Glioma response assessment: Classic pitfalls, novel confounders, and emerging imaging tools.

Neuroimaging plays a pivotal role in the care of patients with infiltrating gliomas, in whom imaging changes are often the first indications of tumor response or progression. Unfortunately, evaluation of glioma response is often not straightforward, even for experienced radiologists. Post-surgical or radiation-related changes may mimic the appearance of disease progression, while medications such as corticosteroids and antiangiogenic agents may mimic tumor response without truly arresting tumor growth or improving patient survival. Immunotherapy response can result in inflammatory changes which manifest as progressively increasing tumor enhancement and edema over months. Many of these pitfalls can be minimized or avoided altogether by the use of modern brain tumor response criteria, while others will require new imaging tools before they can be fully addressed. Advanced MRI methods and novel positron emission tomography (PET) agents are proving important for this purpose, and their role will undoubtedly continue to grow in the future.

Adult Pilocytic Astrocytoma: An Institutional Series and Systematic Literature Review for Extent of Resection and Recurrence.

INTRODUCTION: Pilocytic astrocytoma is a classically benign tumor that most often affects pediatric patients. Rarely, it occurs during adulthood. We present a case series and systematic literature review of adult pilocytic astrocytoma (APA) to examine the clinical presentation, extent of resection, and recurrence rate associated with this tumor in this population. MATERIALS AND METHODS: Our institutional records were retrospectively reviewed for cases of pilocytic astrocytoma in adults. A PubMed search identified English-language studies of pathology-proven APA. A meta-analysis was performed to determine the relationship between extent of tumor resection and recurrence. RESULTS: Forty-six patients with APA were diagnosed at our institution (mean age 33.6 ± 13.3; 24 [52%] female). Twenty-four patients (52%) underwent gross total resection, 11 (24%) subtotal resection, 4 (9%) near total resection, 4 (9%) observation after biopsy, and 3 (6%) radiotherapy alone. Tumors recurred or progressed in 6 (13%) patients, of whom 4 were treated by STR and 2 were treated by radiotherapy alone. Thirty-nine (95%) patients were still alive at last follow-up. A systematic literature review identified 415 patients with APA in 38 studies. Including our case series, 7 studies reported extent of resection, follow-up, and recurrence. Of 254 patients with a weighted mean follow-up of 77.7 ± 49.6 (31-250) months, 129 (51%) were treated with gross total resection, and 125 (49%) underwent subtotal resection. Tumor recurred in 79 (31%) patients, 22 (27%) after gross total resection and 57 (73%) after subtotal resection (P < 0.001). CONCLUSIONS: Pilocytic astrocytoma rarely presents during adulthood. Overall, prognosis is favorable and survival rates are high. APA recurrence is more likely after STR, and the goal of surgery should always be GTR when feasible.

The consistency of myocardial strain derived from heart deformation analysis.

The purpose of this study was to assess the consistency of semi-automated myocardial strain analysis by prototype software across field strengths, temporal resolutions, and examinations. 35 volunteers (48 ± 13 years; 20% women) and 25 patients (54 ± 12 years; 44% women) without significant cardiac dysfunction underwent cine cardiac magnetic resonance imaging (CMR) at 1.5 T with a temporal resolution of 39.2 msec. 34 subjects also underwent imaging at 3.0 T; 16 had repeat examinations within 14 days; and 9 underwent CMR with temporal resolutions of 12.5 and 39.2 msec on the same day. Prototype heart deformation analysis (HDA) software was used to retrospectively quantify strain from segmented balanced steady state free precession (bSSFP) cinegraphic images. Myocardial contours were automatically generated on short axis images and drawn at end-diastole by two independent reviewers on long-axis images. Contours were automatically propagated throughout the cardiac cycle. Global and regional peak systolic strain were compared across observers, field strengths, temporal resolutions, and examinations. Inter-observer agreement was excellent (ICC > 0.87, p < 0.01). Inter-examination variability was low, ranging from 1.7 (1.0-2.4)% to 2.5 (1.9-3.1)%, except for radial strain: 9.2 (7.6-10.5)%. Most global and regional strain values were not significantly different across field strengths and temporal resolutions (p > 0.05). Normal global peak systolic strain values with HDA were -25.0 (-24.0 to -26.1)% (LV circumferential), 60.5 (55.3 to 65.6)% (LV radial), -22.3 (-20.5 to - 24.0)% (LV longitudinal), and -26.0 (-23.8 to -28.2)% (RV longitudinal). HDA prototype software enabled efficient and consistent quantification of myocardial strain from conventional bSSFP cine CMR data, demonstrating clinical feasibility.

Treatment of ruptured complex and large/giant ruptured cerebral aneurysms by acute coiling followed by staged flow diversion.

OBJECT Flow-diversion treatment has been shown to be associated with high rates of angiographic obliteration; however, the treatment is relatively contraindicated in the acute phase following subarachnoid hemorrhage (SAH) as these patients require periprocedural dual antiplatelet therapy. Acute coiling followed by flow diversion has emerged as an intriguing and feasible treatment option for ruptured complex and giant aneurysms. In this study the authors report outcomes and complications of patients with ruptured aneurysms undergoing coiling in the acute phase followed by planned delayed flow diversion. METHODS This case series includes patients from 2 institutions. All patients underwent standard endovascular coiling in the acute phase after SAH with the intention and plan to proceed with flow diversion at a later date. Outcomes studied included angiographic occlusion, procedure-related complications, and long-term clinical outcome as measured using the modified Rankin Scale. RESULTS A total of 31 patients underwent coiling in the acute phase with the intention to undergo flow diversion at a later date. The mean aneurysm size was 15.8 ± 7.9 mm. Of the 31 patients undergoing coiling, 4 patients could not undergo further flow-diverter therapy: 3 patients (9.7%) died of complications of subarachnoid hemorrhage and 1 patient had permanent morbidity as a result of perioperative ischemic stroke (3.1%). Twenty-seven patients underwent staged placement of flow diverters after adequate recovery. The median time to treatment was 16 weeks. There was one case of aneurysm rebleeding following coil treatment. There were no cases of permanent morbidity or mortality resulting from flow-diverter treatment. Twenty-four patients underwent imaging follow-up; 18 of these patients had aneurysms that were completely or nearly completely occluded (58.1% on an intent-to-treat basis). At last follow-up (mean 18.3 months), 25 patients had mRS scores ≤ 2 (80.6% on an intent-to-treat basis). CONCLUSIONS Staged treatment of ruptured complex and giant intracranial aneurysms with coiling in the acute phase and flow-diverter treatment following recovery from SAH is both safe and effective. In this series, no cases of rebleeding occurred during the interval between coiling and flow diversion. This strategy should be considered as a valid option in patients presenting with these challenging ruptured aneurysms.

Paraclinoid aneurysms: is there a new endovascular standard?

OBJECTIVES: Paraclinoid aneurysms are challenging lesions to treat with traditional surgical and conventional endovascular techniques despite modern improvements in technique and technology. Flow diversion emerged recently as a promising new therapy that overcomes limitations related to the wide-neck and fusiform morphology, and importantly addresses the underlying diseased parent artery from which the aneurysm arises. METHODS: We reviewed the current literature regarding the safety and efficacy of flow diversion therapy for treatment of paraclinoid aneurysms. RESULTS: Early results suggest excellent ability for flow diversion to remodel the diseased parent artery and achieve durable complete angiographic occlusion of the aneurysm with acceptable rates of peri-procedural risk. DISCUSSION: Flow diversion therapy can achieve durable and high rates of obliteration that surpass traditional methods of management for paraclinoid aneurysms. However, caution is warranted when considering this treatment modality due to several concerning and often-unpredictable complications associated with this technology.

Brain carcinoid metastases: outcomes and prognostic factors.

OBJECT: Carcinoid tumors are rare and have generally been regarded as indolent neoplasms. Systemic disease is often incurable; however, patients may live years with this disease. Furthermore, metastatic brain lesions are extremely uncommon. As such, few series have examined outcomes and prognostic factors in those with brain involvement. METHODS: The authors performed a retrospective review of patients who underwent primary treatment at Mayo Clinic in Rochester, Minnesota, for metastatic carcinoid tumors to the brain between 1986 and 2011. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier statistics. Cox proportional hazards were used to determine predictors of survival. RESULTS: Fifteen patients underwent primary treatment for metastatic carcinoid tumors to the brain between 1986 and 2011. Their mean age was 58 ± 12 years. Eighty percent (n = 12) of patients underwent surgery, whereas 2 received stereotactic radiosurgery and 1 had whole-brain radiation therapy (WBRT) as the primary treatment. The median follow-up duration was 19 months (maximum 124 months). Systemic disease progression occurred in 73% and was the leading cause of death in known cases, while intracranial disease recurred in 40%. The median PFS and OS were 21 and 19 months, respectively. The use of adjuvant WBRT correlated with improved PFS (HR 0.15, CI 0.0074-0.95, p = 0.044). Those who underwent surgery as primary modalities trended toward longer progression-free intervals (p = 0.095), although this did not reach significance. CONCLUSIONS: Metastatic carcinoid disease to the brain appears to have a worse prognosis than that of other extracranial metastases. Although there was a trend toward a survival advantage in patients who underwent surgery and WBRT, further study is needed to establish definitive treatment recommendations.

Atypia predicting prognosis for intracranial extraventricular neurocytomas.

OBJECT: The literature, at present, provides limited information about extraventricular neurocytomas (EVNs) and is almost exclusively composed of case reports or small case series. Treatment for EVNs has largely been guided by results from central neurocytoma outcome studies. The authors present an analysis of all reported intracranial EVN cases to establish if tumor histopathological features can substratify EVN into groups with differing prognosis and help guide treatment decisions. METHODS: The authors identified studies reporting histology, treatment modality, and outcomes for patients with intracranial EVN. The rates of recurrence and survival for patients were compared using Kaplan-Meier analysis. Atypical tumors, defined by MIB-1 labeling index exceeding 3% or atypical histological features, were compared with typical tumors, and patients 50 years of age or older were compared with those younger than 50 years of age. RESULTS: Eighty-five patients met the inclusion criteria, and 27% of them had an atypical histology. Typical EVNs had a better prognosis than atypical EVNs after primary treatment, with a 5-year recurrence rate of 36% compared with 68% (p < 0.001), and a 5-year mortality rate of 4% compared with 44%, respectively (p < 0.001). Age younger 50 years was associated with a better prognosis than age equal to or greater than 50 years, with a 5-year recurrence rate of 33% and 74%, respectively (p < 0.001), and a 5-year mortality rate of 4% and 52%, respectively (p < 0.001). Multivariate analysis demonstrated that atypical EVNs carried significantly increased risk for recurrence (hazard ratio [HR] 4.91, p < 0.001) and death (HR 22.91, p < 0.01). Gross-total resection was superior to subtotal resection (STR) alone in tumor control rates for typical EVNs (95% and 68%, p < 0.05), and there was a trend for adjuvant external-beam radiotherapy to benefit STR. There was suggestion of similar trends in patients with atypical EVNs. CONCLUSIONS: There are at least 2 distinct histological subtypes of EVN, with different prognostic significances. Atypia or MIB-1 labeling index greater than 3% is a significant predictor of poor prognosis for EVNs. Complete resection or more aggressive attempts at providing adjuvant therapy following STR appear to improve the prognosis for patients with EVNs. Although the authors' results are informative, there are limitations to their analysis. Given the relatively modest total number of cases reported, as well as the nature of the disaggregated analysis, the authors were not able to use formal meta-analytical methods to limit the impact of between center heterogeneity. Additionally, they were not able to control for individual differences in data analysis and presentation across the different studies included in their analysis.

Anatomic location is a risk factor for atypical and malignant meningiomas.

BACKGROUND: Grade II and III meningiomas have higher rates of tumor recurrence than grade I meningiomas after surgery and/or external irradiation. As the utility of noninvasive treatments for brain tumors increases, it is becoming increasingly important to assess the likelihood that a tumor is not benign before treatment initiation. Hence, the authors have reviewed a large series of their patients to determine risk factors for higher-grade pathology, with particular interest paid to tumor location. METHODS: The authors reviewed 378 patients presenting at their institution from 2000 to 2007 with histologically confirmed meningioma, central pathology grading according to the World Health Organization 2000 guidelines, and tumor location confirmed with preoperative imaging. They performed univariate and multivariate logistic regression on potential risk factors for high-grade pathology. RESULTS: Risk factors for grade II/III pathology included nonskull base location (2-fold) and male sex (2-fold). Patients with prior surgery had a 3-fold increased incidence of higher-grade meningiomas at presentation at the authors' center. The authors controlled for this referral bias by performing a multivariate regression, and analysis without patients receiving prior treatment. Ninety-seven percent of operations were performed for tumor size and clinical symptoms, whereas <3% were performed for interval growth or features concerning higher-grade pathology. CONCLUSIONS: Nonskull-base meningiomas, male sex, and prior surgery impart increased risk for grade II or III pathology. This increased risk translates to probable poorer prognosis and increased likelihood of recurrence after treatment. Thus, it is prudent to take these specific variables into consideration in conjunction with the complete clinical presentation when advising patients regarding their prognosis.

Incidence, risk factors, and outcome of venous infarction after meningioma surgery in 705 patients.

Central to safe and effective surgical resection of meningiomas is consideration of the venous anatomy both near and intrinsic to the tumor. The exact incidence of venous infarction following meningioma surgery has not been established. To determine this incidence, we present a large multivariate analysis of 705 patients undergoing craniotomy for resection of a histologically proven meningioma at our institution between 1991 and 2007. Clinical information was retrospectively reconstructed using patient medical records and radiologic data. Venous infarctions were identified by postoperative CT scans or MRI that demonstrated the typical imaging findings. Stepwise multivariate logistic regression analysis was performed to test the association with approach used and the rate of venous infarction, controlling for multiple independent variables. The overall rate of venous infarction (n=705) was 2.0% of all patients (95% confidence interval [CI], 0.9-3.0%). Interestingly, on multivariate logistic regression analysis, we found the use of a bifrontal craniotomy was the sole independent predictor of venous infarction in this regression model (odds ratio, 3.18; 95% CI, 1.03-9.77; p<0.05). We found that the rate of venous infarction was significantly reduced in the extended bifrontal group compared to the group not receiving biorbital osteotomies (0% versus 8.9%, χ(2)p<0.05). We demonstrated that the most important factor determining the risk of venous infarction is the approach used to access the tumor.

Early surgical intervention in adult patients with ganglioglioma is associated with improved clinical seizure outcomes.

Gangliogliomas are rare central nervous system tumors, most commonly affecting children and young adults. Chronic seizure and epilepsy are the most frequent presentation of patients with gangliogliomas. In this report, we review the modern literature regarding the effects of early surgical intervention on the clinical outcome of patients with ganglioglioma. A boolean search of PubMed using key words "ganglioglioma", "adult", "seizure control", "treatment", "surgical intervention", and "observation", alone and in combination was performed. The inclusion criteria for articles were that: (i) clinical outcomes were reported specifically for gangliogliomas; (ii) data were reported for adult patients older than the age of 18 years; (iii) treatment data were included for the treatment of gangliogliomas; and (iv) ganglioglioma was the only pathological diagnosis for the evaluation of the tumor. Data were analyzed as a whole then stratified into two groups: early and late treatment intervention. The query identified a total of 99 articles including 1,089 cases of ganglioglioma meeting our inclusion and exclusion criteria. There was a 55% prevalence of males, representing a statistically significant predilection (51-59%, 95% confidence interval). Seizure control was significantly improved when surgical intervention occurred less than 3 years after symptom onset (78% versus 48%; p = 0.0001). Ganglioglioma in adults represents a rare group of tumors, and our systematic analysis suggests a higher prevalence in males. Our findings also support that an early surgical intervention is significantly associated with improved clinical seizure control.

Beyond audiofacial morbidity after vestibular schwannoma surgery.

OBJECT: Outcomes following vestibular schwannoma (VS) surgery have been extensively described; however, complication rates reported in the literature vary markedly. In addition, the majority of reports have focused on outcomes related to cranial nerves (CNs) VII and VIII. The objective of this study was to analyze reported morbidity unrelated to CNs VII and VIII following the resection of VS. METHODS: The authors performed a comprehensive search of the English language literature, identifying and aggregating morbidity and death data from patients who had undergone microsurgical removal of VSs. A subgroup analysis based on surgical approach and tumor size was performed to compare rates of CSF leakage, vascular injury, neurological deficit, and postoperative infection. RESULTS: One hundred articles met the inclusion criteria, providing data for 32,870 patients. The overall mortality rate was 0.2% (95% CI 0.1-0.3%). Twenty-two percent of patients (95% CI 21-23%) experienced at least 1 surgically attributable complication unrelated to CNs VII or VIII. Cerebrospinal fluid leakage occurred in 8.5% of patients (95% CI 6.9-10.0%). This rate was markedly increased with the translabyrinthine approach but was not affected by tumor size. Vascular complications, such as ischemic injury or hemorrhage, occurred in 1% of patients (95% CI 0.75-1.2%). Neurological complications occurred in 8.6% of cases (95% CI 7.9-9.3%) and were less likely with the resection of smaller tumors (p < 0.0001) and the use of the translabyrinthine approach (p < 0.0001). Infections occurred in 3.8% of cases (95% CI 3.4-4.3%), and 78% of these infections were meningitis. CONCLUSIONS: This study provides statistically powerful data for practitioners to advise patients about the published risks of surgery for VS unrelated to compromised CNs VII and VIII.

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma.

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson's chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33-41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ(2) P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05-5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available.

The complement cascade as a mediator of tissue growth and regeneration.

Recent evidence has demonstrated that the complement cascade is involved in a variety of physiologic and pathophysiologic processes in addition to its role as an immune effector. Research in a variety of organ systems has shown that complement proteins are direct participants in maintenance of cellular turnover, healing, proliferation and regeneration. As a physiologic housekeeper, complement proteins maintain tissue integrity in the absence of inflammation by disposing of cellular debris and waste, a process critical to the prevention of autoimmune disease. Developmentally, complement proteins influence pathways including hematopoietic stem cell engraftment, bone growth, and angiogenesis. They also provide a potent stimulus for cellular proliferation including regeneration of the limb and eye in animal models, and liver proliferation following injury. Here, we describe the complement cascade as a mediator of tissue growth and regeneration.

Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme.

The antiapoptotic protein FLIP(S) is a key suppressor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human glioblastoma multiforme (GBM) cells. We previously reported that a novel phosphatase and tensin homologue (PTEN)-Akt-atrophin-interacting protein 4 (AIP4) pathway regulates FLIP(S) ubiquitination and stability, although the means by which PTEN and Akt were linked to AIP4 activity were unclear. Here, we report that a second regulator of ubiquitin metabolism, the ubiquitin-specific protease 8 (USP8), is a downstream target of Akt, and that USP8 links Akt to AIP4 and the regulation of FLIP(S) stability and TRAIL resistance. In human GBM xenografts, levels of USP8 correlated inversely with pAkt levels, and genetic or pharmacologic manipulation of Akt regulated USP8 levels in an inverse manner. Overexpression of wild-type USP8, but not catalytically inactive USP8, increased FLIP(S) ubiquitination, decreased FLIP(S) half-life, decreased FLIP(S) steady-state levels, and decreased TRAIL resistance, whereas short interfering RNA (siRNA)-mediated suppression of USP8 levels had the opposite effect. Because high levels of the USP8 deubiquitinase correlated with high levels of FLIP(S) ubiquitination, USP8 seemed to control FLIP(S) ubiquitination through an intermediate target. Consistent with this idea, overexpression of wild-type USP8 decreased the ubiquitination of the FLIP(S) E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP(S) interaction, whereas siRNA-mediated suppression of USP8 increased AIP4 ubiquitination. Furthermore, the suppression of FLIP(S) levels by USP8 overexpression was reversed by the introduction of siRNA targeting AIP4. These results show that USP8, a downstream target of Akt, regulates the ability of AIP4 to control FLIP(S) stability and TRAIL sensitivity.

Complement and the central nervous system: emerging roles in development, protection and regeneration.

As expanding research reveals the novel ability of complement proteins to promote proliferation and regeneration of tissues throughout the body, the concept of the complement cascade as an innate immune effector has changed rapidly. In particular, its interactions with the central nervous system have provided a wealth of information regarding the ability of complement proteins to mediate neurogenesis, synaptogenesis, cell migration, neuroprotection, proliferation and regeneration. At numerous phases of the neuronal and glial cell cycle, complement proteins exert direct or indirect influence over their behavior and fate. Neuronal stem cells differentiate and migrate in response to complement, and it prevents injury and death in adult cells in response to toxic agents. Furthermore, complement proteins promote survival via anti-apoptotic actions, and can facilitate clearance and regeneration of injured tissues in various models of CNS disease. In summary, we highlight the protean abilities of complement proteins in the central nervous system, underscoring an exciting avenue of research that has yielded greater understanding of complement's role in central nervous system health and disease.

Amaurosis in infancy due to craniopharyngioma: a not-exceptional but often misdiagnosed symptom.

Since children may not be able to complain of progressive reduction in optic acuity, visual assessment in infancy may present practical difficulties. The authors report a case of craniopharyngioma, which led a young child to early blindness before the correct diagnosis could be made. Similar to other reported cases, the authors found that surgery did not substantially modify the preoperative visual deficit. They conclude that minimal improvement in visual acuity can be expected despite successful microsurgical removal of the tumor.

Posttreatment prognosis of patients with esthesioneuroblastoma.

OBJECT: There is no Class I evidence to guide the appropriate management of esthesioneuroblastoma (EN). Most data currently guiding treatment come from small- or modest-sized series gathered at individual centers that have concluded that surgery with radiotherapy is the preferred treatment. In this study, the authors summarize the published literature on treatment outcomes in patients with EN. The objective was to ascertain what variables predict prognosis in these patients and to determine the relative effect of different therapies. METHODS: The authors identified 205 published studies containing treatment outcomes for surgery, radiotherapy, chemotherapy, or multimodal treatment. Using Kaplan-Meier analysis, the survival of patients who received surgery was compared with that in those who received surgery and radiotherapy. Additionally, Kadish staging was compared with low- and high-grade Hyams criteria to assess for subgroup prognostic significance in survival differences. RESULTS: Nine hundred fifty-six patients met the inclusion criteria, with a median follow-up time of 3 years. Kaplan-Meier analysis demonstrated no difference in survival between patients who underwent surgery alone and those who underwent surgery plus radiotherapy at 5 years (78 vs 75%) or 10 years (67 vs 61%, respectively) (p = 0.3). Univariate analysis demonstrated worse survival in cases involving Kadish Grade C tumors, Hyams Grade 3 and 4 tumors, and in patients older than 65 years of age. Multivariate analysis demonstrated that Hyams Grade 3 and 4 lesions carried significant risk (proportional hazard = 4.83, p < 0.001) with 5- and 10-year survival of 47 and 31%. CONCLUSIONS: A biopsy should always be obtained in cases suspected of EN because histology is a strong prognostic indicator and will help guide appropriate treatment. Unimodal surgery and combined surgery/radiotherapy appear to be of equivalent efficacy with respect to survival in patients with EN. Chemotherapy should be considered in high-grade EN.

Heat shock proteins in glioblastomas.

Glioblastoma multiforme is the most common primary central nervous system tumor. The prognosis for these malignant brain tumors is poor, with a median survival of 14 months and a 5-year survival rate below 2%. Development of novel treatments is essential to improving survival and quality of life for these patients. Endogenous heat shock proteins have been implicated in mediation of both adaptive and innate immunity, and there is a rising interest in the use of this safe and multifaceted heat shock protein vaccine therapy as a promising treatment for human cancers, including glioblastoma multiforme.