一、摘要

1．恶性胶质瘤首选治疗策略：手术切除[1]。

2．基本原则：最大范围安全切除肿瘤（maximal safe tumor resection）。即在最大程度保存正常神经功能的前提下，最大范围手术切除肿瘤病灶。（强烈推荐）复旦大学附属华山医院神经外科吴劲松

3．不能实施最大范围安全切除肿瘤者，可酌情采用肿瘤部分切除术、开颅活检术或立体定向（或导航下）穿刺活检术，以明确肿瘤的组织病理学诊断。（推荐）

二、正文

1．手术目的：⑴ 全切除肿瘤；⑵ 降低肿瘤细胞负荷，为辅助放化疗创造有利条件；⑶ 明确组织病理学诊断；⑷ 化疗药物筛选；⑸ 降低颅内压；⑹ 缓解神经功能障碍。

2．手术预后相关因素：⑴ 肿瘤级别；⑵ 年龄（≤65岁vs. >65岁）；⑶ 术前神经功能状况（KPS≥70 vs. <70）；⑷ 肿瘤切除程度（全切除vs. 非全切除）；⑸ 病灶部位和数量[2]；⑹ 原发或复发。（II级证据：Laws 2003；多个一致性III级证据：Simpson 1993，Rostomily 1994，Lacroix 2001）

3．手术策略：

强烈推荐对于局限于脑叶的原发性高级别（WHO III~IV级）或低级别（WHO II级）恶性胶质瘤应争取最大范围安全切除肿瘤。胶质瘤通常呈膨胀性浸润性生长，但局部易受脑沟、脑回的限制，多沿白质纤维束走向扩展。基于胶质瘤的生长方式及血供特点，推荐采用显微神经外科技术，以脑沟、脑回为边界，沿肿瘤边缘白质纤维束走向作解剖性切除，以最小程度的组织和神经功能损伤获得最大程度的肿瘤切除，并明确组织病理学诊断。

推荐对于：（1）优势半球弥漫浸润性生长、（2）病灶侵及双侧半球、（3）老年患者（>65岁）、（4）术前神经功能状况较差（KPS<70）、（5）脑内深部或脑干部位的恶性脑胶质瘤、⑹ 脑胶质瘤病，可酌情采用肿瘤部分切除术、开颅活检术或立体定向（或导航下）穿刺活检。肿瘤部分切除术具有比单纯活检术更高的生存优势。活检主要适用于邻近功能区皮质或位置深在而临床无法手术切除的病灶。活检主要包括立体定向（或导航下）活检和开颅手术活检。立体定向（或导航下）活检适用于位置更加深在的病灶，而开颅活检适用于位置浅表或接近功能区皮质的病灶。

在尽可能缩小肿瘤体积，降低肿瘤细胞负荷，并明确组织病理学性质后，实施个体化、规范化辅助放化疗。

4．术后切除程度评估：

强烈推荐于手术后早期（<72小时）复查MRI，以手术前和手术后影像学检查的容积定量分析为标准，评估胶质瘤切除范围。高级别恶性胶质瘤的MRI的T1WI增强扫描是目前公认的影像学诊断“金标准”；低级别恶性胶质瘤宜采用MRI的T2WI或FAIR序列影像。

在不具备复查MRI条件的单位，推荐于术后早期（＜72小时）复查CT。

5．辅助手术切除并改善手术效果的新技术：

影像导引外科新技术有助于实现最大范围安全切除恶性脑胶质瘤。推荐：常规神经导航、功能神经导航（functional neuronavigation）、术中神经电生理监测技术（例如，皮层功能定位和皮层下刺激神经传导束定位）、术中MRI实时影像（intraoperative imaging）神经导航。可推荐：荧光引导显微手术、术中B超影像实时定位。

6．支持推荐意见的证据

⑴ 肿瘤切除程度是高级别恶性胶质瘤的独立预后因素之一，肿瘤全切除与手术后复发间期和生存时间密切相关。（多个一致性II级证据：Ammirati 1987，Albert 1994，Wirtz 2000，Laws 2003；III级证据Ammirati 1987，Simpson 1993，Lacroix 2001，Buckner 2003）

⑵ 目前倾向于认为最大范围安全切除肿瘤有助于延长低级别恶性胶质瘤的复发间期（II级证据：Berger，1994）。低级别恶性胶质瘤（WHO II级）部分切除与全切除相比，病例复发风险是1.4倍，死亡风险是4.9倍（II级证据：Claus 2005）。但肿瘤全切除与手术生存时间的相关性研究还未获得I级证据（Keles 2001）。

⑶ 脑胶质母细胞瘤（GBM）术后早期MRI检查发现有肿瘤残余的病例死亡风险是无肿瘤残余病例的6.595倍。（II级证据：Albert 1994）

⑷ GBM部分切除术具有比单纯活检术更高的生存优势。（III级证据，Simpson 1993）

⑸ 活检的诊断准确率高于影像学诊断，但是受肿瘤的异质性、靶区选择等因素影响仍存在误诊率。一项回顾性分析研究显示与开颅手术相比较，立体定向活检的术后并发症较低（12.3% vs. 3.7%），但误诊率高达49%（III级证据，Jackson 2001）。另一项关于开颅手术切除比较立体定向活检治疗老年人HGG的随机对照研究显示（II级证据，Vuorinen 2003），开颅手术切除（包括全切除和次全切除）比立体定向活检可获得2.757倍的中位生存期（95% CI 1.004C7.568，p＝0.049），但总收益有限，并且两者的恶化进展时间无明显差异。另有研究显示（III级证据，Hall 1998）：活检的相关致残因素为：基底节损伤、丘脑损伤、糖尿病及手术当天的高血糖症。致残率为3.5％，致死率为0.7％，均与穿刺引起的出血有关。

⑹ 恶性胶质瘤影像学全切除，有助于改善患者术后神经功能状况，并提高生存质量。（III级证据：Ammirati 1987，Sawaya 1998，Whittle 1998，Brown 2005）

⑺ 高级别恶性胶质瘤达99%切除后，可以使肿瘤细胞负荷由109降低至107，术后辅助放化疗，有助于延长患者生存期。（I级证据：Stewart 2002）

⑻ 通过对恶性胶质瘤术后早期MRI的研究显示，术区周边环形强化主要与以下因素有关：①局部血脑屏障破坏；②肉芽组织增生；③血管自身调节功能紊乱引起的过度灌注。手术后72小时内复查MRI可以减少以上因素干扰，降低假阳性率。约80%的肿瘤复发灶源自于术后早期MRI检查发现的肿瘤残余部位。（II级证据：Albert 1994）

⑼ 神经导航有助于提高胶质瘤的手术全切除率（多个一致性III级证据：Du 2003等）。功能神经导航可提高运动区恶性脑胶质瘤全切率，降低术后致残率，改善患者远期生活质量，并使患者术后死亡风险降低43.0%（II级证据：Wu 2007）。功能神经导航手术同样适用于皮层语言区和视觉区胶质瘤手术。分别采用常规MRI重建颅脑结构模型、fMRI-BOLD定位脑皮层功能区、DTI显示皮层下神经传导束，在明确病灶边界的同时精确定位邻近神经功能区。术中神经电生理监测技术是胶质瘤术中脑功能皮层和皮层下神经传导束定位的标准技术（II级证据：Keles 2004；多个一致性III级证据：Berger 1992，Duffau 2003，Bello 2006和2007）。已有研究采用术中神经电生理监测技术分别证实BOLD和DTI用于脑功能皮层和皮层下传导通路的可靠性（多个一致性III级证据：Fandino 1999，Berman 2007，Bello 2008）。最新的术中MRI实时影像导航技术可以提高脑胶质瘤手术全切除率，改善临床预后。其有效性也已获得多个一致性II级证据（Wirtz 2000，Claus 2007）和III级证据（Black 1999，Nimsky 2006，Muragaki 2006，Senft 2008）。

三、本文局限性

1．本文对证据分级和推荐意见是基于当前公开发表的文献和资料，尚未收全当前全球所有的相关文献，可能存在选择性偏倚。

2．由于每个研究的分析角度不同，对证据分级和推荐意见发展阶段的划分也存在差异，本文结论仅供同行借鉴和参考。

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[1] 基于恶性胶质瘤的生物学特性，依据组织学边界，治愈性切除肿瘤目前仍无法实现。临床手术切除范围系依据肿瘤的影像学边界。