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Tom Mikkelsen, Pei-Sha Yan, Khang-Loon Ho, Mansoureh Sameni, Bonnie F. Sloane and Mark L. Rosenblum

✓ The poor prognosis of patients with malignant gliomas is at least partially due to the invasive nature of these tumors. In this study, the authors investigated the possibility that the cysteine protease cathepsin B (CB) is a participant in the process of glial tumor cell invasion. To accomplish this, an immunohistochemical analysis was made of the localization of antibodies to CB in biopsies of five specimens of normal brain, 16 astrocytomas, 33 anaplastic astrocytomas, and 33 glioblastomas multiforme.

Staining was scored according to the percentage of positive cells and the intensity of the stain, graded from 0 to 3+. Staining for CB was not seen in any of five samples of normal brain except for occasional neuronal cell bodies and microglia. Only five (31%) of 16 astrocytomas showed a small percentage of positive cells (0.01%–3%) that were stained in a light, diffuse cytoplasmic pattern (1+). Twenty-nine (87.8%) of 33 anaplastic astrocytomas showed positive light, granular staining in 2% to 40% of cells. In anaplastic astrocytoma, the staining within a tumor was heterogeneous with intensities of 1+ (17%), 1+ to 2+ (29%), or 2+ (55%). In contrast, all 33 (100%) glioblastomas were positive in 10% to 90% of cells. The staining was present in a coarse, granular pattern with an intensity of 2+ (12%) or 3+ (88%). Tumor cells infiltrating into brain adjacent to malignant gliomas stained positively in 26 cases that could be evaluated for glioblastoma multiforme; these invading cells frequently followed penetrating blood vessels as typical “secondary structures of Scherer.” Moderate to intense CB staining associated with endothelial proliferation in high-grade tumors was also observed, especially in regions of tumor infiltration into adjacent normal brain. These results provide evidence consistent with the hypothesis that CB is functionally significant in the process of tumor invasion and angiogenesis in the clinical progression of the malignant phenotype in astrocytomas.

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Jack P. Rock, Stephen Haines, Lawrence Recht, Mark Bernstein, Raymond Sawaya, Tom Mikkelsen and Jay Loeffler


In January 1998 the Guidelines and Outcomes Committee of the American Association of Neurological Surgeons (AANS) issued a charge for the development of evidence-based practice parameters focusing on the treatment of patients with single metastasis to the brain. The charge was imposed in response to the significant controversy surrounding questions relating to the optimal management strategies for patients with single brain metastasis.


A team consisting of physicians from the AANS, the American Academy of Neurology, and the American Association of Therapeutic Radiation Oncology convened and the literature was reviewed. Methodically drawing from the best of Class I, II, and III levels of available evidence, authors sought to determine how the literature addressed and disposed of the question of the optimal management for an adult with a known history of cancer and a single meta-static brain lesion. Framing the question in this specific manner allowed researchers to focus directly on treatment issues, without having to consider diagnostic issues.


The results of the evidence-based analysis demonstrated that there was insufficient information to establish standards of care. Data from the literature does, however, support a guideline stating that surgical resection accompanied by whole brain radiation therapy is associated with the best survival rate. Additional lower-quality evidence supports an option for management with radiosurgery.