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.     

髓母细胞瘤预后影响因素的Cox模型分析

目的分析影响髓母细胞瘤预后的相关因素。方法应用Cox回归模型,对60例髓母细胞瘤患者的年龄、性别、病程、肿瘤体积、切除范围、放疗、uPA、uPAR、KDR9项指标进行预后单因素及多因素分析。结果Cox回归分析显示反应肿瘤生物学行为的uPA、uPAR和KDR与预后存在高度负相关关系。结论uPA、uPAR和KDR是决定髓母细胞瘤预后的最重要危险因素。     

髓母细胞瘤的临床与病理

随着分子生物学技术的飞速发展,对髓母细胞瘤的发生发展有了更多的了解与深刻的认识。现就其诊断、治疗预后及相关分子生物学应用作一综述。     

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。     

髓母细胞瘤复发、播散性种植及预后的相关因素分析

目的探讨影响髓母细胞瘤术后局部复发、播散性种植和预后的临床因素。方法回顾性分析我科收治并经病理确认的43例髓母细胞瘤患者,采用Log-Rank法分析肿瘤的T分期、切除程度、放疗方式对患者术后肿瘤复发、播散性种植及生存时间的影响。结果获得随访的41例患者中,3年、5年总体生存率分别为68.3%、50.1%,肿瘤的T分期、切除程度、放疗方式对患者术后复发时间、术后总生存时间的影响均存在统计学差异;肿瘤的T分期、放疗方式对患者播散性种植时间的影响存在统计学差异,而切除程度对其影响无明显统计学差异。结论处于T1、T2期的肿瘤、接受全脑-脊髓放疗的患者手术距离发生复发、播散性种植的时间和术后总生存时间较长,手术全切除能延缓术后复发和延长术后生存时间,但对发生播散性种植的时间无影响。     

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…     

成人髓母细胞瘤诊断和治疗研究进展

髓母细胞瘤(medulloblastoma,MB)是一种恶性原发性中枢神经系统肿瘤,好发于儿童,成人较为少见,成人MB的每年发病率仅有6/1000万[1]。临床医生常将其忽视,误诊为室管膜瘤、血管母细胞瘤和胶质瘤等其他疾病。成人MB的治疗包括手术切除肿瘤,术后辅以全脑全脊髓放疗(craniospi?nal irradi...     

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～…     

成人髓母细胞瘤的临床特点与治疗

目的研究成人髓母细胞瘤的临床特点及治疗措施。方法20例成人髓母细胞瘤，其中男性13例，女性7例，平均年龄26．6岁，平均病程5．5月。所有病人接受显微神经外科手术治疗，15例病人术后接受放疗，4例行术后化疗。结果肿瘤全切除15例，近全切除2例，部分切除3例，无手术死亡。术后复发6例，中枢神经系统种植转移2例，术后2年生存率90％，术后5年生存率75％。结论通过手术全切除肿瘤和术后全中枢轴放疗可使成人髓母细胞瘤患者得到较好的治疗效果。     

人髓母细胞瘤中细胞周期素依赖激酶抑制物p27KIP1的表达及预后关系

目的检测p27蛋白在人髓母细胞瘤中的表达及定位情况,探讨p27与髓母细胞瘤预后的关系。方法应用免疫组化SP法和激光共聚焦显微术检测57例髓母细胞瘤标本中p27蛋白的表达及其定位情况,结合随访资料进行生存分析。结果在全部57例髓母细胞瘤标本中,p27阳性表达为32.41%～96.53%,平均为64.34%±18.10%,Kaplan-Meier生存曲线分析示p27高表达组≥80%较低表达组(<80%)有显著性差异(P<0.0001);以p27阳性表达率60%为截取值,两组间生存曲线有显著性差异(P<0.0001)。激光共聚焦显微术检测显示p27在肿瘤细胞质中有表达,生存曲线分析显示在全部病例及儿童病例组中有显著性差异(P<0.05),而在成人病例组中则无显著性差异P>0.05。Cox比例风险模型分析显示p27表达降低和p27在细胞质中呈阳性表达在髓母细胞瘤中的相对危险度分别为4.5(95%CI2.3～6.7)、3.4(95%CI1.6～4.1)。结论在髓母细胞瘤中p27表达有不同水平的减低,p27表达的降低及p27在细胞质呈阳性表达是人髓母细胞瘤的危险因素,p27在人髓母细胞瘤中具有预后判断意义的最佳截取值为阳性表达率60%。     

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     

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.     

uPA和KDR在髓母细胞瘤中的表达及意义

目的 研究尿激酶型纤溶酶原激活剂（urokinase-type plasminogen activator,uPA)和KDR（vascular endothelia growth factor receptor-2)在髓母细胞瘤中的表达及临床意义。方法 应用免疫组化LSAB法检测50例髓母细胞瘤中uPA和KDR的表达，结合临床随访，使用Cox回归统计分析和Spearman相关分析。结果 uPA和KDR的染色定位于肿瘤细胞和血管内皮细胞。Cox归分析显示uPA和KDR是影响生存时间的独立的预后因子，它与预后存在高度负相关关系。Spearman相关分析显示uPA和KDR存在正相关关系。结论 uPA和KDR可能是预测髓母细胞瘤预后的独立的预后因子。uPA和KDR两者正相关关系。     

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...     

Fetal origin of the medulloblastoma: Evidence from growth analysis of two cases

Summary Growth analysis of medulloblastomas was performed in two children. They initially manifested symptoms at the age of 3 years and 9 months and at the age of 2 months respectively. Computerized tomography (CT) scans were obtained at different points in each case. The growth curves were drawn on a semilogarithmic graph by calculating the tumor volume on CT on the assumptions that the tumor started from a single tumor cell and that the growth rate was constant. By extrapolating the curves back, tumor inception was estimated to have occurred respectively at the 14–23rd week and at the 16–17th week of gestation. Additional cell kinetic data were obtained from DNA analysis of surgical pathology specimens. Calculated cell-cycle times were 22–32 h for both cases. The S phases comprised 26.3% and 27% and the G₀G₁ phases 66.8% and 62% of the cell cycle, respectively, for case 1 and 2. Assuming a labelling index of 14%, the cell loss factors were estimated to be 97% and 74% (case 1 and case 2 respectively). The seventeenth week of gestation in humans corresponds to the timing of events occurring postnatally at days 3–18 in the developing cerebella of rodents, i.e., at the time of maximal activity in the migration and differentiation of the cells of the fetal external granular layer. Medulloblastomas have been experimentally induced in rodents by the injection of oncogenic viruses during the neonatal period, and statistical data on the epidemiology of human medulloblastomas have suggested a possible association with the contamination of polio vaccine by the SV 40 virus. Therefore, it seems reasonable to assume that these medulloblastomas originated in the cerebellum during the period of active development of the cerebellum.     

原发性脊髓胶质母细胞瘤的临床特点及预后因素分析

目的 探讨原发性脊髓胶质母细胞瘤的临床特点及其预后影响因素.方法 回顾性纳入2008年1月至2015年12月四川大学华西医院神经外科行手术治疗的14例原发性脊髓胶质母细胞瘤患者,总结其临床特征并分析影响患者预后的因素.结果 14例患者中,近全切除4例,部分切除5例,活检5例.9例术后接受放、化疗,3例仅行化疗,2例未行放、化疗.中位随访时间为15个月（5-26个月）,1年和2年生存率分别为79％ （11/14）和7％（1/14）.中位总生存期（OS）为15个月,中位无进展生存期（PFS）为8个月.单因素Log-rank分析显示,年龄以及是否进行术后放疗均为OS和PFS的影响因素（均P〈0.05）;术前Karnofsky功能状态评分（KPS）为OS的影响因素（P=0.033）,但并非PFS的影响因素（P=0.106）;性别、肿瘤切除程度以及病理学结果均非OS及PFS的影响因素（均P〉0.05）.单因素Cox回归分析显示,年龄、术后是否放疗均影响OS和PFS（均P〈0.05）;而术前KPS仅影响OS（P=0.046）.多因素Cox逐步回归分析显示,术后是否放疗为影响OS和PFS的惟一因素（均P 〈0.05）,放疗者较未放疗者的生存期长.结论 原发性脊髓胶质母细胞瘤临床罕见且预后极差.肿瘤切除程度与患者的预后无关,术后联合放疗能在一定程度上延长患者的生存期.     

Stratification of medulloblastoma on the basis of histopathological grading

Medulloblastoma (WHO grade IV) is an embryonal tumour of the cerebellum and the most common malignant central nervous system tumour in children. Despite significant advances in treatment, 5-year survival rates are still less than 70%, suggesting the presence of subgroups with different response to radio/chemotherapy. In the present study, we re-evaluated a series of 347 medulloblastomas from the SIOP II clinical trial of the International Society of Paediatric Oncology to identify features predictive of clinical outcome. Relapse free survival for medulloblastomas with severe anaplasia [5-year rate: S(60)=49.5%], was significantly shorter than for tumours with moderate or mild anaplasia S(60)=65.4%; P=0.001). The difference between both groups was even larger when the presence or absence of extensive apoptosis was included (46.5 vs. 66.7%; P=0.0216). Other histological features including nodularity, necrosis, vascular proliferation and the presence of β-catenin mutations (7% of cases) were not predictive for relapse free survival. These findings indicate that degree of anaplasia is the most significant histologic feature predictive of the survival of medulloblastoma patients.     

髓母细胞瘤CyclinD1、P16的表达及其与临床病理特点和预后的关系

目的检测髓母细胞瘤CyclinD1和P16的表达,分析它们与临床病理特点之间的关系,探讨其对髓母细胞瘤预后的影响。方法通过免疫组化方法并用图像分析系统检测CyclinD1和P16在髓母细胞瘤和正常小脑组织中表达的积分光密度(IOD),分析它们与临床病理特点及预后的关系。结果(1)正常小脑组织CyclinD1表达较低,髓母细胞瘤表达增高;P16在正常小脑组织中呈现高表达,而髓母细胞瘤出现降低;(2)髓母细胞瘤CyclinD1和P16表达情况与患者年龄、肿瘤部位、病理类型、是否伴坏死、分化程度及分化方向有关(P<0.01或P<0.05);(3)经单因素分析和多因素分析显示肿瘤分化程度、CyclinD1和P16表达与患者生存期存在密切关系(P=0.0000)。结论(1)髓母细胞瘤中CyclinD1和P16表达改变,反映了肿瘤细胞增殖活性和细胞周期活性发生了改变,并且不同临床病理特点的髓母细胞瘤,增殖活性和细胞周期活性改变的程度并不一致。(2)髓母细胞瘤临床病理特点的不同更深层次的原因之一是肿瘤细胞CyclinD1和P16发生了不同变化从而导致肿瘤细胞形成各自不同的细胞周期改变。(3)CyclinD1和P16表达改变,为髓母细胞瘤的预后判断和临床治疗提供了新的思路。