of lymph node metastasis in gastric cancer. However, the diagnosis of lymphatic invasion is sometimes difficult by hematoxylin-eosin (H&E) staining. Immunostaining using D2-40 was performed to study the distribution of lymphatic vessel and lymphatic invasion in a series of 78 primary gastric cancers. D2-40 showed specific staining for the lymphatic vessels, but not for blood vessels. The lymphatic invasion was most frequently found in the upper half of submucosal layer. Positive rate of lymphatic invasion by H&E staining was 27% (21/78), and that by D2-40 was 44% (34/78). Lymphatic invasion on H&E staining was diagnosed as false negative in 17 (21.8%) of 78 primary gastric cancers and false positive in 4 (5.1%) of 78 primary gastric cancers. Sensitivity for lymph node metastasis by the lymphatic invasion diagnosed by D2-40 was significantly higher (89%, 24/27) than by H&E staining (41%, 11/27). These results suggest that the diagnosis of lymphatic invasion by D2-40 is more sensitive than H&E staining. Sensitivity for the prediction of lymph node metastasis from the lymphatic invasion status in primary tumor by D2-40 was significantly higher than by H&E staining. Based on our results, we recommend the use of D2-40 immunoreactions for the routine evaluation of lymphatic invasion in gastric cancer.     

Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer

Introduction: Cervical cancer is the second leading cause of cancer morbidity and mortality for women around the world. Long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although downregulation of lncRNA GAS5 in several cancers has been studied, its role in cervical cancer remains unknown. The aim of this study is to investigate the expression, clinical significance and biological role in cervical cancer. Methods: Expression of GAS5 was analyzed in cervical cancer tissues by quantitative Real-time PCR (qRT-PCR). And its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress GAS5 expression in cervical cancer cells. In vitro assays were performed to further explore the biological functions of GAS5 in cervical cancer. Results: We found that GAS5 expression was markedly downregulated in cervical cancer tissues than in corresponding adjacent normal tissues. Decreased GAS5 expression was significantly correlated with FIGO stage, vascular invasion and lymph node metastasis. Moreover, cervical cancer patients with GAS5 lower expression have shown significantly poorer overall survival than those with higher GAS5 expression. And GAS5 expression was an independent prognostic marker of overall survival in a multivariate analysis. In vitro assays our data indicated that knockdown of GAS5 promoted cell proliferation, migration, and invasion. Conclusions: Our study presents that lncRNA GAS5 is a novel molecule involved in cervical cancer progression, which provide a potential prognostic biomarker and therapeutic target.     

Importance of tumour cell invasion in blood and lymphatic vasculature among patients with endometrial carcinoma

Aims:  Vascular invasion is a prognostic marker for many cancers, including endometrial carcinoma. Immunohistochemistry using D2-40 and CD31 antibodies makes it possible to differentiate between lymphatic vascular invasion (LVI) and blood vessel invasion (BVI). The aim was to examine lymphatic and blood vessel invasion separately and their associations with clinicopathological characteristics and prognosis.
Methods and results:  Immunohistochemistry was performed on a retrospective population-based series of endometrial carcinoma. Altogether, 31% of the 276 tumours showed lymphatic involvement, whereas 18% showed blood vessel invasion. LVI and BVI were associated with histopathological variables such as histological grade and tumour growth pattern. Patients without vascular invasion had the best prognosis and those with BVI (with or without LVI) had the worst outcome, whereas patients with LVI had an intermediate survival on univariate analysis. Multivariate models indicated that both LVI and especially BVI had independent prognostic importance. Among endometrioid carcinomas, BVI was still significant.
Conclusions:  Our findings support the biological importance of vascular spread through the haematogenic and lymphatic routes in endometrial cancer. The significant correlation found with clinical phenotype indicates that these markers may be relevant for patient management.     

人直肠癌组织淋巴管的微细分布

目的研究人直肠癌淋巴管的微细分布和结构特征,为进一步探讨癌组织的淋巴道转移机理提供形态学依据。方法取直肠癌手术切除的组织,按不同部位取材,812树脂包埋,半薄切片光镜观察淋巴管的形态及结构特征。结果在癌中心区未见淋巴管,癌周围区的淋巴管密度较正常区增多,直肠癌周边区淋巴管的体密度和数密度均明显高于正常区(P<0.05,P<0.01)且管腔扩张,管壁常见到溶解、破坏,并见癌细胞团靠近扩张的毛细淋巴管。结论癌周围区的淋巴管有数量及形态结构的改变,增加了癌细胞淋巴道转移的机会。直肠癌的淋巴道转移可能以溶解、破坏淋巴管壁而进入淋巴管为主要途径。     

胆管癌对血管和神经周围间隙的侵犯及肿瘤血管生成在浸润和转移中的意义

对４０例胆管癌标本切片进行血管内膜下弹力纤维ＶＢ：ＨＥ、ＦⅧＲＡｇ：ＶＢ：Ｈ及ＨＥ染色，结果显示，血管侵犯者３１例（７７．５％），表现为４种类型，即血管壁受侵、游离癌细胞侵入、部分栓塞和完全栓塞。肿瘤血管密度（ＴＶＤ）与转移发生明显相关。发生神经周围间隙浸润者共３３例（８２．５％），神经周围浸润指数（ＰＮＩ）与器官或组织转移发生率相关。研究表明，血管和神经周围间隙均是重要的转移途径。肿瘤血管生成是浸润、转移发生必不可少的环节。ＴＶＤ和ＰＮＩ对于判断患者术后预后具有一定的参考意义。