光动力辅助显微手术治疗脑胶质瘤

目的观察血啉甲醚介导光动力辅助显微手术治疗脑胶质瘤的近期疗效和随访效果。方法1999年至2001年期间,34例恶性脑胶质瘤病人给予光动力辅助手术治疗。暴露肿瘤前3h,静脉推注光敏剂,显微镜下切除肿瘤后应用光动力治疗仪对肿瘤残腔进行激光照射(200J/cm2)以杀伤残存肿瘤细胞。术后避光3d,观察近期临床表现,出院后定期随访治疗效果。结果术后近期效果满意临床症状缓解或消失,出院时Karnofsky记分升高者28例,Karnofsky记分无变化者6例,Karnofsky记分改善率82%(28/34);全部病例无皮肤光敏反应;术后1年生存率为77%(26/34);术后2年生存率为53%。结论激光光动力疗法是一种有效的脑胶质瘤辅助治疗方法近期临床效果满意,有利于提高生存率和生存质量,延长患者生命。     

光动力疗法辅助手术治疗功能区脑胶质瘤

目的 介绍光动力疗法辅助手术治疗功能区脑胶质瘤的方法和疗效。方法 1999年7月至2000年6月收治的脑胶质瘤病人中,有10例给予光动力辅助手术治疗。术中暴露肿瘤的同时静脉推注光敏剂,显微镜下切除肿瘤后,应用LH400型激光动力治疗仪对肿瘤残腔进行光动力照射,以杀伤残存肿瘤细胞。术后避光3d,随访其术后效果。结果 术后近期临床效果满意,无皮肤光毒反应;随访至今全部病例临床症状改善,未见肿瘤复发。结论 激光光动力疗法是一种有效的脑胶质瘤辅助治疗方法,它与手术结合综合治疗功能区脑胶质瘤,有利于减轻脑损伤,减少功能缺失,提高病人生存质量和疗效。     

铱192核素行脑胶质瘤间质内放疗的动物实验与临床初步应用

目的：采用动物实验用立体定向技术瘤内置管作间质内放疗的生物学效应研究及临床初步应用分析。方法：动物实验用Ｇ４２２皮下荷瘤鼠模型及Ｃ６脑胶质瘤脑荷瘤鼠进行，每种分２．５Ｇｙ、１０Ｇｙ照射组及对照三组，观察皮下荷瘤鼠经间质内照射后的肿瘤生长抑制及脑荷瘤鼠经内照射后的鼠生长期延长情况及病理学观察。实验结果表明用铱１９２后装瘤内置管行间质内照射可引起肿瘤生长明显受到抑制，脑荷瘤鼠照射后生存期显著延长。临床应用：在此基础上我们用铱１９２后装机瘤内置管对５６例脑深部胶质瘤进行了铱１９２核素瘤间质内照射，肿瘤位于大脑半球深部２５例；基底节区１３例；三脑室后部１１例；脑室内４例；小脑内３例。３０例为原发胶质瘤，２６例为术后复发胶质瘤。行单管单点照射３９例；双管１５例；三管治疗２例；照射剂量３５～６５Ｇｙ，平均５６．５Ｇｙ。一般住院１５～２０天，无手术严重并发症，无死亡。１、２、３年存活率分别为９２．８％、８３．９％和７１．４％。结论：经实验与临床初步应用证明，铱１９２核素脑瘤内置管间质内放疗是治疗脑深部胶质瘤的一种有效方法     

恶性脑胶质细胞瘤的问质化疗

目的：总结8年来利用术中埋置在残瘤腔的化疗囊对213例恶性脑胶质瘤患行间质化疗(interstitial chemotherapty)的早期及远期疗效。方法：于术中对肿瘤行尽可能多切除的残瘤腔内埋置自行研制的化疗囊,术后进行经皮穿刺注入卡氨芥(BCNU)的癌内化疗。结果：能明显延长患的生存期和改善生存质量。213例患生存期超过1年140例(65．73％),3年生存51例(23．94％),5年生存21例(9.86％),7年生存9例(4.23％),显高于国内外相关的报道。结论：利用化疗囊对恶性脑胶质瘤的间质化疗经长期临床观察和病理学资料证实,是一种适用于大脑半球胶质瘤治疗的新方法。其优点是给药操作简便、能发挥脂溶性药物最大药效、无全身毒副作用和其他并发症。     

光动力学治疗后C6胶质瘤血管内皮生长因子的表达

目的 探讨光动力学治疗（PDT）后C6胶质瘤血管内皮生长因子（VEGF）的表达。方法 在不同剂量（5mg/kg，10mg／kg，20mg/kg，30mg／kg）光敏剂——血卟啉衍生物（HPD）条件下，激光照射裸鼠皮下C6胶质瘤。在治疗后不同时间检测瘤组织中VEGF的表达。结果 在5mg/kg剂量组VEGF的表达在PDT24h后达高峰，与对照组及治疗后3d、7d和10d相应值比，差异显著（P〈0．01）。其它剂量组VEGF表达亦在治疗后24h达高峰，但与治疗后其它时间比，相差无显著性（P〉0．05）。结论 PDT治疗后24hVEGF表达达高峰，针对VEGF的抗血管治疗应在24h内进行。     

复发难治部位恶性胶质瘤的手术及治疗策略

研究背景复发恶性胶质瘤由于肿瘤浸润而侵犯重要神经或脑深层结构,进一步增加再次手术和治疗的难度。因此,如何制定合理的治疗策略,在最大限度切除肿瘤的同时保证患者基本生存质量,是目前争论的热点。本文旨在探讨复发恶性胶质瘤的合理治疗方式和最佳手术策略。方法对4例典型复发恶性胶质瘤患者术前影像、术中操作、术后并发症,以及远期随访结果进行综合评价,阐述对其治疗策略。结果其中2例术后MRI检查显示复发肿瘤位于T2WI少量水肿残余部位;1例根据T2WI所示于术中行水肿带扩大切除,术后近期出现感觉性失语和右侧肢体乏力,经改善脑循环、高压氧,辅助针灸及物理康复训练症状明显改善;1例脑干胶质瘤采取激光刀精确"雕刻式"手术切除,术后未出现明显神经功能障碍表现,恢复良好。4例患者术后均接受替莫唑胺(200mg/kg,5d/28d)化疗,平均随访(14.00±12.50)个月。结论对于明显复发的恶性胶质瘤患者,再次手术仍是延长生存时间的关键,扩大切除T2WI所示水肿带能减少肿瘤复发机会。在保持患者术后基本生存质量(Karnofsky生活质量评分>70分)基础上,应采用病灶扩大全切除;而针对毗邻脑功能区的肿瘤病灶,则应采取精确"雕刻式"切除,尽量减少肿瘤细胞残留。     

联合靶向治疗复发恶性脑胶质瘤的研究

目的 比较单独采用贝伐珠单抗治疗和贝伐珠单抗联合替莫唑胺剂量密集疗法治疗复发恶性脑胶质瘤的疗效. 方法 回顾性分析首都医科大学附属北京天坛医院神经外科自2008年6月到2012年6月收治的38例复发恶性脑胶质瘤患者资料,26例采用贝伐珠单抗单药治疗(单药组),12例采用替莫唑胺剂量密集疗法联合贝伐珠单抗化疗(联合治疗组),观察其无进展生存期及不良反应. 结果 单药组中位无进展生存时间为21.8周,6个月无进展生存率为37.8％;联合治疗组中位无进展生存时间为34.7周,6个月无进展生存率为52.7％,差异具有统计学意义(x2=8.161,辟0.023). 结论 贝伐珠单抗能提高复发恶性脑胶质瘤患者的无进展生存时间,联合治疗在延长复发恶性胶质瘤患者的无进展生存期方面优于单药组,可推荐为复发恶性脑胶质瘤的治疗方式.     

显微手术切除加125I粒子置入治疗复发性脑胶质瘤12例分析

目的研究12例复发性脑胶质瘤显微手术切除加125I粒子置入治疗复发性脑胶质瘤的近期治疗效果。方法对12例复发性恶性脑胶质瘤患者行开颅显微手术全切除,术中在瘤床植入125I粒子,每颗粒子活度0.3~0.4mCi,病灶周边剂量50~80Gy。随访6~18个月,观察肿瘤再次复发率和患者病死率。结果全组12例获得6~18个月的随访。12例中有2例复发病例,复发的时间分别是在治疗后9个月和15个月。有2例死亡病例,1例在术后15月复发放弃治疗后死亡,另1例在术后4月死于并发症,其余9例粒子聚集病灶无扩大化表现,CT增强也未见肿瘤复发。无1例发生急性放射性反应。有2例出现粒子游走,但无功能损害的表现。有4例粒子周围出现的水肿持续达4~7月,给以脱水治疗后好转。有2例病人术后肿瘤残腔出血,保守治疗好转。全组病人抗癫治疗,无癫病例发生。结论显微手术切除加125I粒子置入,可提高复发性脑胶质瘤的疗效。     

脑胶质瘤同步内放疗和内化疗的临床研究

目的 探讨术中埋置在残瘤腔间质内化疗囊和Ommaya囊对31例恶性脑胶质瘤患者行同步间质内放疗（interstitial brachytherapty）间质内化疗、（interstitial chemotherapty）的疗效。方法 于术中尽可能多的切除肿瘤并在残瘤腔内埋置^32P放疗囊和Ommaya囊，并做化疗药物体外敏感检测后选择高抑制率化疗药物，术后同步进行经皮穿刺注入^32P及敏感化疗药物。结果 能明显延长患者的生存期及改善生存质量，31例患者1年生存22例（71％）、2年生存20例（65％）、3年生存19例（61％）。结论 同步间质内放疗、内化疗能有效抑制肿瘤生长，控制复发，延长生态期，改善生存质量，是一种可供选择的综合治疗胶质瘤的有效的方法。     

瘤床处应用化疗药物治疗脑胶质瘤21例分析

目的 研究瘤床处直接应用化疗药物治疗脑胶质瘤的临床效果。方法 1996-12～1998-03共收治21例脑胶质瘤病人，经过手术和术后放疗免疫治疗，并给予血管内化疗，随访观察疗效；1998-04～2003-04收治25例脑胶质瘤病人给予同样综合治疗，但化疗方法不同，后者是在脑胶质瘤手术中用化疗药冲洗处理瘤灶，术后定期用化疗泵直接注入化疗药于瘤床处进行观察、比较。结果 改变化疗方案后的病人生存年限得以延长，生存质量明显改善。结论 瘤床处直接应用化疗药避开了血脑屏障，降低了全身积压药浓度和毒副作用，提高化疗在瘤床处的浓度和作用时间，从而提高了脑胶质瘤的治疗效果。     

Subclinical photodynamic therapy treatment modifies the brain microenvironment and promotes glioma growth

Photodynamic therapy (PDT) has been clinically investigated as an adjuvant local therapy for brain tumors. Therapeutic interventions intended to promote tumor cell death can also promote changes in the tumor microenvironment that could favor tumor growth. We have previously shown that PDT can activate pro-angiogenic factors in the normal rodent brain. This study seeks to further elucidate the effects of subtherapeutic doses of Photofrin-PDT on normal brain and to establish a mouse model for studying glioma progression in an environment modified by oxidative stress. Photofrin was administered to nude mice, and a defined intracranial area was illuminated with laser to deliver an optical dose equivalent to 80 J/cm(2). Three and 7 days after PDT, mice were sacrificed and brains were fixed and analyzed by immunohistochemistry. PDT treatment resulted in transient increase in cell proliferation, associated with a robust activation of astrocytes and microglia in the treated region, without causing substantial cell death. To test how this modified environment would affect glioma growth, human glioblastoma U87 cells were implanted in the PDT-treated hemisphere or in the control brain subjected to sham surgery. Significantly larger tumors were observed after 3 weeks in the PDT treated brains relative to control treatment. Our results indicate that subclinical Photofrin-PDT locally alters the brain homeostasis without inflicting significant disruption to the tissue architecture, providing a model to study the effects of the microenvironment on glioma growth, with implications for the optimization of the clinical use of PDT for brain tumors.     

Photodynamic therapy of malignant brain tumours

Fifty patients with malignant supratentorial tumours were treated with intra-operative photodynamic therapy (PDT); in 33 cases the tumour was recurrent. In 45 patients the tumour was a cerebral glioma and in 5 cases a solitary cerebral metastasis. All patients received a porphyrin photosensitizer 18-24 hours pre-operatively. Photoillumination was carried out at 630 nm to a tumour cavity created by radical tumour resection and/or tumour cyst drainage. The light energy density ranged from 8 to 175 J/cm2. In 8 patients additional interstitial light was administered. The operative mortality was 4%. Follow up has ranged from 1 to 30 months. The median survival for the 45 primary malignant tumours was 8.6 months with a 1 and 2 year actuarial survival rate of 32% and 18%, respectively. In 12 patients a complete or near complete CT scan response was identified post PDT. These patients tended to have a tumour geometry (eg. cystic) that allowed complete or near complete light distribution to the tumour. The median survival for this group was 17.1 months with a 1 and 2 year actuarial survival of 62% and 38%, respectively. In the 33 cases who did not have a complete response the median survival was 6.5 months with a 1 and 2 year actuarial survival of 22% and 11%, respectively. Photodynamic therapy of malignant brain tumours can be carried out with acceptable risk. Good responses appear to be related to adequate light delivery to the tumour.     

Photofrin介导光动力学治疗胶质瘤后细胞凋亡的检测

目的 研究光动力学治疗前后肿瘤残腔壁组织细胞凋亡情况，观察光动力学治疗效果，以期为进一步改善临床应用奠定基础。方法 手术中在切除或大部分切除胶质瘤之后的肿瘤残腔壁，分别于光动力学治疗（PDT）前后在对应点取少量组织，分别对标本行TUNEL法凋亡细胞免疫组化病理检验及HE染色。结果 病理切片共29张，光动力学治疗前16张仅3张出现凋亡细胞，细胞凋亡率平均0．05％；光动力学治疗后的13张均出现了阳性染色细胞，细胞凋亡率平均39．16％。结论 Photofrin介导光动力学治疗胶质瘤可以诱导肿瘤细胞的快速凋亡。     

Antitumour effect of MX2, a new morpholino anthracycline against C6 glioma cells and its cytotoxic effect in combination with photodynamic therapy.

MX2, a novel lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to Adriamycin (ADM) against murine and human tumour cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells in vitro and in vivo was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. The drug concentration required for 50% inhibition of cell growth (IC50) of MX2 for C6 glioma cells was 6.5 +/- 1.0 ng/ml, which was lower than for ADM and nitrosourea (ACNU). The growth of C6 glioma cells inoculated intracerebrally in mice was inhibited by intravenous (iv) injection of MX2 at doses ranging from 1.0-3.0 mg/kg suggesting that MX2 may be clinically effective against human malignant gliomas. Mild photocytotoxicity of MX2 against C6 cells in vitro was observed at high concentrations of MX2 illuminated with white light but not red light (> 630 nm). In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) resulted in cyto- and photo-toxicity of C6 glioma cells irrespective of whether the cells were treated with MX2 either immediately after red light illumination following incubation with HpD, or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.     

恶性脑胶质瘤预后相关多因素分析

目的 了解恶性脑胶质瘤的治疗现状,分析不同治疗方法对患者生存期的影响,研究影响恶性脑胶质瘤预后的相关因素,为规范化、个体化治疗恶性脑胶质瘤提供指导.方法 依据治疗方式不同,对我院自2001年1月至2010年1月经术后病理证实为恶性脑胶质瘤,且随访成功的68例患者进行回顾性分析.结果 全组病例1、2、5年生存率分别为54.2％、41.9％、16.2％.平均生存时间(29.4±5.18)个月.Cox模型多因素分析显示影响预后的独立因素有:年龄、肿瘤级别、肿瘤切除程度(P＜0.05);Log - rank检验单因素分析发现与预后相关的因素有:年龄、肿瘤级别、治疗方式(P＜0.05).结论 恶性胶质瘤的预后较差,特别是Ⅳ级的胶质母细胞瘤.术后采取以手术、放化疗为主的综合治疗可以延长患者生存时间,改善预后.     

恶性胶质瘤术后放化疗效果及影响因素分析

目的分析恶性胶质瘤术后放、化疗的效果与影响因素。方法以我院收治的60例恶性胶质瘤患者为研究对象,所有患者接受手术治疗,并于术后进行放、化疗,分析影响放疗与化疗效果的各项因素。结果 7例完全缓解,36例部分缓解,总缓解率为71.67%(43/60);随访发现复发23例(38.33%),死亡27例(45.00%),存活33例(55.00%)。结论恶性胶质瘤手术疗效受术前癫痫发作、肿瘤病理分级、肿瘤全切因素影响,于术后采用放疗结合替莫唑胺进行化疗,效果良好,值得临床推广。     

恶性胶质瘤cyclinD1及p16表达与预后相关性研究

目的 探讨恶性胶质瘤细胞周期蛋白D1(cyclinD1)和p16蛋白表达与手术及放射治疗后肿瘤复发的相关关系。方法 在我院行手术全切及正规放射治疗的恶性胶质瘤患中，已证实复发62例，肿瘤标本检测cyclinD1和p16蛋白的表达情况，结合传统预后因素(性别、年龄、病程、肿瘤大小、肿瘤性质)采用Kaplan—Meier方法并用logrank检验对肿瘤复发进行单因素分析，多因素分析采用COX逐步回归模型。结果 病程、肿瘤大小、肿瘤性质和cyclinD1及p16蛋白表达情况均可作为恶性胶质瘤手术及放射治疗后复发的独立预测因素，多因素分析显示p16蛋白表达和肿瘤病理性质对肿瘤复发的预测作用较强。结论 肿瘤细胞cyclinD1和p16蛋白表达可能与手术及放射治疗后复发的时间长短有关。     

术前加术后中性粒细胞与淋巴细胞比值预测胶质瘤患者的预后研究

目的 研究术前加术后外周血中性粒细胞与淋巴细胞比值(NLR)对胶质瘤患者预后的预测价值.方法 回顾性分析110例经手术、病理检查确诊的胶质瘤患者的临床资料.将术前和术后NLR低于临界值的记为0,术前和术后NLR高于临界值的记为1.术前NLR加术后NLR记为PP-NLR,则PP-NLR=0或1或2;按患者的PP-NLR将...     

5-ALA介导的光动力治疗鼠C6胶质瘤的实验研究

目的研究以5-氨基乙酰丙酸（5-ALA）作为光敏剂的光动力治疗（PDT）对大鼠C6胶质瘤移植瘤的效果。方法通过皮下接种C6胶质瘤细胞建立大鼠移植胶质瘤模型。将24只荷瘤大鼠平均随机分成3组：A组按剂量20mg／kg在瘤内注射5-ALA，2h后在肿瘤局部行激光照射；B组行单纯激光照射，不予任何光敏剂；C组为荷瘤空白对照组，不给任何治疗。PDT后不同时间，测量肿瘤体积并观察其组织学变化。结果治疗后第4、8和14天A组肿瘤体积与B、C组相比明显缩小（P〈0．05），组织学上可见大量肿瘤细胞坏死。结论5-ALA作为光敏剂介导的PDT能使大鼠C6胶质瘤移植瘤组织坏死，生长速度明显减慢，有望成为胶质瘤治疗的新途径。     

Diagnostic utility of IDH1- and p53-mutation analysis in secondary gliosarcoma

We report on a 47-year-old woman in whom an anaplastic astrocytoma was resected in 2006. Postoperative radiation had to be interrupted because of a wound infection necessitating explantation of the infected bone flap and implantation of a titanium mesh. Subsequently, radiation therapy was completed and temozolomide was administered for 45 cycles. In the beginning of 2010 a new contrast enhancing mass was seen in the former tumor region. The mass was subtotally excised and showed no histomorphological similarity to the first lesion but represented a highly pleomorphic and mainly sarcomatoid differentiated malignant tumor. The lack of expression of GFAP or MAP-2 raised the question of a secondary malignancy, however, molecular genetic analysis of IDH1 and p53 revealed the same mutations in the anaplastic astrocytoma from 2006 as in the sarcomatoid tumor operated in 2010. Furthermore, accumulation of mutated IDH1 and TP53 protein could be demonstrated immunohistochemically. Thus, the second tumor represented the rare instance of recurrence of an anaplastic astrocytoma as a secondary gliosarcoma and a second malignant neoplasm was ruled out. The postoperative therapy and the inflammation might have contributed to the severe change in morphological phenotype of the glioma.