Transdifferentiation of glioblastoma stem-like cells into mural cells drives vasculogenic mimicry in glioblastomas.

Recent evidence has shown that glioblastoma stem-like cells (GSCs) can transdifferentiate into endothelial cells and vascular-like tumor cells. The latter pattern of vascularization indicates an alternative microvascular circulation known as vasculogenic mimicry (VM). However, it remains to be clarified how the GSC-driven VM makes a significant contribution to tumor vasculature. Here, we investigated 11 cases of glioblastomas and found that most of them consisted of blood-perfused vascular channels that coexpress mural cell markers smooth muscle α-actin and platelet-derived growth factor receptor ß, epidermal growth factor receptor, and vascular endothelial growth factor receptor 2 (Flk-1), but not CD31 or VE-cadherin. This microvasculature coexisted with endothelial cell-associated vessels. GSCs derived from patients with glioblastomas developed vigorous mural cell-associated vascular channels but few endothelial cell vessels in orthotopic animal models. Suppression of Flk-1 activity and gene expression abrogated GSC transdifferentiation and vascularization in vitro, and inhibited VM in animal models. This study establishes mural-like tumor cells differentiated from GSCs as a significant contributor to microvasculature of glioblastoma and points to Flk-1 as a potential target for therapeutic intervention that could complement current anti-angiogenic treatment.

A technique for mapping cortical areas associated with speech arrest.

BACKGROUND: Awake craniotomy with cortical stimulation is the standard for language mapping in patients with tumors near or within the language cortex. Reliable identification of the speech cortex is difficult, however, and adjunctive pre- and intraoperative techniques have inconsistent reliability. OBJECTIVES: We describe a technique based on direct cortical stimulation which localizes speech areas by correlating vocal cord activation in the anesthetized patient with speech arrest in the awake patient. METHODS: Direct cortical stimulation is applied to the patient and the vocal cords are visualized by fiberoptic endoscopy. The cortical site that produces vocal cord activation is identified. Once the patient is awakened, cortical stimulation is repeated and sites that produce speech arrest are identified. RESULTS: We have performed this technique in 3 patients and have consistently correlated vocal cord activation with speech arrest in all patients. These areas of activation also correlate with areas of functional MRI BOLD activation obtained from the expressive language paradigms. CONCLUSIONS: Colocalization of the site of vocal cord activation in the asleep patient to the site of speech arrest in the awake patient represents an adjunct for defining speech areas. This technique is useful for patients unable to tolerate awake craniotomy.

A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction.

BACKGROUND: The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE: To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN: Multicenter randomized trial. SETTING: Four teaching hospitals. PATIENTS: Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS: Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES: Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS: From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS: Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS: There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration.

Traumatic brain injury in intoxicated patients.

BACKGROUND: We sought to evaluate the effect alcohol intoxication may have had in nonsurgically treated patients with severe traumatic brain injury. METHODS: The Montreal General Hospital Traumatic Brain Injury Registry was used to identify all adult patients with a Glasgow Coma Scale score < or =8 at admission, within a 15-month period. All charts were retrospectively reviewed. RESULTS: Twenty-three patients had toxic blood alcohol levels (BAL > or =21.7 mmol/L), 24 were alcohol negative (BAL <3 mmol/L), and 10 were alcohol-influenced or had unknown BAL. Patients were more likely to have intracranial pressure monitoring if they had multiple intracranial hemorrhages, sustained multiple injuries, or had a post-resuscitative Glasgow Coma Scale score < or =8. Intoxicated patients had a mean delay of 151 minutes more in the insertion time of an intracranial pressure monitoring device, compared with alcohol-negative patients. CONCLUSIONS: Alcohol was a confounding factor in the treatment of some of our patients.

Intraoperative use of indocyanine green fluorescence videography for resection of a spinal cord hemangioblastoma.

BACKGROUND AND IMPORTANCE: Indocyanine green (ICG) fluorescence videography has been recently applied to the neurosurgical field, mostly in the management of cerebral aneurysms, but has had limited description in the subspecialty of spine or oncological neurosurgery. We describe a novel application of this previously defined surgical tool to assist in the resection of a residual spinal cord hemangioblastoma. CLINICAL PRESENTATION: Our patient is a 49-year-old woman with a residual symptomatic cervical hemangioblastoma that was previously embolized and resected at another institution. After initial symptomatic improvement, she returned with progressive symptoms, increasing radiographic spinal cord edema, and a residual lesion at the level of C1. We resected the remaining tumor with the adjuvant use of ICG fluorescence videography. Intraoperative injection of ICG clearly identified a component of the tumor underlying adhesive, opaque arachnoid that was not visualized by direct microscopy. Immediate postresection ICG videography suggested a complete resection was achieved which was later corroborated by postoperative magnetic resonance imaging. CONCLUSION: The adjuvant use of ICG videography is a useful surgical tool that permits greater visualization of the complete extent of the lesion, particularly in managing recurrent or residual lesions obscured by adhesions.