Assessing the efficacy and safety of hemangioblastoma embolization: A comprehensive systematic review and meta-analysis.

BACKGROUND: Hemangioblastomas (HBs) are highly vascular tumors linked to substantial morbidity and mortality. Recently, interventional neuroradiology has evolved rapidly, spurring interest in preoperative embolization as a possible HB treatment. PURPOSE: This study evaluates the effectiveness and safety of preoperative embolization in managing HB. METHODS: Adhering to PRISMA guidelines, this meta-analysis considered randomized and nonrandomized studies meeting specific criteria, encompassing intracranial HB and preoperative embolization. Primary outcomes were preoperative embolization efficacy and safety. Complications were classified as major (cerebellar ischemia, ischemic strokes, intratumoral hemorrhage, subarachnoid hemorrhage) and minor (transient nystagmus, slight facial nerve palsy, nausea, transient dysarthria, hemiparesis, hemisensory impairment, thrombotic complications, extravasation). RESULTS: Thirteen studies involving 166 patients with preoperative embolization before HB resection were included. Two studies using the Glasgow Outcome Scale (GOS) showed 5 patients with good recovery, 6 with moderate disability, and 3 with severe disability. Major complications occurred in 1% (95% CI: 0% to 3%), and minor complications occurred in 1% (95% CI: 0% to 4%). Intraoperative blood loss during resection was estimated at 464.29 ml (95% CI: 350.63 ml to 614.80 ml). CONCLUSION: Preoperative embolization holds promise in reducing intraoperative bleeding risk in neurosurgical intracranial HB treatment, primarily due to its low complication rates. Nonetheless, additional research and larger-scale studies are essential to establish its long-term efficacy and safety. These findings highlight preoperative embolization as a valuable tool for HB management, potentially enhancing future patient outcomes.

von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance.

von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. RECOMMENDATIONS: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

Efficacy and safety of current treatment options for peripheral retinal haemangioblastomas: a systematic review.

IMPORTANCE: Approximately twenty per cent of Von Hippel-Lindau patients with retinal haemangioblastomas (RH) suffer from visual impairment. Various treatment options are available for peripheral RH. However, management of peripheral RH is complex due to multifocality and bilaterality. OBJECTIVE: To summarize published evidence on efficacy and safety of different interventions for peripheral RH and to provide treatment recommendations for specialists. EVIDENCE REVIEW: Comprehensive searches were performed using Medline, Embase, Web of Science and Google Scholar database on 4 March 2020. English publications that described outcomes related to efficacy or complications in at least two patients with peripheral RH were included. Efficacy and safety were estimated by complete tumour eradication rate, pretherapeutic and treatment-related complication rate. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to calculate the risk estimate of complications between treatment options. FINDINGS: Twenty-seven articles were included in this review describing nine different treatment options for peripheral RH: laser photocoagulation (n = 230), cryotherapy (n = 50), plaque radiotherapy (n = 27), vitreoretinal surgery (n = 88), photodynamic therapy (PDT; n = 14), transpupillary thermotherapy (TTT; n = 10), external beam radiotherapy (n = 3), systemic treatment (n = 7) and intravitreal anti-VEGF (n = 2). Complete tumour eradication was achieved in 86.7% (95% CI: 83.5-89.9%) of all eyes. For the different treatments, this was after laser photocoagulation 89.9% (86.1-93.7%), cryotherapy 70.2% (57.0-83.4%), plaque radiotherapy 96.3% (89.1-100.0%), vitreoretinal surgery (100.0%), PDT 64.3% (38.3-90.3%) and TTT 80.0% (53.8-100.0%). No complete tumour eradication was achieved after systemic therapy, external beam radiotherapy or intravitreal anti-VEGF. Photodynamic therapy and vitreoretinal surgery showed the highest complication rate after treatment compared to the other treatments (OR 10.5 [95% CI: 2.9-38.4]) and (OR 5.9 [95% CI: 3.4-9.9]), respectively. Cases that had pretherapeutic complications showed a higher treatment-related complication rate (OR 14.8 [95% CI: 7.3-30.0]) than cases without complications before treatment. CONCLUSIONS AND RELEVANCE: These findings suggest that laser photocoagulation is the safest and most effective treatment method for peripheral RH up to 1.5 mm in diameter. Vitreoretinal surgery has the highest success rate for complete tumour eradication and may be the most suitable treatment option in the presence of pretherapeutic complications and for larger tumours.

Aggressive-fungating retinal hemangioblastoma.

Retinal hemangioblastomas are one of the most common and early manifestations of Von Hippel-Lindau disease. Early detection is the key in their management. When left untreated, these benign neoplasms may continue to grow and result in scleral infiltration and extraocular extension warranting enucleation of the globe.

Multimodal Imaging in the Diagnosis of Exophytic Juxtapapillary Retinal Capillary Hemangioblastoma.

PURPOSE: Exophytic juxtapapillary retinal capillary hemangioblastoma (JRCH) can be difficult to diagnose. We explore the value of multimodal imaging to aid in the diagnosis. DESIGN: Retrospective case series. METHODS: Medical records and multimodal imaging studies were reviewed on all patients diagnosed with RCH at Bascom Palmer Eye Institute, Miami, Florida, between January 2013 and December 2019. Patients with exophytic lesions within 2 mm of the disc were included. One patient from the Baylor College of Medicine, Houston, Texas was included. Patient demographics, referring diagnosis, history of von Hippel-Lindau syndrome, initial and last visual acuity, and treatments were recorded. Fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), OCT angiography, and B-scan images were reviewed. RESULTS: Twelve patients were identified with exophytic JRCH. The mean age was 54 years (range 38-73 years). Five patients had von Hippel-Lindau syndrome. The most common referral diagnoses were choroidal neovascularization and neuroretinitis. Imaging features included nodular outer retinal thickening with shadowing and intra-/subretinal fluid on OCT, hypoautofluorescence on fundus autofluorescence, middle to outer retinal hypervascularity on OCT angiography, early hyperfluorescence with late leakage on fluorescein angiography, and lack of choroidal vascular lesion on indocyanine green angiography. Treatments included photodynamic therapy (6 patients), intravitreal anti-vascular endothelial growth factor therapy (6 patients), argon laser photocoagulation (2 patients), intravitreal or sub-Tenon's triamcinolone (3 patients), and observation (4 patients). CONCLUSIONS: A key to the accurate diagnosis of exophytic JRCH is its intraretinal location, typically involving the outer retinal layers, which results in a clinical appearance that is distinct from the more common and easily recognizable endophytic RCH. Multimodal imaging can aid in ruling out choroidal neovascularization and disc edema by demonstrating an absence of involvement of those structures.

Masked malignant phenotype with a benign appearance: beat-up copy number profile may be the key for hemangioblastoma dissemination.

Dissemination of histologically benign hemangioblastoma is rare; approximately 30 cases have previously been reported, and all cases occurred several months to years after surgical resection. Herein, we report a case of hemangioblastoma in which leptomeningeal dissemination occurred 2 years after hypofractionated radiation therapy (39 Gy/13 fractions). The tumor was treated primarily with radiation without surgical resection. Biopsy of the disseminated lesion confirmed histological diagnosis as histologically benign hemangioblastoma. Ki67 index was not remarkably elevated for hemangioblastomas. In addition, the methylation class determined by the methylation profiling classifier developed by the German Cancer Research Center (DKFZ)/University Hospital Heidelberg/German Consortium for Translational Cancer Research was consistent with that of common hemangioblastomas. However, genetic analyses showed significant gains and losses throughout the whole genome, indicating that highly aberrant copy number profiles may be the key to elucidating this rare but life-threatening clinical entity. Accumulation of more detailed case reports based on the comparison of specimens obtained before and after surgery or radiation is necessary to better understand the pathophysiology of the dissemination phenotype of hemangioblastoma.

Intermixed arteriovenous malformation and hemangioblastoma: case report and literature review.

We report the third presentation of an intermixed arteriovenous malformation and hemangioblastoma. The rare occurrence of the diagnostic histologic features of both a neoplasm and vascular malformation in a single lesion is more common in gliomas, as angioglioma, and is termed an 'intermixed' lesion. We review the literature concerning the developmental biology of each lesion, and potential interplay in the formation of an intermixed vascular neoplasm and vascular malformation. The roles of cellular origin, genetic susceptibility, favourable microenvironment, altered local gene expression and key regulatory pathways are reviewed. Our review supports angiography and genetic profiling in intermixed lesions to inform management strategies. Consideration should be given to multimodality therapeutic interventions as required, including microsurgical resection, stereotactic radiosurgery and further research to exploit emerging molecular targets.

A solitary hemangioblastoma of the posterior brain fossa: the role of radiotherapy.

We report here the case of a patient admitted for management of posterior fossa cerebral hemangioblastoma. A 16-year-old male patient with a history of intracranial hypertension syndrome consisting of progressively worsening headache, vomiting, especially morning and jet vomiting, and decreased visual acuity. The patient's symptomatology worsened a few days later with the appearance of a disturbance of balance with enlargement of the sustentation polygon. The patient initially benefited from a brain computed tomography (CT) scan that objectified a solidocystic process of the posterior brain fossa. The patient then underwent a surgical excision that was considered partial and the diagnosis of hemangioblastoma was made on the surgical specimen. Since the surgical removal was partial the patient was referred to our training where he received external radiotherapy on his hemangioblastoma of the posterior brain fossa. The patient was examined one month after the end of irradiation; he presented a spectacular improvement in his neurological symptomatology with a clear regression of balance disorders. The standard treatment for cerebellar hemangioblastoma is complete microsurgical removal, but our results show a high level of efficacy for fractional photon radiotherapy after partial surgery of this benign tumour.

MANAGEMENT OF RETINAL HEMANGIOBLASTOMA IN VON HIPPEL-LINDAU DISEASE.

PURPOSE: To review the current state of diagnosis and management of retinal hemangioblastoma and retinal vascular proliferation arising from von Hippel-Lindau (VHL) disease. METHODS: A review of the literature was performed. Consensus was reached among authors regarding current practice, with reference to published data where possible. RESULTS: von Hippel-Lindau disease and its ocular manifestations are relatively rare, and there is limited evidence in the literature on which to base management. There was consensus on core principles, including 1) recognition and diagnosis of von Hippel-Lindau disease when present, with appropriate referral for care of this potentially lethal systemic condition; 2) regular ophthalmic evaluation for individuals with von Hippel-Lindau disease, to identify and offer timely treatment for new or active retinal hemangioblastomas; 3) ablative treatment of retinal hemangioblastomas that can be safely destroyed, to lower risk of vision loss; 4) observation or consideration of nonablative treatments for retinal hemangioblastomas that cannot be safely destroyed; and 5) observation of asymptomatic retinal vascular proliferation, with consideration of vitrectomy for lesions exerting effects on vision. CONCLUSION: Ocular outcomes can be gratifying in many cases with appropriate management. Improved understanding of the molecular basis for the disease creates an opportunity for rational design of better therapies.

Treatment Outcome of Intracranial Tumor Embolization in Japan: Japanese Registry of NeuroEndovascular Therapy 3 (JR-NET3).

Embolization for intracranial tumor is performed as a standard endovascular treatment. A retrospective, multicenter, observational study was conducted to clarify the nature, frequency, and risk factors of complications in intracranial tumor embolization. Patients were derived from the Japanese Registry of NeuroEndovascular Therapy (JR-NET3) using data taken from January 2010 through December 2014 in Japan. A total of 40,169 patients were enrolled in JR-NET3, of which, 1,545 patients (3.85%) with intracranial tumors underwent embolization. The primary end point was the proportion of patients with a modified Rankin scale (mRS) score of 0-2 (independency) at 30 days after embolization. The secondary end point was the occurrence of complications related to the procedures. The risk factors of the development of complications were analyzed. The proportion of patients with mRS scores ≤2 at 30 days after procedure was 89.5%. Complications occurred in 57 of the 1544 patients (3.7%). Multivariate analysis showed that target vessels other than external carotid artery (ECA) (OR, 3.56; 95% CI, 2.03-6.25; P <0.001) and use of liquid material (OR, 2.65; 95% CI, 1.50-4.68; P <0.001) were significantly associated with the development of complications. In JR-NET3, the primary end point was 89.5%, and the procedure-related complication rate was 3.7%. Embolization from other than ECA was significant risk factor of the complications. In addition, increasing usage of liquid embolic material worsened the risk of complications.

Management and outcomes of pregnant patients with central nervous system hemangioblastoma.

The study aims to assess the management and maternal and fetal outcomes of pregnancies complicated by central nervous system (CNS) hemangioblastoma. Twenty-four female patients with CNS hemangioblastoma, who were pregnant in a tumor-burden status, were identified. Their medical charts, treatments, and follow-up materials were carefully reviewed. Of the included 24 CNS patients with hemangioblastoma (14 intracranial and 10 spinal hemangioblastomas), 5 patients (20.8%) were diagnosed with Von Hippel-Lindau disease (VHL). The median age of these patients at admission was 27.5 years. Intracranial hypertension was a common presenting symptom for patients with intracranial hemangioblastoma and was observed in 85.7% (12/14) of cases; the other 10 patients with spinal hemangioblastomas all suffered from paresthesia. Overall, 66.7% (16/24) of patients with CNS hemangioblastoma went through the gestational course with conventional observation; 16.6% (4/24) of patients accepted a ventriculo-peritoneal shunt (VPS) to delay the tumor resection; and 16.7% (4/24) of patients needed urgent tumor resection even when symptomatic treatments were given. Variable symptom improvement was seen when patients had follow-up visits at a median of 32.5 months. No maternal death or tumor recurrence was identified. For the fetal prognoses, one (4.2%) pregnancy ended in a spontaneous miscarriage and for (16.7%) pregnancies were interrupted; the other 19 (79.2%) live births were in good status without any congenital malformations. Symptomatic treatment was the first choice for pregnant patients with CNS hemangioblastoma. When needed, urgent tumor resection could be safely achieved with careful maternal and fetal monitoring. Both maternal and fetal prognoses were favorable during follow-up.

Assessment of care pattern and outcome in hemangioblastoma.

Due to its rarity, current literature assessing prognostic factors and survival outcomes of hemangioblastoma is limited. Patients with histologically confirmed hemangioblastoma were identified from the US National Cancer Data Base. 1488 patients met inclusion criteria. 644 patients underwent gross total resection (GTR), 220 subtotal resection (STR)/biopsy, 60 stereotactic radiosurgery (SRS), 15 external beam radiotherapy (EBRT), 51 surgery followed by radiotherapy (SR + RT) and 498 no treatment. Independent predictors of shorter OS included age ≥ 40 (HR, 3.897; 95% CI, 2.341-6.487; p < 0.001), Charlson-Deyo score ≥ 1(HR, 1.756; 95% CI, 1.213-2.544; p = 0.003), tumor location in the brainstem (HR, 1.955; 95% CI, 1.129-3. 384; p = 0.017) compared to cerebellum, no treatment (HR, 2530; 95% CI, 1.533-4.177; p < 0.001) and receipt of EBRT (HR, 2.860; 95% CI, 1.073-7.618; p = 0.036) compared to STR/biopsy. GTR was associated with longer OS (HR 0.617; 95% CI, 0.391-0.974; p = 0.038), while SRS had comparable OS to STR/biopsy. The overall trend of OS by treatment modality was consistent after matching to age- and sex-matched US population data. In patients younger than 40 years, treatment was not a significant predictor of OS. In conclusion, GTR remained the optimal treatment for hemangioblastoma. SRS may perform similarly to surgery alone. Treatment was not a significant predictor of survival in younger patients.

[Retinal hemangioblastoma: Treatment strategy and long-term follow-up in a retrospective cohort]. / Hémangioblastomes rétiniens : stratégie thérapeutique et suivi à long terme dans une cohorte rétrospective.

INTRODUCTION: Retinal hemangioblastoma (RH) is a benign vascular tumor frequently associated with Von Hippel-Lindau disease (VHL). Tumor growth of RH may lead to deterioration of visual acuity, which can be difficult to treat. Early diagnosis may reduce complication rate and side effects of treatment. The present retrospective study evaluates the long-term follow-up and complications of RH treatment as a function of the therapeutic strategy used. MATERIALS AND METHODS: The study included patients with RH, followed at Croix Rousse university hospital, Lyon between 2010 and 2017. The following clinical features were recorded : age at diagnosis, presenting symptom, presence of VHL disease, treatments used, post-therapeutic complications and visual outcomes. RESULTS: Seven eyes of five patients were included in our study. Eighty percent of the patients had a mutation in the VHL gene. Four eyes (57%) were treated with laser photocoagulation and three eyes (43%) were treated with cryotherapy. The mean duration of follow-up was 35 months. One of the eyes treated using laser photocoagulation was complicated by an early epiretinal membrane with no visual consequence. Of the eyes treated by cryoapplication, one was complicated by a vitreous hemorrhage, and another by a rhegmatogenous retinal detachment, both of which resulted in a decrease in visual acuity. CONCLUSION: The long-term outcome for patients treated for RH was relatively good. Complications were strongly correlated with the initial size of the vascular tumor. Early diagnosis seems to improve visual outcomes. Ophthalmologic monitoring should be part of the systemic, multidisciplinary management.

The HIF and other quandaries in VHL disease.

Mutations in VHL underlie von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome with several subtypes depending on the risk of developing certain combination of classic features, such as clear cell renal cell carcinoma (ccRCC), hemangioblastoma and pheochromocytoma. Although numerous potential substrates and functions of pVHL have been described over the past decade, the best-defined role of pVHL has remained as the negative regulator of the heterodimeric hypoxia-inducible factor (HIF) transcription factor via the oxygen-dependent ubiquitin-mediated degradation of HIF-α subunit. Despite the seminal discoveries that led to the molecular elucidation of the mammalian oxygen-sensing VHL-HIF axis, which have provided several rational therapies, the mechanisms underlying the complex genotype-phenotype correlation in VHL disease are unclear. This review will discuss and highlight the studies that have provided interesting insights as well as uncertainties to the underlying mechanisms governing VHL disease.

Functional Outcome After Resection of Von Hippel-Lindau Disease-Associated Cauda Equina Hemangioblastomas: An Observational Cohort Study.

BACKGROUND: Cauda equina hemangioblastomas in von Hippel-Lindau (VHL) disease can cause significant neurological signs and symptoms. Despite their associated morbidity, the management of these tumors remains incompletely defined. OBJECTIVE: To determine optimal management, we analyzed the functional outcomes after resection of these tumors. METHODS: VHL patients who underwent surgical resection of cauda equina hemangioblastomas at the National Institutes of Health and the University of Virginia were included. Clinical and radiological follow-up was performed at 6- to 12-month intervals after surgery. RESULTS: Fifteen patients underwent 18 operations for 21 cauda equina hemangioblastomas (median follow-up 5.9 years). Patients often presented with multiple symptoms, including pain (67%), numbness (50%), urinary complaints (33%), and weakness (11%). Median preoperative tumor volume was 1.2 cm 3 . Four tumors at 3 operations were not resected due to a motor nerve root origin. Gross total resection was achieved in 14 surgeries (93% of operations when resection was attempted). New mild (non-function limiting) neurological symptoms were noted after 11 operations (61%), which most often (64%) resolved within 2 weeks of surgery. At 6-month follow-up, 15 patients (83%) were stable, 2 (11%) were improved, and 1 (6%) was worse. Histological analysis revealed that all tumors originated from within the involved nerve fascicle. CONCLUSIONS: VHL-associated cauda equina hemangioblastomas have an intrafascicular origin and require interruption of the rootlet of origin for complete resection. Motor nerve root involvement may preclude complete resection but strategies including bony decompression and/or interruption of vascular supply may provide a therapeutic option. Nevertheless, most VHL patients with symptom-producing lesions improve with resection.

[Preoperative Embolization for Solid Cerebellar Hemangioblastoma on the Day of Surgery:Two Case Reports].

Surgical resection of solid cerebellar hemangioblastomas can be challenging because of the profuse blood supply and tight space. We report two cases of solid cerebellar hemangioblastomas treated via surgical resection with the aid of preoperative endovascular embolization on the day of surgery. Case 1: A 36-year-old woman presented with a two-month history of headache and vomiting. Magnetic resonance imaging(MRI)revealed a right cerebellar solid mass, mild hydrocephalus, and apparent peritumoral edema. Angiogram showed a highly vascularized mass, three feeding arteries from the superior cerebellar artery(SCA), and a dilated vein draining into the confluence. We performed preoperative embolization of the three feeders with 15% n-butyl-2-cyanoacrylate(NBCA). Final angiogram showed an absence of tumor staining. Tumor resection was performed on the same day, and gross total resection was achieved with no complications. Case 2: A 36-year-old man presented with a four-month history of headache and numbness in the left upper extremity. MRI revealed a right cerebellar solid mass with peritumoral edema. Angiogram showed a highly vascularized mass with two feeding arteries from the right SCA, one from the left posterior inferior cerebellar artery(PICA), and a dilated vein draining into the confluence. Preoperative embolization was performed with 15% NBCA, and complete devascularization was achieved. Tumor resection was performed on the same day, and gross total resection was achieved with no complications. In conclusion, preoperative embolization with NBCA on the day of surgery is a safe and effective adjunctive treatment for solid cerebellar hemangioblastoma.

CNS hemangioblastomatosis in a patient without von Hippel-Lindau disease.

We report on a case of disseminated CNS hemangioblastoma, also referred to as hemangioblastomatosis, involving the supratentorial compartment and the entire spine. The patient presented with new onset headache, gait difficulties and memory deficits many years following resection of a hemangioblastoma from the cerebellum. The patient's family history was negative for von Hippel-Lindau (VHL) disease, and his personal history was negative for any additional VHL-defining lesions. Imaging revealed extensive dural caking and nodularity both supratentorially and in the spine, along with scattered parenchymal tumors showing a more typical appearance for hemangioblastoma. Biopsy of the dural thickening revealed histologic features compatible with hemangioblastoma. Genetic testing for VHL was eventually completed, and no evidence of a germline VHL mutation was detected.

Expression of angiopoietins in central nervous system hemangioblastomas is associated with cyst formation.

PURPOSE: This study aimed to determine the expression of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and endothelial tyrosine kinase receptor (Tie-2) in central nervous system (CNS) hemangioblastomas (HBs) and explore the correlation with peritumoral cyst formation. METHOD: A total of 22 paraffin-embedded specimens derived from 11 cyst-associated and 11 solid solitary CNS HBs were collected for streptavidin-peroxidase immunohistochemical staining. The expression levels of Ang-1, Ang-2 and Tie-2 in cystic and solid HBs were estimated and compared according to the integrated optical density (IOD) of staining in the sections. To further confirm the differential expression of Ang-1 and Ang-2 between cystic and solid HBs, an additional 9 frozen specimens from 5 cyst-associated and 4 solid solitary HBs were collected for Western blot analysis. Clinical histories and radiological records of the patients were reviewed retrospectively. RESULTS: Compared to normal cerebellum tissue, Ang-1, Ang-2 and Tie-2 were prominently overexpressed in both the stromal cells and endothelial cells of CNS HBs. The expression of Ang-2 and the ratio of Ang-2/Ang-1 in the cystic group were significantly higher than those in the solid group. The intensity of Ang-2 expression in the cystic group was negatively correlated with age. There was no correlation between the expression level of the proteins and sex, tumor location, tumor volume or cyst volume. CONCLUSIONS: Ang/Tie signaling is upregulated in HBs and is likely associated with the process of intense vascularization and cyst formation. Higher Ang-2 levels and a higher Ang-2/Ang-1 ratio may contribute to cyst formation by increasing the vascular permeability. The decrease in Ang-2 expression with advanced age in cystic-associated HBs may be associated with the reduced growth rate of peritumoral cysts among elderly patients. Ang-2 shows great potential as an effective therapeutic target of symptomatic CNS HBs associated with cysts.

Role of preoperative embolization of intramedullary hemangioblastoma.

OBJECT: Hemangiobastomas (HB) are rare lesions accounting for 1 to 5% of all spinal cord tumors. Due to their hypervascular nature, an angiography may be proposed preoperatively in order to identify tumoral vascular anatomy. Preoperative embolization may be indicated to reduce intraoperative bleeding, thus facilitating tumor resection and minimizing surgical risk. The aim of this paper is to report our experience of preoperative embolization in intramedullary hemangioblastomas. METHODS: We performed a retrospective analysis of all patients operated on for intramedullary hemangioblastomas between 1995 and 2014 who had undergone embolization before surgery. RESULTS: Seven patients were analyzed: there were 6 females and 1 male, mean age 43years, 6 patients had Von Hippel-Lindau disease. Four tumors were located in the cervical spine and three in the dorsal spine. The average maximum sagittal diameter was 19mm (range 8-32mm), while the average maximum axial diameter was 11.5mm (range 6-21mm). The embolic agent used was Histoacryl (NBCA). Endovascular embolization was routinely performed the day before surgery. One patient experienced a major preoperative complication with a vertebrobasilar infarctus with consequent unilateral cerebellar syndrome and gait instability. Minor extravasation of embolic agent was observed in two cases. In one of these two cases, there was also the penetration of the embolic agent in the tumor; the resection was impossible due to the hard consistency of the tumor. In the other 6 patients, the resection was total. Six patients had identical preoperative and postoperative McCormick score and one patient shifted to a better score at follow-up. CONCLUSION: Preoperative endovascular embolization is an effective adjunct treatment. It is useful in reducing the surgical bleeding and thus the operative risks. The procedure is not always safe and complications could occur. We recommend preoperative embolization in selected cases.