儿童髓母细胞瘤的综合治疗

儿童中枢神经系统原发肿瘤占所有儿童期肿瘤的 2 0 % ,发生率仅次于白血病居于第二位。髓母细胞瘤(ｍｅｄｕｌｌｏｂｌａｓｔｏｍａＭＢ)占儿童原发脑肿瘤的 2 0 % ,其发生率仅次于星形细胞瘤[1] 。发病高峰年龄在 7岁左右。髓母细胞瘤具有高度的软脑膜转移倾向 ,尤其在低龄儿童中常见。髓母细胞瘤 (ＭＢ)起源于小脑蚓部向四脑室生长 ,是最常见的儿童原发恶性脑肿瘤 ,是中枢神经系统恶性程度最高的神经上皮性肿瘤之一 ,属于原始神经外胚层肿瘤 (ｐｒｉｍｉｔｖｅｎｅｕｒｃｅｐｉｔｈｅｌｉａｌｔｕｍｏｒｓＰＮＥＴＳ)的一种 ,在ＷＨＯ的神…     

不同联合放化疗方式对儿童髓母细胞瘤疗效的系统评价

目的系统评价不同的联合放化疗方式对儿童髓母细胞瘤的疗效。方法计算机检索MEDLINE/Pub Med、Embase和Cochrane Library等数据库,对纳入的随机对照试验(randomized controlled trials,RCT)采用Rev Man5.3进行Meta分析。结果共纳入10篇RCT文献,1807例患者。Meta分析结果显示髓母细胞瘤术后联合放化疗与术后单纯放疗相比,能提高3年总生存率(overall survival,OS)[RR=1.18,95%CI(1.02,1.37),P0.05]和高危险组患者5年无事件生存率(event-free survival,EFS)或无病生存率(disease-free survival,DFS)[RR=1.27,95%CI(1.01,1.59),P0.05]。先放疗后持续化疗的方案和先化疗后放疗的"三明治"方案相比,能提高髓母细胞瘤M0级别患者5年OS[RR=1.46,95%CI(1.19,1.79),P0.05]和5年EFS/DFS[RR=1.29,95%CI(1.06,1.55),P0.05],能提高M1级别患者5年OS[RR=2.26,95%CI(1.03,4.97),P0.05]。结论手术切除后联合放化疗治疗儿童髓母细胞瘤效果优于术后单纯放疗。术后先放疗后化疗的方案优于术后先化疗后放疗的"三明治"方案。     

儿童髓母细胞瘤诊治进展

髓母细胞瘤的手术方式和放化疗策略的不断优化使多数患儿的治疗和预后得到明显提高,但近年研究证明预后不仅仅和手术以及放化疗的策略有关,而且和肿瘤多样化的内在生物学特性有密切联系,一些生物学标志物对肿瘤的诊断、治疗方式选择和预后评价有重要意义。髓母细胞瘤的复发和转移以及婴幼儿的治疗仍是难点,改善低危患儿长期预后和进一步提高高危患儿生存率将是未来研究的课题。     

儿童髓母细胞瘤诊治进展

髓母细胞瘤的手术方式和放化疗策略的不断优化使多数患儿的治疗和预后得到明显提高，但近年研究证明预后不仅仅和手术以及放化疗的策略有关，而且和肿瘤多样化的内在生物学特性有密切联系，一些生物学标志物对肿瘤的诊断、治疗方式选择和预后评价有重要意义。髓母细胞瘤的复发和转移以及婴幼儿治疗仍是难点，改善低危患儿长期预后和进一步提高高危患儿生存率将是未来研究的课题。     

显微外科治疗儿童髓母细胞瘤

目的 用显微技术切除儿童髓母细胞瘤,砬少手术并发症,提高术后生存质量。方法 对３４例儿童髓平细胞瘤的临床资料进行分析。结果 ３４例均采用显微手术治疗,全切２７例,次全切除４例,部分切除３例,手术死亡２例,死亡率为５．９％,获随该列,临床治愈２４例,着状改善６例,５年生存率为５０％。结论 微创的显微外科技术是保证减少术后并发症,获得良好预后的关键。对于大多数患儿,建议术后辅以放疗。     

儿童髓母细胞瘤的治疗

报道２～１５岁儿童髓母细胞瘤５４例，６例因肿瘤转移他处死亡，２例因肿瘤出血死亡，４６例采用手术治疗，手术死亡２例，死亡率为４．４％。全切除肿瘤３９例，部分切除３例，亚全切除４例，随访４０例，１例因肿瘤属Ｔ－４级死亡，临床治愈２７例，症状改善１２例，５年生存率为５０％，推荐放射治疗为首选，就诊断及治疗进行了讨论。     

髓母细胞瘤的手术治疗

髓母细胞瘤生长迅速，常占据四脑室引起脑积水，治疗以手术和术后放疗为主。我院自1990-01-2005-06手术治疗28例，报告如下。     

儿童髓母细胞瘤显微手术治疗及术后并发症探讨

目的探讨儿童髓母细胞瘤显微手术及术后并发症问题。方法回顾性分析经小脑蚓部切开联合四脑室正中孔入路显微手术切除儿童髓母细胞瘤及术后并发症53例。全部经病理证实。结果全部病例术前均行MRI检查,46例同时行CT检查。手术全切除47例(88.7%)、次全切除6例(11.3%)。术后51例高颅压症状消失,临床体征改善,2例死亡。术后发生咸默症5例,其中合并下颏关节脱位1例。术后昏迷2例,呼吸机辅助人工呼吸2周1例,遗留一侧肢体轻瘫2例。中枢性面瘫2例。肿瘤位于小脑蚓部12例,四脑室内18例。小脑蚓部和四脑室内者23例。肿瘤血供来源于小脑后下动脉37例。全部病例均打通中脑导水管。术后37例患者随访6个月至5年3个月。35例接受放疗。其中30例未见复发和转移。4例原位复发,2例脊髓播种性转移。结论儿童髓母细胞瘤由于其临床特点诊断多无困难,但个性化深入了解肿瘤病理解剖及其与周围组织比邻有利于最大限度切除肿瘤。采用显微手术全切除肿瘤组织、解除导水管梗阻、妥善保护小脑后下动脉及其分支、避免伤及脑干及四脑室底是手术操作的关键。病程进展迅速,肿瘤巨大者术后生存质量及生存期更差,早期就诊尤为重要。     

髓母细胞瘤的显微手术治疗

髓母细胞瘤是中枢神经系统恶性程度最高的神经上皮性肿瘤之一。好发于儿童,约占儿童颅内肿瘤的20%,多位于第四脑室顶上的小脑蚓部,生长极为迅速,手术不易全切除。就诊时常肿瘤巨大并有脑积水,故手术风险大,治疗较困难。现将我院从1995年至今的79例手术病例的临床资料分析报告如下。1临床资料1.1一般资料本组患者79例,男59例,女20例,年龄1～48岁,平均8.9岁,其中<3岁10例,3～10岁51例,>10岁18例;病程3～30周,平均6周。以恶心、呕吐67例,头痛63例,共济失调55例,头围增大16例,小脑危象12例。1.2影像学检查行CT或MRI检查示,肿瘤直径<3cm9例,3～…     

三维适形放疗同期鞘内注射化疗后全身化疗治疗高危髓母细胞瘤

目的 总结全程三维适形放疗(3DCRT)同期鞘内注射化疗后全身化疗治疗高危髓母细胞瘤(MB)的疗效. 方法 南方医科大学珠江医院肿瘤中心自2005年1月至2008年1月行3D CRT联合鞘内注射及全身化疗治疗已沿脑脊液播散的高危MB患者20例,其中脑脊液中找到肿瘤细胞15例,MRI发现脊髓结节状种植5例.采用3DCRT进行全脑全脊髓放疗(CSI)及局部追量,放疗同期应用阿糖胞苷、氨甲喋呤等鞘内注射,放疗后应用盐酸尼莫司汀、替莫唑胺等全身化疗,回顾性分析患者的临床资料并总结疗效. 结果 本组患者中位随访时间48.5个月.治疗结束3个月后患者总体完全缓解(CR) 18例(90.0％),部分缓解(PR)1例(5.0％),稳定(SD)1例(5.0％);4例治疗失败死亡.1例局部复发.3例脊髓种植进展.患者中位生存时间53个月,3年总生存率(OS)和3年无病生存率(DFS)分别为80.0％、75.5％.不良反应主要为血液、消化系统的毒性反应,未出现Ⅳ度骨髓抑制. 结论 全程3DCRT同期鞘内注射化疗后全身化疗治疗高危MB安全、有效,预后好.     

Prognostic role of chemotherapy,radiotherapy dose,and extent of surgical resection in adult medulloblastoma

PurposeAdult medulloblastoma is rare, and management is extrapolated from pediatric cases. This investigation evaluated the prognostic role of chemotherapy (and sequencing thereof), the degree of resection, and craniospinal irradiation (CSI) dose.MethodsThe National Cancer Database was queried for adult (age ≥18) medulloblastoma. Resection was coded as gross (GTR) or subtotal resection (STR) or biopsy only; concurrent chemoradiotherapy (CRT) was defined as receipt within 14 days of each other. Statistics included Kaplan-Meier overall survival (OS) analysis and Cox proportional hazards modeling.ResultsOf 1144 patients, 613 had coded surgical information; 242 (39%) did not undergo surgery, 277 (45%) underwent STR, and 94 (15%) had GTR. A total of 428 (37.4%) did not receive chemotherapy, 348 (30.4%) received sequential CRT, and 368 (32.2%) underwent concurrent CRT. Of the 711 patients with CSI dose information, 202 (28.4%) received 23–30 Gy CSI and 509 (71.6%) patients received 30–36 Gy. Median follow-up was 56.5 months. Extent of resection did not correlate with 10-year OS (74.2% biopsy only, 72.7% STR, 82.2% GTR, p > 0.05 all comparisons) or on Cox multivariate analysis. Chemotherapy was associated with higher OS (65.6% vs. 51.2%, p = 0.035) and a trend towards significance on multivariate assessment (p = 0.082). Sequencing of chemotherapy and CSI dose were not associated with OS (p > 0.05 for both).ConclusionsAlthough causation cannot be implied, neither the extent of resection nor CSI dose associated with OS in adult medulloblastoma. Chemotherapy could have utility in higher-risk patients; concurrent administration may not be beneficial, especially given therapy-induced neuro-cognitive sequelae.     

Outcome of children with posterior fossa medulloblastoma: a single institution experience over the decade 1994–2003

Aim While the impact of radiotherapy in the management of medulloblastoma was recognised, the introduction of chemotherapy was investigated in clinical trials and shown to confer an additional advantage. We reviewed the outcome of a series of consecutive patients to assess the impact in a population-based clinical establishment. Materials and methods A series of 38 children treated for medulloblastoma at Birmingham Children’s Hospital between 1994 and 2003 was analysed. The effect of surgery, radiotherapy, chemotherapy and metastasis on survival was analysed. Results The overall 5-year survival rate was 61.4% for the 36 patients who had resective surgery, while 2 patients had biopsy only and died within a few months. There was no operative mortality. The incidence of hydrocephalus needing permanent shunting was higher in the first 3 years of life (p = 0.007, chi-square). The 5-year survival rate of patients with total and sub-total excision of medulloblastoma was 61.1% and 61.8%, respectively. The 5-year survival rate of patients older than 3 years was 73.4% and for patients under 3 years was 36.3% (p = 0.007, log rank). Metastases at presentation did not influence survival. All deaths occurred in the first 32 months. Conclusion The contribution of chemotherapy in the improvement of the overall survival appears more evident in children younger than 3 years or presenting with metastases. The absence of significant difference in survival between patients with total or sub-total excision of medulloblastoma supports the view that total excision of medulloblastoma can be avoided when the risk for potential intra-operative damage and consequent neurological deficits is high.     

经膜帆入路手术治疗第四脑室髓母细胞瘤

目的 探讨经膜帆入路显微手术肿瘤第四脑室髓母细胞瘤的方法及疗效。方法 回顾性分析2014年11月至2020年7月经膜帆入路显微手术治疗的17例第四脑室髓母细胞瘤的临床资料。结果 肿瘤全切除15例（88.2%）,次全切除2例（11.8%）。15例颅内压增高症状术后明显缓解;1例脑积水术后未缓解,改行脑室-腹腔分流术;1例术后因呼吸衰竭死亡。术后未出现小脑性缄默及眼球震颤等并发症。出院时,GOS评分5分13例（76.5%）,4分3例（17.6%）,1分1例（5.9%）。结论 髓母细胞瘤的治疗以显微手术为主,经膜帆入路是到达第四脑室肿瘤的一种安全有效的术式,可减少小脑相关并发症,改善髓母细胞瘤病人的临床预后。     

Multidisciplinary treatment of medulloblastomas in childhood

The analysis of 65 medulloblastomas in children treated at the National Institute of Pediatrics, Mexico City, between 1971 and 1986 is reported. The patients were staged retrospectively. Ninety percent presented without metastasis in the subarachnoid space or the spinal fluid. Following surgery, all patients underwent radiotherapy to the brain, posterior fossa, and spinal cord. For the last 35 patients, chemotherapy was added to the treatment regimen. The actuarial survival was 55% at 6 years in the group with chemotherapy versus 27% to the group without chemotherapy, with a statistically significant difference (P<0.01).     

化、放疗联合治疗儿童颅内生殖细胞瘤34例临床随诊观察

目的：观察颅内生殖细胞瘤经过化疗并辅以中低剂量放疗后的疗效及对儿童生长发育的影响。方法：自1993年12月至2001年12月共对63例颅内生殖细胞瘤的儿童进行静脉化疗并辅以中低剂量放疗，随访到34例，其中肿瘤位于松果体区20你，松果体区并鞍区6例，鞍区4例，松果体区并脑室内3例，底节区1例。使用药物为长春新碱、甲氨蝶呤、平阳霉素及顺铂。用药后每周化验2次血常规，1次血生化，以观察周围血象变化及心、肝、肾功能情况，并进行针对性治疗。4周后如血常规及血生化的各项指标均正常，再行第二疗程化疗。2个疗程结束后1个月，在肿瘤病灶局部补充中低剂量（25-35Gy）的放疗。每个疗程间进行CT或MRI检查，观察肿瘤消退的情况。：34例患者随访最短1年，最长7年。1例为手术加全剂量放疗后2年肿瘤复发，此次化疗进行2个疗程，但化疗后未再补充放疗，4年后肿瘤复发，家属放弃治疗，患者死亡。1例化、放疗后5年肿瘤复发，再行2疗程化疗，疗效较首次治疗差，其余32例（94％）化、放疗后1-7年，复查MRI显示肿瘤无复发，患者生存质量良好，儿童生长发育及智力均未受影响。结论：静脉化疗辅以中低剂量放疗应为治疗儿童颅内生殖细胞瘤的最佳方案。     

Prognosis of medulloblastoma in infants

The prognosis of medulloblastoma in children less than 3 years old is usually considered to be rather poor. However, recent experiences with this type of tumour seem to indicate that survival in this specific subgroup of patients can be longer than expected. Nineteen infants with posterior fossa tumours treated by the authors in the period 1983–1994, all of them with symptoms presenting during the 1st year of life and all operated on before the end of the 2nd year of life, have been retrospectively analysed. Total tumour removal was achieved in 14 cases, subtotal in 1 and partial in 3. One subject underwent only a biopsy of the tumour. In 14 patients a CSF shunt was inserted. Chemotherapy was administered to 18 out of the 19 patients in the series. At the time of the study, 11 children had died (57.9%) and 8 were alive (42.1%; mean survival 86.5 months). One patient died of complications secondary to the surgical treatment. Three patients died because of local recurrence of the tumour after apparent total excision, death supervening 5, 12 and 18 months after the surgical treatment. A further 2 patients in whom total tumour removal had been performed died 3 and 17 months after surgery of local recurrence of the disease associated with regional metastases. Progression of the residual tumour, accompanied by metastatic dissemination in 3 cases, accounted for death in the other 5 patients who did not survive. Brain stem infiltration appeared to be the most significant adverse prognostic factor. All 8 long-term survivors had their tumour totally excised. Five of them underwent radiotherapy when at least 2 years old. On the basis of the results, the authors conclude that the current prognosis of infants with medulloblastoma is not necessarily any worse than that of older children with the same disease and that chemotherapy can be particularly useful in this subgroup of patients, as shown by 3 long-term survivals obtained in children treated with this type of therapy only. Received: 12 December 1996     

儿童髓母细胞瘤患者临床因素与预后的相关性分析

目的 探讨影响儿童髓母细胞瘤(MB)患者预后的临床因素.方法 选择中山大学附属第一医院神经外科自2001年11月至2010年7月收治的儿童MB患者47例,采用Kaplan-Meier生存分析法和Cox回归模型分析患者年龄、性别、病程、肿瘤部位、术前转移、肿瘤切除程度、病理亚型、脑干侵袭程度、放疗与手术的时间间隔、化疗对生存时间即预后的影响.结果 本组患者2年生存率为91.4%,5年生存率为50%.Kaplan-Meier生存分析显示肿瘤全切或次全切者生存率高于大部分切除者,术前无转移患者生存率高于有转移者,放疗与手术的时间间隔≤42 d者生存率高于时间间隔>42 d者,差异均有统计学意义(P<0.05).Cox 回归模型分析显示术前转移、放疗与手术的时间间隔为儿童MB患者预后的影响因素,术前无转移、放疗与手术的时间间隔≤42 d患者预后较好.结论 术前有无转移和放疗与手术的时间间隔是影响儿童MB患者预后的独立因素.

Abstract：

Objective To analyze the correlation between the prognosis of pediatric medulloblastoma (MB) and its relevant clinical factors. Methods Forty-seven children with MB,admitted to our hospital from November 2001 to July 2010, were chosen;a retrospective analysis, using Kaplan-Meier survival tested by log-rank and Cox proportional hazards regression model, was performed to identify the correlation between the prognosis of pediatric MB and relevant clinical factors which included age, gender, course of disease, tumor location, pathological subtype, preoperative metastasis,extent of tumor resection, interval between surgery and radiation, brainstem invasion and chemotherapy.Results The 2-year survival rate of these patients was 91.4%, and 5-year survival rate 50%.Kaplan-Meier curves indicated that patients with total or subtotal tumor resection had a significantly higher survival rate than those with partial resection (P<0.05);patients without preoperative metastasis had a significantly higher survival rate than those with preoperative metastasis (P<0.05);and patients with interval between surgery and radiation≤42 d had a significantly higher survival rate than those with interval between surgery and radiation >42 d (P<0.05). Cox proportional hazards regression analysis indicated that preoperative metastasis (RR, 6.808;95%CI, 1.844 to 25.113;P<0.05) and interval between surgery and radiation (RR, 5.642;95% CI, 2.042 to 15.587;P<0.05) were the influencing factors for prognosis of MB. Patients without preoperative metastasis and with interval between surgery and radiation ≤42 d enjoyed good prognosis results. Conclusion Both preoperative metastasis and interval between surgery and radiation are independent factors for prognosis of pediatric MB.     

TSP2在人髓母细胞瘤组织中的表达及意义

目的 探讨血栓素结合蛋白2(TSP2)在人髓母细胞瘤组织中的表达及意义.方法 选取2007年6月～2014年10月手术切除的髓母细胞瘤组织110例和颅脑损伤内减压术中切除的正常脑组织40例,采用免疫组织化学染色法检测TSP2的表达,根据染色评分分为高表达和低表达.用多因素Cox比例回归风险模型分析髓母细胞瘤病人生存时间...