The role of neurosurgery in advancing pediatric CNS tumor care worldwide.

Introduction: There is substantial inequity in survival outcomes for pediatric brain tumor patients residing in high-income countries (HICs) compared to low- and middle-income countries (LMICs). To address disparities in pediatric cancer survival, the World Health Organization (WHO) established the Global Initiative for Childhood Cancer (GICC) to expand quality care for children with cancer. Research question: To provide an overview of pediatric neurosurgical capacity and detail the burden of neurosurgical diseases impacting children. Material and methods: A narrative review of the current context of global pediatric neurosurgical capacity as it relates to neurooncology and other diseases relevant to children. Results: In this article, we provide an overview of pediatric neurosurgical capacity and detail the burden of neurosurgical diseases impacting children. We highlight concerted advocacy and legislative efforts aimed at addressing unmet neurosurgical needs in children. Finally, we discuss the potential implications of advocacy efforts on treating pediatric CNS tumors and outline strategies to improve global outcomes for children with brain tumors worldwide in the context of the WHO GICC. Discussion and conclusion: With both global pediatric oncology and neurosurgical initiatives converging on the treatment of pediatric brain tumors, significant strides toward decreasing the burden of pediatric neurosurgical diseases will hopefully be made.

Pediatric Neurosurgical Capacity for the Care of Children With CNS Tumors Worldwide: A Cross-Sectional Assessment.

PURPOSE: Efforts to address inequities in the treatment of pediatric CNS tumors and the burden of childhood cancer globally have prompted the designation of low-grade glioma as one of six index cancers for the World Health Organization Global Initiative for Childhood Cancer. Understanding the importance of neurosurgical interventions and evaluating pediatric neurosurgical capacity may identify critical interventions to improve outcomes for children with low-grade glioma and other CNS tumors. METHODS: An online, cross-sectional survey assessing pediatric neurosurgical practice and capacity was distributed to members of the International Society of Pediatric Neurosurgery. The survey included 36 items covering domains including patient volume, available infrastructure, scope of practice, case distribution, and multidisciplinary care. RESULTS: Responses from 196 individuals from 61 countries, spanning all WHO regions, were included. Ninety-six (49.0%) were from high-income countries, 57 (29.1%) were from upper-middle-income countries, 42 (21.4%) were from lower-middle-income countries (LMICs), and 1 was (0.5%) from a low-income country. Most respondents had a catchment population of ≥ 1 million and indicated the availability of basic neurosurgical resources such as a dedicated neurosurgical operating theater and surgical microscope. The presence of a neurosurgical intensive care unit, inpatient rehabilitation services, and infection monitoring showed similar availability across country groups. Quantitative scoring of 13 infrastructure and service items established that fewer resources were available in low-income countries/LMICs and upper-middle-income countries compared with high-income countries. The volume of pediatric CNS tumor cases and case distribution did not vary according to World Bank country groups. CONCLUSION: This study provides a comprehensive evaluation of pediatric neurosurgical capacity across the globe, establishing variability of resources on the basis of the country income level. Our findings suggest that pediatric neurosurgeons in LMICs may benefit from key neurosurgical instrumentation and increased support for multidisciplinary brain tumor programs and childhood cancer research efforts.

Equity in neurosurgery: a worldwide survey of women neurosurgeons.

OBJECTIVE: The global neurosurgery workforce does not have a defined stance on gender equity. The authors sought to study and characterize the demographic features of the international women neurosurgery community and to better understand the perceptions and reflections of their neurosurgical careers. The objective was to define and characterize the workplace inequities faced by the global women neurosurgeon community. METHODS: A 58-item cross-sectional survey was distributed to the global women neurosurgery community. The survey was distributed via an online and mobile platform between October 2018 and December 2020. Responses were anonymized. The authors utilized chi-square analysis to differentiate variables (e.g., career satisfaction) between various groups (e.g., those based on academic position). The authors calculated 95% CIs to establish significance. RESULTS: Among 237 respondents, approximately 40% were between the ages of 26 and 35 years. Within their respective departments, 45% identified themselves as the only woman neurosurgeon in their practice. Forty-three percent stated that their department supported women neurosurgeons for leadership roles. Seventy-five percent of respondents were members of organized neurosurgery professional societies; of these, 38% had been involved in leadership roles. Almost 60% of respondents postponed their decision to get pregnant because of resident or work-related influences. CONCLUSIONS: This survey provides international feedback for characterizing and understanding the experiences of women neurosurgeons worldwide. Future research should aim to understand all neurosurgeons' experiences throughout the pipeline and career life cycle of neurosurgery in order to improve the field of neurosurgery.

Serial assessment of measurable residual disease in medulloblastoma liquid biopsies.

Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.

Global neurosurgery: the current capacity and deficit in the provision of essential neurosurgical care. Executive Summary of the Global Neurosurgery Initiative at the Program in Global Surgery and Social Change.

OBJECTIVE: Worldwide disparities in the provision of surgical care result in otherwise preventable disability and death. There is a growing need to quantify the global burden of neurosurgical disease specifically, and the workforce necessary to meet this demand. METHODS: Results from a multinational collaborative effort to describe the global neurosurgical burden were aggregated and summarized. First, country registries, third-party modeled data, and meta-analyzed published data were combined to generate incidence and volume figures for 10 common neurosurgical conditions. Next, a global mapping survey was performed to identify the number and location of neurosurgeons in each country. Finally, a practitioner survey was conducted to quantify the proportion of disease requiring surgery, as well as the median number of neurosurgical cases per annum. The neurosurgical case deficit was calculated as the difference between the volume of essential neurosurgical cases and the existing neurosurgical workforce capacity. RESULTS: Every year, an estimated 22.6 million patients suffer from neurological disorders or injuries that warrant the expertise of a neurosurgeon, of whom 13.8 million require surgery. Traumatic brain injury, stroke-related conditions, tumors, hydrocephalus, and epilepsy constitute the majority of essential neurosurgical care worldwide. Approximately 23,300 additional neurosurgeons are needed to address more than 5 million essential neurosurgical cases-all in low- and middle-income countries-that go unmet each year. There exists a gross disparity in the allocation of the surgical workforce, leaving large geographic treatment gaps, particularly in Africa and Southeast Asia. CONCLUSIONS: Each year, more than 5 million individuals suffering from treatable neurosurgical conditions will never undergo therapeutic surgical intervention. Populations in Africa and Southeast Asia, where the proportion of neurosurgeons to neurosurgical disease is critically low, are especially at risk. Increasing access to essential neurosurgical care in low- and middle-income countries via neurosurgical workforce expansion as part of surgical system strengthening is necessary to prevent severe disability and death for millions with neurological disease.

Retrospective single-surgeon study of 1123 consecutive cases of anterior cervical discectomy and fusion: a comparison of clinical outcome parameters, complication rates, and costs between outpatient and inpatient surgery groups, with a literature review.

OBJECTIVE Outpatient anterior cervical discectomy and fusion (ACDF) is becoming more common and has been reported to offer advantages over inpatient procedures, including reducing nosocomial infections and costs, as well as improving patient satisfaction. The goal of this retrospective study was to evaluate and compare outcome parameters, complication rates, and costs between inpatient and outpatient ACDF cases performed by 1 surgeon at a single institution. METHODS In a retrospective study, the records of all patients who had undergone first-time ACDF performed by a single surgeon in the period from June 1, 2003, to January 31, 2016, were reviewed. Patients were categorized into 2 groups: those who had undergone ACDF as outpatients in a same-day surgical center and those who had undergone surgery in the hospital with a minimum 1-night stay. Outcomes for all patients were evaluated with respect to the following parameters: age, sex, length of stay, preoperative and postoperative pain (self-reported questionnaires), number of levels fused, fusion, and complications, as well as the presence of risk factors, such as an increased body mass index, smoking, and diabetes mellitus. RESULTS In total, 1123 patients were operated on, 485 (43%) men and 638 (57%) women, whose mean age was 50 years. The mean follow-up time was 25 months. Overall, 40.5% underwent 1-level surgery, 34.3% 2-level, 21.9% 3-level, and 3.2% 4-level. Only 5 patients had nonunion of vertebrae; thus, the fusion rate was 99.6%. Complications occurred in 40 patients (3.6%), with 9 having significant complications (0.8%). Five hundred sixty patients (49.9%) had same-day surgery, and 563 patients (50.1%) stayed overnight in the hospital. The inpatients were older, were more commonly male, and had a higher rate of diabetes. Smoking status did not influence the length of stay. Both groups had a statistically significant reduction in pain (expressed as a visual analog scale score) postoperatively with no significant difference between the groups. One- and 2-level surgeries were done significantly more often in the outpatient setting (p < 0.001). The complication rate was 4.1% in the outpatient group and 3.0% in the inpatient group; there was no statistically significant difference between the 2 groups (p = 0.339). Significantly more complications occurred with 3- and 4-level surgeries than with 1- and 2-level procedures (p < 0.001, chi-square test). The overall average inpatient cost for commercial insurance carriers was 26% higher than those for outpatient surgery. CONCLUSIONS Anterior cervical discectomy and fusion is safe for patients undergoing 1- or 2-level surgery, with a very significant rate of pain reduction and fusion and a low complication rate in both clinical settings. Outpatient and inpatient groups undergoing 3- or 4-level surgery had an increased risk of complications (compared with those undergoing 1- or 2-level surgery), with a negligible difference between the 2 groups. This finding suggests that these procedures can also be included as standard outpatient surgery. Comparable outcome parameters and the same complication rates between inpatient and outpatient groups support both operative environments.

Recurrent craniopharyngioma after conformal radiation in children and the burden of treatment.

OBJECT: In this paper the authors present their experience treating children with recurrent craniopharyngioma who were initially managed with surgery followed by conformal radiation therapy (CRT). METHODS: A departmental oncology information system was queried to identify all children (< 18 years old) who received CRT for a craniopharyngioma between 1998 and 2010 (inclusive) and specifically those who experienced tumor progression. For each patient, the authors recorded the type of recurrence (solid, cystic, or both), the time interval to first progression and each subsequent progression, the associated treatment complications, and disease status at last follow-up evaluation. RESULTS: Among the 97 patients that met criteria for entry into this study, 18 (18.6%) experienced tumor progression (9 cystic, 3 solid, 6 cystic and solid). The median time to first recurrence was 4.62 years (range 1.81-9.11 years). The subgroup included 6 female and 12 male patients with a median age of 7.54 years (range 3.61-13.83 years). Ten patients experienced first progression within 5 years of CRT. The 5- and 10-year treatment-free survival rates for the entire cohort were 89.0% (95% confidence interval [CI] 80.5%-93.9%) and 76.2% (95% CI 64%-85%), respectively. Seven patients had a single episode of progression and 11 had more than 1. The time interval between each subsequent progression was progressively shorter. The 18 patients underwent 38 procedures. The median follow-up duration for this group was 9.32 years (range 4.04-19.0 years). Three patients died, including 1 from perioperative complications. CONCLUSIONS: Craniopharyngioma progression after prior irradiation is exceedingly difficult to treat and local control is challenging despite repeated surgical procedures. Given our results, gross-total resection may need to be the surgical goal at the time of first recurrence, if possible. Decompressing new cyst formation alone has a low rate of long-term success.

Assessment of hemispheric dominance for receptive language in pediatric patients under sedation using magnetoencephalography.

Non-invasive assessment of hemispheric dominance for receptive language using magnetoencephalography (MEG) is now a well-established procedure used across several epilepsy centers in the context of pre-surgical evaluation of children and adults while awake, alert and attentive. However, the utility of MEG for the same purpose, in cases of sedated patients, is contested. Establishment of the efficiency of MEG is especially important in the case of children who, for a number of reasons, must be assessed under sedation. Here we explored the efficacy of MEG language mapping under sedation through retrospective review of 95 consecutive pediatric patients, who underwent our receptive language test as part of routine clinical evaluation. Localization of receptive language cortex and subsequent determination of laterality was successfully completed in 78% (n = 36) and 55% (n = 27) of non-sedated and sedated patients, respectively. Moreover, the proportion of patients deemed left hemisphere dominant for receptive language did not differ between non-sedated and sedated patients, exceeding 90% in both groups. Considering the challenges associated with assessing brain function in pediatric patients, the success of passive MEG in the context of the cases reviewed in this study support the utility of this method in pre-surgical receptive language mapping.

Antibiotic-impregnated shunt systems versus standard shunt systems: a meta- and cost-savings analysis.

OBJECT: Infection is a serious and costly complication of CSF shunt implantation. Antibiotic-impregnated shunts (AISs) were introduced almost 10 years ago, but reports on their ability to decrease the infection rate have been mixed. The authors conducted a meta-analysis assessing the extent to which AISs reduce the rate of shunt infection compared with standard shunts (SSs). They also examined cost savings to determine the degree to which AISs could decrease infection-related hospital expenses. METHODS: After conducting a comprehensive search of multiple electronic databases to identify studies that evaluated shunt type and used shunt-related infection as the primary outcome, 2 reviewers independently evaluated study quality based on preestablished criteria and extracted data. A random effects meta-analysis of eligible studies was then performed. For studies that demonstrated a positive effect with the AIS, a cost-savings analysis was conducted by calculating the number of implanted shunts needed to prevent a shunt infection, assuming an additional cost of $400 per AIS system and $50,000 to treat a shunt infection. RESULTS: Thirteen prospective or retrospective controlled cohort studies provided Level III evidence, and 1 prospective randomized study provided Level II evidence. "Shunt infection" was generally uniformly defined among the studies, but the availability and detail of baseline demographic data for the control (SS) and treatment (AIS) groups within each study were variable. There were 390 infections (7.0%) in 5582 procedures in the control group and 120 infections (3.5%) in 3467 operations in the treatment group, yielding a pooled absolute risk reduction (ARR) and relative risk reduction (RRR) of 3.5% and 50%, respectively. The meta-analysis revealed the AIS to be statistically protective in all studies (risk ratio = 0.46, 95% CI 0.33-0.63) and in single-institution studies (risk ratio = 0.38, 95% CI 0.25-0.58). There was some evidence of heterogeneity when studies were analyzed together (p = 0.093), but this heterogeneity was reduced when the studies were analyzed separately as single institution versus multiinstitutional (p > 0.10 for both groups). Seven studies showed the AIS to be statistically protective against infection with an ARR and RRR ranging from 1.7% to 14.2% and 34% to 84%, respectively. The number of shunt operations requiring an AIS to prevent 1 shunt infection ranged from 7 to 59. Assuming 200 shunt cases per year, the annual savings for converting from SSs to AISs ranged from $90,000 to over $1.3 million. CONCLUSIONS: While the authors recognized the inherent limitations in the quality and quantity of data available in the literature, this meta-analysis revealed a significant protective benefit with AIS systems, which translated into substantial hospital savings despite the added cost of an AIS. Using previously developed guidelines on treatment, the authors strongly encourage the use of AISs in all patients with hydrocephalus who require a shunt, particularly those at greatest risk for infection.