甲氨喋呤鞘内注射+全脑放疗治疗脑膜转移癌疗效观察

目的观察甲氨喋呤鞘内注射+全脑放疗及单纯全脑放疗治疗脑膜转移癌(CM)疗效及不良反应。方法 76例确诊的脑膜转移癌患者随机分试验组采用甲氨喋呤鞘内注射+全脑放疗,对照组采用单纯全脑放疗,评价疗效及不良反应。结果试验组疾病控制率(DCR)65.7%,明显高于对照组39.4%,差异有统计学意义(P0.05)。中位PFS、中位OS试验组均明显高于对照组,差异有统计学意义(P0.05)。甲氨喋呤鞘内注射联合全脑放疗与单纯全脑放疗可明显提高患者生活质量,未增加放疗不良反应。结论甲氨喋呤鞘内注射+全脑放疗治疗脑膜转移癌较单纯全脑放疗可明显提高疗效、无进展生存期及总生存期,明显提高患者生存质量,未增加放疗不良反应。     

肺癌转移致脑膜癌病12例临床分析

目的 分析12例肺癌致脑膜癌病患者的临床特征.方法 对12例经脑脊液细胞学证实的肺癌致脑膜癌病患者的临床资料进行分析.结果 首发症状多为头痛、呕吐,头颅CT或MRI检查多无异常发现,脑脊液检查颅内压均有不同程度增高,脑脊液生化检查蛋白升高者多见,细胞学检查均见癌细胞,形态与原发肿瘤相似,经治疗后25%的患者获得缓解.结论 对以头痛、呕吐发病,伴颅内压增高及脑膜刺激征,且CT及MRI检查无明显异常者,应高度警惕脑膜癌病的可能,鞘内注射加全身化疗是有效的治疗手段.     

脑膜癌病的诊断治疗进展

正脑膜癌病(meningeal carcinomatosis,MC)是指各种恶性肿瘤转移至硬脑膜、软脑膜、脑脊液及蛛网膜下腔,一般脑和脊髓内并无瘤块,属于癌症患者晚期阶段严重的中枢神经系统(central nervous system,CNS)并发症~([1])。大约10%~30%的实体肿瘤患者会发生CNS的转移,其中4%~15%表现为MC~([2])。该病具有较高的病死率及致残率,预后极差,目前并无统一的治疗方法,多采取姑息治疗来缓解患者的     

难治性小细胞肺癌脑膜转移伴脑转移瘤一例

目的报告1例难治性小细胞肺癌脑膜转移伴脑转移瘤患者的诊断与治疗经过。方法与结果 1例44岁男性广泛期小细胞肺癌患者,经根治性放射治疗、药物化疗和预防性脑照射后1年6个月出现脑膜转移伴脑转移,采取多学科诊疗模式即螺旋断层放射治疗联合替莫唑胺同步化疗、甲氨蝶呤+地塞米松鞘内注射化疗和全身系统性治疗,脑转移后生存期为16个月,死于颅外病变进展。结论对于难治性小细胞肺癌脑和(或)脑膜转移患者,应积极采取多学科诊疗模式,合理应用多种治疗方法、兼顾综合治疗与个体化治疗。     

脑膜癌并发脑静脉窦血栓形成1例报告

脑膜癌病(meningeal earcinomatosis,MC)又称癌性脑膜炎,是以腩和脊髓的软腩(脊)膜内转移性肿瘤细胞弥漫性或多灶性、局限性浸润为特点的中枢神经系统转移瘤.其发病率仍占全身癌转移者的4%～7%[1-3].     

石家庄及周边地区结核性脑膜炎的分析

目的探讨结核性脑膜炎(TBM)的临床流行病学和临床特点。方法对河北医科大学第二医院1995至2013年间收治的1029例TBM的住院病例进行分析。结果 119年间本院共收治TBM的患者1029例,男女比例1.5:1,发病年龄38.6±15.6岁。TBM患者2004至2008年较1999至2003年增加了11.0%,2009至2013年较2004至2008年增加了52.7%,2013年住院患者为最多,为108例。春季(27.2%)和夏季(27.9%)较秋季(22.7%)和冬季(22.2%)住院患者多,患者主要分布在河北省南部地区,以石家庄(49.76%)、保定(49.76%)、邢台(12.73%)为主,多数患者居住于农村(65.2%),以农民(73.47%)为主,其次为学生(9.7%)。TBM主要集中在20~30岁年龄组(24.5%),其次为40~50岁年龄组(16.23%)。结论石家庄及周边地区TBM确诊患者有明显增加趋势,做好预防工作及早诊断、早治疗。     

脑膜癌病的临床与病理特点

目的探讨脑膜癌病的临床与病理特点。方法回顾性分析142例脑膜癌病患者的临床及脑脊液(CSF)细胞学资料和免疫细胞化学标记结果。结果本组患者临床特点:头痛123例(86.62%),头晕19例(13.38%),发热26例(18.31%),视物模糊10例(7.04%)。CSF检查及免疫标记:全部患者CSF中均发现癌细胞;癌细胞上皮膜抗原(EMA)( ),细胞角蛋白(CK)( ),CD14(-),胶质纤维酸性蛋白(GFAP)(-)。其中99例(69.72%)CK低分子( )、高分子(-),诊断为转移性腺癌;33例(23.24%)CK高分子( )、CK低分子(-),诊断为转移性鳞癌;10例(7.04%)CK高分子( )、CK低分子( ),考虑为腺鳞癌。105例找到原发灶,其中67例(47.18%)确诊为肺癌;23例(16.20%)在消化道内找到原发灶;9例(6.34%)为乳腺癌;子宫内膜癌、卵巢癌、肝癌各1例。另有37例(26.06%)未找到原发灶。诊断明确的患者中,15例失访,另90例中有82例(91.11%)于确诊后3～14个月死亡。未找到原发灶的患者中,有6例失访,另31例中有28例(90.32%)在确诊后2～13个月内死亡。结论脑膜癌病患者以头痛、头晕为主要临床表现,并可伴有发热及视物模糊。CSF细胞学检查是诊断脑膜癌病的主要依据,通过免疫细胞化学的方法,可以确定转移癌细胞。脑膜癌病患者预后较差。     

脑膜癌病7例临床分析

脑膜癌病是指脑和脊髓软膜的弥漫性癌转移，它不是一种独立疾病，而是恶性肿瘤转移到中枢神经系统的特殊形式，即癌细胞浸润脑膜形成，故也称癌性脑膜炎。我科于1996年1月～2003年7月共收治7例脑膜癌病患者，现报告如下。     

7例鞘内化疗致截瘫分析

癌性脑膜病病人用氨甲喋呤(MTX)行鞘内化疗后,导致截瘫的发生率很低,临床报道也很少。我院近20年来收治的癌性脑膜病行鞘内化疗的病人有245例,发生截瘫7例,占2.85%,本文就截瘫的发生原因作一分析。1　临床资料一般资料:7例截瘫病人中,男5例,女2例,年龄最小17岁,最大67岁,平均年     

脑膜癌病患者脑脊液常规 生化检测的特点分析

目的探讨脑膜癌病患者脑脊液常规及生化改变特点,评价其对脑膜癌病的诊断价值。方法回顾性分析92例脑膜癌病患者的临床及脑脊液检查资料,总结其脑脊液压力、白细胞数、葡萄糖、蛋白和氯化物含量的分布规律。结果脑脊液常规生化检查异常者95.60%,主要表现为糖降低(73.03%),其中≤1.0 mmol/L者占14.61%;其次为颅内压升高(71.76%),最高可达400cmH2O,其中300cmH2O者占18.82%;蛋白升高(70.79%),其中1g/L者占39.33%;氯化物降低(52.81%),均未低于100mmol/L;WBC升高不明显,54例(6136%)患者WBC≤10×106/L,其余34例WBC升高的患者中,29例(85.29%)WBC≤100×106/L。结论脑膜癌病患者脑脊液常规生化检查异常率高,颅内压及蛋白不同程度显著升高,葡萄糖降低,白细胞升高和氯化物降低不明显是其主要特点。     

Diagnosis and treatment of carcinoid meningitis: a challenge to the neurologist and oncologist

BACKGROUND: Two clinical types of leptomeningeal metastases from solid tumors are observed: local and disseminated. The former (meningeal carcinomatosis) consists in nodular infiltration of leptomeninges, while the latter (carcinomatous meningitis)--in tumor cells free floating in the cerebrospinal fluid and adhering as a monolayer to the surface of neural structures. Despite the same etiology, the two types of metastasis differ in their clinical manifestation and prognosis. Meningeal carcinomatosis is more frequently diagnosed nowadays due to advances in neuroimaging techniques and the long survival of breast cancer patients. Patients with local, nodular infiltration of leptomeninges may survive many years without symptoms of the disease. On the other hand, carcinomatous meningitis, with its usually violent course and short survival, has become a major problem for oncologists and neurologists because of limited efficacy and considerable toxicity of the treatment. AIMS: The purpose of this article is to review the current knowledge about carcinomatous meningitis in breast cancer patients, taking into account pathophysiology, clinical symptoms, diagnosis, treatment and prognosis. The second aim was to present the authors' experience with the treatment of breast cancer patients suffering from carcinomatous meningitis. MATERIAL AND METHODS: 37 patients with breast cancer and carcinomatous meningitis were treated in the Oncology Center, Warsaw, in the years 2000-2002. Their mean age was 51. The diagnosis was based on results of neurological examination, MRI scan, and the presence of neoplastic cells in the cerebrospinal fluid. In a majority of cases combined treatment was applied, including intrathecal administration of cytostatics, intravenous systemic chemotherapy and radiotherapy. RESULTS: The observation period ranged from 2 to 33 months. A response to the treatment was achieved in 76% of the patients. Their median overall survival was 19 weeks, mean 18 weeks. Seven patients (19%) survived for over 6 months. CONCLUSIONS: The ever-growing incidence of carcinomatous meningitis in the course of breast cancer has become a serious clinical problem for neurologists and oncologists. Treatment results are disappointing, although the combined modality treatment appears to be the best option. New pharmacological approaches to the treatment of meningeal malignancy are required to improve the outcome of patients with carcinomatous meningitis.     

规范治疗与脑胶质瘤患者的预后

目的探讨规范治疗对改善脑胶质瘤患者预后的重要意义。方法收集自2000年1月至2006年3月在我院治疗的有完整病案记录、随访资料和明确病理诊断的149例脑胶质瘤患者的资料。参照2005年美国National Comprehensive Cancer Network的诊疗规范，以及中山大学肿瘤防治中心脑胶质瘤单病种诊疗指引，将149例胶质瘤患者按照治疗情况分为规范治疗与不规范治疗两组，并对患者术后的生存状况及功能情况进行评估。结果低级别胶质瘤患者的中位生存时间规范治疗组为85个月和不规范治疗组为42个月，高级别胶质瘤患者规范治疗组为51个月，不规范治疗组为23个月，两组相较，均差异显著（P〈0．01）。低级别胶质瘤患者无疾病进展生存时间规范治疗组为66个月，不规范治疗组为33个月；高级别胶质瘤患者规范治疗组为32个月，不规范治疗组为13个月，两组相较，均差异显著（P〈0.01）。规范治疗组高、低级别胶质瘤患者的一年、两年及五年生存率均高于不规范治疗组（P〈0．05）。治疗后规范治疗组患者KPS功能评分显著高于不规范治疗组（P〈0．01）。结论规范治疗能明显改善脑胶质瘤患者预后，延长其生存时间，提高其生活质量，所以在神经肿瘤医生中强调对胶质瘤的规范治疗十分迫切。     

Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis

OBJECTIVE: To determine the value of vascular endothelial growth factor (VEGF) in CSF as a marker for carcinomatous meningitis (CM). METHODS: The concentration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic diseases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM. RESULTS: High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in matched sera were comparable to other disease groups. In patients with CM, the concentration of VEGF in CSF decreased significantly following antineoplastic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumor patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or infectious neurologic disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer infiltrating the meninges. CONCLUSION: In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.     

Intrathecal chemotherapy for refractory disseminated medulloblastoma

Objective To analyze the effect of intrathecal (IT) chemotherapy for disseminated medulloblastoma. Materials and methods Twenty-one patients received IT chemotherapy using the chemotherapeutic agents of methotrexate (MTX) and nitrosoureas (ACNU, MCNU) including nine patients for residual leptomeningeal lesions after initial surgery and radiation, and 12 for a recurrence with leptomeningeal dissemination. Of these 21 patients, 12 received a lumbar and/or ventricular bolus injection of the chemotherapeutic agents, one received the ventriculolumbar perfusion of the agents, and eight received both the perfusion and bolus injection. The doses ranged from 6–7 mg/m² of ACNU for perfusion and 3–3.5 mg/m² of ACNU, MCNU, or MTX for the bolus injection, and the cycles were administered from 3 to 12 times for perfusion and from 5 to 54 times for the bolus injection. The effects of chemotherapy were assessed by both radiological and cytological examinations, and the clinical symptoms were also assessed. Radiological and/or cytological responses were observed in 10 of 21 patients (47.6%), including seven cases demonstrating a complete remission. The 5-year overall survival rate and 5-year survival rate after dissemination were 61.5 and 46.4%, respectively. Five patients who received a lumbar bolus injection of nitrosoureas experienced paraplegia and double incontinence. One patient who received a ventricular injection of nitrosoureas experienced truncal ataxia. Conclusion IT chemotherapy was found to be effective in some cases with refractory disseminated medulloblastoma and it seems to be an appropriate treatment choice for leptomeningeal recurrence. However, the frequent bolus injections of nitrosoureas should be avoided to prevent the side effects.     

Diffuse lower motor neuron disease in a carcinomatous meningitis

INTRODUCTION: Between 4 and 15% of solid cancers are associated with carcinomatous meningitis ant its unfavorable prognosis. The clinical presentation of neoplastic meningitis typically associates cerebral signs, cranial nerve involvement, and medullary or radicular symptoms. OBSERVATION: We report a case of a 58-year-old woman, with a history of breast cancer in remission since 8 years, who presented an acute paraparesia and a pure motor deficit of the left arm. This diffuse lower motor neuron disease was the inaugural sign of carcinomatous meningitis. CONCLUSION: The diagnosis of cacinomatous meningitis is based on medullar MRI and lumbar puncture. In same cases, clinical signs are limited to a pure diffuse lower motor neuron disease.     

63例脑膜转移瘤预后因素分析

目的 探讨脑膜转移瘤(CM)的预后因素.方法 对天津医科大学附属肿瘤医院自1998年至2008年确诊的63例CM患者的临床资料进行回顾性分析,主要分析因素有性别、年龄、原发灶类别、KPS评分、确诊原发灶与发现脑膜转移瘤间隔时间、治疗方式、放疗剂量、原发灶控制情况等,Kaplan-Meier法计算生存期并绘制生存曲线,log-rank法进行检测验证,Cox多因素回归模型进行预后分析.结果 截止到随访结束,所有患者均已死亡,总生存期为2～732d,1年生存率为7.9%(5/63),中位生存期为67 d.Cox模型多因素分析显示KPS评分、原发灶控制情况、确诊原发灶与发现脑膜转移瘤间隔时间为独立预后因素.结论 CM主要预后因素为KPS评分、原发灶控制情况、确诊原发灶与发现脑膜转移瘤间隔时间.CM最佳治疗模式有待进一步研究,针对患者具体情况的个体化治疗值得在临床推广.     

Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report

Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte^®) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte).     

Increased intrathecal synthesis of fibronectin in bacterial and carcinomatous meningitis

Immunoreactive fibronectin (Fn) was quantified in paired cerebrospinal fluid (CSF) and serum samples from patients with bacterial meningitis (n = 46), tick-borne encephalitis (TBE) (n = 6), HIV infection (n = 6), Guillain-Barré syndrome (n = 5), carcinomatous meningitis (n = 11), multiple sclerosis (n = 15), disk disease (n = 11), and controls (n = 28). A highly significant elevation of CSF Fn was found in bacterial meningitis, TBE, and carcinomatous meningitis. There were no significant differences in serum Fn between any of the groups. An Fn index to estimate the rate of intrathecal Fn synthesis reached the highest value in bacterial meningitis. Our findings suggest that CSF Fn may be an indicator of adequate host reaction and tissue repair. For diagnostic purposes, the determination of CSF Fn probably does not add much to routine CSF laboratory tests.     

Lymphomatous meningitis in AIDS-related systemic non-Hodgkin''s lymphoma: a report of eight cases.

Meningeal involvement occurred in eight (22%) of 36 adult patients with AIDS-related systemic non-Hodgkin's lymphoma, seen over a 10-year period. Clinical symptoms consisted of cranial nerve palsies, radicular involvement, headache or diffuse encephalopathy. CSF examination established the diagnosis in all cases. Systemic disease had been diagnosed seven to 33 weeks before lymphomatous meningitis in six patients, whereas in the remaining two patients diagnoses of systemic and meningeal disease were made simultaneously. All patients had intermediate or high grade lymphomas and widespread disease. In contrast to non-AIDS related lymphomas, bone marrow involvement at initial staging cannot be used to select patients for prophylactic treatment, as seven of our eight patients had no initial bone marrow involvement. In this retrospective review, prognosis of lymphomatous meningitis was extremely poor, with a mean survival of only five weeks. Survival of patients with systemic lymphoma who eventually developed lymphomatous meningitis was 4.0 months compared with 7.2 months for those who did not. Lymphomatous meningitis appears to have the worst outcome of all AIDS-related neurological complications, regardless of treatment.