1、Clinical outcome of neurofibromatosis type 2-related vestibular schwannoma: treatment strategies and challenges,浙江大学医学院附属邵逸夫医院神经外科郭洪彬,The most difficult is ,What causes acoustic neuroma,Neurofibromatosis(NF2),NF2, a genetic disorder, occurs with a frequency of 1 in 30,000 to 1 in 50,000 births. The
2、hallmark of this disorder is bilateral acoustic neuromas (an acoustic neuroma on both sides). This creates the perplexing problem of the possibility of complete deafness if the tumors are left to grow unchecked.,Introduction,Neurofibromatosis type 2 (NF2) is an autosomal dominant multiple neoplasia
3、syndrome that results from a mutation in NF2 tumor suppressor gene on chromosome 22 q 122 神经纤维瘤病2型是一种常染色体显性遗传的多发性肿瘤综合征。是由染色体22q12-2突变所致。,A distinctive feature of NF2 is bilateral vestibular schwannomas (VSs) with a mean age of diagnosis of 25 years NF2的一个区别性特征是双侧的前庭神经鞘瘤，诊断时平均年龄为25岁。,4例耳,12例耳,8例耳,8例耳
4、,Discussion,NF2 is a devastating disease with multiple intracranial and extracranial tumors 24. The growth pattern of NF2-related VSs can be various. However, some show saltatory pattern after a quiescent period 5. NF2是一种破坏性强的多发性的颅内颅外肿瘤。NF2相关的VS的生长模式多种多样。有时是在一段静止期后接着爆发性生长。,Outcome after treating VS
5、of patients with NF2 is usually worse than that of sporadic VS resulting from aggressive growth pattern . Careful observation is mandatory for NF2-related VS patients because growth pattern is usually unpredictable. In addition, the hearing status may become abruptly aggravated. NF2相关的前庭神经鞘瘤的预后比散发的前
6、庭神经鞘瘤的差，原因就是它有时表现为进展极快的生长模式。密切的观察随访是必须的，因为它的生长模式不可预测。而且，患者的听力可能急剧恶化。,Microsurgical resection was the standard treatment for VS in NF2 patients.However, considering the quality of life including preservation of hearing function, surgery alone may not be suitable for long-term management of patients。显
7、微手术切除术是治疗NF2相关的前庭神经鞘瘤的标准治疗。但是，鉴于对患者生活质量和听力保存的考虑，从长期病情管理的角度来说，单纯手术也许并不适合。,performed in relatively larger sized tumors than tumors that s-GKS performed in, hearing preservation rate in f-GKS was poorer than that of s-GKS. GKS, including fractionated GKS, might be relatively efficient in local control
8、of patients with small-sized tumor and serviceable hearing. 分次伽马刀治疗的组的肿瘤体积比单次伽马刀治疗组的大，可以解释分次伽马刀治疗组的听力保留的结果为什么比单次伽马刀组的差。伽马刀组，包括分次和单次的，在对于小体积肿瘤病人的听力保留方面，可能相对有效。However, we could not regard it as an absolute treatment modality in that the hearing status eventually deteriorated in many cases. Therefore,
9、 radiosurgery should be carefully considered for selected patients with NF2但是我们也不能把伽马刀治疗看做是绝对好的治疗方式，因为很多患者听力状态最终恶化了。因此，选择放射治疗时也应慎重。,The most important factor to determine optimal time of intervention is the maintenance of hearing at least in one ear. Thus, annual MRI scan and audiometric examination
10、 are mandatory. If their hearing starts to deteriorate or the tumor size start to increase, hearing preservation surgery (HPS) should be attempted. 选择治疗干预时机的一个重要的考虑因素是保留至少一只耳朵的听力。因此，进行每年的MRI平扫和听力检查是必须的。如果患者的听力开始恶化，或者肿瘤开始增大，听力保留手术应该被考虑进行。,If only other cure methods?,techniques such as cochlear implan
11、ts (CIs) and auditory brain stem implants (ABIs) can be considered to accommodate useful hearing. If hearing could not be preserved but with cochlear nerve action potential (CNAP) during respective surgery, then CI can be implanted at the time of surgery. However, if CNAP could not be observed, ABI
12、is recommended instead。 人工电子耳蜗技术和脑干听觉植入技术可以被考虑用于保留听力。如果手术中，听力无法保留，但耳蜗神经动作电位尚存，可以在术中植入人工电子耳蜗。如果耳蜗动作电位也观察不到，那么ABI脑干听觉植入装置应被推荐使用。,同侧耳的听力3看对侧耳的听力耳的听力3看耳的听力,1，看肿瘤大小。2，看同侧听力。3，看对侧听力。,NF2: bevacizumab- VEGF blockade(贝伐单抗-VEGF阻断剂),Immunohistochemistry shows VEGF expression in all vestibular schwannomas and
13、VEGF receptor 2 expression in 32% of the tumor vessels.免疫组化显示，血管内皮生长因子（vascular endothelial growth factor，VEGF）在所有听瘤上表达。VEGF receptor 2 在32%的听瘤血管上表达。VEGF blockade improves hearing in some patients with neurofibromatosis type 2 (NF2) and is associated with a reduction in tumor volume in most growing
14、vestibular schwannomas.VEGF受体阻滞剂提高一部分NF2患者的听力，伴随大部分的前庭神经鞘瘤的体积缩小。,After bevacizumab treatment of these 10 tumors, 9 tumors shrank and 6 tumors showed a response on imaging, which was maintained in 4 tumors during 11 to 16 months of follow-up.10例接受贝伐单抗治疗的患者中，9例的肿瘤缩小，6例在影像学上有反应表现，其中的4例在之后的11至16个月的随访时间内
15、维持。Overall, treatment was well tolerated and was not discontinued in any patients because of side effects.所有的患者都能耐受这种治疗，没有一例因副作用而停止治疗。,The median time to response for both volumetric reduction and hearing improvement was 3 months.肿瘤体积缩小和听力提高的平均起效时间为3个月。furthermore, the only predictive, clinical mark
16、er was the mean apparent diffusion coefficient value, a radiologic marker of vasogenic edema.而且，临床上唯一的一个预测指标是表观弥散系数值，也是一个反应血管源性脑水肿的放射指标。,Discontinuation of bevacizumab was linked to an increase in tumor volume and a decline in hearing in some patients.停用贝伐单抗后，一些患者的肿瘤体积缩小，听力下降。The optimal duration of treatment for NF2 patients is unknown.NF2患者的最佳的治疗时长目前不清楚。Genetic instability can contribute to therapeutic failure.基因的不稳定性是治疗失败的一个原因。,小结：,1，NF2相关的听瘤是一种全身性疾病的局部表现，治疗上应个性化。2，应尽可能的保留至少一侧耳的听力。3，可以辅助使用人工电子耳蜗等装置。4，贝伐单抗-VEGF阻断剂，另外一种治疗方式。,
