成人髓母细胞瘤的临床特征和总体生存预后列线图：基于SEER数据库分析

目的 基于监测、流行病学和最终结果 （SEER）数据库调查所有成人髓母细胞瘤（MB）患者的人口统计学、预后和预后因素,建立临床预后模型预测成人MB患者的生存时间。方法 从SEER数据库选取1973—2019年确诊的病例,通过单变量和多变量分析,评估年龄、诊断年份、性别、人种、肿瘤部位、肿瘤大小、病理类型、总分期、手术方式、放疗和化疗的使用对总生存率的影响。构建并验证预测成人MB的1、3和5 a生存率列线图。结果 数据清理后,纳入784例成人MB患者。最后一次随访时患者的平均生存时间为96个月。在多变量分析中,年龄、诊断年份、肿瘤部位、组织学类型和放疗均显示与2组患者的生存率独立相关。建立临床列线图,列线图的C-指数为0.628 5 (0.594 4～0.662 6)。1 a、3 a和5 a的校准曲线显示,列线图预测与实际观察结果 之间具有良好的一致性,列线图的内部验证表明该预测方式可区分高危与低危病人。结论 建立预测成人MB患者总体生存率的列线图可帮助临床准确预测患者的预后并进行进一步的治疗。     

STK40在脑胶质瘤中的表达及其临床意义的生信分析

目的 探讨丝氨酸/酸酸蛋白激酶40（STK40）在脑胶质瘤中的表达及其临床意义。方法 计算机检索GEPIA数据库,运用生物信息学方法分析STK40在胶质瘤组织及正常脑组织中的表达差异;同时,检索CGGA数据库中693例脑胶质瘤的基因信息及临床资料,运用Kaplan-Meier生存曲线分析STK40表达水平与脑胶质瘤生存预后的关系;采用多因素Cox比例回归风险模型分析脑胶质瘤生存预后的影响因素。结果 GEPIA数据库分析显示,胶质母细胞瘤组织STK40表达水平较正常脑组织明显增高（P<0.05）。STK40表达水平与胶质瘤病理级别呈正相关,随胶质瘤病理级别增高,STK40表达水平明显增高（P<0.0001）。多因素Cox风险比例回归模型分析结果显示,STK40高表达是脑胶质瘤生存预后不良的独立危险因素（P<0.05）。Kaplan-Meier生存曲线分析显示,STK40高表达组中位总生存期较低表达组明显缩短（P<0.0001）;而且STK40高表达明显降低胶质瘤放/化疗的效果（P<0.0001）。Pearson相关性分析显示,ERK下游产物SRF与STK40呈明显正相关（r=0.45;P<0.0001）,JNK下游产物ATF2与STK40表达水平呈明显负相关（r=-0.167;P<0.0001）。结论 胶质瘤STK40呈高表达,与病人生存预后不良有关,其作用机制可能与ERK/MAPK及JNK/MAPK信号通路有关。     

原发性人脑胶质瘤的预后影响因素:基于SEER数据库的分析

目的 探讨原发性人脑胶质瘤病人预后影响因素。方法 通过SEER*Stat（8.3.8版本）软件搜集SEER数据库2004~2015年原发性人脑胶质瘤病人的临床资料,采用R（4.0.2版本）软件进行单因素与多因素Cox回归分析,通过Kaplan-Meier生存曲线分析不同治疗方式和婚姻状态与病人预后的关系。结果 共纳入符合标准的原发性人脑胶质瘤18 523例。多因素Cox回归分析结果显示,年龄≥30岁、肿瘤直径≥2 cm、病理级别高、肿瘤位于额叶以外部位、离婚、丧偶为原发性胶质瘤预后不良的独立危险因素（P<0.05）,手术治疗、术后放疗、化疗是原发性胶质瘤预后的独立保护因素（P<0.05）。生存曲线分析结果显示,手术治疗（全切除或部分切除肿瘤）、术后放疗、化疗均明显延长原发性胶质瘤病人的生存期（P<0.05）,婚姻状态为结婚的病人预后明显好于丧偶的病人（P<0.05）。结论 对原发性人脑胶质瘤,尽可能手术全切除肿瘤,同时术后辅助放化疗,能够延长病人的生存时间。同时,临床应加强病人心理干预。     

脑胶质瘤FBLIM1的表达及临床意义

目的 探讨FBLIM1在脑胶质瘤中的表达及临床意义。方法 采用R软件分析UCSC数据库中癌症基因组图谱联合基因型组织表达数据集（TCGA、TARGET、GTEx）中的662例胶质瘤和1 157例正常脑组织的FBLIM1表达水平。利用TCGA数据库698例胶质瘤mRNA-seq及临床数据分析FBLIM1表达与胶质瘤临床特征的关系,用Cox比例回归风险模型分析胶质瘤生存预后的影响因素,采用Kaplan-Meier法分析TCGA数据库及中国脑胶质瘤基因组图谱（CGGA）数据库共计1 975例胶质瘤的FBLIM1表达与生存预后的关系。结果 胶质瘤FBLIM1表达水平较正常脑组织明显增高（P<0.05）,且肿瘤WHO分级越高,FBLIM1表达水平越高（P<0.05）;胶质瘤FBLIM1表达与IDH基因状态、1p/19q联合缺失、WHO分级及病人年龄显著相关（P<0.05）;FBLIM1过表达为胶质瘤病人生存预后不良的独立危险因素（OR=1.444;95% CI 1.032~2.020;P<0.05）;生存曲线分析显示FBLIM1高表达的胶质瘤病人中位总生存期较低表达病人明显缩短（P<0.05）。结论 胶质瘤FBLIM1呈高表达,与病人生存预后不良相关。     

IDH突变调控BMP2、COL27A1和SERPINA5基因表达影响人脑胶质瘤的生存预后

目的 探讨异柠檬酸脱氢酶（IDH）突变影响胶质瘤临床预后的潜在分子机制。方法 计算机检索CGGA和TCGA数据库,获取胶质瘤RNA测序数据（RNA-seq）,应用生物信息学分析方法分析IDH突变改善胶质瘤临床预后的潜在分子机制。结果从TCGA数据库下载胶质母细胞瘤（GBM）和低级别胶质瘤（LGG）相关RNA-seq,从CGCA数据量下载648例胶质瘤的RNAseq(234例GBM和414例LGG),从GEO数据量下载单细胞RNA-seq数据GSE131928数据集（28例IDH野生型GBM）。GO和KEGG分析显示,IDH突变显著下调胞外基质（ECM）相关基因表达,GEPIA分析显示BMP2、COL27A1、SERPINA5、VEGFA基因表达水平与胶质瘤生存预后有关,多因素Cox比例回归风险模型分析显示BMP2、COL27A1、SERPINA5基因表达是胶质瘤生存预后独立影响因素,BMP2联合SERPINA5预测胶质瘤生存预后效果最好。结论 我们结果提示胶质瘤IDH基因突变,可能通过调控BMP2、COL27A1和SERPINA5基因表达,影响病人生存预后。     

儿童脑干胶质瘤生存时间的相关因素分析

目的探讨影响儿童脑干胶质瘤生存时间的相关因素。方法回顾性分析33例儿童脑干胶质瘤病人的临床资料。应用Kaplan-Meier法进行单因素分析,分析临床、影像和病理组织学因素对生存时间的影响。差异的显著性检验应用Log-rank法,对单因素分析中P<0.05者进行COX回归多因素模型分析。结果单因素分析显示影响生存时间的因素包括:发病年龄、发病到就诊时间、入院时KPS评分、肿瘤部位、病理级别、肿瘤生长类型以及治疗方法(均P<0.05)。多因素分析显示:病人的发病到就诊时间(P=0.034)及肿瘤生长类型(P=0.046)对生存时间的影响更为显著。结论儿童脑干胶质瘤的生存时间与多种因素有关,手术切除可延长生存时间。     

胶质瘤新分类法的研究进展

胶质瘤的传统分类是WHOⅠ-Ⅳ级的组织学分类,已不能完全适应临床治疗和预后估计的需要。近年来根据胶质瘤分子遗传学研究进展,提出了从分子水平重新考虑胶质瘤分类的设想,并在间变型少突胶质瘤及胶质母细胞瘤等分子亚型研究中取得了突破性进展,对临床治疗及预后估计有显著指导作用。新的分类模式将是组织形态学、分子遗传学、神经影像学等相结合,并能精确指导临床个体化新疗法和有效判断预后的理想方法。     

星形母细胞瘤2例临床病理分析

星形母细胞瘤(astroblastomas)是比较罕见的、有一定组织学特征的胶质瘤,其发病率仅占胶质瘤的0.45%～2.8%.由于该肿瘤同时具有星形细胞瘤和室管膜瘤的特征,在起源方面一直存有争议;由于发病率低,临床缺乏对该肿瘤的认识,在诊断方面也易与其它肿瘤混淆,导致治疗不当.     

针对脑胶质瘤相关通路治疗的研究进展

正胶质瘤是颅内发病率最高的肿瘤,约占颅内神经组织原发性肿瘤的45%。世界卫生组织(World Health Organization,WHO)将胶质瘤按组织学分为Ⅰ~Ⅳ级,其中Ⅰ、Ⅱ级为低级别胶质瘤,Ⅲ、Ⅳ级为高级别胶质瘤~([1])。Ⅰ级预后最好,大部分经治疗后可以达到临床治愈,被认为是良性肿瘤;Ⅳ级恶性程度最高,又称作胶质母细胞瘤(glioblastoma,GBM),占所有胶质瘤的55%。根据2016年WHO中枢神经系     

人脑胶质瘤组织BIRC2表达变化及临床意义

目的 探讨人脑胶质瘤组织含杆状病毒IAP重复蛋白2（BIRC2）表达变化及临床意义。方法 从GEO数据库获取人脑胶质瘤的基因表达芯片进行差异表达基因分析,并借助TCGA数据库对筛选出的BIRC2基因在人脑胶质瘤中的表达及预后进行分析,同时通过GSEA分析BIRC2在人脑胶质瘤中的作用机制进行预测。结果 从GEO数据库筛选GSE66354芯片中筛选出BIRC2为上调表达基因。TCGA数据库分析结果表明,BIRC2在多形性胶质母细胞瘤中的表达显著高于正常脑组织（P<0.05）,预后分析表明BIRC2高表达胶质瘤病人预后更差（P<0.05）,GSEA分析显示BIRC2的作用主要发生在蛋白质翻译启动等过程。结论 本文结果提示BIRC2可能与人脑胶质瘤的发生、发展有关,检测BIRC2基因可用于评估人脑胶质瘤病人预后。     

Analysis of Isocitrate Dehydrogenase 1 Mutation in 97 Patients with Glioma

The objective of this study is to investigate the expression and significance of isocitrate dehydrogenase 1 (IDH1) mutation in different subtypes of human gliomas. Direct DNA sequencing, western blot, and immunohistochemistry were used to detect IDH1 mutation and IDH1 gene expression levels in 97 cases of glioma and 9 cases of other CNS tumors. IDH1 mutation was heterozygous, with wild-type arginine 132 replaced by histidine (R132H). Expression in different glioma subtypes was (1) 0 out if 5 in pilocytic astrocytoma; (2) 15 out of 22 in diffuse astrocytoma, 6 out of 9 in oligodendroglioma, 4 out of 6 in oligoastrocytoma, and 0 out of 4 in ependymoma; (3) 11 out of 19 in anaplastic astrocytoma, 4 out of 7 in anaplastic oligodendroglioma, 3 out of 4 in anaplastic oligoastrocytoma, and 0 out of 3 in anaplastic ependymoma; and (4) 1 out of 6 in primary glioblastoma, 8 out of 10 in secondary glioblastoma, and 0 out of 2 in medulloblastoma. IDH1 mutation is a somatic mutation that is found only in some glioma subtypes. It can be used as a molecular marker for glioma subtypes. For example, it can be used to distinguish primary glioblastoma from secondary glioblastoma, combining TP53 mutation and loss of heterozygosity involving 1p/19q. It can also be used as a marker for some gliomas. For example, it can be used to distinguish pilocytic astrocytoma from diffuse astrocytoma, combining detected BRAF proto-oncogene mutations.     

急性前循环供血区梗死的磁共振弥散加权成像表现与病因的关系

目的 探讨急性前循环供血区梗死的磁共振弥散加权成像(DWI)表现与病因的关系。方法 回顾性调查急性前循环供血区梗死的患者507例,分别进行DWI影像学病灶分型与中国缺血性脑卒中亚型(CISS)分型,并分析两者之间的关系。结果 急性前循环供血区梗死的DWI影像学病灶分型与CISS分型相关(r_s=-0.133,P=0.003)。其中,33例小穿通支供血区梗死(χ²=63.220,P=0.000),68例前循环供血区散发梗死(χ²=33.420,P=0.000)和44例单侧前循环供血区多发梗死(χ²=63.220,P=0.000),与大动脉粥样硬化(LAA)有关; 6例单发的皮质梗死(χ²=8.570,P=0.003),15例单发的皮质-皮质下梗死(χ²=33.309,P=0.000),13例单侧前循环供血区多发梗死(χ²=8.882,P=0.003),与心源性脑卒中(CS)有关; 87例小穿通支供血区梗死(χ²=39.918,P=0.000)与穿支动脉疾病(PAD)有关; 除此之外,有小部分前循环供血区散发梗死(χ²=4.311,P=0.038)有其他病因(OE)。结论 急性前循环供血区梗死发病初期可以通过病灶的DWI病灶分型来推测病因。     

胶质瘤放射敏感性与EGFR表达关系的探讨

目的探讨EGFR的表达水平与胶质瘤放射敏感性的关系。方法应用免疫组织化学SABC法检测EGFR在5例正常脑组织,2种胶质瘤细胞系及82例不同放射敏感性胶质瘤中的表达。结果EGFR在正常脑组织未见表达,在两种胶质瘤细胞系表达率为100%。EGFR在髓母细胞瘤、室管膜瘤、少枝胶质细胞瘤、低(Ⅰ~Ⅱ级)及高级别(Ⅲ~Ⅳ级)星形细胞瘤、多形性胶质母细胞瘤的表达率呈依次上升趋势。髓母细胞瘤表达率最低,与其他各组均有显著性差异(P<0.05)。结论EGFR表达水平与胶质瘤的不同放射敏感性可能相关。     

The changing epidemiology of paediatric brain tumours: a review from the Hospital for Sick Children

Purpose  This study examines the changing epidemiology of paediatric brain tumours over the past three decades (1980–2008) in a single institution, SickKids, Toronto, Canada. Methods  We classified 1,866 surgical pathology cases of brain tumours in children under the age of 19 according to the World Health Organization 2007 consensus and analysed them by gender, histological tumour type, age distribution and decade. Results  Males showed a slightly higher predominance with 56.8% of cases overall. The main histological tumour types were low-grade (I/II) astrocytomas (26.4%), medulloblastoma (10.6%), anaplastic astrocytoma/glioblastoma multiforme (7.1%) and ependymoma (7.0%). Over three decades, an increasing proportion of certain tumour types, including pilocytic astroctoma, atypical teratoma/rhabdoid tumours and neuronal/mixed neuronal-glial tumours was seen. Conclusions  Our results are consistent with those published with similar methodologies in other countries. Any changes in the epidemiology of childhood central nervous system tumours over the past three decades may be attributed in part to changing classification systems, improved imaging technologies and developments in epilepsy surgery; however, continued surveillance remains important.     

Paediatric brain tumours treated at a single,tertiary paediatric neurosurgical referral centre from 1999 to 2010 in Australia

Paediatric brain tumours are the most common solid tumour of childhood and the most common cancer cause of death among children. A retrospective review of 313 histopathologically proven brain tumours over an 11-year period has been performed at the Children’s Hospital Westmead, New South Wales, Australia, to determine proportions and locations of different tumours, age distribution, survival rates and usage of various treatment modalities. Pilocytic astrocytoma was the most common paediatric brain tumour (29%) followed by medulloblastoma (12%) and ependymoma (6%). Most tumours were histologically benign (59%), and 42% of tumours were located in the posterior fossa. The average age at diagnosis was 7.9 years. About 50% of children were treated with surgery alone, whereas the other 50% had surgery or biopsy plus adjuvant treatment. The overall one-year survival rate was 89% and the five-year survival rate was 80%. The five-year survival rates for pilocytic astrocytoma was 91%; medulloblastoma, 75%; ependymoma, 82%; and high grade glioma, 15%. Thus, a large proportion of paediatric brain tumours were histologically benign and were treated with surgery alone, but a subset of benign tumours required adjuvant treatment and were associated with mortality (25%). The overall survival rates were high and are improving, although for some tumours, such as high grade glioma, the outlook remains poor.     

Expression of insulin-like growth factor I receptors in human brain tumors: comparison with epidermal growth factor receptor by using quantitative autoradiography

By using quantitative autoradiographic techniques, receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were analyzed in 13 samples of human brain tumors (4 low grade astrocytomas, 7 glioblastomas, 1 anaplastic ependymoma and 1 medulloblastoma). High number of specific binding sites for IGF-I and EGF were homogeneously present in tissue sections derived from glioblastoma. In low grade astrocytoma, relatively high numbers of binding site for EGF were observed, but there was no significant difference in concentrations of IGF-I binding sites between tumors and control cortex. In medulloblastoma, only IGF-I binding sites were present. These observations might indicate that both IGF-I and EGF are involved in the growth modulation of human gliomas possibly through paracrine or autocrine mechanisms. Antagonists to growth factors or monoclonal antibody against those receptors could have the way for therapeutic application for gliomas.     

Characterisation of molecular alterations in microdissected archival gliomas

Classification of gliomas according to their molecular characteristics may be important in future histopathological diagnosis. However, gliomas frequently display heterogeneity at the histological, biological and molecular level. In this study of archival diagnostic gliomas, precision microdissection was used to enrich samples in the most malignant cells or to investigate intratumoural histological heterogeneity. Analysis of tumour samples microdissected from the most aggressive regions, representative of the histopathological diagnosis, revealed PTEN mutations in 4/14 anaplastic astrocytomas, 4/13 glioblastomas and 1 gliosarcoma, but not in 19 low-grade gliomas. Using a novel PCR procedure and direct sequence analysis of the entire coding sequence, TP53 mutations were detected in 1/3 pilocytic astrocytomas, 3/13 astrocytomas, 4/14 anaplastic astrocytomas, 5/13 glioblastomas and 1 gliosarcoma. All but one of the tumours with TP53 mutation showed p53 immunopositivity, but 5 low-grade and 10 high-grade gliomas had p53 protein nuclear accumulation in the absence of detectable mutation. p53 status was unrelated to p21 expression. Neither PTEN nor TP53 mutations influenced the proliferative index or microvessel density of high-grade astrocytomas. Unusual findings include: TP53 mutation in a juvenile pilocytic astrocytoma; TP53 and PTEN mutations in a de novo glioblastoma, a gliosarcoma with identical mutations in gliomatous and sarcomatous components, and an infratentorial anaplastic astrocytoma with an earlier supratentorial grade II astrocytoma bearing the same TP53 mutation but not the PTEN mutation or loss of heterozygosity (LOH) of 10q23. Similarly, the transition to high-grade histology was associated with acquisition of PTEN mutations and 10q23.3 LOH in two de novo high-grade tumours with regions of low-grade histology.     

Cortical ependymoma or monomorphous angiocentric glioma?

Ependymoma is the third most common childhood intracranial tumor after medulloblastoma and pilocytic astrocytoma. Most ependymomas occur in the posterior fossa and spinal cord but only five cases confined to the cerebral cortex have been reported. The current case is a 5‐year‐old boy with a somewhat ill‐defined cortical tumor diagnosed as pilocytic astrocytoma on biopsy, and treated with radiotherapy. Nine years later, resection of the essentially unaltered tumor was performed for treatment of intractable seizures. Histologically, the tumor had some areas with the typical appearance of ependymoma as well other areas which contained piloid cells. There was also evidence of focal infiltrative growth. These findings bore resemblance to a recently described entity monomorphous angiocentric glioma/angiocentric neuroepithelial tumor, which combines features of ependymoma with pilocytic and diffuse astrocytomas. Both cortical ependymomas and angiocentric monomorphous glioma/angiocentric neuroepithelial tumor appear to be low‐grade tumors although their rarity makes accurate prognosis problematic. The current case has features of both entities, suggesting they may be closely related.     

Follow-up and quality of survival of 67 consecutive children with CNS tumors

We report the finding at follow-up in 67 consecutive children with central nervous system tumors treated over a 5-year-period at a single institution. The diagnoses were supratentorial astrocytoma (n = 12), cerebellar astrocytoma (n = 10), ependymoma (n = 9), medulloblastoma (n = 9), brain stem glioma (n = 6), optic pathway glioma (n = 5), and others (n = 16). The survival rates were 83% for supratentorial astrocytomas at a median of 46.5 months, 90% for cerebellar astrocytomas and 55% for ependymomas at 40 months, respectively, 55% for medulloblastomas at 22 months, 33% for brain stem gliomas at 23 months, and 80% for optic pathway gliomas at 49 months. With regard to neurological sequelae, 13 patients were treated for epilepsy, 13 patients had mild to moderate neurological deficits, and 4 patients were severely disabled. Seventeen of 37 tested patients performed below average on formal neuropsychometric testing, one-fourth attended special education courses, and at least one-fourth suffered from behavioral and adjustment problems.     

河南豫东地区乡镇居民脑卒中的流行病学特征及高危因素分析

目的 研究河南商丘地区乡镇40岁以上人群其脑卒中的流行病学特征和诱发的高危因素。方法 抽取本院脑卒中数据库中符合本研究要求的资料,最终确定有9736份资料参与本研究,主要收集以下信息如一般体格检查:身高、体重、体重指数(BMI)、收缩压和舒张压、脉搏、脉率和心脏听诊; 实验室检测指标:血脂(TG、TC、HDL-C、LDL-C)、空腹血糖、糖化血红蛋白; 脑卒中组和非脑卒中组患者的各指标的比较采用卡方检验或独立样本t检验,Logistic多因素回归模型分析影响脑卒中发生的独立危险因素。结果 随机抽取虞城县城关镇、睢县涧岗乡、虞城县李老家乡、商丘市刘口乡、商丘梁园区平原社区、梁园区长征社区、新城社区的调研资料,根据各项指标最终纳入本研究的有9736人,脑卒中发生者812例,发病率为8.3%; 脑卒中组和非脑卒中组比较,年龄(χ²=2.981,P=0.009)、受教育程度(χ²=26.126,P=0.000)、高血压病(χ²=35.277,P=0.000)、血脂异常(χ²=169.767,P=0.000)、吸烟(χ²=5.761,P=0.017)、饮酒(χ²=197.634,P=0.000)、既往有短暂性脑缺血发作史(χ²=569.438,P=0.000)、饮食情况(χ²=36.078,P=0.000)和身体锻炼(χ²=118.259,P=0.000)方面均有明显差异,性别(χ²=2.544,P=0.111)、民族(χ²=0.250,P=0.617)、BMI(χ²=0.128,P=0.900)、工作情况(χ²=0.030,P=0.862)和糖尿病(χ²=1.980,P=0.159)等情况无明显差异。经过Logistic多因素回归分析显示年龄≥60岁(P=0.002)、高中及以下文化程度(P=0.028)、高血压病(P=0.001)、血脂异常(P=0.018)、既往有短暂性脑缺血发作史(P=0.004)和不进行锻炼(P=0.015)等因素均为诱发脑卒中发生的独立危险因素。结论 豫东地区年龄≥60岁、高中及以下文化程度、高血压病、血脂异常、既往有短暂性脑缺血发作史和不进行锻炼均为诱发脑卒中的独立危险因素,当地相关部门可定期开展义诊活动,举办健康讲座,科普对脑卒中的认识,鼓励居民定期体检,降低脑卒中的发生率