Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in f f50% to 60% of glioblastoma multiforme tumors, and the most common EGFR mutant, EGFRvIII, is expressed in 24% to 67% of cases. We sought to determine whether glioblastoma multiforme expression of either overexpressed wild-type EGFR or the mutant EGFRvIII is an independent predictor of overall patient survival.Experimental Design: Glioblastoma multiforme patients (n = 196) underwent a _ > > 95% volumetric tumor resection followed by conformal radiation. Their EGFR and EGFRvIII status was determined by immunohistochemistry and survival analyses were done.Results: In our study of glioblastoma multiforme patients, 46% (n = 91) failed to express EGFR, 54% (n = 105) had overexpression of the wild-type EGFR, and 31% (n = 61) also expressed the EGFRvIII. Patients within groups expressing the EGFR, EGFRvIII, or lacking EGFR expression did not differ in age, sex, Karnofsky performance scale score, extent of tumor resection, or radiation. The median overall survival times for patients with tumors having EGFR expression absent, overexpressed only, or mutant (EGFRvIII) were 0.96, 0.98, and 1.07 years, respectively. However, for patients surviving _ > > 1 year, these values were 2.03, 2.02, and 1.21 years (P < < 0.0001; log-rank test comparing EGFRvIII with all others). This effect remained significant in the multivariate analysis after adjustment for all other cofactors including age and Karnofsky performance scale score (rate ratio 4.34; 95% confidence interval, 2.21-8.51). Conclusions:Neither the overexpressed wild-type EGFR nor EGFRvIII was an independent predictor of median overall survival in this selected cohort of patients who underwent extensive tumor resection. However, in patients surviving _ > > 1 year, the expression of EGFRvIII was an independent negative prognostic indicator.

Nitric oxide (NO) is a gaseous chemical messenger which has functions in the brain in a variety of broad physiological processes, including control of cerebral blood flow, interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, and release of neurotransmitters. As might be expected from the numerous and complex roles that NO normally has, it can have both beneficial and detrimental effects in disease states, including traumatic brain injury. There are two periods of time after injury when NO accumulates in the brain, immediately after injury and then again several hours-days later. The initial immediate peak in NO after injury is probably due to the activity of endothelial NOS and neuronal NOS. Pre-injury treatment with 7-nitroindazole, which probably inhibits this immediate increase in NO by neuronal NOS, is effective in improving neurological outcome in some models of traumatic brain injury (TBI). After the initial peak in NO, there can be a period of relative deficiency in NO. This period of low NO levels is associated with a low cerebral blood flow (CBF). Administration of L-arginine at this early time improves CBF, and outcome in many models. The late peak in NO after traumatic injury is probably due primarily to the activity of inducible NOS. Inhibition of inducible NOS has neuroprotective effects in most models.

BACKGROUND.Carcinoid tumors rarely metastasize to the brain. The objectives of the current study were to assess the frequency of brain metastasis from carcinoid tumors, determine correlates of survival, and describe treatment modalities and their outcomes. METHODS. BetweenJanuary 1977 and December 2003, 1633 patients with a carcinoid tumor were registered at The University of Texas M. D. Anderson Cancer Center. Of those, 24 patients (1.5%) had a diagnosis of brain metastasis. The authors collected demographic and clinical data and performed a statistical analysis. RESULTS.The median age at the time patients were diagnosed with brain metastasis was 60 years. The metastases were treated with whole-brain radiotherapy (WBRT) alone in 7 patients (29%), and 12 patients (50%) underwent surgical resection, 7 of whom (29%) also received WBRT. The median survival time for the entire cohort after diagnosis of the primary tumor was 2.3 years (95% confidence interval [CI], 0.5-4.1 years), and the median survival time after the diagnosis of brain metastasis was 10.0 months (95% CI, 4.0 -16.0 months). The longest median survival observed after the diagnosis of brain metastasis (3.2 years) occurred in patients who underwent resection and received WBRT. In the multivariate analysis, the adjusted rate ratio for comparison of all treatments versus combination of neurosurgical intervention and WBRT was 5.7 (95% CI, 1.3-26.1; P ϭ 0.024). A positive effect of surgery followed by WBRT on the duration of survival was detected in patients with a single metastasis (P ϭ 0.084) as well as in those with multiple metastases (P ϭ 0.018). CONCLUSIONS.Prolonged survival was observed in patients Ͻ 65 years old as well as in those who underwent surgery and received WBRT in comparison with other treatments. Whenever feasible, neurosurgical resection followed by WBRT seems to be the indicated treatment in patients with brain metastases from carcinoid tumors.

The purpose of this study was to examine the patterns of change in microdialysate concentrations of glucose, lactate, pyruvate, and glutamate in the brain during periods of hypoxia/ischemia identified by monitoring brain tissue pO2 (PbtO2). Of particular interest was a better understanding of what additional information could be obtained by the microdialysis parameters that was not available from the PbtO2. Fifty-seven patients admitted with severe traumatic brain injury who had placement of both a brain tissue pO2 (PbtO2) and microdialysis probe were studied. The microdialysis probe was perfused with Ringer's solution at 0.3 microL/min and dialysate was collected at 1-h intervals. The concentration of glucose, pyruvate, lactate, and glutamate were measured in each dialysate sample. Changes in the microdialysis parameters were examined during episodes where the PbtO2 decreased to below 10 mm Hg. Ten episodes of tissue hypoxia/ischemia identified by a decrease in PbtO2 below 10 mm Hg were observed during the period of monitoring. The concentration of the dialysate glucose closely followed the PbtO2. The dialysate pyruvate concentration was more variable and in some patients transiently increased as the PbtO2 dropped below 10 mm Hg. The dialysate concentration of lactate was significantly increased as the PbtO2 decreased to less than 10 mm Hg. Dialysate glutamate was significantly elevated only when PbtO2 decreased to very low levels. Although changes in the PbtO2 provided the earliest sign of hypoxia/ischemia, the microdialysis assays provided additional information about the consequences that the reduced tissue pO2 has on brain metabolism, which may be helpful in managing these critically ill patients.

Although the level of CBF is probably only one of the factors that determines the PbtO2 response to hyperoxia, it is apparent from these results that the areas of the brain that would most likely benefit from improved oxygenation are the areas that are the least likely to have increased PbtO2.

The inability of cerebral vessels to regulate CBF normally may play a role in the vulnerability of the injured brain to secondary ischemic insults. These studies indicate that this vulnerability continues and even increases beyond the first 24 hours postinjury. Local factors affecting cerebrovascular tone may be responsible for these findings.

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Hypodensity on plain CT scans does not always indicate reduction in CBF. This association was found more commonly when the low-density area was associated with a contusion. In hypodense areas associated with infarction, rCBF was variable and not commonly in the ischemic range at the time the CBF measurement was obtained.