听神经瘤分子生物学研究

听神经瘤起源于前庭神经雪旺细胞。单侧与双侧听神经瘤即Ⅱ型神经纤维瘤病（neurofibromatosis type2,NF2）,其肿瘤形成机制基本相同。大量研究表明NF2基因突变是发病的主要分子机制,其编码蛋白产物的多种表达调控与肿瘤发生密切相关,有研究指出,其它肿瘤相关基因、生长调节基因、神经生长因子、细胞凋亡转录物等可能参与听神经瘤的形成。本文对听神经瘤分子生物学研究的进展加以综述。     

听神经瘤分子生物学研究

听神经瘤起源于前庭神经雪旺细胞。单侧与双侧听神经瘤即Ⅱ型神经纤维瘤病(neurofibromatosis type2,NF2),其肿瘤形成机制基本相同。大量研究表明NF2基因突变是发病的主要分子机制,其编码蛋白产物的多种表达调控与肿瘤发生密切相关,有研究指出,其它肿瘤相关基因、生长调节基因、神经生长因子、细胞凋亡转录物等可能参与听神经瘤的形成。本文对听神经瘤分子生物学研究的进展加以综述。     

听神经瘤患者外淋巴的抗原性及蛋白含量

已证实听神经瘤患者血液淋巴细胞与听神经瘤浸液在试管内表现有细胞介导免疫(CMI)反应。本文研究听神经瘤患者外淋巴与其他听神经瘤患者血液单核细胞有无CMI反应,并探讨其与外淋巴生化成份的关系。     

双侧听神经瘤研究进展

散发的听神经瘤 (ａｃｏｕｓｔｉｃｎｅｕｒｏｍａ)即单侧听神经瘤 ,双侧听神经瘤在常染色体显性遗传的家族性肿瘤综合征即Ⅱ型神经纤维瘤病 (ｎｅｕｒｏｆｉｂｒｏｍａｔｏｓｉｓｔｙｐｅ 2 ,ＮＦ2 )中出现。位于第 2 2号染色体长臂上的ＮＦ2肿瘤抑制基因的突变是单侧和双侧听神经瘤的分子机制。其肿瘤发生机理符合“两次打击”模型。现将对目前有关双侧听神经瘤的研究进展加以综述。历史回顾　　Ｗｉｓｈａｒｔ在 182 2年报道了一个在 2 1岁时两耳听力丧失 ,经尸体解剖证实有双侧听神经瘤及多个颅内肿瘤的病例 ,被认为是第一个有记载的Ｎ…     

保存听力手术的听神经瘤复发率

一些学者在研究听神经瘤与蜗神经和内耳道底侧壁的关系后认为,保存听力的手术易导致肿瘤复发。作者对351例听神经瘤进行手术治疗,其中66例保存第Ⅷ神经,其中37例术后随诊5年以上。统计分析28例(76%)患者,手术时听神经瘤平均1.1cm,术后随诊5～13年,经CT及MRI检查,未发现肿瘤复发。作者认为行保存听力的听神经瘤手术的病例选择为,肿     

髓鞘结构在听神经瘤组织中的检测

目的:探讨来源于施万细胞的人类听神经细胞瘤组织中是否存在髓鞘结构及其细胞学特点。方法:应用免疫荧光标记、Western blotting及电镜等方法检测听神经瘤组织中的髓鞘结构及重要髓鞘蛋白。结果:电镜结果发现:听神经瘤组织中虽然缺失成熟的轴索结构但可以检测到早期的髓鞘样结构。免疫荧光研究和Western blotting研究结果显示:听神经瘤组织中检测不到轴索的标志性抗体——神经丝200的表达。并且启动髓鞘化的前哨信号及髓鞘致密化的重要组成蛋白——髓鞘碱性蛋白在听神经瘤组织中也无法检测到。而一种非成熟施万细胞的标志抗体——神经生长因子受体p75,在听神经瘤组织中可以检测到其表达。结论:在听神经瘤组织中的施万细胞失去了完成髓鞘化进程和重新形成致密的髓鞘并包绕轴索的能力,处于前髓鞘化施万细胞阶段。     

囊性听神经瘤成瘤研究新进展

听神经瘤为颅内常见肿瘤,分为实性和囊性,囊性听神经瘤生物学行为特殊,症状严重,治疗棘手,疗效不佳,故对听神经瘤囊性变机制的研究具有重要临床意义。听神经瘤囊性变机制仍未完全清楚,国内外学者主要从组织形态学、细胞分布、蛋白表达、基因组学等现象对囊性听神经瘤成瘤机制进行分析。肿瘤的发生本质上是体内原癌与抑癌基因失调所致,未来基因组学和表观遗传学研究将为听神经瘤囊性变机制提供更多信息。     

听神经瘤的治疗抉择 ——实现肿瘤切除与神经功能保护的完美统一

听神经瘤治疗方法包括显微手术、放射治疗、保守观察。随着听神经瘤生长规律研究的进展与显微手术技术的不断进步,治疗方式的选择争议不断。回顾近年来听神经瘤治疗的文献并结合研究结果,以神经功能保留和患者远期生活质量作为评价和选择治疗方法的依据,认为出现症状的听神经瘤患者,应首选手术治疗;乙状窦后入路适应于大、中、小各型听神经瘤,肿瘤全切除率高,死残率和并发症发生率低,能很好的保留面神经功能和听力,是治疗听神经瘤的较好选择。放射治疗是部分听神经瘤患者可选择的替代治疗方法。听神经瘤的保守观察需审慎。     

听神经瘤的来源

多数听神经瘤是神经鞘瘤,来源于前庭神经。Schuknecht认为听神经鞘瘤可来源于内听道的任何部位,Neely和Ylikoski认为肿瘤来源的部位主要在前庭下神经远端到胶质雪旺氏细胞联结处(glioschwannia junction)即在中枢神经和周围神经间移行处。作者对人和动物的前庭神经节超微结构研究以及小听神经瘤标本的初步观察,提示听神经鞘瘤可能来源于Scarpa神经节,在Scarpa神经节里有异常细胞存在。 20例听神经瘤标本中,11例听神经鞘瘤来源于前庭下神经,两侧来源于前庭神经,但不能确定是来源于前庭上支抑或前庭下支。其余     

听神经瘤的生物学特性

听神经瘤系源于第Ⅷ颅神经鞘膜上的肿瘤,属良性肿瘤,但因其发病部位若任肿瘤生长可危及生命。目前,临床上对听神经瘤患者治疗方案的选择和实施存在一定争议,因此,对听神经瘤生物学行为的研究有助于深化对本病发病规律的认识。本文将近年来有关听神经瘤生物学特性方面的研究作一综述。     

Neurotrophic factor expression in vestibular schwannoma. An overview

The vestibular schwannoma is a benign, slow-growing neoplasm that originates from the neurolemmal sheath of the vestibular branch of the VIIIth cranial nerve. This tumor entity accounts for 6 % of all intracranial tumors and the annual incidence of newly diagnosed vestibular schwannoma is reported as 13 per million. The molecular pathogenesis of both sporadic vestibular schwannoma and those occurring in neurofibromatosis type II appears to be associated with an aberration of a tumor suppressor gene on chromosome 22q12. The biological background for the various growth patterns of vestibular schwannoma is, however, largely unknown. This differing clinical and biological behaviour of vestibular schwannoma may be explained by the presence of neurotrophic factors. The results of recent immunohistochemical studies demonstrate the co-expression of transforming growth factor (TGF)-beta 1 and glial cell line-derived neurotrophic factor (GDNF) in vestibular schwannoma and suggest a trophic synergism of both neurotrophic factors in this tumor. Moreover, expression of numerous different neurotrophic factors has been shown in studies of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), neuregulin (NRG) and erythropoietin (EPO) indicating a biological role in development, maintainance or growth of vestibular schwannoma. In this article, we summarize the findings on neurotrophic factor expression and discuss their characteristics and biological role in vestibular schwannoma.     

Merlin蛋白在听神经瘤组织中的表达与分布

目的明确听神经瘤中merlin蛋白的表达及其在细胞内的分布。方法收集临床诊断并且经过术后病理证实的听神经瘤组织石蜡包埋标本54例,用免疫组织化学方法分析merlin蛋白在肿瘤组织中的表达,取三叉神经痛和晚期梅尼埃病患者接受手术治疗术中切除的神经组织作为对照组。用Western blot方法测试肿瘤组织中merlin蛋白的电泳迁移行为。用图像分析方法计算每例患者的阳性表达率,将merlin蛋白表达阳性率与患者年龄、性别、肿瘤生长指数、肿瘤直径和临床分期进行比较。结果merlin蛋白在听神经瘤组织中有不同程度的表达,阳性率为0～87．5％,平均(46．66±5．75)％,与肿瘤生长指数之间无明显相关性,与患者年龄、性别、肿瘤直径和临床分期无明显相关性。merlin细胞内分布部位有一定差异,以细胞核内、核周分布为主,也有部分分布于细胞质中。Western blot显示在听神经瘤组织中merlin蛋白位于65 000和125 000。结论在听神经瘤组织中存在merlin蛋白的表达,其在细胞内分布部位有一定变异。听神经瘤组织中merlin蛋白可能同时与其他蛋白以复合物的形式存在。     

Distinct spontaneous shrinkage of a sporadic vestibular schwannoma

We present a case with outspoken spontaneous vestibular schwannoma shrinkage and review the related literature. The patient was initially diagnosed with a left-sided, intrameatal vestibular schwannoma, which subsequently grew into the cerebello-pontine angle (CPA), followed by total shrinkage of the CPA component without any intervention over a 12-year observation period. The literature on spontaneous tumor shrinkage was retrieved by searching the subject terms “vestibular schwannoma, conservative management” in PubMed/MEDLINE database, without a time limit. Of the published data, the articles on “shrinkage” or “negative growth” or “regression” or “involution” of the tumor were selected, and the contents on the rate, extent and mechanism of spontaneous tumor shrinkage were extracted and reviewed. The reported rate of spontaneous shrinkage of vestibular schwannoma is 5–10% of patients managed conservatively. Extreme shrinkage of the tumor may occur spontaneously.     

听神经瘤S518磷酸化Merlin蛋白的表达及与CD44结合特性

目的 探讨听神经瘤组织中S518磷酸化对Merlin蛋白与细胞表面糖蛋白CD44结合能力的影响及其与肿瘤生长的关系.方法 35例听神经瘤组织标本均经过病理学证实,用免疫组织化学技术和免疫印迹技术分析S518磷酸化Merlin蛋白的表达、组织学分布情况,以手术中切除的正常颅神经作对照.将各标本中S518磷酸化Merlin条带的相对灰度值与听神经瘤临床分期、瘤体大小、病程及囊性变进行相关分析.用免疫沉淀技术比较野生型Merlin蛋白及S518磷酸化Merlin蛋白与CD44结合能力的差异.结果 在听神经瘤组织中Merlin蛋白发生S518磷酸化且分布集中于核周;正常对照神经组织中Merlin也发生S518磷酸化,但是其含量较听神经瘤组织低.S518磷酸化的Merlin蛋白在听神经瘤组织中的表达量与临床分期、肿瘤大小、病程及囊性变之间无统计学相关关系.在听神经瘤组织中,与S518磷酸化的Merlin蛋白结合的CD44量高于与野生型Merlin蛋白结合的CD44的量.结论 在听神经瘤组织中,S518磷酸化的Merlin蛋白与CD44的结合能力增加,CD44与野生型Merlin蛋白和S518磷酸化Merlin蛋白结合后可能产生不同细胞生物学行为.     

Simultaneous contralateral vestibular schwannoma and glomus jugulare tumor: a case report

To the best of our knowledge, only 3 cases of a simultaneous vestibular schwannoma and a glomus jugulare tumor have been previously reported in the literature. In all 3 cases, the lesions were located on the same side. We report a new case of simultaneous vestibular schwannoma and glomus jugulare tumor that is unique in that the two lesions arose on opposite sides. The glomus tumor was treated with embolization followed by radiotherapy, while the schwannoma was managed via radiologic observation.     

Postoperative quality of life in vestibular schwannoma patients measured by the SF36 Health Questionnaire

OBJECTIVE: To quantify the postoperative quality of life in patients following surgical treatment for vestibular schwannoma. STUDY DESIGN: Patient self-assessment using the short form 36 (SF36) multidimensional quality of life health questionnaire. Sex- and age-matched normalized scores were calculated using a standardized process and accepted normative data. SETTING: Tertiary referral skull base unit. RESULTS: An 80% response rate (90 patients) was achieved. The postoperative quality of life in vestibular schwannoma patients, as quantified by seven of the eight SF36 health scales was less than the appropriate matched healthy standard. Comparison of a variety of preoperative patients and tumor factors-different operative approaches (translabyrinthine and retrosigmoid), tumor size (group cut of points of tumor diameter 1.5 mm and 2.5 mm), patient sex, and ranking of patient age-showed no statistically significant difference in measured quality of life outcomes for each of these traditional predictors. CONCLUSION: Reduced quality of life in patients after surgical treatment for vestibular schwannoma, coupled with the low tumor growth rates and minimal preoperative symptoms, supports a conservative approach to patient management. The advantages and disadvantages of a variety of approaches used to measure the quality of life after surgical treatment of vestibular schwannoma and their impact on clinical decision making for patients, are discussed.     

Controversies in building a management algorithm for vestibular schwannomas

PURPOSE OF REVIEW: The present review examines the various mainstream treatment options, benefits and risks, and controversies involved in developing a management algorithm for treatment of vestibular schwannoma. RECENT FINDINGS: Advances in microsurgery and radiosurgery have made tremendous contributions to management of vestibular schwannoma; however, considerable controversy still exists. The auditory and facial nerve functional outcomes have improved with use of intraoperative monitoring for vestibular schwannoma removal and with lower radiosurgery doses; however, risks to the facial and auditory nerves still exist. Observing vestibular schwannomas for growth with serial magnetic resonance imaging is an increasingly popular option for small vestibular schwannomas that allows patients to enjoy hearing and facial function. SUMMARY: The risks and benefits of each treatment option must be weighed for each patient, and management decisions regarding vestibular schwannomas should be individualized for each patient depending on tumor anatomy, patient preferences, and symptoms.     

Vestibular schwannoma: negative growth and audiovestibular features

At the University Medical Center Utrecht, non-operative management was used for 44 patients with a unilateral vestibular schwannoma between 1990 and 1997. During that period, consecutive tumor sizes were determined by magnetic resonance imaging. Three of the 44 patients showed an average decrease in tumor size of 16.7% according to American Academy of Otolaryngology-Head and Neck Surgery standards. This study describes the initial vestibular status and audiometric changes measured over up to 10 years in these three patients. Vestibular function was determined once, by means of the bithermal caloric test, the torsion test, the saccade test, the smooth pursuit test, and the registration of spontaneous nystagmus. The three patients had severe vestibular paresis on the affected side. Pure-tone and speech audiometry were performed at regular intervals. Although the size of their tumors decreased, their hearing gradually deteriorated, just as it does in the majority of patients with a growing or stable vestibular schwannoma. The observations presented here suggest that the development of symptoms in a vestibular schwannoma does not differentiate between patients with a stable, growing or shrinking tumor. The development of symptoms may be the result of the same pathogenetic mechanism. Received: 3 July 2000 / Accepted: 12 May 2001     

听神经瘤术后单侧耳聋听力重建问题初探

摘要：目的探讨听神经瘤术后单侧耳聋患者人工听觉重建的效果。方法回顾性分析2016年7~12月上海交通大学医学院附属第九人民医院耳鼻咽喉头颈外科收治的听神经瘤术后单侧耳聋行人工听觉植入患者8例,其中同侧一期骨桥植入患者6例,二期同侧骨桥植入2例。比较术前及术后1年噪声下言语识别能力以及生活质量改变。结果所有病例均成功手术,肿瘤均完全切除。至随访1年,8例患者均正常使用听觉植入装置。骨桥植入患者噪声下言语识别能力明显提高,生活质量明显改善。结论骨桥可以帮助听神经瘤术后单侧耳聋患者有效地进行听觉功能重建,需要根据患者情况制订个体化的治疗方案。