Stereotactic radiosurgery and resection for treatment of multiple brain metastases: a systematic review and analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) has recently emerged as a minimally invasive alternative to resection for treating multiple brain metastases. Given the lack of consensus regarding the application of SRS versus resection for multiple brain metastases, the authors aimed to conduct a systematic literature review of all published work on the topic. METHODS: The PubMed, OVID, Cochrane, Web of Science, and Scopus databases were used to identify studies that examined clinical outcomes after resection or SRS was performed in patients with multiple brain metastases. Radiological studies, case series with fewer than 3 patients, pediatric studies, or national database studies were excluded. Data extracted included patient demographics and mean overall survival (OS). Weighted t-tests and ANOVA were performed. RESULTS: A total of 1300 abstracts were screened, 450 articles underwent full-text review, and 129 studies met inclusion criteria, encompassing 20,177 patients (18,852 treated with SRS and 1325 who underwent resection). The OS for the SRS group was 10.2 ± 6 months, and for the resection group it was 6.5 ± 3.8 months. A weighted ANOVA test comparing OS with covariates of age, sex, and publication year revealed that the treatment group (p = 0.045), age (p = 0.034), and publication year (0.0078) were all independently associated with OS (with SRS, younger age, and later publication year being associated with longer survival), whereas sex (p = 0.95) was not. CONCLUSIONS: For patients with multiple brain metastases, SRS and resection are effective treatments to prolong OS, with published data suggesting that SRS may have a trend toward lengthened survival outcomes. The authors encourage additional work examining outcomes of treatments for multiple brain metastases.

History of Women in Neurosurgery (WINS).

In 2020, the Women in Neurosurgery (WINS) organization, a joint section of the AANS and Congress of Neurological Surgeons, celebrated 30 years since its inception. In this paper, the authors explore the history of WINS from its beginnings through its evolution over the past three decades. The achievements of the group are highlighted, as well as the broader achievements of the women in the neurosurgical community over this time period.

Trends in glioblastoma: outcomes over time and type of intervention: a systematic evidence based analysis.

INTRODUCTION: Despite aggressive treatment with chemoradiotherapy and maximum surgical resection, survival in patients with glioblastoma (GBM) remains poor. Ongoing efforts are aiming to prolong the lifespan of these patients; however, disparities exist in reported survival values with lack of clear evidence that objectively examines GBM survival trends. We aim to describe the current status and advances in the survival of patients with GBM, by analyzing median overall survival through time and between treatment modalities. METHODS: A systematic review was conducted according to PRISMA guidelines to identify articles of newly diagnosed glioblastoma from 1978 to 2018. Full-text glioblastoma papers with human subjects, ≥ 18 years old, and n ≥ 25, were included for evaluation. RESULTS: The central tendency of median overall survival (MOS) was 13.5 months (2.3-29.6) and cumulative 5-year survival was 5.8% (0.01%-29.1%), with a significant difference in survival between studies that predate versus postdate the implementation of temozolomide and radiation, [12.5 (2.3-28) vs 15.6 (3.8-29.6) months, P < 0.001]. In clinical trials, bevacizumab [18.2 (10.6-23.0) months], tumor treating fields (TTF) [20.7 (20.5-20.9) months], and vaccines [19.2 (15.3-26.0) months] reported the highest central measure of median survival. CONCLUSION: Coadministration with radiotherapy and temozolomide provided a statistically significant increase in survival for patients suffering from glioblastoma. However, the natural history for GBM remains poor. Therapies including TTF pooled values of MOS and provide means of prolonging the survival of GBM patients.

Propensity for different vascular distributions and cerebral edema of intraparenchymal brain metastases from different primary cancers.

PURPOSE: This study seeks to ascertain whether different primary tumor types have a propensity for brain metastases (BMs) in different cerebral vascular territories and cerebral edema. METHODS: Consecutive adult patients who underwent surgical resection of a BM at a tertiary care institution between 2001 and 2011 were retrospectively reviewed. Only patients with the most common primary cancers (lung, breast, skin-melanoma, colon, and kidney) were included. Preoperative MRIs were reviewed to classify all tumors by cerebral vascular territory (anterior cerebral artery-ACA, lenticulostriate, middle cerebral artery-MCA, posterior cerebral artery-PCA, posterior fossa, and watershed), and T2-weighted FLAIR widths were measured. Chi square analyses were performed to determine differences in cerebral vascular distribution by primary tumor type, and one-way ANOVA analyses were performed to determine FLAIR signal differences. RESULTS: 669 tumors from 388 patients were classified from lung (n = 316 BMs), breast (n = 144), melanoma (n = 119), renal (n = 47), and colon (n = 43). BMs from breast cancer were less likely to be located in PCA territory (n = 18 [13%]; χ2 = 6.10, p = 0.01). BMs from melanoma were less likely to be located in cerebellar territory (n = 11 [9%]; χ2 = 14.1, p < 0.001), and more likely to be located in lateral (n = 5 [4%]; χ2 = 4.56, p = 0.03) and medial lenticulostriate territories (n = 2 [2%]; χ2 = 6.93, p = 0.009). BMs from breast and melanoma had shorter T2-FLAIR widths, with an average [IQR] of 47.2 [19.6-69.2] mm (p = 0.01) and 41.2 [14.4-62.7] mm (p = 0.002) respectively. Conversely, BMs from renal cancer had longer T2-FLAIR widths (64.2 [43.6-80.8] mm, p = 0.002). CONCLUSIONS: These findings suggest that different primary tumor types could have propensities for different cerebral vascular territories and cerebral edema.

Evaluation of Risk of Gastrostomy and Ventriculoperitoneal Shunt Placement in Pediatric Patients: A Systematic Review of the Literature.

A subset of patients with neurologic deficits require ventriculoperitoneal shunt (VPS) placement in addition to gastrostomy tubes (GTs). At present, the literature is inconsistent with respect to the sequence and time period between procedures that yields the lowest risk profile for GT and VPS placement. The purpose of this systematic literature review was to determine if time elapsed between VPS and GT placement was associated with infection (peritoneal and/or CSF). A systematic literature review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. PubMEd/MEDLINE, Scopus, Ovid, Cochrane, and EMBASE databases were queried. Precise search terminology is available in the body of the manuscript. The initial database query yielded 88 unique articles. After abstract screening, 28 articles were identified and 6 met criteria for inclusion in the final analysis. The included studies were all retrospective analyses and reported data for 217 patients between the years of 1988 and 2016. Across all included studies, the infection rate after VPS and GT placement during the studies' surveillance period was 15.2% (n = 33/217). The cumulative rate of all reported complications in patients with both VPS and GT was 24.0% (n = 52/217). These studies suggest that placement of GT in patients with preexisting VPS does not significantly contribute to increased shunt or intraperitoneal infection. Future studies should determine the optimal time interval between VPS and GT placement and to identify the most appropriate prophylactic antibiotic regimen.

Minimally invasive tubular retractor-assisted biopsy and resection of subcortical intra-axial gliomas and other neoplasms.

BACKGROUND: Deep-seated, subcortical tumors represent a surgical challenge. The traditional approach to these lesions involve large craniotomies, fixed retractor systems, and extensive white matter dissection, each with their own associated morbidity. We describe our experience with the use of tubular retractors for accessing these deep-seated lesions. METHODS: Fifty consecutive patients operated on for an intra-axial brain tumor (both biopsies and resection) from January 2016 to December 2017 by a single surgeon using tubular retractors with exoscopic visualization were prospectively identified and included in this consecutive case series. RESULTS: Thirty-five patients (70%) underwent surgical resection and 15 (30%) underwent excisional biopsy for tumors located a median (interquartile range [IQR]) distance of 5.4 (4.5-6.1) cm below the cortical surface within the thalamus and/or basal ganglia in 12 (24%), centrum semiovale in 17 (34%), cerebellar in 8 (16%), peri-Rolandic in 6 (12%), visual tracts in 5 (10%), and intraventricular in 2 (4%). The median IQR percent resection was 100 (95-100)% and all patients had diagnostic tissue. Pathology was high grade glioma in 30 (60%), metastatic in 14 (28%), and cavernoma in 2 (4%). The postoperative median IQR KPS was 80 (80-90), where 18 (36%) had improved, 29 (58%) stable, and 3 (6%) worsened KPS as compared to preoperatively. CONCLUSIONS: The tubular retractor is a useful tool in the armamentarium of brain tumor surgery, and the exoscope provides an ergonomic means of visualizing the surgical field. It is meant to be used as a tool to access and resect deep-seated lesions while preserving and displacing superficial white matter tracts and cortical regions, provide a protected corridor to minimize inadvertent tissue injury during the resection, and circumferential tissue retraction to minimize risk of ischemia and damage to white matter tracts. As with any procedure, there is a learning curve with this surgical adjunct.

Acute care for the three leading causes of mortality in lower-middle-income countries: A systematic review.

According to the World Health Organization, the three leading causes of mortality in lower-middle-income countries (LMIC) are ischemic heart disease (IHD), stroke, and lower respiratory infections (LRIs), causing 111.8, 68.8, and 51.5 annual deaths per 100,000, respectively. Due to barriers to healthcare, patients frequently present in critical stages of these diseases. Measured implementations in critical care in LMIC have been published; however, the literature has not been formally reviewed. We performed a systematic review of the literature indexed in PubMed as of October 2017. Abstracts were limited to human studies in English, French, and Spanish, conducted in LMIC, and containing quantitative data on acute care of IHD, stroke, and LRI. The search resulted in 4994 unique abstracts. Through multiple rounds of screening using criteria determined a priori, 161 manuscripts were identified: 38 for IHD, 20 for stroke, 26 for adult LRI, and 78 for pediatric LRI. These studies, predominantly from Asia, demonstrate successful diagnostic and treatment measures used in providing acute care for patients in LMIC. Given that, only four manuscripts originated in Central or South America, original research from these areas is lacking. IHD, stroke, and LRIs are significant causes of mortality, especially in LMIC. Diagnostic and therapeutic interventions for IHD (monitoring, medications, thrombolytics, percutaneous intervention, coronary artery bypass graft), stroke (therapeutic hypothermia, medications, and thrombolytics), and LRI (oxygen saturation measurement, diagnostic ultrasound, administration of oxygen, appropriate antibiotics, and other medications) have been studied in LMIC and published.

On-the-Go Training: Downloadable Modules to Train Medical Students to Care for Adult Female Sexual Assault Survivors.

Introduction: Every medical provider encounters patients who have experienced sexual assault, and a patient's interaction with the medical system can impact long-term outcomes. Training to provide appropriate, compassionate care for this population is lacking in most medical school curricula. This educational resource contains three downloadable modules to train medical students in providing improved care for adult female survivors of sexual assault so students can feel more confident and empowered in caring for this population. Methods: The modules are composed of an informational video on initial medical management, a patient interview simulation video, and a set of audio interviews on suggestions for practice. Interdisciplinary experts assisted in the modules' development. Associated materials include a 10 question pre- and posttest of medical knowledge, with additional survey questions to assess student attitudes and satisfaction outcomes. Results: A cohort of 32 medical student volunteers from all class years tested the modules. Overall, student scores improved 20% (95% confidence interval, 16%-23%) from pre- to posttest. Students reported that their comfort in caring for an adult female sexual assault survivor increased after completion of the modules (p = .025). On the whole, students reported on the postsurvey that the modules enhanced their education, improved their comfort, and were appropriate for their level of education. Discussion: These modules can enrich an undergraduate medical curriculum in a currently underaddressed topic, the care of female survivors of sexual assault. Empowering and educating students to care for this patient population can result in improved health outcomes.

Epidemiology of Emergency Medical Services (EMS) Utilization in Four Indian Emergency Departments.

Introduction Without a universal Emergency Medical Services (EMS) system in India, data on the epidemiology of patients who utilize EMS are limited. This retrospective chart review aimed to quantify and describe the burden of disease and patient demographics of patients who arrived by EMS to four Indian emergency departments (EDs) in order to inform a national EMS curriculum. METHODS: A retrospective chart review was performed on patients transported by EMS over a three-month period in 2014 to four private EDs in India. A total of 17,541 patient records were sampled from the four sites over the study period. Of these records, 1,723 arrived by EMS and so were included for further review. RESULTS: A range of 1.4%-19.4% of ED patients utilized EMS to get to the ED. The majority of EMS patients were male (59%-64%) and adult or geriatric (93%-99%). The most common chief complaints and ED diagnoses were neurological, pulmonary, cardiovascular, gastrointestinal, trauma, and infectious disease. CONCLUSIONS: Neurological, pulmonary, cardiovascular, gastrointestinal, trauma, and infectious disease are the most common problems found in patients transported by EMS in India. Adult and geriatric male patients are the most common EMS utilizers. Emergency Medical Services curricula should emphasize these knowledge areas and skills. Wijesekera O , Reed A , Chastain PS , Biggs S , Clark EG , Kole T , Chakrapani AT , Ashish N , Rajhans P , Breaud AH , Jacquet GA . Epidemiology of Emergency Medical Services (EMS) utilization in four Indian emergency departments. Prehosp Disaster Med. 2016;31(6):675-679.

Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer.

Recent research advances have established mesenchymal stem cells (MSCs) as a promising vehicle for therapeutic delivery. Their intrinsic tropism for brain injury and brain tumors, their lack of immunogenicity, and their ability to breach the blood-brain barrier make these cells an attractive potential treatment of brain disorders, including brain cancer. Despite these advantages, the efficiency of MSC homing to the brain has been limited in commonly used protocols, hindering the feasibility of such therapies. In the present study, we report a reproducible, comprehensive, cell culture-based approach to enhance human adipose-derived MSC (hAMSC) engraftment to brain tumors. We used micro- and nanotechnological tools to systematically model several steps in the putative homing process. By pre-exposing hAMSCs to glioma-conditioned media and the extracellular matrix proteins fibronectin and laminin, we achieved significant enhancements of the individual homing steps in vitro. This homing was confirmed in an in vivo rodent model of brain cancer. This comprehensive, cell-conditioning approach provides a novel method to enhance stem cell homing to gliomas and, potentially, other neurological disorders.

When gross total resection of a glioblastoma is possible, how much resection should be achieved?

OBJECTIVE: The efficacy of extensive resection on prolonging survival for patients with glioblastoma (GBM) is controversial because prior studies have included tumors with dissimilar resection capabilities. The true isolated effect of increasing resection on survival for GBM therefore remains unclear. METHODS: Adult patients who underwent surgery of an intracranial newly diagnosed GBM at an academic tertiary-care institution from 2007 to 2011 were reviewed. Preoperative images were reviewed by 3 neurosurgeons independently. Tumors considered amenable to gross total resection based on preoperative imaging by all neurosurgeons were included. Multivariate proportional hazards regression analysis was used to identify if an association existed between residual volume (RV) and extent of resection (EOR) with survival. RESULTS: Of the 292 patients with newly diagnosed GBM, 84 (29%) were amenable to gross total resection. The median (interquartile range) pre and postoperative tumor volumes were 27 (13.8-54.4) and 0.9 (0-2.7) cm(3), respectively. The mean percent resection was 91.7% ± 1.3%. In multivariate analysis, after controlling for age, functional status, and adjuvant therapies, RV (hazards ratio [HR] [95% confidence interval (CI)] = 1.114 [1.033-1.193], P = 0.006) and EOR (HR [95% CI] = 0.959 [0.934-0.985], P = 0.003) were each independently associated with survival. The RV and EOR with the greatest reduction in the risk of death was <2 cm(3) and >95%, respectively. Likewise, RV (HR [95% CI] = 1.085 [1.010-1.178], P = 0.01) and EOR (HR [95% CI] = 0.962 [0.930-0.998], P = 0.04) each remained independently associated with recurrence. CONCLUSION: This is the first study to evaluate RV and EOR in a more uniform population of patients with tumors of similar surgical capabilities. This study shows that achieving a decreased RV and/or an increased EOR is independently associated with survival and recurrence in those patients with tumors with similar resection capacities.

Identifying better surgical candidates among recursive partitioning analysis class 2 patients who underwent surgery for intracranial metastases.

OBJECTIVE: The management of patients with brain metastases is typically dependent on their prognosis. Recursive partitioning analysis (RPA) is the most commonly used method for prognosticating survival, but has limitations for patients in the intermediate class. The aims of this study were to ascertain preoperative risk factors associated with survival, develop a preoperative prognostic grading system, and evaluate the utility of this system in predicting survival for RPA class 2 patients. METHODS: Adult patient who underwent intracranial metastatic tumor surgery at an academic tertiary care institution from 1997 to 2011 were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify preoperative factors associated with survival. The identified associations were then used to develop a grading system. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analyses. RESULTS: A total of 421 (59%) of 708 patients were RPA class 2. The preoperative factors found to be associated with poorer survival were: male gender (P < 0.0001), motor deficit (P = 0.0007), cognitive deficit (P = 0.0004), nonsolitary metastases (P = 0.002), and tumor size >2 cm (P = 0.003). Patients having 0-1, 2, and 3-5 of these variables were assigned a preoperative grade of A, B, and C, respectively. Patients with a preoperative grade of A, B, and C had a median survival of 17.0, 10.3, and 7.3 months, respectively. These grades had distinct survival times (P < 0.05). CONCLUSIONS: The present study devised a preoperative grading system that may provide prognostic information for RPA class 2 patients, which may also guide medical and surgical therapies before any intervention is pursued.

Mesenchymal stem cells from human fat engineered to secrete BMP4 are nononcogenic, suppress brain cancer, and prolong survival.

PURPOSE: Glioblastoma is the most common adult primary malignant intracranial cancer. It is associated with poor outcomes because of its invasiveness and resistance to multimodal therapies. Human adipose-derived mesenchymal stem cells (hAMSC) are a potential treatment because of their tumor tropism, ease of isolation, and ability to be engineered. In addition, bone morphogenetic protein 4 (BMP4) has tumor-suppressive effects on glioblastoma and glioblastoma brain tumor-initiating cells (BTIC), but is difficult to deliver to brain tumors. We sought to engineer BMP4-secreting hAMSCs (hAMSCs-BMP4) and evaluate their therapeutic potential on glioblastoma. EXPERIMENTAL DESIGN: The reciprocal effects of hAMSCs on primary human BTIC proliferation, differentiation, and migration were evaluated in vitro. The safety of hAMSC use was evaluated in vivo by intracranial coinjections of hAMSCs and BTICs in nude mice. The therapeutic effects of hAMSCs and hAMSCs-BMP4 on the proliferation and migration of glioblastoma cells as well as the differentiation of BTICs, and survival of glioblastoma-bearing mice were evaluated by intracardiac injection of these cells into an in vivo intracranial glioblastoma murine model. RESULTS: hAMSCs-BMP4 targeted both the glioblastoma tumor bulk and migratory glioblastoma cells, as well as induced differentiation of BTICs, decreased proliferation, and reduced the migratory capacity of glioblastomas in vitro and in vivo. In addition, hAMSCs-BMP4 significantly prolonged survival in a murine model of glioblastoma. We also demonstrate that the use of hAMSCs in vivo is safe. CONCLUSIONS: Both unmodified and engineered hAMSCs are nononcogenic and effective against glioblastoma, and hAMSCs-BMP4 are a promising cell-based treatment option for glioblastoma.

Harvey Cushing and "birth hemorrhage": early pediatric neurosurgery at The Johns Hopkins Hospital.

Of Harvey Cushing's many contributions to neurosurgery, one of the least documented is his early surgical intervention in children and his pioneering efforts to establish pediatric neurosurgery as a subspecialty. Between 1896 and 1912 Cushing conducted nearly 200 operations in children at The Johns Hopkins Hospital. A review of his records suggests that the advances he made in neurosurgery were significantly influenced by his experience with children. In this historical article, the authors describe Cushing's treatment of 6 children, in all of whom Cushing established a diagnosis of "birth hemorrhage." By reviewing Cushing's operative indications, techniques, and outcomes, the authors aim to understand the philosophy of his pediatric neurosurgical management and how this informed his development of neurosurgery as a new specialty.