儿童髓母细胞瘤中VEGFR-2的表达

目的：探讨血管内皮生长因子受体VEGFR－2在儿童髓母细胞瘤中的表达及临床意义。方法：采用免疫组化LSAB法检测84例获随访的儿童髓母细胞瘤中的VEGFR－2表达，按术后生存期3，5，10年分为A，B，C三组，使用Cox回归统计分析。结果：84例儿童髓母细胞瘤中，VEGFR－2阳性表达74例（88．09％），A，B，C三组间VEGFR－2阳性表达分别为100％，88．89％，55．33％（P＜0．01），Cox回归分析显示VEGFR－2是影响生存时间的一个独立的预后因子，它与预后存在负相关关系。结论：VEGFR－2表达水平可作为儿童髓母细胞瘤的预后指标之一。     

Paediatric medulloblastoma: Patterns of care and radiotherapy quality assurance in Australia

The purpose of this study was to document how children in Australia with medulloblastoma are being treated and to evaluate the quality of radiotherapy (RT) delivered. The Radiotherapy Database of the Australian and New Zealand Children’s Haematology and Oncology Group was used to identify 46 children with medulloblastoma younger than the age of 15 years treated with radical intent by craniospinal irradiation between 1997 and 1999 inclusively. Twenty‐six patients had completely resected disease without evidence of disease spread. Of these, 16 patients received a craniospinal RT dose of <25 Gy in addition to chemotherapy. RT treatment immobilization methods varied, as did planning methods. RT dose to critical structures was recorded on treatment plans for only 15% of patients. The average systematic error in shield placement at the posterior orbit was 5.2 mm, and two‐thirds of patients were ‘overshielded’ at this site. Adequate coverage of the distal end of the thecal sac was achieved in fewer than 50% of on‐treatment verification films for 21 of 45 patients. With a reduction in RT dose to the craniospinal axis for paediatric medulloblastoma, greater attention is needed for patient immobilization, documentation of RT dose to critical structures and the placement and reproducibility of shielding.     

Ganglioglial Differentiation in Medulloblastoma

A case of cerebellar medulloblastoma with clusters of mature ganglion cells and glial cells is described. The patient, a 15 -year -old girl, underwent three operations followed each time by radiation and chemotherapy during the four-year clinical course. Histologically, the ganglion cells were clearly identifiable by their abundant eosino-philic cytoplasm, round nuclei with prominent nucleoli, tigroid granules, and argyrophilic fibrils and axons. Im-munohistochemically, the cells were NSE- and NF positive, and ultrastructurally they contained abundant tubules and filaments, neurosecretory granules and well developed rough endoplasmic reticulum. There were many cells transitional in appearance between primitive cells and mature ganglion cells. The tumor also had many mature yet atypical astrocytes and oligodendrocytes. The exact mechanism of the extensive neuronal and glial maturation of medulloblastoma cells is unclear, but the repetitive surgical interventions, radiation and chemotherapy might have had certain cytostatic effects on rapidly dividing medulloblastoma cells, giving them a chance to mature into postmitotic cells with potential for neuronal and glial differentiation. Acta Pathol Jpn 40: 50–56, 1990.     

儿童髓母细胞瘤的MRI和CT诊断

目的 分析儿童髓母细胞瘤的MRI和CT影像学表现,提高诊断该病的准确性。材料和方法 收集经手术病理证实的髓母细胞瘤14例,均行MRI和CT检查,其中男11例,女3例,年龄为3-12岁,结果 髓母细胞瘤好发于男性儿童,常见于小脑蚓部,MRI扫描T1加权像呈等或稍低信号,T2加权像呈等或略高于脑灰质信号,增强后呈中等至明显强化,CT平扫为等或稍高密度影,注药后呈轻至中度强化,结论 对儿童髓母细胞瘤定位和定性,MRI明显优于CT。     

29例髓母细胞瘤术后放射治疗

目的：回顾２９ 例髓母细胞瘤术后放疗,对影响生存情况的因素进行分析。方法：手术后病理证实的２９例髓母细胞瘤,先行卡氮芥（ＢＣＮＵ）化疗,再行６０钴常规分割照射：全脑剂量（ＤＴ）２２～４０ Ｇｙ;原发病灶追加ＤＴ１５～２２ Ｇｙ;全脊髓轴ＤＴ２５～３５ Ｇｙ。结果：１、３、５、８ 年生存率分别为８９．６％ （２６／２９）、５５．２％ （１６／２９）、３０．４％ （７／２３）、２５．０％ （４／１６）。结论：病人生存期长短与手术切除范围、术后接受放疗时间、放射剂量及是否行化疗有关。     

Remediation of learning difficulties in children after treatment for a cerebellar medulloblastoma: A single-case study

In the process of establishing a methodology for individualized remediation programmes in children treated for cerebellar tumour, this study followed prospectively over 11 years a young child treated for a medulloblastoma at 18 months of age throughout the rehabilitation process. Repeated neuropsychological and academic evaluations evidenced temporary disruptive behaviour, deficient manual and visual abilities, attention and working memory difficulties, but preserved language abilities, in relation with vermian and left cerebellar damage. However, the described remediation programmes and interventions allowed the child to have fluent progression in school. Limits and benefits of rehabilitation are discussed.

Con el propósito de establecer una metodología para los programas de remedio individualizados en niños tratados por tumores cerebelares, se estudiaron en forma prospectiva durante 11 años a niños de 18 meses de edad tratados por un meduloblastoma, a lo largo del proceso de rehabiitación. En relación al daño cerebelar y vermiano se pusieron en evidencia, a través de evaluaciones académicas y neuropsicológicas aplicadas en forma repetida, una conducta alterada en forma temporal, una deficiencia en las habilidades visuales y manuales, y la presencia de dificultades en la atención y en la memoria de trabajo, pero sin alteraciones en el lenguaje. Sin embargo, los programas de remedio y las intervenciones descritos le permitieron al niño tener una progreso correcto en la escuela. Se discuten los beneficios y los límites de la rehabilitación. Palabras clave: Cerebelo, meduloblastoma, remedio, resultado, rehabilitación en equipo     

髓母细胞瘤组织MEF2C表达与预后相关性分析

目的：探讨肌细胞增强因子2C（myoeyte enhancer factor2C，MEF2C）表达情况与髓母细胞瘤患者预后的关系。方法：选取3家三级甲等医院2001-01—01—2007—12-31病理确诊的髓母细胞瘤患者56例，其中泰安市中心医院12例．齐鲁医院26例，山东省立医院18例；对照组脑组织取自泰安市中心医院2010-01-01-2010—12—3112例非肿瘤脑外伤患者。免疫组织化学法检测56例髓母细胞瘤患者肿瘤组织和12例非肿瘤患者脑组织中MEF2C的表达；收集髓母细胞瘤患者临床资料，应用统计学方法对髓母细胞瘤患者进行生存分析。结果：髓母细胞瘤患者肿瘤组织MEF2C相对高表达率为53．6％（30／56），非肿瘤患者脑组织MEF2C相对高表达率为0（0／12），两组比较差异有统计学意义，χ2=11．50，P=0．001；肿瘤患者肿瘤组织MEF2C相对高表达组与相对低表达组间生存时间的差异有统计学意义，χ2=4．34，P=0．037。MEF2C相对高表达（p=0．023）、肿瘤转移（P=0．042）与患者3年生存率降低显著有关，而患者性别、年龄、肿瘤大小、肿瘤部位与患者3年生存率无关，P值均〉0．05。结论：MEF2C在患者肿瘤组织中的高表达可降低患者3年生存率，是患者预后不良的危险因素之一。     

PDE5 inhibitors enhance the lethality of standard of care chemotherapy in pediatric CNS tumor cells

We determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with clinically relevant chemotherapies to kill medulloblastoma cells. In medulloblastoma cells PDE5 inhibitors interacted in a greater than additive fashion with vincristine/etoposide/cisplatin to cause cell death. Knockdown of PDE5 expression recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy drugs. Expression of dominant negative caspase 9 did not significantly inhibit chemotherapy lethality but did significantly reduce enhanced killing in combination with the PDE5 inhibitor sildenafil. Overexpression of BCL-XL and c-FLIP-s suppressed individual and combination drug toxicities. Knockdown of CD95 or FADD suppressed drug combination toxicity. Treatment with PDE5 inhibitors and chemotherapy drugs promoted autophagy which was maximal at ~12 h post-treatment, and in a cell type-dependent manner knockdown of Beclin1 or ATG5 either suppressed or enhanced drug combination lethality. PDE5 inhibitors enhanced the induction of chemotherapy-induced DNA damage in a nitric oxide synthase-dependent fashion. In conclusion, our data demonstrate that the combination of PDE5 inhibitors with standard of care chemotherapy agents for medulloblastoma represents a possible novel modality for future treatment of this disease.     

Updates and review of neoplastic paediatric neuropathology

Tumours of the central nervous system are the second most common type of malignancy in the paediatric population, after haematopoietic malignancies. With the 2016 edition of the WHO Classification of the Tumours of the Central Nervous System (CNS), a diagnostic approach to paediatric CNS malignancies has been adopted, which increasingly incorporates molecular parameters, as well as histologic features. This classification system represents a major restructuring of many paediatric central nervous system tumours. This review aims to highlight the areas in the WHO 2016 classification system that have undergone the greatest changes in paediatric tumours of the central nervous system, as well as to review the key histologic and clinical components of these entities. The greatest changes in classification were adopted in embryonal tumours and paediatric diffuse midline gliomas with histone H3 mutations, while low grade astrocytic and glioneuronal tumours also underwent important grading changes.