Characteristics of malignant brain tumor-associated epileptic spasms.

Although epilepsy is the most common comorbidity of brain tumors, epileptic spasms rarely occur. Brain tumors associated with epileptic spasms are mostly low-grade gliomas. To date, few studies in the literature have reported on malignant (Grades 3-4) brain tumors associated with epileptic spasms. Thus, we aimed to investigate the characteristics of malignant brain tumor-associated epileptic spasms. We retrospectively reviewed patients with malignant brain tumors and epileptic spasms in our institution. Data on demographics, tumor histology, magnetic resonance imaging, epileptic spasm characteristics, electroencephalography, and treatment responsiveness were also collected. Six patients were included. In all cases, the brain tumors occurred in infancy in the supratentorial region and epileptic spasm onset occurred after the completion of brain tumor treatment. Anti-seizure medication did not control epileptic spasms; two patients were seizure-free after epileptic surgery. Although all patients had developmental delays caused by malignant brain tumors and their treatment, developmental regression proceeded after epileptic spasm onset. Two patients who achieved seizure-free status showed improved developmental outcomes after cessation of epileptic spasms. This is the first report of the characteristics of malignant brain tumor-associated epileptic spasms. Our report highlights a difficulties of seizure control and possibillity of efficacy of epileptic surgery in this condition. In malignant brain tumor-associated epileptic spasms, it is important to proceed with presurgical evaluation from an early stage, bearing in mind that epileptic spasms may become drug-resistant.

Factors associated with longer survival among older medicare patients after diagnosis of supratentorial primary brain malignancies: a retrospective cohort study.

OBJECTIVES: Despite recent advances, the prognosis for primary malignant brain tumors (PMBTs) remains poor. Some commonly prescribed medications may exhibit anti-tumor properties in various cancers, and neurodegenerative diseases may activate pathways that counteract gliomagenesis. Our study is focused on determining if there is a correlation between the use of metformin, beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), or the presence of Parkinson's disease (PD), and the survival rates following a diagnosis of a PMBT. METHODS: This analysis of the 100% Texas Medicare Database identified patients aged 66+ years diagnosed with a supratentorial PMBT from 2014-2017. Cox proportional hazards regression was employed to analyze survival following diagnosis and associations of survival with surgical intervention, radiation, PD diagnosis, and prescription of metformin, beta-blockers, ACEIs, or ARBs. RESULTS: There were 1,943 patients who met study criteria, and the median age was 74 years. When medication utilization was stratified by none, pre-diagnosis only, post-diagnosis only, or both pre- and post-diagnosis (continuous), continuous utilization of metformin, beta-blockers, ACEIs, or ARBs was associated with prolonged survival compared to no utilization (hazard ratio [HR]:0.45, 95% CI:0.33-0.62; HR:0.71. 95% CI:0.59-0.86; HR:0.59, 95% CI:0.48-0.72; and HR:0.45, 95% CI:0.35-0.58 respectively). PD was also associated with longer survival (HR:0.59-0.63 across the four models). DISCUSSION: Our study suggests that metformin, beta-blockers, ACEIs, ARBs, and comorbid PD are associated with a survival benefit among geriatric Medicare patients with supratentorial PMBTs.

Significant perioperative parameters affecting postoperative complications within 30 days following craniotomy for primary malignant brain tumors.

BACKGROUND: The occurrence of postoperative complications within 30 days (PC1M) of a craniotomy for the removal of a primary malignant brain tumor has been associated with a poor prognosis. However, it is still unclear to early predict the occurrence of PC1M. This study aimed to identify the potential perioperative predictors of PC1M from its preoperative, intraoperative, and 24-h postoperative parameters. METHODS: Patients who had undergone craniotomy for primary malignant brain tumor (World Health Organization grades III and IV) from January 2011 to December 2020 were enrolled from a databank of Kaohsiung Veterans General Hospital, Taiwan. The patients were classified into PC1M and nonPC1M groups. PC1M was defined according to the classification by Landriel et al. as any deviation from an uneventful 30-day postoperative course. In both groups, data regarding the baseline characteristics and perioperative parameters of the patients, including a new marker-kinetic estimated glomerular filtration rate, were collected. Logistic regression was used to analyze the predictability of the perioperative parameters. RESULTS: The PC1M group included 41 of 95 patients. An American Society of Anesthesiologists score of > 2 (aOR, 3.17; 95% confidence interval [CI], 1.19-8.45; p = 0.021), longer anesthesia duration (aOR, 1.16; 95% CI, 0.69-0.88; p < 0.001), 24-h postoperative change in hematocrit by > - 4.8% (aOR, 3.45; 95% CI, 1.22-9.73; p = 0.0019), and 24-h postoperative change in kinetic estimated glomerular filtration rate of < 0 mL/min (aOR, 3.99; 95% CI, 1.52-10.53; p = 0.005) were identified as independent risk factors for PC1M via stepwise logistic regression analysis. When stratified according to the age of ≥ 65 years (OR, 11.55; 95% CI, 1.30-102.79; p = 0.028), the reduction of kinetic estimated glomerular filtration rate was more robustly associated with a higher risk of PC1M. CONCLUSIONS: Four parameters were demonstrated to significantly influence the risk of PC1M in patients undergoing primary malignant brain tumor removal. Measuring and verifying these markers, especially kinetic estimated glomerular filtration rate, would help early recognition of PC1M risk in clinical care.

Non-enhancing Glioblastoma: A Case Report.

Glioblastoma multiforme (GBM) is a malignant adult brain tumor that is visualized as an enhancing lesion on post-contrast magnetic resonance imaging (MRI). In this study, we present a rare case of non-enhancing GBM that required histopathological examination for a definitive diagnosis. Our findings emphasize the critical role of biopsy in the diagnosis and treatment of GBMs, particularly in cases of non-enhancing lesions on MRI.

Perfusion-Weighted Imaging: The Use of a Novel Perfusion Scoring Criteria to Improve the Assessment of Brain Tumor Recurrence versus Treatment Effects.

INTRODUCTION: Imaging surveillance of contrast-enhancing lesions after the treatment of malignant brain tumors with radiation is plagued by an inability to reliably distinguish between tumor recurrence and treatment effects. Magnetic resonance perfusion-weighted imaging (PWI)-among other advanced brain tumor imaging modalities-is a useful adjunctive tool for distinguishing between these two entities but can be clinically unreliable, leading to the need for tissue sampling to confirm diagnosis. This may be partially because clinical PWI interpretation is non-standardized and no grading criteria are used for assessment, leading to interpretation discrepancies. This variance in the interpretation of PWI and its subsequent effect on the predictive value has not been studied. Our objective is to propose structured perfusion scoring criteria and determine their effect on the clinical value of PWI. METHODS: Patients treated at a single institution between 2012 and 2022 who had prior irradiated malignant brain tumors and subsequent progression of contrast-enhancing lesions determined by PWI were retrospectively studied from CTORE (CNS Tumor Outcomes Registry at Emory). PWI was given two separate qualitative scores (high, intermediate, or low perfusion). The first (control) was assigned by a neuroradiologist in the radiology report in the course of interpretation with no additional instruction. The second (experimental) was assigned by a neuroradiologist with additional experience in brain tumor interpretation using a novel perfusion scoring rubric. The perfusion assessments were divided into three categories, each directly corresponding to the pathology-reported classification of residual tumor content. The interpretation accuracy in predicting the true tumor percentage, our primary outcome, was assessed through Chi-squared analysis, and inter-rater reliability was assessed using Cohen's Kappa. RESULTS: Our 55-patient cohort had a mean age of 53.5 ± 12.2 years. The percentage agreement between the two scores was 57.4% (κ: 0.271). Upon conducting the Chi-squared analysis, we found an association with the experimental group reads (p-value: 0.014) but no association with the control group reads (p-value: 0.734) in predicting tumor recurrence versus treatment effects. CONCLUSIONS: With our study, we showed that having an objective perfusion scoring rubric aids in improved PWI interpretation. Although PWI is a powerful tool for CNS lesion diagnosis, methodological radiology evaluation greatly improves the accurate assessment and characterization of tumor recurrence versus treatment effects by all neuroradiologists. Further work should focus on standardizing and validating scoring rubrics for PWI evaluation in tumor patients to improve diagnostic accuracy.

Corrigendum: Photodynamic therapy for malignant brain tumors in children and young adolescents.

[This corrects the article DOI: 10.3389/fonc.2022.957267.].

Metastatic secondary gliosarcoma: patient series.

BACKGROUND: Gliosarcoma is a rare and highly malignant cancer of the central nervous system with the ability to metastasize. Secondary gliosarcoma, or the evolution of a spindle cell-predominant tumor after the diagnosis of a World Health Organization grade IV glioblastoma, has also been shown to metastasize. There is little information on metastatic secondary gliosarcoma. OBSERVATIONS: The authors present a series of 7 patients with previously diagnosed glioblastoma presenting with recurrent tumor and associated metastases with repeat tissue diagnosis consistent with gliosarcoma. The authors describe the clinical, imaging, and pathological characteristics in addition to carrying out a systematic review on metastases in secondary gliosarcoma. LESSONS: The present institutional series and the systematic review of the literature show that metastatic secondary gliosarcoma is a highly aggressive disease with a poor prognosis.

Outcomes After Supratentorial Craniotomy for Primary Malignant Brain Tumor Resection in Adult Patients: A National Surgical Quality Improvement Program Analysis.

BACKGROUND: The rate of complications remains significant after craniotomy for supratentorial primary malignant brain tumors despite recent advances. OBJECTIVE: The goal of this study is to characterize factors associated with these complications. METHODS: Data were extracted from the National Surgical Quality Improvement Program database from 2016 to 2019. Patients who underwent a craniotomy for resection of supratentorial primary malignant brain tumors were included. Covariates included demographics/comorbidities, preoperative laboratory values, American Society of Anesthesiologists (ASA) classification, operative time, and postoperative complications. Multivariable logistic regression with backward and forward selection was used to evaluate independent predictors of death, prolonged hospitalization, postoperative stroke with neurologic deficit (CVA), and unplanned readmission. Predictive fit of the model was evaluated using the area under the receiver operating curve (AUC). RESULTS: Of 8965 included cases, the 30-day postoperative risks were 1.9% for CVA, 10.1% for unplanned readmission, 1.2% for prolonged hospitalization, and 2.4% for death. Age, ASA category, disseminated cancer, preoperative functional dependence, and postoperative respiratory complications were predictors of 30-day mortality (AUC, 0.83; P < 0.001). CVA was best predicted by increased operation time (P < 0.001), age, ASA category, and recent weight loss (AUC, 0.63; P = 0.009). Prolonged hospitalization was predicted by nonelective surgery status, time from admission to surgery, reintubation, and postoperative sepsis (AUC, 0.78; P < 0.001). Unplanned readmission was predicted by chronic steroid use, postoperative thrombotic complications after surgery, organ/space surgical site infection, deep vein thrombosis, postoperative systemic sepsis, and septic shock (AUC, 0.68; P < 0.001). CONCLUSIONS: Our study identifies predictors of major 30-day complications after craniotomy for this subset of patients with brain tumor.

Vascular endothelial growth factor and risk of malignant brain tumor: A genetic correlation and two-sample Mendelian randomization study.

Objective: The relationship between vascular endothelial growth factor (VEGF) and the risk of malignant brain tumors has always been a concern in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders, coinheritability and reverse causality. We aimed to investigate the causal relationship between VEGF and different types of malignant brain tumors. Methods: Using publicly available summary data from genome-wide association studies (GWAS) of VEGF (n=16,112) and different types of malignant brain tumors (n=174,097-174,646), we adopted a standard two-sample bidirectional Mendelian randomization (MR) to estimate potential causal associations of circulating VEGF levels and the risk of malignant brain tumors. Inverse variance weighted (IVW) was used as the primary analysis method to estimate causality. MR-Egger regression, weighted median (WM), penalty weighted median (PWM), MR robust adjusted profile score (MR.RAPS) and causal analysis using summary effect estimates (CAUSE) methods were used in sensitivity analyses to verify the robustness of the findings. Meanwhile, we applied the MR pleiotropy residual sum and outlier (MR-PRESSO) test and PhenoScanner tool to identify and remove potential horizontal pleiotropic single nucleotide polymorphisms (SNPs). Additionally, linkage disequilibrium score regression (LDSC) analysis was conducted to assess the coinheritability of exposure and outcome. Results: A total of 6 (VEGF), 12 (malignant brain tumor), 13 (brain glioblastoma) and 12 (malignant neoplasm of meninges) SNPs were identified as valid instrumental variables. No evidence supported a causal relationship between circulating VEGF levels and the risk of malignant brain tumors (forwards: odds ratio (OR) = 1.277, 95% confidence interval (CI), 0.812~2.009; reversed: ß = 0.005, 95% CI, -0.029~0.038), brain glioblastoma (forwards: OR (95% CI) = 1.278(0.463~3.528); reversed: ß = 0.010, 95% CI, -0.002~0.022) and malignant neoplasm of meninges (forwards: OR (95% CI) = 0.831(0.486~1.421); reversed: ß = 0.010, 95% CI, -0.030~0.050) using the main IVW method. Outliers and pleiotropy bias were not detected by sensitivity analyses and pleiotropy-robust methods in any estimates. LDSC failed to identify genetic correlations between VEGF and different types of malignant brain tumors. Conclusions: Our findings reported no coinheritability and failed to provide evidence for causal associations between VEGF and the risk of different types of malignant brain tumors. However, certain subtypes of VEGF for which genetic predictors have not been identified may play a role and need to be further investigated.

L3MBTL3 is induced by HIF-1α and fine tunes the HIF-1α degradation under hypoxia in vitro.

HIF-1α plays a crucial part in hypoxia response by transcriptionally upregulating genes to adapt the hypoxic condition. HIF-1α is under severe cellular control as its exceptional activation is always associated with tumorigenesis and tumor progression. Here, we report L3MBTL3 serves as a novel negative regulator of HIF-1α. It is upregulated during hypoxia and acts as a transcriptional target of HIF-1α. In the nuclei, L3MBTL3 makes an interaction with HIF-1α and promotes its ubiquitination and degradation. These findings indicate L3MBTL3 forms a negative feedback loop with HIF-1α in vitro to dampen the hypoxic response.

Interhospital transfer of pediatric patients with malignant brain tumor not associated with increased mortality, but safe routine discharge.

OBJECTIVE: Interhospital transfer (IHT) to obtain a higher level of care for pediatric patients requiring neurosurgical interventions is common. Pediatric patients with malignant brain tumors often require subspecialty care commonly provided at specialized centers. The authors aimed to assess the impact of IHT in pediatric neurosurgical patients with malignant brain tumors to identify areas of improvement in treatment of this patient population. METHODS: Pediatric patients (age < 19 years) with malignant primary brain tumors undergoing craniotomy for resection between 2010 and 2018 were retrospectively identified in the Nationwide Readmissions Database. Patient and hospital data for each index admission provided by the Nationwide Readmissions Database was analyzed by univariate and multivariate analyses. Further analysis evaluated association of IHT on specific patient- or hospital-related characteristics. RESULTS: In a total of 2279 nonelective admissions for malignant brain tumors in pediatric patients, the authors found only 132 patients (5.8%) who underwent IHT for a higher level of care. There is an increased likelihood of transfer when a patient is younger (< 7 years old, p = 0.006) or the disease process is more severe, as characterized by higher pediatric complex chronic conditions (p = 0.0004) and increased all patient refined diagnosis-related group mortality index (p = 0.02). Patients who are transferred (OR 1.87, 95% CI 1.04-3.35; p = 0.04) and patients who are treated at pediatric centers (OR 6.89, 95% CI 4.23-11.22; p < 0.0001) are more likely to have a routine discharge home. On multivariate analysis, transfer status was not associated with a longer length of stay (incident rate ratio 1.04, 95% CI 0.94-1.16; p = 0.5) or greater overall costs per patient ($20,947.58, 95% CI -$35,078.80 to $76,974.00; p = 0.50). Additionally, IHT is not associated with increased likelihood of death or major complication. CONCLUSIONS: IHT has a significant role in the outcome of pediatric patients with malignant brain tumors. Transfer of this patient population to hospitals providing subspecialized care results in a higher level of care without a significant burden on overall costs, risks, or mortality.

Novel Therapies in Glioblastoma Treatment: Review of Glioblastoma; Current Treatment Options; and Novel Oncolytic Viral Therapies.

One of the most prevalent primary malignant brain tumors is glioblastoma (GB). About 6 incidents per 100,000 people are reported annually. Most frequently, these tumors are linked to a poor prognosis and poor quality of life. There has been little advancement in the treatment of GB. In recent years, some innovative medicines have been tested for the treatment of newly diagnosed cases of GB and recurrent cases of GB. Surgery, radiotherapy, and alkylating chemotherapy are all common treatments for GB. A few of the potential alternatives include immunotherapy, tumor-treating fields (TTFs), and medications that target specific cellular receptors. To provide new multimodal therapies that focus on the molecular pathways implicated in tumor initiation and progression in GB, novel medications, delivery technologies, and immunotherapy approaches are being researched. Of these, oncolytic viruses (OVs) are among the most recent. Coupling OVs with certain modern treatment approaches may have significant benefits for GB patients. Here, we discuss several OVs and how they work in conjunction with other therapies, as well as virotherapy for GB. The study was based on the PRISMA guidelines. Systematic retrieval of information was performed on PubMed. A total of 307 articles were found in a search on oncolytic viral therapies for glioblastoma. Out of these 83 articles were meta-analyses, randomized controlled trials, reviews, and systematic reviews. A total of 42 articles were from the years 2018 to 2023. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. One of the most prevalent malignant brain tumors is still GB. Significant promise and opportunity exist for oncolytic viruses in the treatment of GB and in boosting immune response. Making the most of OVs in the treatment of GB requires careful consideration and evaluation of a number of its application factors.

Expression and role of deleted in malignant brain tumor protein 1 in acute respiratory distress syndrome rats induced by sepsis / 中华危重病急救医学

Objective:To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers.Methods:Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis.Results:Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/β-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). Conclusion:DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.

Safety comparison of high-dose methotrexate via different intravenous infusion devices in pediatric patients with malignant brain tumors / 中国药房

OBJECTIVE To compare the safety of high-dose methotrexate （HD-MTX） via peripherally inserted central catheter （PICC） and totally implantable venous access port （TIVAP） in pediatric patients with malignant brain tumors. METHODS Patients with malignant brain tumors who received HD-MTX via PICCs or TIVAPs in our hospital from July 2018 to April 2022 were retrospectively analyzed. Clinical data were collected to compare differences in blood concentration of methotrexate （MTX），the incidence of adverse events （including adverse drug reactions and catheter-related complications） and length of stay in hospital. Multivariate linear regression was applied to analyze the factors that influenced the blood concentration of MTX. RESULTS A total of 107 patients were included in the study，with 65 patients in the PICC group and 42 patients in the TIVAP group. Blood concentration of MTX at 24 h （C24 h） in TIVAP group was significantly higher than PICC group （[ 126.87±61.99） μmol/L vs. （102.45±48.77） μmol/L，P＜0.05）. There was no significant difference in blood concentration of MTX at 42 h （C42 h），compared with PICC group （P＞0.05）. Results of multivariate linear regression analysis showed that TIVAP was associated with the increase of C24 h（P＜0.05）. No significant differences were observed in the incidence of adverse events and the length of stay in the hospital between 2 groups （P＞0.05）. CONCLUSIONS Risk of adverse events is not increased，although the MTX C24 h level is elevated after administration of TIVAP. TIVAP is a safe choice for HD-MTX therapy with implementing therapeutic drug monitoring.

Photodynamic therapy for malignant brain tumors in children and young adolescents.

Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young adolescents. This was a single-center, non-randomized, phase I/II clinical study. The primary endpoints were the safety of treatment with talaporfin sodium (TS) (phase I) and overall survival (OS) after PDT (phase II). The secondary endpoint was progression-free survival (PFS) after PDT. The TS dose was determined by dose escalation from 10 to 20 to 40 mg/m2 for every three cases starting from the initial enrolled case. Eight patients with a mean age of 170.2 months (129-214 months) at the time of PDT received nine procedures with a mean follow-up duration of 16.8 months (1-42 months) after PDT. Histopathological diagnoses included supratentorial anaplastic ependymoma (n = 2), anaplastic astrocytoma (n = 1), diffuse midline glioma with H3K27M mutation (n = 1), glioblastoma (n = 3), and pediatric high-grade glioma (n = 1). The outcome was survival in five patients and death in three patients. Recurrence occurred in six of the eight patients; the remaining two were recurrence-free after PDT. Therefore, OS and PFS were calculated as 21 and 6 months, respectively. Seizures and fevers, which were likely surgery-related symptoms, were commonly observed. Photosensitive skin rashes or liver dysfunction, which are common adverse effects in adults, were not observed. Our results showed that TS can be used safely in children at doses comparable to those used in adults, as there was no major complication associated with TS administration. However, we cannot make a definitive conclusion about the efficacy of PDT because of the small number of participants. Accumulating cases was difficult because of the rarity of pediatric brain tumors and the difficulty in making a preoperative differential diagnosis, considering the wide range of histopathological findings. Moreover, the psychological stress associated with light-shielding management in pediatric patients was more severe than initially expected. In conclusion, TS at doses comparable to those used in adults may be safe for use in children and young adolescents between the ages of 6 and 20 years. However, further studies are needed to clarify its efficacy.

Is intraoperative MRI use in malignant brain tumor surgery a health care burden? A matched analysis of MarketScan Database.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is a useful adjunct for resection of primary malignant brain tumors (MBTs). The aim of our study is to investigate the impact of iMRI on health care utilization in patients who underwent craniotomy for resection of MBTs. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT 4th edition, from 2008 to 2020. We included patients ≥ 18 years of age who underwent a craniotomy with at-least one year follow-up. Outcomes were length of stay (LOS), discharge disposition, hospital/emergency room (ER) re-admissions, outpatient services, medication refills and corresponding payments. RESULTS: Of 6,640 patients who underwent craniotomy for MBTs, 465 patients (7%) had iMRI used during the procedure with 0.7% per year increase in iMRI use during the study period. Patients without iMRI use had higher complications at index hospitalization compared to those with iMRI use (19% vs. 14%, p = 0.04). There was no difference in the ER admission rates among the patients who underwent surgery with and without iMRI use at 6-months and 1-year after the index procedure. In terms of post-discharge payments, no significant differences were noted among the patients without and with iMRI use at 6-months ($81,107 vs. $ 81,458, p = 0.26) and 1-year ($132,657 vs. $ 118,113, p = 0.12). CONCLUSION: iMRI use during craniotomy for MBT gradually increased during the study period. iMRI did not result in higher payments at index hospitalization, 6-months, and 1-year after the index procedure.

A phase II pilot randomized controlled trial to assess the feasibility of the "supra-marginal" surgical resection of malignant glioma (G-SUMIT: Glioma supra marginal incision trial) study protocol.

BACKGROUND: High-grade gliomas are the most common primary malignant brain tumor in adults having a median survival of only 13-16 months. This is despite the current standard of maximal safe surgical resection followed by fractionated radiotherapy and chemotherapy. Extending the tumor resection limit beyond the gadolinium (GAD)-enhancing margin (i.e., supra-marginal resection) could in principle provide an added survival benefit as it has been shown that > 80% of post-operative tumor recurrence is within a 2-cm region surrounding the original GAD-enhancing margin. However, this must be weighed against the risk of potential damage to functional brain tissue. METHODS: In this phase II pilot randomized control trial (RCT), we aim to assess the feasibility of "supra-marginal" resection extending 1 cm beyond the enhancing tumor in adults with radiographic evidence of GAD-enhancing intra-axial tumor consistent with high-grade glioma in a safe anatomical location and a Karnofsky Performance Score > 60. With six academic institutions with established neurosurgical oncology practices in participation, we aim to enroll 72 patients over 2 years. Primary outcomes include evaluating the feasibility of performing a large-scale trial with regard to recruitment, allocation, and outcome documentation as well as safety data. Secondary outcomes include determining if there is an increased survival benefit with supra-marginal resection and impact on quality of life (Modified Rankin Scale (mRS), EuroQol-5D (ED-5D), 30-day all-cause mortality). DISCUSSION: Recent studies have revealed survival advantages comparing supra-marginal resection to standard attempt at gross total resection (GTR) with no additional perioperative surgical risk; however, the current quality of evidence is low and under-powered. Therefore, there are no current practice guidelines, and the philosophy of surgical resection is guided by individual surgeon preferences on an individual patient basis. This creates additional uncertainty and is potentially detrimental to our patients. This clinical equipoise supports the need for an adequately powered RCT to determine whether a supra-marginal resection can have a positive impact on survival for patients with HGGs. Our pilot RCT will test the feasibility of comparing the standard gross total resection of GAD-enhancing tumors and supra-marginal resection to prepare for a larger definitive multicenter RCT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04737577. Registered on February 4, 2021.

Comparison of the quality of death between primary malignant brain tumor patients and other cancer patients: results from a nationwide bereavement survey in Japan.

PURPOSE: No studies have investigated the association between malignant brain tumor and the quality of dying, which is an important outcome in end-of-life care. This study aimed to clarify whether the quality of dying and related factors in patients with malignant brain tumor differ from those in patients with other malignant diseases. METHODS: This was a secondary analysis of data collected by two nationwide, multicenter, bereavement surveys of palliative care units in Japan. This analysis included 14,171 bereaved family members (160 patients with malignant brain tumors). The quality of dying was examined using the good death inventory (GDI), a validated tool widely used in palliative care settings. RESULTS: Patients with malignant brain tumors were younger (p < 0.0001) and had a longer palliative care unit stay during their end-of-life (p < 0.0001) than others. The total GDI score was significantly lower in patients with malignant brain tumors than others (p < 0.0001). Five GDI items were significantly lower in the malignant brain tumor group than other cancer group: "Being able to stay in one's favorite place" (p = 0.03); "Trusting the physician" (p = 0.003); "Not being a burden to others" (p = 0.01); "Being independent in daily activities" (p = 0.01); and "Feeling that one's life is worth living" (p = 0.001). CONCLUSION: This study showed that the quality of dying of patients with malignant brain tumors was lower compared to other cancers, suggesting the need to review care for patients with malignant brain tumors based on their characteristics.

Anticancer Mechanisms of Berberine: A Good Choice for Glioblastoma Multiforme Therapy.

The most typical malignant brain tumor, glioblastoma multiforme (GBM), seems to have a grim outcome, despite the intensive multi-modality interventions. Literature suggests that biologically active phytomolecules may exert anticancer properties by regulating several signaling pathways. Berberine, an isoquinoline alkaloid, has various pharmacological applications to combat severe diseases like cancer. Mechanistically, it inhibits cell proliferation and invasion, suppresses tumor angiogenesis, and induces cell apoptosis. The antitumoral effect of berberine in GBM is increasingly recognized. This review sheds new light on the regulatory signaling mechanisms of berberine in various cancers, proposing its potential role as a therapeutic agent for GBM.

Care of the Patient Undergoing Robotic-Assisted Brain Biopsy With Stereotactic Navigation: An Overview.

Brain tumors can cause pressure, swelling, and functional changes to the surrounding tissue and lead to sensorimotor symptoms. Such tumors are either benign or malignant and their origin can be primary or metastatic. Although diagnostic studies (eg, computed tomography and magnetic resonance imaging) can reveal a mass and provide information on its location, size, and relationship to surrounding structures, the most definitive way to make a diagnosis requires a brain biopsy tissue sample. The robotic-assisted technique with stereotactic navigation allows the neurosurgeon to merge preoperative scans with a computer program to provide a map of the planned surgical trajectory and use the robot to obtain the biopsy. The robotic-assisted brain biopsy with navigation provides improved accuracy with small incisions that may not be possible using non-robotic-assisted techniques. This article provides background information and an overview of the nursing considerations for patients undergoing robotic-assisted brain biopsy procedures.