伽玛刀治疗后脑膜瘤再手术原因及病理学分析

The analysis of craniotomy and pathology of meningiomas after failed Gamma knife radiosurgery

目的通过分析伽玛刀治疗后又开颅手术病例的影像学和病理组织学变化，深入评价立体定向放射外科（SRS）治疗脑膜瘤的放射生物学效应。方法32例伽玛刀治疗后又在天坛医院实施开颅手术的脑膜瘤患者，男13例，女19例；平均年龄51．3岁。伽玛刀治疗至开颅手术的时间2～168个月，超过5年的12例。WHOⅠ级的脑膜瘤21例，WHOⅡ级9例，WHOⅢ级2例。全组中有18例伽玛刀治疗前有开颅手术史；在天坛医院接受伽玛刀治疗有完整治疗计划的16例。本研究对所有病例术前的神经影像和临床资料进行了分析；对外科手术的标本做详细的组织病理学观察，并对8例伽玛刀前后病理标本做了肿瘤细胞增殖活性的比较。结果绝大多数患者因临床症状、体征加重而接受手术治疗。影像上肿瘤明显增大的16例，反应性膨大或伴灶周水肿10例；肿瘤无明显变化2例；肿瘤皱缩2例，肿瘤出血2例。病理学提示，无论何种亚型的脑膜瘤，SRS引发肿瘤实质和基质的变化主要为凝固性坏死，并可见凋亡细胞的增多，续之由疤痕组织逐步取代，这个病理过程持续数年至十余年。射线控制肿瘤的间接作用是造成血管的增生性病变，管腔逐渐狭窄、闭塞，使瘤细胞得不到生长的营养供给。本组伽玛刀治疗前后的病理标本比较，未见到放射外科治疗后肿瘤细胞增殖活跃的迹象。反复开颅或伽玛刀治疗的病例多由于肿瘤本身的因素。结论伽玛刀对颅内深部小型的、手术后残留或复发的脑膜瘤是一种非常有效的治疗手段，SRS对脑膜瘤的主要放射生物学作用为肿瘤细胞的杀伤和血管机制。非典型性及恶性脑膜瘤容易复发，需要综合治疗。本组没有观察到高能量射线激发肿瘤细胞生长活跃的病理学现象。

Objective To analyze the neuro -imaging and surgical pathological changes of meningiomas in different time intervals after failed Gamma Knife treatment, to provide more pathological evidence of the clinical effect of a focused single high - dose gamma irradiation. Methods In this study, 32 patients with meningiomas underwent craniotomy after failed CKS. There were 13 male and 19 female patients with a mean age of 51.3 years （range 19 -73 years）. The time interval between radiosurgery and craniotomy was 2 to168 months （median 27.5 months）, and more than 5 years in 12 cases. The histopathological grade of meningiomas revealed WHO Ⅰ in 21 cases, WHO Ⅱ in 9, and WHO Ⅲ in 2. There were 18 patients who had open surgery before GKS, and 16 patients were treated by GKS with detail plan data in our center. All the radiologieal and clinical data have been analyzed before surgery. Histopathological investigations were performed on surgical pathology materials, and the proliferative activity of tumor cells were compared before and after GKS in 8 cases. Results Most of the patients underwent later craniotomy with clinical symptoms and signs aggravating. In the neuro - imaging, the tumor was significantly enlarged in 16 cases; tumor swollen with peripheral edema in 10; tumor unchanged in 2; shrinkage in 2; tumor bleeding in 2. A hisopathological study revealed that SRS evokes coagulative necrosis of tumor parenehyma and stroma, the apoptotic cells increasing, and then scar tissue is gradually replaced untilyears, even more than ten years. Also, the indirect affect of tumor controlled was proliferative vasculopathy induced by irradiation, that the tumor cell cannot get blood supply due to narrowing of the lumen, until its complete obliteration. Those pathological changes are no matter what subtype meningiomas. There was not any increase of the tumor cell proliferative activity pathologically before and after gamma knife treatment in our specimens. The main reason of patients, who underwent repeat open surgery or GKS, was due to the factor of the tumor itself. Conclusions Radiosurgery is a rdatively effective treatment modality for intracranial meningiomas at the small and deep site, and/or the recurrence after open surgery, but it is not preferred GKS when the tumor is symptomatic because of the mass effects. The radiobiological effect of GKS treating meningiomas is mainly both cellular effects and vascular mechanisms. For atypical meningioma, the patients need comprehensive treatments. This ionizing energy of high dose irradiation has not excited the increase of tumor cell proliferative activity in our observation.