Role of edema in peritumoral cyst formation.

Peritumoral cysts (those arising immediately adjacent to the tumor mass) are frequently associated with benign and malignant tumors of the brain and spinal cord (syringomyelia). The cystic component of central nervous system (CNS) tumors and associated peritumoral cysts are often the cause of clinical symptoms. Because of the common occurrence of peritumoral cysts with CNS neoplasms and the morbidity associated with them, advanced imaging, histological, and molecular techniques have been used to determine the mechanism underlying cyst formation and propagation. Based on evidence from such studies, edema appears to be a common precursor to peritumoral cyst formation in the CNS. Mediators of vascular permeability acting locally in the tumor and/or hydrodynamic forces within abnormal tumor vasculature appear to drive fluid extravasation. When these forces overcome the ability of surrounding tissue to resorb fluid, edema and subsequent cyst formation occur. These findings support the concept that the tumor itself is the source of the edema that precedes cyst formation and that resection of tumors or medical therapies directed at decreasing their vascular permeability will result in the resolution of edema and cysts.

[1]  Michael A. Finn,et al.  Edema is a precursor to central nervous system peritumoral cyst formation , 2005, Annals of neurology.

[2]  L. Aiello,et al.  Rapid and durable recovery of visual function in a patient with von hippel-lindau syndrome after systemic therapy with vascular endothelial growth factor receptor inhibitor su5416. , 2002, Ophthalmology.

[3]  W. Reinhold,et al.  Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. , 1993, The Journal of clinical investigation.

[4]  R. R. Lonser,et al.  von Hippel-Lindau disease , 2003, The Lancet.

[5]  T. Shawker,et al.  Elucidating the pathophysiology of syringomyelia. , 1999, Journal of neurosurgery.

[6]  J. Moringlane,et al.  Detection and quantification of vascular endothelial growth factor/vascular permeability factor in brain tumor tissue and cyst fluid: the key to angiogenesis? , 1994, Neurosurgery.

[7]  John A Butman,et al.  Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion. , 2002, Journal of neurosurgery.

[8]  R K Jain,et al.  Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. , 1988, Cancer research.

[9]  E. Oldfield,et al.  Pathogenesis of tumor-associated syringomyelia demonstrated by peritumoral contrast material leakage. Case illustration. , 2006, Journal of neurosurgery. Spine.

[10]  R. Liščák,et al.  Low-grade gliomas treated by fractionated gamma knife surgery. , 2005, Journal of neurosurgery.

[11]  P F Morrison,et al.  Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. , 1995, Journal of neurosurgery.

[12]  S. Richard,et al.  Treatment of von Hippel-Lindau retinal hemangioblastoma by the vascular endothelial growth factor receptor inhibitor SU5416 is more effective for associated macular edema than for hemangioblastomas. , 2003, American journal of ophthalmology.

[13]  P F Morrison,et al.  Convection-enhanced delivery of macromolecules in the brain. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Qin,et al.  Effect of brain irradiation on blood-CSF barrier permeability of chemotherapeutic agents. , 1997, American journal of clinical oncology.

[15]  H. Wurzer,et al.  Analysis of Fluid in Cysts Accompanying Various Primary and Metastatic Brain Tumours: Proteins, Lactate and pH , 1998, Acta Neurochirurgica.

[16]  Christopher J. Brown,et al.  Evidence for rapid fluid flow from the subarachnoid space into the spinal cord central canal in the rat , 1996, Brain Research.

[17]  T. Nose,et al.  Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. , 1996, Cancer research.

[18]  R T Borchardt,et al.  Vascular endothelial growth factor affects permeability of brain microvessel endothelial cells in vitro. , 1996, The American journal of physiology.

[19]  E. Oldfield,et al.  The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease. , 2003, Journal of neurosurgery.

[20]  T. Merchant,et al.  Effects of fractionated radiation on the brain vasculature in a murine model: blood-brain barrier permeability, astrocyte proliferation, and ultrastructural changes. , 2006, International journal of radiation oncology, biology, physics.

[21]  E. Papavassiliou,et al.  Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. , 1996, The Journal of clinical investigation.

[22]  K. Gwan Go,et al.  The Pathogenesis of Cysts Accompanying Intra-axial Primary and Metastatic Tumors of the Central Nervous System , 1998, Journal of Neuro-Oncology.

[23]  Barry W Wessels,et al.  Safety and Feasibility of Convection-enhanced Delivery of Cotara for the Treatment of Malignant Glioma: Initial Experience in 51 Patients , 2005, Neurosurgery.

[24]  R. Weil,et al.  Surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease. , 2003, Journal of neurosurgery.

[25]  Yue Cao,et al.  Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  G J Murray,et al.  Image-guided, direct convective delivery of glucocerebrosidase for neuronopathic Gaucher disease , 2007, Neurology.

[27]  C. Palmer,et al.  Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression. , 1997, Neurosurgery.

[28]  K. Ohtomo,et al.  Gamma knife surgery for hemangioblastomas. , 2005, Journal of neurosurgery.

[29]  Tracy T Batchelor,et al.  AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. , 2007, Cancer cell.

[30]  M. Berger,et al.  Progress Report of a Phase I Study of the Intracerebral Microinfusion of a Recombinant Chimeric Protein Composed of Transforming Growth Factor (TGF)-α and a Mutated form of the Pseudomonas Exotoxin Termed PE-38 (TP-38) for the Treatment of Malignant Brain Tumors , 2003, Journal of Neuro-Oncology.

[31]  Y. Mori,et al.  Gamma knife radiosurgery for low-grade astrocytomas: results of long-term follow up. , 2000, Journal of neurosurgery.

[32]  S. Coca,et al.  Vascular Permeability Factor Expression in Cerebellar Hemangioblastomas: Correlation with Tumor-associated Cysts , 2004, Journal of Neuro-Oncology.

[33]  Mitchel S Berger,et al.  Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies. , 2006, Neurosurgical focus.

[34]  K. Hemminki,et al.  Familial risks in nervous system tumors. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[35]  A. Holodny,et al.  MRI of high-grade glial tumors: correlation between the degree of contrast enhancement and the volume of surrounding edema , 1997, Neuroradiology.

[36]  E. Oldfield,et al.  Direct convective delivery of macromolecules to the spinal cord. , 1998, Journal of neurosurgery.

[37]  O. R. Blaumanis,et al.  Evidence for a ‘Paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space , 1985, Brain Research.

[38]  T. Merchant,et al.  Rd permeability and leukocyte adhesion in the rat blood-brain barrier: modulation with anti-ICAM-1 antibodies , 2003 .

[39]  D. Áfra,et al.  Cysts in malignant gliomas. Identification by computerized tomography. , 1980, Journal of neurosurgery.

[40]  H. van Mameren,et al.  On the pathogenesis of brain tumour cysts: a volumetric study of tumour, oedema and cyst , 2000, Neuroradiology.

[41]  A. Kalnin,et al.  Correlation between the degree of contrast enhancement and the volume of peritumoral edema in meningiomas and malignant gliomas , 1999, Neuroradiology.

[42]  Susan M. Chang,et al.  Dynamic susceptibility contrast perfusion imaging of radiation effects in normal‐appearing brain tissue: Changes in the first‐pass and recirculation phases , 2005, Journal of magnetic resonance imaging : JMRI.

[43]  U Klose,et al.  Role of hydrodynamic processes in the pathogenesis of peritumoral brain edema in meningiomas. , 2000, Journal of neurosurgery.

[44]  J. Boëthius,et al.  Gamma knife radiosurgery for pilocytic astrocytomas. , 2002, Journal of neurosurgery.

[45]  H. Dvorak,et al.  Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. , 1983, Science.

[46]  E. Blaauw,et al.  The pathogenesis of cerebral gliomatous cysts. , 1992, Neurosurgery.

[47]  R. Sestini,et al.  Genetic insights into familial tumors of the nervous system , 2004, American journal of medical genetics. Part C, Seminars in medical genetics.

[48]  J. Bruce,et al.  Vascular permeability induced by protein product of malignant brain tumors: inhibition by dexamethasone. , 1987, Journal of neurosurgery.

[49]  T H Shawker,et al.  Pathophysiology of syringomyelia associated with Chiari I malformation of the cerebellar tonsils. Implications for diagnosis and treatment. , 1994, Journal of neurosurgery.

[50]  M. Toi,et al.  Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. , 2001, The Lancet. Oncology.

[51]  A. Obwegeser,et al.  Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression , 2000, Acta Neuropathologica.

[52]  R. Weil,et al.  Surgical management of brainstem hemangioblastomas in patients with von Hippel-Lindau disease. , 2008, Journal of neurosurgery.

[53]  Y. Kakuta,et al.  Cyst formation following gamma knife surgery for intracranial meningioma. , 2005, Journal of neurosurgery.

[54]  Y. Song,et al.  Improved efficacy of chemotherapy for glioblastoma by radiation-induced opening of blood-brain barrier: clinical results. , 2001, International journal of radiation oncology, biology, physics.

[55]  J. Jääskeläinen,et al.  Gamma knife radiosurgery in 11 hemangioblastomas. , 1996, Journal of neurosurgery.

[56]  H. Wurzer,et al.  Cystic lesions accompanying extra-axial tumours , 1999, Neuroradiology.

[57]  E. Oldfield,et al.  Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors , 1997, Nature Medicine.

[58]  Ted,et al.  Address Reprint Requests To , 2008 .

[59]  A. Vortmeyer,et al.  Proteomic analysis of hemangioblastoma cyst fluid , 2006, Cancer biology & therapy.