血管内栓塞治疗颅内动脉瘤

颅内动脉瘤破裂后早期行血管内栓塞治疗可防止其再破裂出血,同时,动脉瘤处理后可安全行腰穿置管或脑室外引流及3H疗法等,以防治蛛网膜下腔出血(SAH)所致脑血管痉挛及脑积水等并发症。因此,一般认为颅内动脉瘤破裂后栓塞治疗越早越好,但颅内动脉瘤破裂后早期病情不稳定,术中肝素化可能会引起再出血,SAH急性期脑血管痉挛使微管置管的难     

成人后颅窝肿瘤术后分流依赖性脑积水相关风险因素分析

目的 探讨后颅窝肿瘤术后分流依赖性脑积水的影响因素及应对方法。方法 收集2020年1月至2022年12月在徐州医科大学附属医院行后颅窝肿瘤切除术的224例成人患者的临床资料作为研究对象,采用多因素Logistics回归分析成人后颅窝肿瘤术后分流依赖性脑积水的影响因素。结果 224例成人后颅窝肿瘤手术患者,有20例(8.9%)患者出现分流依赖性脑积水需行脑室腹腔分流术。多因素logistics回归分析发现肿瘤非全切除、术前脑室周围水肿、术后出血、瘤周水肿是成人后颅窝肿瘤术后分流依赖性脑积水的独立危险因素。结论 成人后颅窝肿瘤术后分流依赖性脑积水与肿瘤非全切除、术前脑室周围水肿、术后出血、瘤周水肿密切相关,临床应针对危险因素制定相应措施,改善预后。     

介入栓塞治疗颅内动脉瘤患者术后预后不良的相关因素分析

目的探讨介入栓塞术治疗颅内动脉瘤(IA)患者术后预后不良的相关因素。方法选取2016年2月至2018年2月间延安大学附属医院收治的行介入栓塞术治疗的93例IA患者,随访至2019年3月31日,采用哥斯拉预后量表(GOS)评估患者预后情况,采用单因素及Logistic多因素分析影响患者术后预后不良的因素。结果介入栓塞术后预后不良者8例(8. 6%),平均GOS得分(1. 84±0. 62)分;预后良好者85例(91. 4%),平均GOS得分(3. 46±1. 15)分,组间比较,差异均有统计学意义(均P <0. 01)。IA患者介入栓塞术后预后不良与介入时机、有无高血压、Fisher分级、肿瘤部位、瘤颈宽度及Hunt-Hess分级有关,差异均有统计学意义(均P <0. 05)。将单因素分析结果中有统计学意义的6个指标纳入多因素Logistic回归方程,高血压、Fisher分级、瘤颈宽度≥4. 5mm及Hunt-Hess分级为影响患者介入栓塞术后预后不良的独立危险因素,差异均有统计学意义(均P <0. 05)。结论影响IA患者介入栓塞术后预后的危险因素为高血压、Fisher分级、瘤颈宽度≥4. 5及Hunt-Hess分级,临床可通过监控以上指标选择合适的治疗方案,以提高手术成功率,减少预后不良发生率。     

颅内表皮样囊肿术后并发脑积水及发热11例临床分析

目的　探讨颅内表皮样囊肿术后并发脑积水及发热的原因、治疗及预后。方法　对近 6年来收治颅内表皮样囊肿 68例术后并发症的临床资料进行回顾性分析。结果　本组有 11例同时合并脑积水及发热 ,给予非手术治疗 ,外引流、腹腔分流等手段 ,其中1例非手术治愈 ,9例行腹腔分流治愈 ,1例腹腔分流失败后改行脑室 -颈静脉分流术治愈。结论　脑积水并发热者在条件许可时可行分流术 ,且预后较好     

TCD 在分级不良颅内动脉瘤中的应用研究

目的：通过采用经颅多普勒（TCD）超声检测分级不良颅内动脉瘤（Hunt-Hess Ⅲ~Ⅴ级）患者的脑血流动力学变化从而调整尼莫地平用量，结合患者临床表现及预后，探究 TCD 在分级不良颅内动脉瘤中的应用价值。方法对照组：31例分级不良颅内动脉瘤患者经验性应用尼莫地平治疗。试验组：常规检测18例分级不良颅内动脉瘤患者在不同时间窗（1 d、3~5 d、7~10 d、12~14 d）的脑血流动力学改变，并依据其大脑中动脉平均血流流速（VMCA ）实时调整尼莫地平用量；蛛网膜下腔出血（SAH）后3个月采用格拉斯哥预后（GOS）评分评价患者预后，对比2组患者预后差别。结果分级不良颅内动脉瘤患者 SAH 后1 d 时 VMCA为（503±127）cm·s -1，3~5 d 时 VMCA 为（827±185）cm·s -1，7~10 d 时 VMCA 为（1358±337） cm·s -1，12~14 d 时 VMCA为（1174±302）cm·s -1。试验组 GOS 评分1分1例，2分2例，3分5例，4分8例，5分2例；对照组 GOS 评分1分3例，2分11例，3分13例，4分3例，5分1例。试验组预后明显优于对照组，差异有统计学意义（P ＜005）。结论分级不良颅内动脉瘤患者很少在 SAH 后1 d 内发生脑血管痉挛（CVS），3~5 d 时 VMCA明显增加，7~10 d 时 VMCA 达到高峰，随后逐渐降低。TCD 为监测 CVS 的有效方法，其可以实时无创检测脑血流量变化，为患者的临床治疗提供循证医学证据，进而改善预后。     

脑血管

微骨窗经侧裂-岛叶入路治疗高血压壳核出血的临床研究；双侧脑室引流加腰穿脑脊液置换治疗重度脑室出血39例；破裂脑动脉瘤栓塞时机与术后蛛网膜下腔出血的治疗；颅内动脉瘤22例栓塞治疗的体会；海绵窦海绵状血管瘤的诊断及显微手术治疗.     

高压氧联合脑室镜辅助颅内动脉瘤夹闭术治疗脑动脉瘤的疗效分析

目的:探讨脑室镜辅助颅内动脉瘤夹闭术联合高压氧对早期脑动脉瘤患者术后血清基质金属蛋白酶-9（MMP-9）、可溶性细胞间黏附分子-1（sICAM-1）水平变化及生活质量的影响。方法:选取2015年4月至2017年1月我院84例早期脑动脉瘤患者，随机数字表法分为对照组（n=42）与研究组（n=42）。常规治疗基础上对照组采取脑室镜辅助颅内动脉瘤夹闭术，研究组采取脑室镜辅助颅内动脉瘤夹闭术+高压氧治疗（治疗10次）。6个月后进行随访，统计对比入院时及末次随访时两组生活质量（SF-36）及日常生活能力（ADL）分值、入院时及治疗结束后第2 d血清MMP-9及sICAM-1水平、并发症发生率、预后效果。结果:治疗后两组SF-36及ADL分值较治疗前增高，且研究组较对照组高，差异有统计学意义（P<0.05）；治疗后两组血清MMP-9及sICAM-1水平较治疗前降低，且研究组较对照组低，差异有统计学意义（P<0.05）；研究组并发症发生率（7.14%）较对照组（19.05%）低，但差异无统计学意义（P>0.05）；研究组预后情况优于对照组，差异有统计学意义（P<0.05）。结论:联合采用脑室镜辅助颅内动脉瘤夹闭术及高压氧治疗早期动脉瘤效果显著，可降低血清MMP-9、sICAM-1水平，提高患者日常生活能力及生活质量，改善预后效果，且可降低并发症发生率。     

以时间理念为基础的护理策略对颅内动脉瘤介入栓塞术患者术后效果的影响

目的探讨以时间理念为基础的护理策略对颅内动脉瘤介入栓塞术患者术后肢体功能、自我护理能力及生活质量的影响。方法选取2014年12月至2017年12月间凤翔县医院收治的100例行介入栓塞术治疗的Hunt-Hess低分级颅内动脉瘤患者,采用随机数表法分为研究组和对照组,每组50例。对照组患者采用术后常规护理,研究组患者采用以时间理念为基础的护理干预。比较两组患者肢体运动功能(FMA)、生活自理能力、生活质量及脑缺血、脑血管痉挛等并发症的发生情况。结果干预后,研究组患者FMA各子项目评分及总分均高于对照组患者,差异均有统计学意义(均P <0. 05)。干预后,研究组患者自理能力评估量表(Barthel)指数分级优于对照组患者,Barthel指数平均值高于对照组患者,差异均有统计学意义(均P <0. 05)。干预后,研究组患者生活质量各子项目评分及总分均高于对照组患者,差异均有统计学意义(均P <0. 05)。研究组患者术后脑血管痉挛发生率低于对照组患者,差异有统计学意义(P <0. 05)。两组患者术后脑缺血发生率比较,差异无统计学意义(P> 0. 05)。结论基于时间理念的护理干预可促进Hunt-Hess低分级颅内动脉瘤介入栓塞术患者的术后康复,减少并发症发生。     

松果体生殖细胞瘤脑脊液播散1例

颅内生殖细胞瘤(germ cell tumors,GCTs)由原始的生殖细胞衍生而来,好发于松果体区,其次为鞍上池,可向蛛网膜下腔及脑室系统种植、播散,但典型松果体生殖细胞瘤脑脊液播散少见,未见大宗报道.我院近期收治1例典型松果体生殖细胞瘤脑脊液播散患者,现报道如下. 1 病例资料 患者,女,19岁.因头昏、嗜睡、多饮、多尿1个月,2012年4月5日在我院行影像检查,报告为松果体区占位性病变并梗阻性脑积水(图1);2012年4月12日入住某部队医院行脑脊液分流减压术以解除梗阻性脑积水(图2),术后4月18日证实梗阻性脑积水解除(图3),并对松果体区肿瘤行伽马刀治疗出院.     

脑室腹腔分流加Ommaya囊置入配合放化疗治疗肺腺癌脑膜转移的临床观察北大核心CSCD

目的探讨在放化疗的基础上给予患者脑室腹腔分流（VP）＋Ommaya囊置入治疗肺腺癌脑膜转移的有效性．．方法对39例我院确诊的肺腺癌脑膜转移患者的临床和随访资料进行回顾性分析。根据治疗方法的不同分成VP分流＋0mmaya囊置入组、单纯Ommaya囊置入组及非手术组。用Kaplan-Meier法进行生存分析并绘制生存曲线,组间差异分析采用Logrank检验。结果全组患者中位生存期为5．1月（0．6-26月）,1年生存率为12．8％（5/39）。行VP分流术后患者体力状况评分平均提高18．2分（P=0．000）,行VP分流＋Ommaya囊置入组与非手术组的中位生存期分别为7．8月和3．2月（X^2=8．450,P=0．015）结论肺腺癌脑膜转移患者预后差,在联合放化疗的基础上给予患者脑室腹腔分流术、经Ommaya囊行脑室内化疗等方式能够有效提高患者生存质量,延长患者的生存期,但尚需大样本临床研究证实,以及多中心之间的合作。     

Analysis on Characteristics and Nursing Points of Surgical and Interventional Treatment for Elderly Cerebral Aneurysm

Objective. The purpose was to explore the characteristics and nursing points of surgical and interventional treatment for elderly cerebral aneurysm. Methods. 100 elderly patients with cerebral aneurysm treated in our hospital from January 2017 to December 2019 were selected, and divided into craniotomy group (40 patients with neurosurgical clipping) and interventional surgery group (60 patients with endovascular interventional embolization) according to the treatment method to compare the operation time, hospitalization time, hospitalization expenses, degree of brain injury, complications and prognostic scores of the patients in two groups. Meanwhile, the relationship between the factors (age, aneurysm size, location) and prognosis of patients was analyzed, and the nursing points were summarized. Results. (1) The operation time and hospitalization time of the interventional surgery group were lower than those of the craniotomy group, but the hospitalization expenses were higher than those of the craniotomy group (P = 0.000). (2) The brain injury indexes of the two groups at 6h and 24h after operation were higher than those before operation, and the indexes of the craniotomy group were higher than those of the interventional surgery group (P = 0.00). (3) The overall complication rate was 16.67% in the interventional surgery group, which was lower than 37.50% in the craniotomy group (P = 0.005). (4) The good recovery rate of GCS score in interventional surgery group was 63.33%, which was higher than 42.50% in craniotomy group (P = 0.040). (5) Univariate analysis. The aneurysm location, preoperative Hunt-Hess grade and combined hyperlipidemia were related to the prognosis of patients (P < 0.05). (6) Multivariate analysis. The aneurysm location and preoperative Hunt-Hess grade were independent factors affecting the prognosis of patients (P < 0.05). Conclusion. Interventional surgery for elderly cerebral aneurysm is superior to craniotomy in reducing surgical trauma and accelerating postoperative recovery, but the hospitalization expenses are higher than those of craniotomy. Aneurysm location and preoperative Hunt-Hess grade were independent factors influencing the prognosis of patients. Postoperative nursing for elderly cerebral aneurysm should start from basic nursing, psychological nursing and symptomatic nursing.     

持续腰椎穿刺引流治疗高位骶骨肿瘤术后脑脊液漏

目的探讨持续腰椎穿刺引流术在高位骶骨肿瘤切除术后脑脊液漏患者中的应用效果。方法采用回顾性对比分析方法。对1998年1月至2011年8月,就诊于我科行高位骶骨肿瘤切除术并有完整病例资料的72例进行分析。纳入标准为：骶骨肿瘤切除患者术中发生硬脊膜损伤且术后发生脑脊液漏的患者,同时排除有持续腰椎穿刺脑脊液引流禁忌证如脑疝、颅内压明显增高、穿刺部位皮肤或软组织感染、全身严重感染败血症或休克、穿刺不能合作、L1以上脑脊液循环通路梗阻等情况的患者。最终符合纳入标准共11例。将2005年3月前行骶骨肿瘤切除术后发生脑脊液漏患者使用单纯伤口旁放置引流管引流的5例作为对照组,2005年3月以后行骶骨肿瘤切除术后发生脑脊液漏的6例为采用持续腰椎穿刺引流治疗组,分别对两组患者脑脊液漏治愈时间和患者一般情况及相关并发症进行对比研究。结果两组患者均无逆行性颅内感染发生,其中单纯放置引流管引流组1例发生手术切口局部感染。持续腰椎穿刺引流患者脑脊液漏愈合时间中位数为14．5（12～18）天,较对照组患者25（23—36）天缩短,两组差异有统计学意义（P=0．004）。腰椎穿刺引流组患者治疗期间骶尾部切口渗液少,肿胀明显较单纯引流组轻,患者自体感觉如伤口疼痛、头晕等症状较单纯引流组轻。两组患者均无低颅压性头痛、无进行性低颅压、气颅、脑疝等并发症发生。 结论持续腰椎穿刺引流治疗骶骨肿瘤切除术后脑脊液漏较单纯伤口旁引流效果好,并且有效缩短脑脊液瘘VI闭合时间。     

Cerebrospinal fluid pharmacokinetics of intraventricular and intravenous aziridinylbenzoquinone

The cerebrospinal fluid (CSF) pharmacokinetics of aziridinylbenzoquinone (AZQ) was studied following i.v. and intraventricular drug administration. Initial studies were performed in six rhesus monkeys with chronic indwelling Ommaya reservoirs. Following intraventricular administration of 0.2 mg of AZQ, elimination was monoexponential with half-lives of 32 and 39 min in ventricular and lumbar CSF, respectively. AZQ clearance (0.2 ml/min) was 5-fold greater than estimated CSF bulk flow, indicating that transcapillary passage and/or metabolism may be important clearance mechanisms for this drug. In spite of its rapid clearance from ventricular CSF, a substantial peak AZQ concentration was achieved in lumbar CSF (12 microM), which was 7 times higher than the peak ventricular CSF level (1.7 microM) achieved following i.v. AZQ administration (16 mg/sq m). Moreover, the mean area under the CSF concentration-time curve in ventricular CSF was 20-fold greater following intraventricular versus i.v. AZQ dosing, despite an 80-fold-lower dose. AZQ was not detectable in plasma (less than 0.06 microM) following intraventricular administration. No animals demonstrated clinical evidence of acute neurotoxicity. Subsequently, intraventricular AZQ was administered to a patient with refractory meningeal leukemia. Intraventricular AZQ (0.5 mg) resulted in a peak ventricular (56 microM) CSF level which was 80-fold higher than ventricular CSF levels achieved following systemic AZQ administration of a dose of 24 mg/sq m in humans. Moreover, intraventricular AZQ yielded substantial CSF levels without detectable plasma concentrations. These data suggest that intraventricular administration of AZQ is feasible and may have pharmacological advantages over systemic administration for the treatment of meningeal neoplasia.     

Methotrexate distribution within the subarachnoid space after intraventricular and intravenous administration

Purpose: Intrathecal methotrexate achieves high concentrations in cerebrospinal fluid (CSF), but drug distribution throughout the subarachnoid space after an intralumbar dose is limited. The objective of this study was to quantify methotrexate distribution in CSF after intraventricular and intravenous administration and to identify factors that influence CSF distribution. Methods: Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received methotrexate by bolus injection (0.5 mg) and infusion (0.05 to 0.5 mg/day over 24 to 168 h) into the lateral ventricle, as well as intravenous infusions. CSF was sampled from the lumbar space, fourth ventricle and the subarachnoid space at the vertex. Methotrexate in CSF and plasma was measured with the dihydrofolate reductase inhibition assay. Results: After bolus intraventricular injection, methotrexate exposure in lumbar CSF ranged from 11% to 69% of that achieved in the fourth ventricle. During continuous intraventricular infusions, methotrexate steady-state concentrations (C_ss) in lumbar CSF and CSF from the vertex were only 20% to 25% of the ventricular CSF C_ss. The dose, duration of infusion, and infusate volume did not influence drug distribution to the lumbar CSF, but probenicid increased the lumbar to ventricular C_ss ratio, suggesting the involvement of a probenicid-sensitive transport pump in the efflux of MTX from the CSF. During the intravenous infusions, the ventricular methotrexate C_ss was lower than the lumbar C_ss and the C_ss in CSF from the vertex. Conclusion: Methotrexate CSF distribution after intraventricular injection was uneven, and at steady-state CSF methotrexate concentrations were lower at sites that were more distant from the injection site. Received: 20 April 1999 / Accepted: 28 July 1999     

Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors.

PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with primary CNS tumors. Cytologic examination of lumbar CSF is routinely used to detect LMD. To determine whether examination of CSF obtained from ventricular shunt taps is a more sensitive method of detecting LMD in these patients, we designed a prospective study to compare the findings of cytologic examinations of CSF obtained from concurrent lumbar and ventriculoperitoneal (VP) shunt taps. PATIENTS AND METHODS: As a part of diagnostic staging, follow-up testing, or both, 52 consecutive patients underwent concurrent lumbar and shunt taps on 90 separate occasions, ranging from the time of diagnosis to treatment follow-up. CSF from both sites was examined cytologically for malignant cells. RESULTS: The median age of the 28 males and 24 females was 7.5 years (range, 0.6 to 21.4 years). The primary CNS tumors included medulloblastoma (n = 29), astrocytoma (n = 10), ependymoma (n = 5), germinoma (n = 3), atypical teratoid rhabdoid tumor (n = 2), choroid plexus carcinoma (n = 2), and pineoblastoma (n = 1). Each site yielded a median CSF volume of 1.0 mL. Fourteen of 90 paired CSF test results were discordant: in 12, the cytologic findings from shunt CSF were negative for malignant cells, but those from lumbar CSF were positive; in two, the reverse was true. Malignant cells were detected at a higher rate in lumbar CSF than in shunt CSF (P =.0018). When repeat analyses were excluded, examination of lumbar CSF remained significantly more sensitive in detecting malignant cells (P =.011). Analysis of the subset of patients with embryonal tumors showed similar results (P =.0008). CONCLUSION: Cytologic examination of lumbar CSF is clearly superior to cytologic examination of VP shunt CSF for detecting leptomeningeal metastases in pediatric patients with primary CNS tumors.     

Intrathecal administration of 4-hydroperoxycyclophosphamide in rhesus monkeys

The preactivated cyclophosphamide analogue, 4-HC, does not require activation by hepatic microsomal enzymes to express its cytotoxic activity and therefore, unlike cyclophosphamide, may be useful for the regional therapy of cancer. In the present study, the pharmacokinetics and toxicology of 4-HC were studied following intraventricular administration of 0.4 mg to rhesus monkeys with chronic indwelling Ommaya reservoirs. 4-HC was measured in cerebrospinal fluid (CSF) and plasma with a high-performance liquid chromatography assay utilizing a fluorometric detector following derivatization with m-aminophenol. The mean peak level of 4-HC in ventricular CSF was 100 microM 5 min after administration. The drug was cleared rapidly and the elimination was monoexponential with a mean half-life of 22 min. The mean clearance from CSF (0.33 ml/min) was 10-fold higher than CSF bulk flow. The drug was distributed throughout the subarachnoid space with lumbar levels approaching ventricular levels by 60 min. Neither acute nor chronic neurotoxicity or systemic toxicity was observed during the 6-wk observation period. Concentrations of 4-HC demonstrated to be cytocidal in vitro against human breast cancer, lymphoid leukemia, and rhabdomyosarcoma were readily achieved in CSF following intraventricular administration. This study demonstrates that intraventricular therapy with 4-HC is feasible and suggests that further study of this approach in the clinical setting should be considered.     

磁共振成像在恶性实体肿瘤脑膜转移诊断及治疗中的应用

目的 探讨磁共振成像（MRI）在恶性实体肿瘤脑膜转移诊断及治疗中的价值.方法 对63例恶性实体肿瘤脑膜转移患者的影像学特点、临床、治疗及随访资料进行回顾性分析.结果 全部患者接受头部MRI检查,26例患者行颈或腰椎MRI检查,表现为脑沟回内结节样强化、脑脊膜线性强化、硬膜增厚强化、室管膜强化、脑室内转移、椎管内转移结节、交通性脑积液、硬膜下积液、影像学阴性.发生室管膜强化、脑室内转移及椎管内种植转移的小细胞癌患者分别为5、7及9例,多于其他病理类型（P=0.002、P=0.009、P＜ 0.000 1）.7例患者鞘内注射化疗后出现癫痫发作,其中5例影像学表现为软脑膜线性强化.33例接受放疗联合鞘内注射化疗综合治疗的患者中3例预后极差,其中2例影像学表现阴性.25例患者治疗后症状明显缓解,其中21例复查头部MRI,影像学缓解程度不一.结论 MRI增强扫描对恶性实体肿瘤脯膜转移患者诊断有重要辅助作用.磁共振表现及临床特点与病理类型具有相关性.影像学表现为软脑膜线性强化型的患者鞘内注射化疗后癫痫发作可能性大,可考虑给予相关预防治疗.MRI不适用于疾病严重程度与预后判断及疗效评估.     

A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases

Leptomeningeal metastases (LMs) are common metastatic complications, occurring in at least 5% of patients with disseminated cancer. Cerebrospinal fluid (CSF) cytology remains the standard for diagnosis and assessment of treatment response, but may be inadequate. Our objective was to compare ventricular and lumbar CSF cytology in patients who had cytologically proven LM and were receiving intra-CSF chemotherapy. Sixty patients with LM, positive lumbar CSF cytology documented at diagnosis, limited extent of CNS disease, and no evidence of CSF flow obstruction were treated with a variety of intra-CSF chemotherapies. All patients underwent a single simultaneous ventricular and lumbar CSF sampling (mean volume of CSF per site examined, 10 ml) to assess response to therapy at either 1 or 2 months after treatment initiation. Ventricular CSF cytology was positive in 44 patients (73%), 35 of whom were also positive by lumbar CSF cytology. Lumbar CSF cytology was positive in 45 patients (75%), of which 35 were also positive by ventricular CSF cytology. Samples were negative at both ventricular and lumbar sites in 6 patients (10%). Paired CSF cytologies were discordant in 19 (32%) patients. The lumbar cytology was negative in 9, whereas the ventricular cytology was positive (lumbar false-negative rate of 17%); the ventricular cytology was negative in 10, whereas the lumbar cytology was positive (ventricular false-negative rate of 20%). In the presence of spinal signs or symptoms of LM, the lumbar CSF cytology was more likely to be positive than was the ventricular (odds ratio = 2.86; 95% confidence interval, 0.86-9.56). Conversely, in the presence of cranial signs or symptoms, the ventricular CSF cytology was more likely to be positive than was the lumbar (odds ratio = 2.71; 95% confidence interval, 0.76-9.71). In this cohort of patients, whose LM was documented initially by positive lumbar CSF cytology, ventricular and lumbar CSF samples obtained during treatment had similar false-negative rates, depending on the site of clinical or radiologic disease. This suggests that both lumbar and ventricular sites must be sampled when assessing treatment response. If clinical or radiographic disease is present only at 1 site, then CSF from that site is more likely to be positive than is CSF obtained from the more distant site.     

大剂量甲氨蝶呤静脉给药时间对淋巴瘤患者脑脊液中药物浓度的影响

背景与目的:甲氨蝶呤(methotrexate,MTX)在脑脊液中高于最小有效治疗浓度是治疗中枢淋巴瘤的必要条件,目前尚不明确大剂量MTX(high doseMTX,HD-MTX)静脉给药时间对MTX穿透血脑屏障的影响.本研究探索HD-MTX静脉不同给药时间对脑脊液中MTX浓度的影响,以获得更好的中枢淋巴瘤防治效果并尽可能减少MTX外周毒性.方法:34例非霍奇金淋巴瘤患者分别接受MTX 1～3g/m2 6 h持续静脉给药或24 h持续静脉给药,其中17例交替使用两种给药方法;采用高效液相色谱法检测MTX停药0 h、24 h、48 h的MTX血清浓度,及停药0 h后脑脊液中MTX浓度;比较两组血中和脑脊液中MTX浓度以及毒性反应,并对影响MTX浓度的因素进行相关分析.结果:给药结束时6 h给药组的MTX血清浓度显著高于24 h给药组:自身对照结果6 h给药组的脑脊液中MTX浓度为0.70 Ixmol/L,明显高于24 h给药组的0.49 Ixmol/L(校正值,P=0.044).MTX的脑脊液浓度与血清浓度呈正相关,中枢侵犯患者脑脊液MTX浓度显著高于无中枢侵犯的患者.自身对照结果6 h组和24 h组Ⅱ～Ⅳ度粘膜炎的发生率分别15.4%和37.8%.Ⅲ～Ⅳ度骨髓抑制的发生率分别为46.2%和67.6%.结论:在提高MTX的中枢浓度和降低外周毒性方面,HD-MTX 6 h给药方案优于24 h给药方案.     

A pharmacokinetic study of intra-CSF administered encapsulated cytarabine (DepoCyt®) for the treatment of neoplastic meningitis in patients with leukemia,lymphoma, or solid tumors as part of a phase III study

Summary Introduction Cytarabine liposome injection (DepoCyt^?), a sterile suspension of the antimetabolite cytarabine, encapsulated into multivesicular, lipid-based particles, has been developed to improve the treatment of neoplastic meningitis (NM) through sustained release of cytarabine. The objective of this study was to determine the pharmacokinetics (PK) of cytarabine after intrathecal administration of 50 mg encapsulated cytarabine (DepoCyt^?) in patients with neoplastic meningitis up to 336 h (14 days) after dosing. Methods This was an open-label study wherein two 50-mg doses of DepoCyt^? were administered 14 days apart via the intraventricular (IVT) route or by lumbar puncture (LP). Cerebrospinal fluid (CSF) samples were collected from eight adult patients at various times up to 14 days after each dose. Plasma samples were also collected within the same time period. CSF samples were analyzed for unencapsulated (free) and encapsulated cytarabine and the cytarabine metabolite, ara-U. Plasma samples were analyzed for free cytarabine and ara-U. The limit of detection was 0.003 μg/mL cytarabine and 0.016 μg/ml for ara-U. Results The concentration of free and encapsulated cytarabine in the ventricular and lumbar CSF ranged from 0.01 to 1500 μg/mL and were detectable up to 14 days post-dosing. Free cytarabine concentrations in plasma were only sporadically detectable. CSF and plasma concentrations of ara-U were low in all samples. Conclusions The administration of intrathecal encapsulation cytarabine prolongs sustained tumor exposure to cytotoxic concentrations of cytarabine (>0.02 μg/ml) with a slow continuous release of cytarabine from the DepoFoam^TM particles, so drug exposure is prolonged over time, resulting in lower peak cytarabine levels and a longer duration of exposure compared with standard cytarabine (Ara-C). This work was performed at Moffitt Cancer Center, Tampa, Florida and University of Florida College of Medicine, Gainesville, Florida. This work was presented in part at the 12th␣International Conference on Brain Tumor Research and Therapy at Keble College, Oxford, United Kingdom on September 20–23, 1997.