To address these difficulties the Japanese EC- IC bypass trial (JET) randomized patients with 70% ICA/MCA stenosis and ,10% increase in cerebral blood flow in response to acetazolamide challenge (normal  30%) 10 to surgical vs medi- cal therapy. A significant decrease in stroke rates was observed in 2 years follow up. 11 Recently, results of the Carotid Occlusion Surgery Study (COSS) were published. 12 The study sought to determine whether patients with atherosclerotic internal carotid artery occlusion (AICAO) randomized to best medical therapy with or without EC-IC bypass surgery had reduced ipsilateral ischemic stroke at 2 years. All patients had symptomatic hemipsheric symp- toms within 120 days and hemodynamic cerebral ischemia identified by PET measurements of oxygen extraction fraction (OEF). The trial was terminated early for futility after 195 patients were randomized. Two-year rates of all stroke and death through 30 days following randomization and ipsilateral ischemic stroke within 2 years were 21% for the surgical group and 22.7% for the nonsurgical group. Thirty- day rates for ipsilateral ischemic stroke were 14.0% for the surgical group and 2.0% in the nonsurgical group. Graft patency was 98% at 30 days and 96% at last follow-up. The mean OEF ratio in the surgical group improved from 1.258 at baseline to 1.109 at the 30- to 60-day postoperative repeat PET scan. Despite excellent graft patency and aug- mented cerebral perfusion, EC-IC bypass sur- gery failed to be beneficial. The 2-year primary end point rate of 21% in the surgical group was close to the rate of 24% in historical data; conversely, the 2-year primary end point rate of 23% in the nonsurgical group was much lower than the rate of 40% projected from historical data. The lower stroke rate has been noted in a number of recent trials and may be attributable to improved outcomes in patients receiving medical therapy. 13,14 The recent randomized clinical trial assessing stenting vs aggressive medical therapy for intracranial stenosis also demonstrated improved overall outcomes for stroke patients and no benefit of endovascular intervention. 13 The study was limited by the low number of patients with the primary outcome, the lack of double blinding and sham surgery, and the variance in power calculations that may have demonstrated efficacy in a larger or completed study. Furthermore, the trial is limited to patients with atherosclerotic internal carotid artery occlusion and hemodynamic compromise demonstrated via PET scan OEF. Prior studies have focused on patients with patients with large vessel stenosis above C2 as well including ICA and MCA stenosis and more studies have been carried out using acetazolamide challenge. Fur- thermore, sub-classifications of patients with severe hemodynamic compromise may be the only cohort benefiting from surgical bypass. Additionally, alternative bypass methods, high flow bypass and new technologies may be beneficial in sub-cohorts of patients, and al- though outcomes for stroke patients are improv- ing, stroke is still a leading cause of disability and death. RICARDO J. KOMOTAR ROBERT M. STARKE E. SANDER CONNOLLY REFERENCES 1. Crowell RM, Yasargil MG. Experimental microvas- cular autografting. Technical note. J Neurosurg. 1969;31(1):101-104. 2. Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. The EC/IC Bypass Study Group. N Engl J Med. 1985;313(19): 1191-1200. 3. Vorstrup S, Brun B, Lassen NA. Evaluation of the cerebral vasodilatory capacity by the acetazolamide test before EC-IC bypass surgery in patients with occlusion of the internal carotid artery. 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The efficacy of direct extracranial-intracranial bypass in the treatment of symptomatic hemodynamic failure secondary to athero-occlusive disease: a systematic review. Clin Neurol Neurosurg. 2009;111(4):319-326. 9. Kappelle LJ, Klijn CJ, Tulleken CA. Management of patients with symptomatic carotid artery occlusion. Clin Exp Hypertens. 2002;24:631-637. 10. Neff KW, Horn P, Dinter D, Vajkoczy P, Schmiedek P, Duber C. Extracranial-intracranial arterial bypass surgery improves total brain blood supply in selected symptomatic patients with uni- lateral internal carotid artery occlusion and insuffi- cient collateralization. Neuroradiology. 2004;46(9): 730-737. 11. Ogasawara K, Ogawa A. [JET study (Japanese EC-IC Bypass Trial)]. Nihon Rinsho. 2006;64(suppl 7):524-527. 12. Powers WJ, Clarke WR, Grubb RL Jr, Videen TO, Adams HP Jr, Derdeyn CP. Extracranial-intracranial bypass surgery for stroke prevention in hemody- namic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. JAMA. 2011;306 (18):1983-1992. 13. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for in- tracranial arterial stenosis. N Engl J Med. 2011;365 (11):993-1003. 14. Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study. Stroke. 2010;41(1):e11-e17. CD90 is Identified as a Marker for Cancer Stem Cells in High-Grade Gliomas Using Tissue Microarrays M olecular characterization of tumors has revolutionized our ability to un- derstand the genetic basis of cancer biology. It is well known that tumor cells have differential expression of surface proteins known as clusters of differentiation (CD) that are unique to a given cell line. Identifying the unique CDs amongst different tumor cells enables molecular fingerprinting of individual tumors. The well-known surface protein CD90 is con- sidered a major marker for human stem cell pluripotency. It has been identified in many cancer stem cells (CSCs) including hematopoi- etic and mesenchymal lines. 1,2 In gliomas, CSCs demonstrate increased resistance to both che- motherapy 3 and radiation 4 ; as a result, they are thought to be largely responsible for tumor recurrence. The presence of CSCs in gliomas has been demonstrated, 5 however, the role of CD90 as a marker of glioma CSC has not been well studied to date. In recent work published by He et al from the University of Michigan, the investigators studied the variable expression patterns of CD90 in high and low grade gliomas vs normal brain tissue. 6 Their work describes three extremely important aspects of CD90 in GBM tumorgenesis: (1) the role of CD90 as a marker for high grade glioma; (2) the role of CD90 in CSC formation; and (3) the location of CD90 1 cells around vascular structures within GBM. In their experiments, glioma tissue was pro- vided from 58 distinct donors whereby 15 samples were GBM, 19 were WHO grade III SCIENCE TIMES NEUROSURGERY VOLUME 70 | NUMBER 4 | APRIL 2012 | N23 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. Downloaded from https://academic.oup.com/neurosurgery/article-abstract/70/4/N23/2617609 by guest on 31 May 2020