Outcomes after craniotomy for resection of craniopharyngiomas in adults: analysis of the National Surgical Quality Improvement Program (NSQIP).

PURPOSE: Craniopharyngiomas occur in suprasellar locations that pose challenges for surgical management. This study evaluates the incidence of complications following craniotomy for craniopharyngioma in adults and investigates risk factors for these complications. METHODS: Patients who underwent craniotomy for excision of craniopharyngioma were identified from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Incidence of 30-day postoperative complications was determined. Multivariable logistic regression identified demographic, comorbid and perioperative characteristics associated with any complication and major (Clavien IV) complications.  RESULTS: There were 143 cases identified. Fifty-one (35.7%) had a complication, twenty (14.0%) experienced a major complication and there were four (2.8%) deaths. The most common complications were: unplanned readmission (13.3%), prolonged ventilation > 48 h (9.8%), and unplanned reoperation (9.3%). In multivariable analysis, variables significantly associated with any complication were: black race (OR 0.16; 95% CI 0.03-0.84; p = 0.03), hypertension (OR 5.04; 95% CI 1.79-14.17; p = 0.002) and longer duration of surgery (OR 1.27; 95% CI 1.01-1.58; p = 0.04). Hypertension (OR 9.33; 95% CI 1.61-54.21; p = 0.01) and longer duration of surgery (OR 1.51; 95% CI 1.05-2.17; p = 0.03) were also significant predictors for major complications. CONCLUSION: One-third of patients undergoing craniotomy for craniopharyngioma resection experienced a postoperative complication. While high, this contrasts previously reported rates of two-thirds. Prolonged operative time and hypertension are positive predictors of major complications. This information can assist in counseling patients and decision-making for management. We note that other treatment approaches, such as endoscopic surgical techniques, radiosurgery and radiation therapy likely have different profiles and predictors of complications.

Comparison of ABC/2 estimation and a volumetric computerized method for measurement of meningiomas using magnetic resonance imaging.

INTRODUCTION: Measurement of tumor growth rates over time for patients with meningiomas has important prognostic and therapeutic implications. Our objective was to compare two methods of measuring meningioma volume: (1) the simplified ellipsoid (ABC/2) method; and (2) perimetric volume measurements using imaging software modules. METHODS: Patients with conservatively managed meningiomas for at least 1.5 years were retrospectively identified from the VCU Brain and Spine Tumor Registry over a 10-year period (2005-2015). Tumor volumes were independently measured using the simplified ellipsoid and computerized perimetric methods. Intra class correlations (CC) and Bland-Altman analyses were performed. RESULTS: A total of 26 patients representing 29 tumors were identified. Across 146 images, there were 24 (16%) images that were non-measurable using standard application commands with the computerized perimetric method. The mean volume obtained using the ABC/2 and computerized perimetric methods were 3.2 ± 3.4 cm3 and 3.4 ± 3.5 cm3, respectively. The mean volume difference was 0.2 cm3 (SE = 0.12; p = 0.10) across measurement methods. The concordance correlation coefficient (CCC) between methods was 0.95 (95% CI 0.91, 0.98). CONCLUSIONS: There is excellent correlation between the simplified ellipsoid and computerized perimetric methods of volumetric analysis for conservatively managed meningiomas. The simplified ellipsoid method remains an excellent method for meningioma volume assessment and had an advantage over the perimetric method which failed to allow measurement of roughly one in six tumors on imaging.

Large-Volume Infusions into the Brain: A Comparative Study of Catheter Designs.

BACKGROUND/AIMS: "Whole-brain" infusions have emerged as a potential need with the promise of disease-modifying therapies for neurodegenerative diseases. In addition, several current clinical trials in brain cancer utilize direct delivery of drugs that are required to fill large volumes. Such requirements may not be well served by conventional single port catheters with their "point source" of delivery. Our aim is to examine infusions into large volumes of heterogeneous tissue, aiming for uniformity of distribution. METHODS: A porous catheter (porous brain infusion catheter, PBIC), designed by Twin Star TDS LLC, for brain infusions was developed for this study and compared with another convection-enhanced delivery catheter (SmartFlowTM NGS-NC-03 from MRI Interventions, a step end-port catheter, SEPC) in current use in clinical trials. The studies were in vivo in porcine brain. A total of 8 pigs were used: the size of the pig brain limited the porous length to 15 mm. The placements of the tips of the two catheters were chosen to be the same (at the respective brain hemispheres). RESULTS: The PBIC and SEPC both performed comparably and well, with the PBIC having some advantage in effecting larger distributions: p ∼ 0.045, with 5 infusions from each. CONCLUSIONS: Given the performance of the PBIC, it would be highly appropriate to use the device for therapeutic infusions in human clinical trials to assess its capability for large-volume infusions.

A systematic review of perioperative seizure prophylaxis during brain tumor resection: the case for a multicenter randomized clinical trial.

OBJECTIVE The majority of neurosurgeons administer antiepileptic drugs (AEDs) prophylactically for supratentorial tumor resection without clear evidence to support this practice. The putative benefit of perioperative seizure prophylaxis must be weighed against the risks of adverse effects and drug interactions in patients without a history of seizures. Consequently, the authors conducted a systematic review of prospective randomized controlled trials (RCTs) that have evaluated the efficacy of perioperative seizure prophylaxis among patients without a history of seizures. METHODS Five databases (PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL/Academic Search Complete, Web of Science, and ScienceDirect) were searched for RCTs published before May 2017 and investigating perioperative seizure prophylaxis in brain tumor resection. Of the 496 unique research articles identified, 4 were selected for inclusion in this review. RESULTS This systematic review revealed a weighted average seizure rate of 10.65% for the control groups. There was no significant difference in seizure rates among the groups that received seizure prophylaxis and those that did not. Further, this expected incidence of new-onset postoperative seizures would require a total of 1258 patients to enroll in a RCT, as determined by a Farrington-Manning noninferiority test performed at the 0.05 level using a noninferiority difference of 5%. CONCLUSIONS According to a systematic review of major RCTs, the administration of prophylactic AEDs after brain tumor resection shows no significant reduction in the incidence of seizures compared with that in controls. A large multicenter randomized clinical trial would be required to assess whether perioperative seizure prophylaxis provides benefit for patients undergoing brain tumor resection.

Accuracy of the ABC/2 Score for Intracerebral Hemorrhage: Systematic Review and Analysis of MISTIE, CLEAR-IVH, and CLEAR III.

BACKGROUND AND PURPOSE: The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography-based planimetry (CTP). METHODS: In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression. RESULTS: In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC (r(2)=0.93) than with site-ABC (r(2)=0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm(3); CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P<0.001). This was consistent with overestimation of ICH volume in 6 of 8 previous studies. Agreement with CTP was greater for RC-ABC (84% within 5 mL; 48% of scans within 20%) than for site-ABC (81% within 5 mL; 41% within 20%). RC-ABC had moderate accuracy for detecting ≥5 mL change in CTP volume between consecutive scans (sensitivity, 0.76; specificity, 0.86) and was more accurate with smaller ICH, thalamic hemorrhage, and homogeneous clots. CONCLUSIONS: ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.

Wilms tumor 1 gene, CD97, and the emerging biogenetic profile of glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor, and current treatment regimens are only marginally effective. One of the most vexing and malignant aspects of GBM is its pervasive infiltration into surrounding brain tissue. This review describes the role of the Wilms tumor 1 gene (WT1) and its relationship to GBM. WT1 has several alternative splicing products, one of which, the KTS(+) variant, has been demonstrated to be involved in the transcriptional activation of a variety of oncogenes as well as the inhibition of tumor suppressor genes. Further, this paper will examine the relationship of WT1 with CD97, a gene that codes for an epidermal growth factor receptor family member, an adhesion G-protein-coupled receptor, thought to promote tumor invasiveness and migration. The authors suggest that further research into WT1 and CD97 will allow clinicians to begin to deal more effectively with the infiltrative behavior displayed by GBM and design new therapies that target this deadly disease.

Delayed Postoperative Intracerebral Hemorrhage Associated With Oral Multikinase Inhibitor Therapy for Cancer: A Case Report.

Regorafenib is a multikinase inhibitor with anti-vascular endothelial growth factor receptor (VEGF) activity used as an antiangiogenic agent for metastatic colorectal cancer treatment and has been studied as a potential therapeutic agent for several other cancer treatments. Adverse reactions commonly reported with the use of regorafenib and similar oral multikinase inhibitors include hemorrhage, gastrointestinal fistulas, hypertension, and incomplete wound healing. We report a case of a 59-year-old man with metastatic colorectal adenocarcinoma post-colostomy on regorafenib treatment presenting to the emergency department with altered mental status. MRI showed a left frontoparietal mass, which was resected with a left frontal craniotomy. Postoperative MRI showed a resection cavity without significant hemorrhage. He had been prescribed regorafenib preceding his hospitalization, which was continued after admission before surgery and on postoperative day 1. Thirty-two hours after surgery, the patient exhibited sudden right-sided facial droop and right arm weakness. Imaging revealed an acute intraparenchymal hemorrhage within and adjacent to the tumor resection bed, which was managed conservatively. The patient was subsequently discharged to an inpatient rehabilitation facility. The unusual timing of the hemorrhage suggests that the hemorrhage was due to adverse effects of regorafenib. Patients undergoing neurosurgery should have regorafenib discontinued in preparation for surgery. Similar management should be considered for other anti-VEGF medications to avoid serious complications.

Superficial siderosis: comparison of two cases indicates two distinct diagnostic entities. Illustrative cases.

BACKGROUND: Superficial siderosis is the deposition of hemosiderin in the superficial layers of the central nervous system. It has been described in patients with chronic leakage of blood into the cerebrospinal fluid or with amyloid angiopathy, often associated with Alzheimer's disease (AD). OBSERVATIONS: We present two cases of superficial siderosis with vastly different symptomatologies and treatment courses. The patient in case 1 had diffuse superficial siderosis demonstrated on T2-weighted magnetic resonance imaging (MRI), appearing mostly in the inferior cerebellum and extending throughout the neuraxis. He presented with hearing loss, spasticity, gait abnormalities, and urinary incontinence. Ultimately, surgical exploration of the thoracic spinal dura revealed an arteriovenous fistula, which was obliterated. His clinical course stabilized but with persistent deficits. The patient in case 2 had a family history of AD and underwent MRI to evaluate for memory impairment, which demonstrated superficial siderosis of the left occipital lobe. Lumbar puncture demonstrated only traumatic contamination by red blood cells, but tau protein analysis was consistent with the diagnosis of AD. LESSONS: Superficial siderosis is a diagnostic term prompted by findings on MRI that can arise due to two different pathological entities. The diagnosis in case 1 should be termed diffuse superficial siderosis and in case 2 should be termed lobar cortical siderosis.

Reducing Gadolinium Exposure in Patients Undergoing Monitoring for Meningiomas.

Background Due to the non-malignant and slow-growing nature of many meningiomas, surveillance with serial magnetic resonance imaging (MRI) serves as an acceptable management plan. However, repeated imaging with gold-standard contrast-based studies may lead to contrast-associated adverse effects. Non-gadolinium T2 sequences may serve as a suitable alternative without the risk of adverse effects of contrast. Thus, this study sought to investigate the agreement between post-contrast T1 and non-gadolinium T2 MRI sequences in the measurement of meningioma growth. Methodology The Virginia Commonwealth University School of Medicine (VCU SOM) brain tumor database was used to create a cohort of meningioma patients and determine the number of patients who had T1 post-contrast imaging accompanied by readily measurable imaging from either T2 fast spin echo (FSE) or T2 fluid-attenuated inversion recovery (FLAIR) sequences. Measurements of the largest axial and perpendicular diameters of each tumor were conducted by two independent observers using T1 post-contrast, T2 FSE, and T2 FLAIR imaging series. Lin's concordance correlation coefficient (CCC) was calculated to assess inter-rater reliability between observers and agreement between measurements of tumor diameter among the different imaging sequences. Results In total, 33 patients (average age = 72.1 ± 12.9 years, 90% female) with meningiomas were extracted from our database, with 22 (66.7%) undergoing T1 post-contrast imaging accompanied with readily measurable imaging from T2 FSE and/or T2 FLAIR sequences. The inter-rater reliability between the measurements of T1 axial and perpendicular diameters was 0.96 (95% confidence interval (CI) = 0.92-0.98) and 0.92 (95% CI = 0.83-0.97), respectively. The inter-rater reliability between the measurements of T2 axial perpendicular diameters was 0.93 (95% = CI 0.92-0.97) and 0.89 (95% CI = 0.74-0.95), respectively. The agreements between the measurement of T1 and T2 FSE axial diameter by each observer were 0.97 (95% CI = 0.93-0.98) and 0.92 (95% CI = 0.81-0.97). The agreements between the measurements of T1 and T2 FSE perpendicular diameter measurements by each observer were 0.98 (95% CI = 0.95-0.99) and 0.88 (95% CI = 0.73-0.95). Conclusions Two-thirds of our patients had meningiomas that were readily measurable on either T2 FSE or T2 FLAIR sequences. Additionally, there was excellent inter-rater reliability between the observers in our study as well as an agreement between individual measurements of T1 post-contrast and T2 FSE tumor diameters. These findings suggest that T2 FSE may serve as a safe and similarly effective surveillance method for the long-term management of meningioma patients.

Growth Analysis of Untreated Meningiomas under Observation.

BACKGROUND: When meningiomas are small or asymptomatic, the decision to observe rather than treat requires balancing the growth potential of the lesion with the outcome and side effects of treatment. The aim of this study is to characterize the growth patterns of untreated meningiomas to better inform the clinical decision-making process. METHODS: Patients with meningiomas were identified from 2005 to 2015. Those without treatment who had been followed for 1.5 years, with three magnetic resonance imaging (MRI) scans, were identified. Scans were measured with orthogonal diameters, geometric mean diameters, and volumes using the ABC/2 method. Regression modeling determined what growth pattern these parameters best approximated. RESULTS: Two hundred and fifteen MRI scans for 34 female (82.9%) and 7 male (17%) patients with 43 tumors were evaluated. Initial tumor volumes ranged from 0.13 to 9.98 mL. The mean and median initial volumes were 2.44 and 1.52 mL, respectively. Follow-up times ranged from 21 to 144 months, with a median of 70 months. There were 12 tumors (28%) whose growth rates were significantly greater than zero. For all tumors, use of a linear regression model allowed accurate prediction of the future size using prior data. CONCLUSION: Three-quarters of presumptive meningiomas managed conservatively do not grow significantly. The remainder have significant growth over time, and the behavior could be approximated with linear regression models.

Metallofullerene-nanoplatform-delivered interstitial brachytherapy improved survival in a murine model of glioblastoma multiforme.

Fullerenes are used across scientific disciplines because of their diverse properties gained by altering encapsulated or surface-bound components. In this study, the recently developed theranostic agent based on a radiolabeled functionalized metallofullerene ((177)Lu-DOTA-f-Gd(3)N@C(80)) was synthesized with high radiochemical yield and purity. The efficacy of this agent was demonstrated in two orthotopic xenograft brain tumor models of glioblastoma multiforme (GBM). A dose-dependent improvement in survival was also shown. The in vivo stability of the agent was verified through dual label measurements of biological elimination from the tumor. Overall, these results provide evidence that nanomaterial platforms can be used to deliver effective interstitial brachytherapy.

Positional aphasia as a manifestation of syndrome of the trephined: illustrative case.

BACKGROUND: The authors report a case of a 66-year-old male who presented acutely with a subdural hematoma who was managed operatively with craniotomy. His course was complicated by a postoperative epidural hematoma, which, on the basis of intraoperative findings at the second surgery, was managed with evacuation of the hematoma and removal of the bone flap. OBSERVATIONS: The patient's subsequent recovery was remarkable for a reproducible positional aphasia in the early postoperative period with an ultimate diagnosis of syndrome of the trephined. The patient's cerebral edema permitted early autologous cranioplasty, which resulted in resolution of the patient's symptoms. LESSONS: The authors believe this case to be the first described of isolated positional aphasia as a manifestation of syndrome of the trephined. Recognition and treatment of the syndrome resulted in a positive patient outcome.

Early mobilization versus bed rest for incidental durotomy: an institutional cohort study.

OBJECTIVE: The aim of this study was to assess whether flat bed rest for > 24 hours after an incidental durotomy improves patient outcome or is a risk factor for medical and wound complications and longer hospital stay. METHODS: Medical records of consecutive patients undergoing thoracic and lumbar decompression procedures from 2010 to 2020 were reviewed. Operative notes and progress notes were reviewed and searched to identify patients in whom incidental durotomies occurred. The need for revision surgery related to CSF leak or wound infection was recorded. The duration of bed rest, length of hospital stay, and complications (pulmonary, gastrointestinal, urinary, and wound) were recorded. The rates of complications were compared with regard to the duration of bed rest (≤ 24 hours vs > 24 hours). RESULTS: A total of 420 incidental durotomies were identified, indicating a rate of 6.7% in the patient population. Of the 420 patients, 361 underwent primary repair of the dura; 254 patients were prescribed bed rest ≤ 24 hours, and 107 patients were prescribed bed rest > 24 hours. There was no statistically significant difference in the need for revision surgery (7.87% vs 8.41%, p = 0.86) between the two groups, but wound complications were increased in the prolonged bed rest group (8.66% vs 15.89%, p = 0.043). The average length of stay for patients with bed rest ≤ 24 hours was 4.47 ± 3.64 days versus 7.24 ± 4.23 days for patients with bed rest > 24 hours (p < 0.0001). There was a statistically significant increase in the frequency of ileus, urinary retention, urinary tract infections, pulmonary issues, and altered mental status in the group with prolonged bed rest after an incidental durotomy. The relative risk of complications in the group with bed rest ≤ 24 hours was 50% less than the group with > 24 hours of bed rest (RR 0.5, 95% CI 0.39-0.62; p < 0.0001). CONCLUSIONS: In this retrospective study, the rate of revision surgery was not higher in patients with durotomy who underwent immediate mobilization, and medical complications were significantly decreased. Flat bed rest > 24 hours following incidental durotomy was associated with increased length of stay and increased rate of medical complications. After primary repair of an incidental durotomy, flat bed rest may not be necessary and appears to be associated with higher costs and complications.

Resolution and Re-ossification of Orbital-Wall Langerhans Cell Histiocytosis Following Stereotactic Needle Biopsy.

Introduction Langerhans cell histiocytosis (LCH) is a rare disease that encompasses a spectrum of clinical syndromes. It is characterized by the proliferation and infiltration of white blood cells into organs or organ systems. Reports of management of these lesions have included biopsy, resection, curettage, radiation, and/or chemotherapy. Case Presentation A 40-year-old man presented with a history of right proptosis and retro-orbital pain and was found to have a lytic mass involving the greater wing of the sphenoid extending into the right orbit. A stereotactic needle biopsy using neuronavigation demonstrated this to be LCH. After no further treatment, the mass spontaneously resolved, with virtual normalization of the orbital magnetic resonance imaging at 10 months following the needle biopsy. The bony defect of the temporal bone caused by the mass also re-ossified following the needle biopsy. Discussion This report highlights the potential for an isolated LCH lesion to regress after simple needle biopsy, an outcome only rarely reported previously. Thus, expectant management of such lesions following biopsy or initial debridement should be considered prior to proceeding with additional treatment.

The Richmond Acute Subdural Hematoma Score: A Validated Grading Scale to Predict Postoperative Mortality.

BACKGROUND: Traumatic acute subdural hematomas (aSDHs) are common, life-threatening injuries often requiring emergency surgery. OBJECTIVE: To develop and validate the Richmond acute subdural hematoma (RASH) score to stratify patients by risk of mortality after aSDH evacuation. METHODS: The 2016 National Trauma Data Bank (NTDB) was queried to identify adult patients with traumatic aSDHs who underwent craniectomy or craniotomy within 4 h of arrival to an emergency department. Multivariate logistic regression modeling identified risk factors independently associated with mortality. The RASH score was developed based on a factor's strength and level of association with mortality. The model was validated using the 2017 NTDB and the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 2516 cases met study criteria. The patients were 69.3% male with a mean age of 55.7 yr and overall mortality rate of 36.4%. Factors associated with mortality included age between 61 and 79 yr (odds ratio [OR] = 2.3, P < .001), age ≥80 yr (OR = 6.3, P < .001), loss of consciousness (OR = 2.3, P < .001), Glasgow Coma Scale score of ≤8 (OR = 2.6, P < .001), unilateral (OR = 2.8, P < .001) or bilateral (OR = 3.9, P < .001) unresponsive pupils, and midline shift >5 mm (OR = 1.7, P < .001). Using these risk factors, the RASH score predicted progressively increasing mortality ranging from 0% to 94% for scores of 0 to 8, respectively (AUC = 0.72). Application of the RASH score to 3091 cases from 2017 resulted in similar accuracy (AUC = 0.74). CONCLUSION: The RASH score is a simple and validated grading scale that uses easily accessible preoperative factors to predict estimated mortality rates in patients with traumatic aSDHs who undergo surgical evacuation.

Wilms' tumor 1 silencing decreases the viability and chemoresistance of glioblastoma cells in vitro: a potential role for IGF-1R de-repression.

Wilms' tumor 1 (WT1) is a transcription factor with a multitude of downstream targets that have wide-ranging effects in non-glioma cell lines. Though its expression in glioblastomas is now well-documented, the role of WT1 in these tumors remains poorly defined. We hypothesized that WT1 functions as an oncogene to enhance glioblastoma viability and chemoresistance. WT1's role was examined by studying the effect of WT1 silencing and overexpression on DNA damage, apoptosis and cell viability. Results indicated that WT1 silencing adversely affected glioblastoma viability, at times, in synergy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cisplatin. To investigate other mechanisms through which WT1 could affect viability, we measured cell cycle distribution, senescence, and autophagy. WT1 silencing had no effect on these processes. Lastly, we examined WT1 regulation of IGF-1R expression. Counterintuitively, upregulation of IGF-1R was evident after WT1 silencing. In conclusion, WT1 functions as a survival factor in glioblastomas, possibly through inhibition of IGF-1R expression.

A biobehavioral perspective on depressive symptoms in patients with cerebral astrocytoma.

More than 51,000 individuals are diagnosed with a primary brain tumor in the United States each year, and for those with the most common type of malignant tumor, an astrocytoma, almost 75% will die within 5 years of diagnosis. Although surgery, radiation, and chemotherapy have improved length of survival, mortality remains high, which underscores the need to understand how other factors affect the disease trajectory. Several recent studies have shown that depressive symptoms are independently associated with reduced quality of life and survival time after controlling for other variables in patients with an astrocytoma. Thus, depressive symptoms represent a significant risk factor for adverse outcomes in this patient population. A growing body of evidence indicates that depressive symptoms are linked to underlying biological phenomena, particularly inflammatory activation modulated through increased peripheral levels of proinflammatory cytokines. Recent research has shown that neoplastic astrocytes respond to elevated proinflammatory cytokine levels by secreting immune mediators within the central nervous system, including cytokines and glial fibrillary acidic protein that promote astrogliosis and angiogenesis and may increase tumor growth and metastasis. However, because these biological factors have not as yet been measured in conjunction with depressive symptoms in these patients, little is known about the interactions that potentially influence the treatment trajectory. To guide future research and to provide a deeper understanding of the factors that may influence depressive symptoms and length of survival in patients with an astrocytoma, a review of the literature was undertaken. Publications over the past 10 years were analyzed to examine the theoretical models and measures of depressive symptoms used in previous research. Although numerous studies have documented the relationship between depression and reduced length of survival, there were several methodological concerns identified, and there were no studies that included biological variables. Yet, research in the basic sciences provides compelling evidence of specific neuroendocrine-immune interactions orchestrated by astrocytes that can cause depressive symptoms and alter the tumor microenvironment so that standard treatments are not as effective. These findings support the need for clinically based research so that we can begin to understand the potentially modifiable biobehavioral mechanisms underlying depressive symptoms in patients with an astrocytoma. Grounded in the biobehavioral research paradigm of psychoneuroimmunology, a novel research program is presented that may provide a new level of understanding regarding the high prevalence of depressive symptoms in patients with an astrocytoma and lead to new treatment strategies, with possible implications for improved symptom management and quality of life in patients with brain tumors.

The Effect of Radiation on Meningioma Volume Change.

BACKGROUND: Radiation therapy is a common treatment for meningiomas. Volume changes of meningiomas in response to radiation are not well characterized. This study seeks to quantify the volume change of meningiomas following radiation. METHODS: Data were collected from a retrospective single-institution database of cases from 2005-2015. Tumors were measured using T1-weighted post-contrast magnetic resonance imaging. Volumes were calculated using the ABC/2 ellipsoidal approximation. RESULTS: A total of 63 patients fit the inclusion criteria; 37 patients (59%) received radiation following resection, 19 (30%) received radiation alone, 4 (6%) received radiation following a biopsy, and 3 (5%) had unknown surgical status. A total of 39 patients (62%) had skull base meningiomas; 43 tumors were World Health Organization (WHO) grade I, and 12 tumors were WHO grade II. Thirteen patients received radiosurgery, 43 received radiotherapy, and 7 received an unknown number of treatments. Eight patients did not attain local control and were excluded from volume analyses. WHO grade I meningiomas saw an average of 33% ± 19% decrease in tumor volume; WHO grade II tumor volumes decreased by an average 30% ± 23%. Radiosurgery saw an average volume decrease of 34% ± 13%, while radiotherapy resulted in volume decrease of 31% ± 21%. For those who achieved local control, there was an average decrease in tumor size of 30% ± 19%, 30% ± 22%, and 41% ± 19% over 0.5-1.5, 2.5-3.5, and >5 years, respectively. CONCLUSIONS: Meningiomas treated with radiation exhibit nonlinear decrease in size over time. The greatest decrease in tumor volume occurs within the first year and begins to plateau 5 years post-radiation treatment.

MDA-7/IL-24 as a cancer therapeutic: from bench to bedside.

The novel cytokine melanoma differentiation associated gene-7 (mda-7) was identified by subtractive hybridization in the mid-1990s as a protein whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared with non-transformed cells. On the basis of conserved structure, chromosomal location and cytokine-like properties, MDA-7, has now been classified as a member of the expanding interleukin (IL)-10 gene family and designated as MDA-7/IL-24. Multiple studies have shown that the expression of MDA-7/IL-24 in a wide variety of tumor cell types, but not in the corresponding equivalent non-transformed cells, causes their growth arrest and ultimately cell death. In addition, MDA-7/IL-24 has been noted to be a radiosensitizing cytokine, which is partly because of the generation of reactive oxygen species and ceramide that cause endoplasmic reticulum stress. Phase I clinical trial data has shown that a recombinant adenovirus expressing MDA-7/IL-24 [Ad.mda-7 (INGN-241)] was safe and had measurable tumoricidal effects in over 40% of patients, which strongly argues that MDA-7/IL-24 may have significant therapeutic value. This review describes what is known about the impact of MDA-7/IL-24 on tumor cell biology and its potential therapeutic applications.

Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered mental status.

The authors present a case of a 56-year-old man with altered mental status. Magnetic resonance imaging (MRI) of the brain revealed non-enhancing abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum. Immunohistochemisty demonstrated precursor T-cell lymphoblastic lymphoma. After treatment with methotrexate, he improved clinically without focal sensorimotor deficits and with improving orientation. MRI showed almost complete resolution of brainstem and cerebral lesions. To the authors' knowledge, there are only five previous reports of primary central nervous system T-cell lymphoblastic lymphoma. Since treatable, it deserves consideration in patients with altered mental status and imaging abnormalities that include diffuse, non-enhancing changes with increased signal on T2-weighted images.