Fluorescence-guided surgery for glioblastoma multiforme using high-dose fluorescein sodium with excitation and barrier filters

We have developed a technique of fluorescence-guided surgery using high-dose fluorescein sodium (20 mg/kg) with excitation and barrier filters for glioblastoma multiforme surgery. This technique was used in 10 patients, with surgery proceeding as expected in all patients. There were no complications or permanent side effects. This method uses filters to help distinguish between the usually invisible tumor and the brain surface, as well as allowing a detailed assessment of the positional relationships with tumor vessels and the surrounding normal vessels. As sufficient yellow staining was present even without filters, delicate microsurgery was also possible under a normal white-light microscope. Both environments could be used as necessary during surgery according to the requirements of resection, thereby improving the reliability and safety of surgery.     

荧光素钠在脑胶质瘤手术中的定位应用

目的回顾性研究荧光素钠在脑胶质瘤手术中的定位应用。方法将16例脑胶质瘤患者随机分为对照组与荧光组,荧光组术中应用荧光素钠定位,2组术后进行肿瘤切除率对比,术后3个月按照Karnofsky量表进行对比,术后6个月复查MRI了解肿瘤复发情况。结果对照组肿瘤全切2例,次全切6例;荧光组肿瘤全切7例,次全切1例。术后3个月按照Karnofsky量表(KPS)评分:对照组有效率12.5%,荧光组有效率50%;16例患者术后随访6个月,行MRI复查,对照组肿瘤复发2例,荧光组未发现肿瘤复发。结论应用荧光素钠作为胶质瘤术中的荧光指导,术中可以实时、直观地判断肿瘤边界,有助于缩短手术时间,提高肿瘤全切率,且经济、方便,为后期综合治疗提供基础,延长患者的生存时间。     

Anaphylactic reaction after fluorescein sodium administration during intracranial surgery

We present a male patient who underwent a fluorescein sodium-guided brain tumor excision and experienced an anaphylactic reaction with severe hypotension and bradycardia. A 54-year-old, 70 kg man of American Society of Anesthesiologists status II was seen with a history of glioma. In the 80th minute of the operation, 20 mg/kg intravenous (i.v.) fluorescein sodium was injected after dural opening. A few minutes later, the anaphylactic reaction was diagnosed. Surgery was ended and the patient was delivered to the intensive care unit with intubation. Laboratory values were: immunoglobulin E, 332 U (upper limit 100 U); and elevated tryptase, 3.12 mg/dL. In view of the expanding use of fluorescein sodium in clinical procedures, physicians should be alerted to this rare but life-threatening adverse event.     

Application of fluorescein sodium videoangiography in surgery for spinal arteriovenous malformation

We present our recent experience with fluorescein sodium videoangiography (FLVA) in the intra-operative evaluation of a patient with conus medullaris arteriovenous malformation (AVM). To our knowledge this is the first report in the literature of use of FLVA in the surgery of spinal AVM. Intra-operative FLVA was done to identify an early filling vessel and to obliterate the site of fistulous connection. This was correlated and confirmed with simultaneous indocyanine green videoangiography (ICGVA). The conus and cauda equina roots could be appreciated and manipulated in relation to this fluorescence. Obliteration was confirmed with FLVA and correlated with ICGVA. There was no untoward reaction to the dye injection. We conclude that FLVA is a useful adjunct in the surgical treatment of conus medullaris AVMs since it is a real time, noninvasive, radiation-free, easily reproducible technique allowing surgical manipulation through the operating oculars with simultaneous visualization of surrounding critical structures.     

荧光素钠在高级别胶质瘤手术价值的研 究简

目的评价荧光素钠指导高级别脑胶质瘤手术切除的准确性。方法回顾性分析50例高级别脑胶质瘤病例资料,术前行增强MRI检查,术中在荧光素钠染色下指导手术切除肿瘤,术后行增强MRI、MRS检查,测量并比较胶质瘤术后术腔壁（a区）、肿瘤侧正常脑组织（b区）及对侧相应区域正常脑组织（c区）的Cho／Cr值及差异。结果a区分别与b区、c区比较,差异有统计学意义（P〈0．05）．b区与c区比较,差异无统计学意义（P〉0．05）。结论在高级别胶质瘤手术中,严格按照荧光素钠的染色范围切除肿瘤,不能全切除肿瘤,需在不影响功能的前提下扩大切除。     

脑转移瘤治疗的研究进展

脑转移瘤是全身恶性肿瘤远距离转移的结果,全身恶性肿瘤死亡尸检中脑转移瘤检出率为10%～50%[1,2],如不治疗,平均生存时间1个月,激素治疗可使生存时间延长至2个月[1～3].     

弥散张量成像联合荧光素钠染色在脑功能区高级别胶质瘤手术中的应用

目的 探讨弥散张量成像（DTI）联合荧光素钠染色技术在脑功能区高级别胶质瘤（HGG）手术中的应用价值.方法 回顾性纳入2014年10月至2016年12月郑州大学第一附属医院神经外科收治的95例脑功能区HGG患者,其中49例（观察组）术前行增强MRI与DTI,术中应用荧光素钠染色技术引导切除肿瘤;46例（对照组）术前行MRI平扫与增强扫描,按传统方法切除肿瘤.术后72 h内复查MRI评估肿瘤切除程度,1个月后评估患者的肌力及Karnofsky功能状态评分（KPS）.结果 观察组的肿瘤全切除率明显高于对照组（83.7％对比45.7％,P＜0.001）.观察组肌力下降的比率明显低于对照组（20.4％对比47.8％,P=0.005）,而KPS评分改善率明显高于对照组（73.5％对比47.8％,P=0.029）.观察组应用荧光素钠染色技术识别胶质瘤范围的灵敏度为91.7％（44/48）,特异度为90.0％ （45/50）.结论 对脑功能区HGG患者应用DTI联合荧光素钠染色技术能够引导最大限度地切除肿瘤,最大程度地保护脑白质纤维束,降低手术致残率,提高患者的生命质量,值得临床推广.     

Angiogenesis in malignant primary and metastatic brain tumors

Patients with malignant primary and metastatic brain tumors have a poor prognosis, despite developments in diagnostic and therapeutic modalities. Therefore in the past decade a search for new therapeutic possibilities has started. The inhibition of angiogenesis, the sprouting of new capillaries from preexisting vasculature, which is an absolute requirement for the growth of tumors beyond a size of a few cubic millimeters, is one of the most promising approaches with which to influence tumor growth. This review focuses on the critical role of angiogenesis in the development of normal brain and the blood-brain barrier. We discuss the importance of angiogenesis in the formation of malignant brain tumors and in blood-brain barrier function in these tumors and possible consequences of altered blood-brain barrier properties for antiangiogenic therapy. Furthermore, results of current clinical trials with antiangiogenic drugs are reviewed, and clinical perspectives of antiangiogenic therapy in malignant brain tumors are outlined. Received: 25 May 1999 Accepted: 7 January 2000     

荧光显微镜在颅内恶性肿瘤切除术中的应用

目的 探讨小剂量荧光素钠（FLS）和560 nm荧光显微镜在切除颅内恶性肿瘤的中应用效果。方法 回顾性分析2016年9月至2018年2月手术治疗的51例颅内恶性肿瘤的临床资料。均在全麻诱导后静脉注射FLS（5 mg/kg）,在 560 nm荧光显微镜下判断肿瘤边界指导完成肿瘤切除。结果 51例中,胶质母细胞瘤33例,间变性星形细胞瘤6例,转移瘤4例,间变性少突胶质细胞瘤3例,胶质肉瘤3例,髓母细胞瘤2例。术中荧光均显影,明显提高肿瘤边界的可视化。肿瘤全切除32例,次全切除13例,部分切除6例。51例无任何过敏反应或其他不良反应。术后随访5~16个月,中位随访时间为9.5个月。术后KPS评分提高16例,下降15例,与术前相同20例。结论 应用小剂量FLS联合560 nm荧光显微镜辅助切除颅内恶性肿瘤安全、有效,有助于辨别肿瘤边界,提高肿瘤切除程度。     

伽玛刀治疗脑转移瘤 (附72例报告)

目的 探讨伽玛刀对脑转移瘤的治疗作用。方法 从2001年9月～2003年9月．79例脑转移患者接受伽玛刀治疗。其中72例(162个病灶)获得完全随访。该72例患者以50％～70％等剂量曲线包绕肿瘤，边缘剂量为14-24Gy，60例患者同时接受全脑照射，外照射剂量为30～40Gv。结果 72例患者(162个病灶)，随访期1～22个月，平均随访期10个月。完全缓解(CR)87例．部分缓解(PR)52例，无变化(NR)23例，总有效率为93．8％。结论 伽玛刀是一种安全的治疗脑转移瘤的方法，它可以缓解神经症状．提高生存质量，局部控制率较高。     

Outcome of repeated radiosurgery for recurrent metastatic brain tumors

OBJECTIVE: We investigated the outcome of repeated gamma knife radiosurgery (GKS) for local or remote recurrence after initial radiosurgery. MATERIAL AND METHODS: We retrospectively reviewed 204 patients who were treated with GKS. Among them 43 patients (21%) underwent GKS more than once. The second GKS was given for recurrence at the previously treated sites in 16 patients, new lesions at remote sites in 13, and both local recurrence and new lesions in 14. RESULTS: The median survival from the first GKS was 36 (7-190) weeks in all patients and 68 (16-156) weeks in 43 patients with repeated GKS. The median time from the first GKS to the second was 37 weeks. The median survival from the second radiosurgical intervention was 32 (7-132) weeks. Local control rate at 6 months after salvage GKS was 90.7%. RPA class was the commonly dominant prognostic factor in both initial and salvage GKS. CONCLUSION: Recurrence is common for patients with metastatic brain tumors after initial radiosurgery. Local control and survival time after salvage treatment are comparable with those after initial radiosurgery. GKS as a salvage treatment may provide additional survival benefit in selected patients.     

66例脑转移瘤的临床分析

目的　探讨脑转移瘤的临床特点和诊断治疗方法 ,提高对脑转移瘤的再认识。方法　回顾我院 1996～ 2 0 0 2年间 66例确诊的脑转移瘤患者的临床资料 ,并做统计分析。结果　 5 1例 ( 77 3 % )脑转移瘤来自肺癌 ,病理类型主要是腺癌。瘤体位于幕上 ,以多发灶为主 ,瘤周指状水肿显著 ,且常明显强化。综合治疗组的平均生存期为 8 5月。结论　CT增强扫描和MRI检查是诊断脑转移瘤的有效手段 ,手术治疗联合放疗及化疗能延长患者的生存期。     

Boron neutron capture therapy of primary and metastatic brain tumors

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10, is irradiated with low energy (0.025 eV) thermal neutrons (n _th) to yield alpha (⁴He) particles and,⁷Li nuclei (¹⁰B+n _th→[¹¹B]→⁴He+⁷Li+2.79 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of¹⁰B andn _th to individual cancer cells to sustain a lethal¹⁰B(n, α)⁷Li reaction. Boron delivery agents include a variety of compounds, such as the sulfhydryl containing polyhedral borane sodium borocaptate (Na₂B₁₂H₁₁SH, [BSH]), boronoporphyrins, boronophenylalanine, carboranyl uridines (CBU), and boronated monoclonal antibodies (MAb). The present review will focus on three delivery systems that currently are under investigation in our laboratories, boronated monoclonal antibodies, carboranyl uridines, and boronophenylalanine. Methodology has been developed to heavily boronate MAb using a precision macromolecule, a “starburst” dendrimer, which can be linked to MAb by means of heterobifunctional reagents. Although the resulting immunoconjugates retain their in vitro immunoreactivity, they lose their in vivo tumor localizing properties and accumulate in the liver. In order to obviate this problem, work is now in progress to produce bispecific MAb, which can simultaneously recognize a tumor-associated antigen and a boronated macromolecule. Boron containing, nucleosides are potential vehicles for incorporating boron compounds into nucleic acids of neoplastic cells. For this purpose, carboranyl uridines have been synthesized with the boron moiety on either the pyrimidine base or on the carbohydrate component. Although such structures appear to be avidly taken up and retained by tumor cells in vitro, only the 5-carboranyl-nucleosides are converted biologically to the nucleotide. There is no evidence, however, that the latter are incorporated into nucleic acids. Other carboranyl nucleosides currently are being synthesized that may have better tumor localizing properties. The potential use of boronophenylalanine as a capture agent for the treatment of melanoma metastatic to the brain also is under investigation. A nude rat model has been developed using human melanoma cells that are stereotactically implanted into the brain. BNCT-treated animals have either had prolonged survival times or continue to live compared to control rats that invariably died of their tumors, thereby suggesting therapeutic efficacy.     

Boron neutron capture therapy of primary and metastatic brain tumors

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10, is irradiated with low energy (0.025 eV) thermal neutrons (n _th) to yield alpha (⁴He) particles and,⁷Li nuclei (¹⁰B+n _th→[¹¹B]→⁴He+⁷Li+2.79 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of¹⁰B andn _th to individual cancer cells to sustain a lethal¹⁰B(n, α)⁷Li reaction. Boron delivery agents include a variety of compounds, such as the sulfhydryl containing polyhedral borane sodium borocaptate (Na₂B₁₂H₁₁SH, [BSH]), boronoporphyrins, boronophenylalanine, carboranyl uridines (CBU), and boronated monoclonal antibodies (MAb). The present review will focus on three delivery systems that currently are under investigation in our laboratories, boronated monoclonal antibodies, carboranyl uridines, and boronophenylalanine. Methodology has been developed to heavily boronate MAb using a precision macromolecule, a “starburst” dendrimer, which can be linked to MAb by means of heterobifunctional reagents. Although the resulting immunoconjugates retain their in vitro immunoreactivity, they lose their in vivo tumor localizing properties and accumulate in the liver. In order to obviate this problem, work is now in progress to produce bispecific MAb, which can simultaneously recognize a tumor-associated antigen and a boronated macromolecule. Boron containing, nucleosides are potential vehicles for incorporating boron compounds into nucleic acids of neoplastic cells. For this purpose, carboranyl uridines have been synthesized with the boron moiety on either the pyrimidine base or on the carbohydrate component. Although such structures appear to be avidly taken up and retained by tumor cells in vitro, only the 5-carboranyl-nucleosides are converted biologically to the nucleotide. There is no evidence, however, that the latter are incorporated into nucleic acids. Other carboranyl nucleosides currently are being synthesized that may have better tumor localizing properties. The potential use of boronophenylalanine as a capture agent for the treatment of melanoma metastatic to the brain also is under investigation. A nude rat model has been developed using human melanoma cells that are stereotactically implanted into the brain. BNCT-treated animals have either had prolonged survival times or continue to live compared to control rats that invariably died of their tumors, thereby suggesting therapeutic efficacy.