Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival.

Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohistochemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median peripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.

Case Report: Clinical Outcome and Image Response of Two Patients With Secondary High-Grade Glioma Treated With Chemoradiation, PCV, and Cannabidiol.

We describe two patients with a confirmed diagnosis of high-grade gliomas (grades III/IV), both presenting with O6-methylguanine-DNA methyltransferase (MGMT) methylated and isocitrate dehydrogenase (IDH-1) mutated who, after subtotal resection, were submitted to chemoradiation and followed by PCV, a multiple drug regimen (procarbazine, lomustine, and vincristine) associated with cannabidiol (CBD). Both patients presented with satisfactory clinical and imaging responses at periodic evaluations. Immediately after chemoradiation therapy, one of the patients presented with an exacerbated and precocious pseudoprogression (PSD) assessed by magnetic resonance imaging (MRI), which was resolved in a short period. The other patient presented with a marked remission of altered areas compared with the post-operative scans as assessed by MRI. Such aspects are not commonly observed in patients only treated with conventional modalities. This observation might highlight the potential effect of CBD to increase PSD or improve chemoradiation responses that impact survival. Further investigation with more patients and critical molecular analyses should be performed.

Angiolipoma intracraniano adjacente a aneurisma sacular cerebral: relato de caso e revisão da literatura / Intracranial Angiolipoma Associated with Cerebral Saccular Aneurysm: Case Report and Review of Literature

Angiolipomas são neoplasias benignas compostas por adipócitos maduros e proliferação vascular angiomatosa de rara ocorrência no Sistema Nervoso Central. É relatado o caso de angiolipoma em cisterna silviana adjacente a aneurisma sacular de artéria cerebral média. São discutidas as características imagenológicas do tumor e a possibilidade de uma origem comum com lesões vasculares intracranianas. Este é o primeiro caso relatado de angiolipoma intracraniano associado a aneurisma de artéria cerebral média.

Angiolipomas are benign neoplasms composed of mature fat cells and vascular angiomatous proliferation of rare incidence in Central Nervous System.It's related a case of angiolipoma in Sylvian fissure associated with cerebral saccular aneurysm of medial cerebral artery. Imagenologic characteristics of the tumor and a possible common origin with intracranial vascular lesions are discussed. This is the first reported case of intracranial angiolipoma involving medial cerebral artery aneurysm.

Impact of preoperative functional magnetic resonance imaging during awake craniotomy procedures for intraoperative guidance and complication avoidance.

BACKGROUND: We wanted to study the role of functional MRI (fMRI) in preventing neurological injury in awake craniotomy patients as this has not been previously studied. OBJECTIVES: To examine the role of fMRI as an intraoperative adjunct during awake craniotomy procedures. METHODS: Preoperative fMRI was carried out routinely in 214 patients undergoing awake craniotomy with direct cortical stimulation (DCS). RESULTS: In 40% of our cases (n = 85) fMRI was utilized for the intraoperative localization of the eloquent cortex. In the other 129 cases significant noise distortion, poor task performance and nonspecific BOLD activation precluded the surgeon from using the fMRI data. Compared with DCS, fMRI had a sensitivity and specificity, respectively, of 91 and 64% in Broca's area, 93 and 18% in Wernicke's area and 100 and 100% in motor areas. A new intraoperative neurological deficit during subcortical dissection was predictive of a worsened deficit following surgery (p < 0.001). The use of fMRI for intraoperative localization was, however, not significant in preventing worsened neurological deficits, both in the immediate postoperative period (p = 1.00) and at the 3-month follow-up (p = 0.42). CONCLUSIONS: The routine use of fMRI was not useful in identifying language sites as performed and, more importantly, practiced tasks failed to prevent neurological deficits following awake craniotomy procedures.

Awake craniotomy for gliomas in a high-field intraoperative magnetic resonance imaging suite: analysis of 42 cases.

OBJECTIVES: The object of this study was to describe the experience of combining awake craniotomy techniques with high-field (1.5 T) intraoperative MRI (iMRI) for tumors adjacent to eloquent cortex. METHODS: From a prospective database the authors obtained and evaluated the records of all patients who had undergone awake craniotomy procedures with cortical and subcortical mapping in the iMRI suite. The integration of these two modalities was assessed with respect to safety, operative times, workflow, extent of resection (EOR), and neurological outcome. RESULTS: Between February 2010 and December 2011, 42 awake craniotomy procedures using iMRI were performed in 41 patients for the removal of intraaxial tumors. There were 31 left-sided and 11 right-sided tumors. In half of the cases (21 [50%] of 42), the patient was kept awake for both motor and speech mapping. The mean duration of surgery overall was 7.3 hours (range 4.0-13.9 hours). The median EOR overall was 90%, and gross-total resection (EOR ≥ 95%) was achieved in 17 cases (40.5%). After viewing the first MR images after initial resection, further resection was performed in 17 cases (40.5%); the mean EOR in these cases increased from 56% to 67% after further resection. No deficits were observed preoperatively in 33 cases (78.5%), and worsening neurological deficits were noted immediately after surgery in 11 cases (26.2%). At 1 month after surgery, however, worsened neurological function was observed in only 1 case (2.3%). CONCLUSIONS: There was a learning curve with regard to patient positioning and setup times, although it did not adversely affect patient outcomes. Awake craniotomy can be safely performed in a high-field (1.5 T) iMRI suite to maximize tumor resection in eloquent brain areas with an acceptable morbidity profile at 1 month.

Stereotactic radiosurgery for metastatic brain tumors: a comprehensive review of complications.

OBJECT: Stereotactic radiosurgery (SRS) is commonly used to treat brain metastases. Complications associated with this treatment are underreported. The authors reviewed a large series of patients who underwent SRS for brain metastases to identify complications and factors predicting their occurrence. METHODS: Prospectively collected clinical data from 273 patients undergoing SRS for 1 or 2 brain metastases at The University of Texas M. D. Anderson Cancer Center between June 1993 and December 2004 were reviewed. Patients who had received prior treatment for their tumor, including whole-brain radiation, SRS, or surgery, were excluded from the study. Data on adverse neurological and nonneurological outcomes following treatment were collected. RESULTS: Three hundred sixteen lesions were treated. Complications were associated with 127 (40%) of 316 treated lesions. New neurological complications were associated with 101 (32%) of 316 lesions. The onset of seizure was the most common complication, occurring in 41 (13%) of 316 SRS cases. On multivariate analysis, progressing primary cancer (hazard ratio [HR]=2.4, 95% CI 1.6-3.6, p<0.001), tumor location in eloquent cortex (HR=2.3, 95% CI 1.6-3.4, p<0.001), and lower (<15 Gy) SRS dose (HR=2.1, 95% CI 1.1-4.2, p=0.04) were significantly associated with new complications. On multivariate analysis, a tumor location in the eloquent cortex (HR=2.5, 95% CI 1.6-3.8, p<0.001) and progressing primary cancer (HR=1.6, 95% CI 1.1-2.5, p=0.03) were significantly associated with new neurological complications. CONCLUSIONS: The authors showed that new neurological and nonneurological complications were associated with 40% of SRS treatments for brain metastases. Patients with lesions in functional brain regions have a significantly increased risk of treatment-related complications.

Positive and negative prognostic variables for patients undergoing spine surgery for metastatic breast disease.

The histology of the primary tumor in metastatic spine disease plays an important role in its treatment and prognosis. However, there is paucity in the literature of histology-specific analysis of spinal metastases. In this study, prognostic variables were reviewed for patients who underwent surgery for breast metastases to the spinal column. Respective chart review was done to first identify all patients with breast cancer over an 8-year period at a major cancer center and then to select all those with symptomatic metastatic disease to the spine who underwent spinal surgery. Univariate and multivariate analyses were used to assess several prognostic variables. Presence of visceral metastases, multiplicity of bony lesions, presence of estrogen receptors (ER), and segment of spine (cervical, thoracic, lumbar, sacral) in which metastases arose were compared with patient survival. Eighty-seven patients underwent 125 spinal surgeries. Those with estrogen receptor (ER) positivity had a longer median survival after surgery compared to those with estrogen receptor negativity. Patients with cervical location of metastasis had a shorter median survival compared with those having metastases in other areas of the spine. The presence of visceral metastases or a multiplicity of bony lesions did not have prognostic value. In patients with spinal metastases from breast cancer, aggressive surgical management may be an option for providing significant pain relief and preservation/improvement of neurological function. Interestingly, in patients undergoing such surgery, cervical location of metastasis is a negative prognostic variable, and ER-positivity is associated with better survival, while presence of visceral or multiple bony lesions does not significantly alter survival.

Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients.

Aggressive surgical management of spinal metastatic disease can provide improvement of neurological function and significant pain relief. However, there is limited literature analyzing such management as is pertains to individual histopathology of the primary tumor, which may be linked to overall prognosis for the patient. In this study, clinical outcomes were reviewed for patients undergoing spinal surgery for metastatic breast cancer. Respective review was done to identify all patients with breast cancer over an eight-year period at a major cancer center and then to select those with symptomatic spinal metastatic disease who underwent spinal surgery. Pre- and postoperative pain levels (visual analog scale [VAS]), analgesic medication usage, and modified Frankel grade scores were compared on all patients who underwent surgery. Univariate and multivariate analyses were used to assess risks for complications. A total of 16,977 patients were diagnosed with breast cancer, and 479 patients (2.8%) were diagnosed with spinal metastases from breast cancer. Of these patients, 87 patients (18%) underwent 125 spinal surgeries. Of the 76 patients (87%) who were ambulatory preoperatively, the majority (98%) were still ambulatory. Of the 11 patients (13%) who were nonambulatory preoperatively, four patients were alive at 3 months postoperatively, three of which (75%) regained ambulation. The preoperative median VAS of six was significantly reduced to a median score of two at the time of discharge and at 3, 6, and 12 months postoperatively (P < 0.001 for all time points). A total of 39% of patients experienced complications; 87% were early (within 30 days of surgery), and 13% were late. Early major surgical complications were significantly greater when five or more levels were instrumented. In patients with spinal metastases specifically from breast cancer, aggressive surgical management provides significant pain relief and preservation or improvement of neurological function with an acceptably low rate of complications.

Resection of brain metastases previously treated with stereotactic radiosurgery.

OBJECT: To date, no report has been published on outcomes of patients undergoing resection for brain metastases who were previously treated with stereotactic radiosurgery (SRS). Consequently, the authors reviewed their institutional experience with this clinical scenario to assess the efficacy of surgical intervention. METHODS: Sixty-one patients (each harboring three or fewer brain lesions), who were treated at a single institution between June 1993 and August 2002 were identified. Patient charts and their neuroimaging and pathological reports were retrospectively reviewed to determine overall survival rates, surgical complications, and recurrence rates. A univariate analysis revealed that patient preoperative recursive partitioning analysis (RPA) classification, primary disease status, preoperative Karnofsky Performance Scale score, type of focal treatment undergone for nonindex lesions, and major postoperative surgical complications were factors that significantly affected survival (p < or = 0.05). In contrast, only the RPA class and focal (conventional surgery or SRS) treatment of nonindex lesions significantly (or nearly significantly) affected survival in the multivariate analysis. Major neurological complications occurred in only 2% of patients. The median time to distant recurrence after resection was 8.4 months; that to local recurrence was not reached. The overall median survival time was 11.1 months, with 25% of patients surviving 2 or more years. Conventional surgery facilitated tapering of steroid administration. Conclusions. The complication, morbidity, survival, and recurrence rates are consistent with those seen after conventional surgery for recurrent brain metastases. Our results indicate that in selected patients with a favorable RPA class in whom nonindex lesions are treated with focal modalities, surgery can provide long-term control of SRS-treated lesions and positively affect overall survival.

Cystic glioblastoma multiforme: survival outcomes in 22 cases.

OBJECT: The goal of this study was to determine whether the presence of a large tumor cyst was associated with improved outcome in patients undergoing surgery for newly diagnosed glioblastomas multiforme (GBMs) by comparing these patients with a matched cohort of patients with noncystic GBMs in clinical features, tumor imaging characteristics, survival, and time to tumor recurrence after surgery. METHODS: A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (> or = 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs. No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9-24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1-16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01-18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8-6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively. CONCLUSIONS: The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature.

Análise de 52 pacientes com traumatismo de crônio atendidos em uti pediátrica: considerações sobre o uso da monitorização da pressão intracraniana / Analysis of 52 patients with head trauma assisted at pediatric intensive care unit: considerations about intracranial pressure monitoring

OBJETIVO:Análise de 52 pacientes pediátricos com trauma de crânio (TCE) assistidos em Unidade de Terapia Intensiva, considerando fatores epidemiológicos do trauma, manifestações clínicas, aspectos tomográficos, variações hemodinâmicas e opções de tratamento da hipertensão intracraniana; avaliar a utilização da monitorização da pressão intracraniana (PIC). MÉTODO:Estudoretrospectivo de 52 pacientes com TCE e 17 destes submetidos a monitorização da PIC. RESULTADO:Houve predominância masculina e a média de idade foi 7,75 anos. Atropelamento foi a principal causa (38,5% dos casos). Encontramos 21,2% dos pacientes com hipotensão arterial. Foram classificados como TCE grave 67,3% dos pacientes. Tivemos graduação tomográfica de Marshall tipo I em 19,2%, II em 65,4%, III em 3,8%, IV em 3,8% e V em 7,7%. Apresentaram crise convulsiva 25%. Foram submetidos a monitorização da PIC 32,7%. A taxa de mortalidade foi 11,5%. O maior valor pressórico ocorreu no segundo dia em 58,8%. CONCLUSÃO: O prognóstico se relacionou com a severidade do trauma, hipotensão arterial, graduação tomográfica de Marshall tipo III e IV e altos valores de PIC. A monitorização da PIC permite facilidades no diagnóstico e tratamento da hipertensão intracraniana

[Analysis of 52 patients with head trauma assisted at pediatric Intensive Care Unit: considerations about intracranial pressure monitoring]. / Análise de 52 pacientes com traumatismo de crânio atendidos em UTI pediátrica: considerações sobre o uso da monitorização da pressão intracraniana.

OBJECTIVES: Analysis of 52 pediatric patients with head trauma assisted at Intensive Care Unit; to present considerations about epidemiologic factors of trauma, clinical presentation, tomografic aspects, hemodynamic changes and treatment options of intracranial hypertension; to present considerations about the intracranial pressure (ICP) monitoring. METHOD: Retrospective study involving 52 patients with head trauma and 17 patients submitted to a ICP monitoring. RESULTS: We found a male predominance, mean age 7.75 years-old, main cause was run over (38.5%); 21.2% patients presentd arterial hypotension; 67.3% were considered severe head trauma. According to Marshall tomografic grading we had 19.2% type I, 65.4% type II, 3.8% type III, 3.8% type IV and 7.7% type V. Seizures occurred in 25% children ICP monitoring was made in 32.7% of all patients. Mortality rate was 11.5%. In 58% the maximum ICP level occured at the second day of trauma. CONCLUSION: Prognosis was related to severity of trauma, arterial hypotension, Marshall's tomografic gradind III and IV and ICP high values. The ICP monitoring was considered useful to allow the identification and treatment of intracranial hypertension.

Orbital apex syndrome due to aspergillosis: case report

We report the case of a 73-year-old female who presented facial numbness and pain in the first division of the trigeminal nerve, ptosis, diplopia and visual loss on the right side for the previous four months. The neurological, radiological and histological examination demonstrated a rare case of invasive fungal aspergillosis of the central nervous system, causing orbital apex syndrome, later transformed in temporal brain abscess. She died ten months later due to respiratory and renal failure in spite of specific antimycotic therapy