成人低级别胶质瘤的治疗进展

胶质瘤是颅内最常见的原发性神经上皮肿瘤．治疗上仍存在高复发率、高致残率、高病死率的问题，成为神经系统继中风之后第二大威胁人类健康的疾病。依据世界卫生组织（WHO）2000年的分类，低级别胶质瘤主要指Ⅰ、Ⅱ级神经上皮性肿瘤。其中Ⅰ级包括毛细胞性星形细胞瘤、胚胎发育不良性神经上皮肿瘤、多形性黄色星形细胞瘤、神经细胞瘤和神经节胶质瘤；Ⅱ级包括星形细胞瘤、少枝胶质瘤和混合性少枝星形细胞瘤。低级别胶质瘤占成人胶质瘤的15％，儿童胶质瘤的25％。     

低级别胶质瘤的治疗

低级别胶质瘤是一类不常见的、原发性脑肿瘤。通常处于非活动状态,但是大部分最终演变成致命性高级别胶质瘤。最新的文献回顾和分析认为,肿瘤较大或有广泛的神经系统症状时应该立即手术切除。术后年轻、肿瘤已全切且包含特定分子学特点的病人,可以只进行观察随访;有高危险因素如:肿瘤残留、年龄大于45岁、神经缺损症状、肿瘤大、有占位效应的病人,建议立即给予辅助治疗。     

边缘系统低级别胶质瘤

目的对起源于边缘系统的低级别胶质瘤广泛性切除的可行性和效果进行分析。方法对作者１９９４年７月至１９９６年１２月进行广泛性切除的７例边缘系统低级别胶质瘤作一回顾性分析。结果７例病人均进行广泛性肿瘤切除,术后头颅ＣＴ或ＭＲＩ检查无肿瘤残存征象,术后除２例病人出现暂时性失语和记忆力减退外,均恢复良好,手术后无严重神经功能障碍和死亡率。结论边缘系统的低级别胶质瘤起源于异生皮层和中间皮层,可通过手术广泛性切除肿瘤而不致损伤重要功能结构。     

低级别胶质瘤临床治疗现状

<正>胶质瘤是颅内最常见的原发性恶性肿瘤。根据病理学特点,世界卫生组织将胶质瘤分为I-IV级,其中I-II级为低级别胶质瘤(low-grade gliomas,LGGs),III-IV级为高级别胶质瘤(high-grade gliomas,HGGs)。LGGs约占颅内胶质瘤的15%,生长缓慢,平均生存时间比HGGs长,会发生间变或去分化形成致命性的HGGs。故对于那些年轻的,症状不明显的,靠近功能区的LGGs患者,是否应积极     

低级别胶质瘤的显微手术治疗

中枢神经系统低级别胶质瘤侵及范围广泛且发病早期多无明显症状及体征，作出临床诊断时肿瘤体积已经较大，肿瘤活检加放疗的效果很不满意。作者自1998年3月至2005年1月应用显微外科技术治疗低级别胶质瘤17例，术后进行放射治疗，取得了良好效果，现报道如下：     

岛叶低级别胶质瘤的显微外科治疗

目的 探讨显微手术切除岛叶低级别胶质瘤的方法和效果。方法 对30例岛叶低级别胶质瘤病人的临床资料进行回顾性分析。结果 肿瘤全切除12例，近全切除14例，部分切除4例，无手术死亡。术后早期偏瘫6例、失语3例、偏瘫和失语3例，经术后3个月随访，仍有2例轻偏瘫、1例失语。结论 经外侧裂入路应用显微外科技术是治疗岛叶低级别胶质瘤的较理想方法。     

丘脑低级别胶质瘤的显微外科治疗

本文分析1990～2000年我院收治的丘脑低级别胶质瘤20例，对手术方法和预后进行探讨，现报告如下。     

Caspase-3与VM26联合对U251作用的研究

目的 研究caspase-3与化疗药物VM26联合对U251细胞系的作用，探讨基因治疗与化疗联合应用治疗胶质瘤的可能性。方法 脂质体包裹Caspase-3转染U251细胞，应用VM26对转染组与未转染组U251细胞进行治疗。通过细胞生长曲线、MTT、TUNEL观察caspase-3高表达与VM26联合对U251的影响。结果 Capase-3在U251细胞中获得高表达，caspase-3高表达未能诱导U251细胞凋亡。VM26作用于转染caspase-3的U251细胞凋亡比对照组显著增加，细胞存活率下降。结论 转染Caspase-3对U251细胞生长无抑制作用，但caspase-3高表达的U251细胞对VM26的化疗敏感性显著增加。     

低级别胶质瘤与癫痫

低级别胶质瘤与癫痫的发生密切相关,但是机制不明.目前研究发现不同肿瘤类型,不同病理级别,不同部位及功能区与非功能区癫痫发生率却有显著的差别.口服抗癫痫药物,治疗原发性肿瘤包括手术,放化疗及生物治疗等措施均能够较好的控制癫痫发作.本文就低级别胶质瘤与癫痫的关系及低级别胶质瘤患者中癫痫的控制作一综述.     

低级别胶质瘤继发癫痫的手术治疗

目的 探讨低级别胶质瘤继发癫痫的手术治疗方法.方法 采用视频脑电、脑磁图定位致痫灶、功能区,手术中联合应用立体定向引导、术中B超、术中皮质电刺激等技术治疗继发癫痫的低级别胶质瘤13例.结果 全部患者在手术切除、保护神经功能的同时,控制了癫痫发作,临床效果良好.结论 多种定位技术的联合应用,可在最大程度切除肿瘤、致痫灶的同时减少脑组织损伤,保留脑功能区皮质,控制癫痫发作,提高患者生活质量.

Abstract：

Objective To explore the methods of surgical treatment of low-grade glioma with secondary epilepsy.Method Video-EEG,magnetoeneephalography ( MEG) were performed to localizated the epileptogenic zone and domain in 13 patients,and stereotactic technology,ultrasound,electrocorticogram (EcoG) were performed intraoperative combinating to treat the low-grade gliomas that lead to epilepsy.Results The seizure was controlled while the tumor was resected and the neural function were protected in all patients.The clinical effect was significant.Conclusions The combination of multiple technology to localize the epileptogenic can resect the tumor or the epileptogenic zone maximum, reduce the injury of normal brain tissue,protect the cortex of brain domain,control the epileptic seizure and improve the patients' quality of life.     

脑胶质瘤替尼泊甙动脉超选择灌注及司莫司汀口服化疗

目的观察脑胶质瘤替尼泊甙动脉（VM_(26)）及口服司莫司汀（MeCCNU）化疗的疗效。方法对68例肿瘤切除手术后的脑胶质瘤病人行VM_(26)动脉超选择灌注及MeCCNU口服化疗,每间隔6－8周为一疗程,首次化疗后6个月将计算机体层摄影（CT）或磁共振成像（MRI）显示的肿瘤体积变化及临床症状评价与化疗前相比较。结果本组68例病人治疗后完全缓解9例（13．2％）,部分缓解27例（39．8％）,稳定19例（27．9％）,恶化11例（16．2％,早期死亡（2．9％）。本组病例1年存活率89．7％,2年72．1％,3年以上存活率22．1％。全部病人无严重并发症及毒性反应。结论对手术切除的胶质瘤病人采用MeCCNU联合化疗,有益于提高胶质瘤病人的生存质量。     

Chemotherapy for low-grade gliomas

Low-grade gliomas are the most common histological type of pediatric brain tumor. They can arise in any part of the nervous system. Although low-grade gliomas are slow growing, they often recur or progress, especially in areas such as the diencephalon or brain stem, where resection is limited by proximity to vital and eloquent structures. Radiation has been used to treat progressive low-grade gliomas, but it is not clear that it improves long-term outcome. Radiotherapy also has potential significant cognitive, endocrine, and vascular side- effects. There is a growing body of evidence to suggest that chemotherapy can delay and may obviate the need for radiation therapy or aggressive surgery. This chapter reviews the published chemotherapeutic trials. Chemotherapy appears to have a major role in the management of children with progressive low-grade gliomas. Received: 12 April 1999     

手术切除结合术后间质内放化疗治疗脑恶性胶质瘤

目的 探讨脑恶性胶质瘤切除术后结合间质内放疗并间质内化疗的临床疗效.方法 32例脑恶性胶质瘤均行显微神经外科手术全切除或次全切除,术中根据术前计算机三维治疗计划系统（TPS）在瘤床上植入^125 I放射性粒子行组织间持续内照射,总量为50～60 Gy,同时于瘤腔内放置Ommagy化疗囊,术后1周开始应用盐酸尼莫司汀（ACNU）行间质化疗,每周1次,连续6周.随访观察肿瘤复发率、患者生存率、中位生存期.结果 32例患者1、2年复发率分别为31.2%、68.8%,1、2、5年生存率分别为94.3%、80.6%、29.1%,中位生存期为92.3周;无明显放疗、化疗并发症.结论 在手术力争全切除肿瘤基础上结合术后间质内放疗、化疗治疗脑恶性胶质瘤,疗效较好,安全而且并发症少.     

贝伐单抗联合化疗治疗复发高级别胶质瘤的疗效观察及安全性分析

目的探讨贝伐单抗联合化疗治疗复发高级别胶质瘤的疗效及安全性。方法回顾性分析2011年3月~2013年12月符合入选标准的11例复发高级别胶质瘤患者,接受贝伐单抗联合替莫唑胺(TMZ)化疗方案治疗。化疗效果按照肿瘤可计算MRI增强范围评价疗效,并观察患者治疗前至再次进展之间KPS、QOL评分改变。不良反应参照WHO抗癌药物急性与亚急性毒性反应分度标准。结果 11例患者全部完成2个周期以上的化疗。疗效评价,总体完全缓解(CR)4例,部分缓解(PR)6例,病情稳定(SD)1例,病情进展(PD)0例,缓解率(RR)为90.9%(10/11),DCR为100%(11/11);中位PFS为5.4个月,中位OS为6.5个月。贝伐单抗联合TMZ所致不良反应以胃肠道反应(66.3%)、骨髓抑制(43.2%)、肾损伤(39.0%)、高血压(27.3%)常见,本组多为Ⅰ、Ⅱ级(35.93%),很少Ⅲ级(2.60%),无Ⅳ级;治疗后患者KPS评分及QOL评分均较治疗前均有改善(均P0.05)。结论贝伐单抗联合TMZ化疗对复发高级别胶质瘤的治疗有良好的抗肿瘤活性和较高的疾病控制率,安全性较高,是一种可优先选择的治疗方法。     

边缘系统低级别胶质瘤与顽固性癫痫

目的 探讨边缘系统低级别胶质瘤致顽固性癫痫的临床特征、手术方法及疗效。方法 对自1993年3月一2000年12月本科因顽固性癫痫进行手术切除的11例边缘系统低级别胶质瘤作一回顾性分析。结果 11例患者中10例以癫痫起病，平均病程26个月，发作类型为复杂性部分性发作和继发性全身发作。11例患者均经扩大翼点入路行胶质瘤全切加上标准前额叶切除。术后病理为少枝突胶质瘤3例，星形细胞瘤Ⅰ级5例，星形细胞瘤Ⅰ—Ⅱ级3例。11例患者随访10个月一3年，复查CT或MRI检查，无肿瘤复发迹象，癫痫控制满意。结论 边缘系统低级别胶质瘤致顽固性癫痫，病程长，久治不愈，年龄偏轻，通过完全的肿瘤切除加上标准前额叶切除，可大大降低肿瘤的复发率，极好地控制癫痫。     

Chemotherapy for diffuse low-grade gliomas in adults

Diffuse low-grade gliomas (LGGs) in adults are progressive brain tumours that are radiologically characterized by slow and continuous growth that precedes anaplastic transformation. Standard treatment includes surgery and radiotherapy though the optimal timing of radiotherapy remains unsettled. Several retrospective and phase II studies have demonstrated that chemotherapy is also an interesting treatment option. However, several questions remain unanswered regarding its optimal use. The present review focuses on past, recent and ongoing developments in LGGs chemotherapy, including response assessment and potential predictive biomarkers of chemosensitivity.     

立体定向等体积切除幕上低级别胶质瘤

目的 探讨立体定向等体积切除术在低级别胶质瘤手术中的应用价值。方法 利用MR导向立体定向等体积切除方法切除大脑半球不同部位的低级别胶质瘤58例，其中功能区39例。对本术式的手术疗效、优越性及注意事项进行分析。结果 全组病例均达到肿瘤影像学全切除。术后症状改善或无变化51例(87．9％)，症状加重7例，除1例未恢复外，其余6例均在短期内恢复。结论 立体定向等体积切除术可以精确定位并确定手术切除范围，有助于提高低级别胶质瘤的全切除率及降低手术并发症的发生。     

Targeted therapy for malignant gliomas

The identification of markers that are associated with tumour but not normal tissue has allowed the development of highly-specific targeted therapies. Monoclonal antibodies, either alone or linked to radioisotopes or toxins, have provided a powerful tool for research, as well as the basis for promising therapeutic agents with less side effects than standard radiotherapy or chemotherapy. A new class of drugs, the tyrosine kinase inhibitors, which interfere with the function of key molecules in cancer-promoting pathways, have had a dramatic effect in haematological malignancy and are being trialled in solid tumours, including glioma. Although the problem of achieving specific, high-level delivery of these various agents to tumours in the brain remains a major issue, encouraging early results with some targeted agents support the attractive theoretical principles of this new paradigm. Further work to identify new molecular targets and to develop agents exploiting them, is needed, as well as confirmation of their safety and efficacy by clinical trials.     

Surgical strategies in low-grade gliomas and implications for long-term quality of life

Reports on long-term health related quality of life (HRQL) after surgery for World Health Organization grade II diffuse low-grade gliomas (LGG) are rare. We aimed to compare long-term HRQL in two hospital cohorts with different surgical strategies. Biopsy and watchful waiting was favored in one hospital, while early resections guided with three-dimensional (3D) ultrasound was favored in the other. With a population-based approach 153 patients with histologically verified LGG treated from 1998–2009 were included. Patients still alive were contacted for HRQL assessment (n = 91) using generic (EQ-5D; EuroQol Group, Rotterdam, The Netherlands) and disease specific (EORTC QLQ-C30 and BN20; EORTC Quality of Life Department, Brussels, Belgium) questionnaires. Results on HRQL were available in 79 patients (87%), 25 from the hospital that favored biopsy and 54 from the hospital that favored early resection. Among living patients there was no difference in EQ-5D index scores (p = 0.426). When imputing scores defined as death (zero) in patients dead at follow-up, a clinically relevant difference in EQ-5D score was observed in favor of early resections (p = 0.022, mean difference 0.16, 95% confidence interval 0.02–0.29). In EORTC questionnaires pain, depression and concern about disruption in family life were more common with a strategy of initial biopsy only (p = 0.043, p = 0.032 and p = 0.045 respectively). In long-term survivors an aggressive surgical approach using intraoperative 3D ultrasound image guidance in LGG does not lower HRQL compared to a more conservative surgical approach. This finding further weakens a possible role for watchful waiting in LGG.     

脑胶质瘤化疗敏感性的体外实验研究

目的 探讨体外培养的脑胶质瘤细胞对化疗药物的敏感性,为临床有效治疗胶质瘤提供实验依据.方法 采用四甲基偶氮唑盐微量酶反应比色法(MTT法)检测26例原代培养胶质瘤细胞在体外对顺铂(DDP)、环磷酰胺(CTX)、5-氟脲嘧啶(5-FU)、长春新碱(VCR)化疗药物的敏感性.结果 19例胶质瘤细胞对单一化疗药物的敏感性从高到低依次为DDP>CFX>5-FU>VCR.患者年龄与药物敏感性均无明显相关性;除DDP外,病理分级与其他药物敏感性无明显相关性.结论 比色法是一种快速、有效检测体外药物敏感性的方法.体外药敏试验对排除无效药物、筛选敏感药物进行个体化的化疗,提高临床化疗效果,具有重要意义.