Is there a "July effect" in pediatric neurosurgery?

PURPOSE: The belief that July, when resident physicians' training year begins, may be associated with increased risk of patient morbidity and mortality is known as the "July effect." This study aimed to compare complication rates after pediatric neurosurgical procedures in the first versus last academic quarters in two national datasets. METHODS: Data were extracted from the National Surgical Quality Improvement Program-Pediatrics (NSQIP-P) database for year 2012 for 30-day complication events and the Kids' Inpatient Database (KID) for year 2012 for in-hospital complication events after pediatric neurosurgical procedures. Descriptive and analytic statistical methods were used to characterize the impact of seasonal variation between the first and last quarters on complications. RESULTS: Three thousand six hundred twenty-four procedures in the NSQIP-P dataset and 14,855 hospitalizations in KID were included in the study cohort. No significant difference was observed between the first and fourth quarters for these complication events: wound disruption/dehiscence, wound infection, nerve injury, bleeding requiring transfusion, central line-associated BSI, deep venous thrombosis/pulmonary embolism, urinary tract infection, renal failure, re-intubation/pulmonary failure, cardiac arrest, stroke, coma, and death. There was no difference in the average length of stay or average length of surgical time. In the NSQIP-P, the first quarter was associated with a significantly increased incidence of pneumonia and unplanned re-operation; there was a trend towards increased incidence of unplanned re-admission and sepsis. In KID, there was no difference in the rate of pneumonia or sepsis. CONCLUSION: For the majority of morbidity and mortality events, no significant difference was found in occurrence rates between the first and last quarters.

Transfrontal and Transsphenoidal Approaches to Pediatric Craniopharyngioma: A National Perspective.

INTRODUCTION: This study compared transsphenoidal (TS) and transfrontal (TF) approaches to craniopharyngioma utilizing a national database. METHODS: The Kids' Inpatient Database (2003, 2006, and 2009) was surveyed for patients with a diagnosis of craniopharyngioma who underwent a subset of surgical interventions to compare TS and TF surgery. Demographics, hospital variables, and complications/comorbidities were analyzed with multivariate regression. RESULTS: 314 admissions (TS = 104, TF = 210) were identified. The mean age was 14.8 (TS) versus 9.8 (TF) years (p < 0.001). The mean number of diagnoses was 4.6 (TS) versus 6.2 (TF) (p < 0.001). Diabetes insipidus was associated with 38% (TS) and 69% (TF). Cerebrospinal fluid (CSF) leak affected 19% TS and 4% TF resections. Other complications and comorbidities included postoperative stroke (2% TS vs. 5% TF), panhypopituitarism (5 vs. 8%), death (0 vs. 1%), cranial nerve deficits (1 vs. 6%), thrombotic events (7 vs. 17%), and seizures (0 vs. 12%). 98% of patients were discharged home after a mean 6-day length of stay (LOS) after TS, whereas 90% of TF patients had a LOS of 12 days. TS cases were more likely to be privately insured (68%) and from higher income brackets (61%) than TF ones (56 and 2%, respectively) (p < 0.05). In multivariate regression models adjusting for age, sex, race, number of diagnoses, surgical approach, hospital volume, and insurance type, the TS approach was associated with an increased incidence of CSF leak (OR 10, p < 0.001). More documented diagnoses (OR 16-60, p < 0.01) and TF approach (OR 2.6, p < 0.01) were associated with an increased incidence of other complications and comorbidities. Age younger than 10 (ß-coefficient 2.3, p = 0.01), more diagnoses (ß-coefficient 1.2, p < 0.001), and TF approach (ß- coefficient 3.0, p < 0.01) were associated with increased LOS. A higher number of diagnoses were associated with nonhome discharge destinations (ß-coefficient 1.29, p < 0.001). CONCLUSION: TS surgery was associated with an increased incidence of CSF leak but shorter LOS; TF surgery was associated with an increased incidence of other complications. Patients undergoing TS surgery were more likely to have private insurance and a higher family income bracket.

AP-1A controls secretory granule biogenesis and trafficking of membrane secretory granule proteins.

The adaptor protein 1A complex (AP-1A) transports cargo between the trans-Golgi network (TGN) and endosomes. In professional secretory cells, AP-1A also retrieves material from immature secretory granules (SGs). The role of AP-1A in SG biogenesis was explored using AtT-20 corticotrope tumor cells expressing reduced levels of the AP-1A µ1A subunit. A twofold reduction in µ1A resulted in a decrease in TGN cisternae and immature SGs and the appearance of regulated secretory pathway components in non-condensing SGs. Although basal secretion of endogenous SG proteins was unaffected, secretagogue-stimulated release was halved. The reduced µ1A levels interfered with the normal trafficking of carboxypeptidase D (CPD) and peptidylglycine α-amidating monooxygenase-1 (PAM-1), integral membrane enzymes that enter immature SGs. The non-condensing SGs contained POMC products and PAM-1, but not CPD. Based on metabolic labeling and secretion experiments, the cleavage of newly synthesized PAM-1 into PHM was unaltered, but PHM basal secretion was increased in sh-µ1A PAM-1 cells. Despite lacking a canonical AP-1A binding motif, yeast two-hybrid studies demonstrated an interaction between the PAM-1 cytosolic domain and AP-1A. Coimmunoprecipitation experiments with PAM-1 mutants revealed an influence of the luminal domains of PAM-1 on this interaction. Thus, AP-1A is crucial for normal SG biogenesis, function and composition.

The Impact of Insurance, Race, and Ethnicity on Age at Surgical Intervention among Children with Nonsyndromic Craniosynostosis.

OBJECTIVE: To examine the impact of demographic factors, including insurance type, family income, and race/ethnicity, on patient age at the time of surgical intervention for craniosynostosis surgery in the US. STUDY DESIGN: The Kids' Inpatient Database was queried for admissions of children younger than 3 years of age undergoing craniosynostosis surgery in 2009. Descriptive data regarding age at surgery for various substrata are reported. Multivariate regression was used to evaluate the effect of patient and hospital characteristics on the age at surgery. RESULTS: Children with private insurance were, on average, 6.8 months of age (95% CI 6.2-7.5) at the time of surgery; children with Medicaid were 9.1 months old (95% CI 8.4-9.8). White children received surgery at mean age of 7.2 months (95% CI 6.5-8.0) and black and Hispanic children at a mean age of 9.1 months (95% CI 8.2-10.1). Multivariate regression analysis found Medicaid insurance (beta coefficient [B]=1.93, P<.001), black or Hispanic race/ethnicity (B=1.34, P=.022), and having 2 or more chronic conditions (B=2.86, P<.001) to be significant independent predictors of older age at surgery. CONCLUSION: Public insurance and nonwhite race/Hispanic ethnicity were statistically significant predictors for older age at surgery, adjusted for sex, zip code median family income, year, and hospital factors such as size, type, region, and teaching status. Further research into these disparities is warranted.

Trends in outcomes, complications, and hospitalization costs for hemispherectomy in the United States for the years 2000-2009.

OBJECTIVE: Hemispherectomy is an established surgical treatment for carefully selected pediatric patients with intractable epilepsy. Published perioperative data report low mortality rates and seizure reduction rates of 50-89%. This study investigates trends in the demographics, hospital utilization, and in-hospital complication rates of patients undergoing hemispherectomy over the past decade in the United States, using the nationally representative Kids' Inpatient Database (KID). METHODS: The KID was queried for all discharges with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code for hemispherectomy in the years 2000, 2003, 2006, and 2009. The patient cohorts from these four time points were compared, analyzing differences in demographic data, insurance and payer status, total cost, length of stay, in-hospital mortality, and complications. National estimates and 95% confidence intervals are reported given the weighted sample design of KID. RESULTS: This study identified an estimated total of 552 hospital admissions for hemispherectomy surgery during the years studied in this cohort. The incidence of this procedure increased from 1.2/100,000 admissions in 2000 to 2.2/100,000 in 2009 (p=0.05). Mean age was 6.7 years (range 0-20). There were no significant changes in demographics (age, gender, or race), hospital descriptors (size or type), insurance type, or zip code income quartile. There was a significant increase in total cost, from $42,807 in 2003 to $57,443 in 2009 (p=0.015) (adjusted to 2009 dollars). There were no trends in postoperative complications. In-hospital mortality occurred in five subjects (0.9%). Ventricular shunt placement during hemispherectomy hospitalizations increased over time from 6.7% to 16.5% (p=0.056). Hospitals that performed two or more hemispherectomies yearly had a significantly decreased incidence of in-hospital mortality (odds ratio [OR] 0.08, p=0.04) and an increased incidence of blood transfusion (OR 3.7, p=0.01) compared to hospitals that performed 0-1 procedures a year. SIGNIFICANCE: Hemispherectomy procedures increased slightly in frequency over the past decade, with no change in demographic characteristics of the patients over time. Rates of mortality and perioperative complications remained low. Total costs have increased significantly over time. In-hospital mortality was lower in higher volume hospitals.

Complications after craniosynostosis surgery: comparison of the 2012 Kids' Inpatient Database and Pediatric NSQIP Database.

OBJECT Research conducted using large administrative data sets has increased in recent decades, but reports on the fidelity and reliability of such data have been mixed. The goal of this project was to compare data from a large, administrative claims data set with a quality improvement registry in order to ascertain similarities and differences in content. METHODS Data on children younger than 12 months with nonsyndromic craniosynostosis who underwent surgery in 2012 were queried in both the Kids' Inpatient Database (KID) and the American College of Surgeons Pediatric National Surgical Quality Improvement Program (Peds NSQIP). Data from published clinical craniosynostosis surgery series are reported for comparison. RESULTS Among patients younger than 12 months of age, a total of 1765 admissions were identified in KID and 391 in Peds NSQIP in 2012. Only nonsyndromic patients were included. The mean length of stay was 3.2 days in KID and 4 days in Peds NSQIP. The rates of cardiac events (0.5% in KID, 0.3% in Peds NSQIP, and 0.4%-2.2% in the literature), stroke/intracranial bleeds (0.4% in KID, 0.5% in Peds NSQIP, and 0.3%-1.2% in the literature), infection (0.2% in KID, 0.8% in Peds NSQIP, and 0%-8% in the literature), wound disruption (0.2% in KID, 0.5% in Peds NSQIP, 0%-4% in the literature), and seizures (0.7% in KID, 0.8% in Peds NSQIP, 0%-0.8% in the literature) were low and similar between the 2 data sets. The reported rates of blood transfusion (36% in KID, 64% in Peds NSQIP, and 1.7%-100% in the literature) varied between the 2 data sets. CONCLUSIONS Both the KID and Peds NSQIP databases provide large samples of surgical patients, with more cases reported in KID. The rates of complications studied were similar between the 2 data sets, with the exception of blood transfusion events where the retrospective chart review process of Peds NSQIP captured almost double the rate reported in KID.

Structural basis for the recognition of tyrosine-based sorting signals by the µ3A subunit of the AP-3 adaptor complex.

Tyrosine-based signals fitting the YXXØ motif mediate sorting of transmembrane proteins to endosomes, lysosomes, the basolateral plasma membrane of polarized epithelial cells, and the somatodendritic domain of neurons through interactions with the homologous µ1, µ2, µ3, and µ4 subunits of the corresponding AP-1, AP-2, AP-3, and AP-4 complexes. Previous x-ray crystallographic analyses identified distinct binding sites for YXXØ signals on µ2 and µ4, which were located on opposite faces of the proteins. To elucidate the mode of recognition of YXXØ signals by other members of the µ family, we solved the crystal structure at 1.85 Å resolution of the C-terminal domain of the µ3 subunit of AP-3 (isoform A) in complex with a peptide encoding a YXXØ signal (SDYQRL) from the trans-Golgi network protein TGN38. The µ3A C-terminal domain consists of an immunoglobulin-like ß-sandwich organized into two subdomains, A and B. The YXXØ signal binds in an extended conformation to a site on µ3A subdomain A, at a location similar to the YXXØ-binding site on µ2 but not µ4. The binding sites on µ3A and µ2 exhibit similarities and differences that account for the ability of both proteins to bind distinct sets of YXXØ signals. Biochemical analyses confirm the identification of the µ3A site and show that this protein binds YXXØ signals with 14-19 µm affinity. The surface electrostatic potential of µ3A is less basic than that of µ2, in part explaining the association of AP-3 with intracellular membranes having less acidic phosphoinositides.

Risk factors and long-term survival in adult patients with primary malignant spinal cord astrocytomas.

Primary intramedullary spinal cord tumors are a rare entity, comprising 4­10 %of all spinal cord tumors. The current report presents data on intramedullary spinal cord anaplastic astrocytomas and glioblastomas in adults using the national surveillance, epidemiology, and end results database (1973­2008), and evaluates the impact of demographic and treatment factors on survival. Eighty nine adults were evaluated (mean age of 43 years); 49 % of patients had anaplastic astrocytoma and 51 % of patients had glioblastoma.88 % of patients had surgical intervention and 85 % of patients had radiotherapy. In univariate analysis, male gender (HR = 0.50, CI: 0.29­0.86, P = 0.01), surgical treatment (HR = 0.37, CI: 0.15­0.93, P = 0.03), and tumor histology (HR = 1.83, CI: 1.06­3.18, P = 0.03) were significant predictors of survival. Results remained significant or marginally significant after multivariate adjustment analyses. Adjuvant radiotherapy and age at diagnosis did not have a significant influence on survival. Future prospective studies from collaborative institutions combining richer detail in perioperative treatment, radiotherapy dosing, chemotherapy treatment, neurologic examinations, functional outcomes, and quality of life measures would contribute to more concrete, evidence-based treatment protocols for adult patients with primary malignant spinal cord astrocytomas.

Choroid plexus tumors in children: a population-based study.

BACKGROUND: Choroid plexus tumors are rare neoplasms that primarily occur in children. The use of the SEER (Surveillance, Epidemiology and End Results) database allows for the analysis of the relationship between prognostic factors and survival. METHODS: We analyzed the SEER database to select pediatric patients (<18 years old) with histologically confirmed diagnoses of choroid plexus papillomas (CPP; WHO Grade 0), atypical CPP (WHO Grade I) and choroid plexus carcinomas (CPC; WHO grade III). In univariate and multivariate analysis, we analyzed the relationship between demographic (age, gender, race, date of diagnosis) and treatment factors (extent of surgical resection, use of adjuvant radiation) on survival. RESULTS: Overall, 168 pediatric subjects with choroid plexus tumors were identified as follows: 75 cases of CPP, 12 cases of atypical CPP and 81 cases of CPC. The median follow-up time was 3.5 years for CPP and 7.7 years for CPC. The median age at diagnosis was 4 years for CPP (10-90th percentile 0-16 years) and 1 year for CPC (10-90th percentile 0-10 years). In univariate regression analysis, CPC histology (ß = -3.2, 95% confidence interval, CI -4.8 to -1.5, p < 0.001) was significantly associated with younger age at diagnosis in comparison to CPP. The mean tumor size was 3.7 cm for CPP and 6.0 cm for CPC (p < 0.001). A higher-grade tumor was associated with significantly increased mortality (hazard ratio, HR = 28.90, 95% CI 3.94-211.83, p = 0.001). Overall survival at 5 years was 98.7% for CPP and 58.5% for CPC (p < 0.001). Among those patients with CPC, gross total resection (GTR) was associated with a significantly lower mortality (HR = 0.21, 95% CI 0.07-0.66, p = 0.007). Overall survival at 5 years was 70.9% after GTR, significantly better than 35.9% after subtotal resection (p = 0.012) and 30% after no surgery (p = 0.003). Radiation treatment was not found to confer a survival benefit in CPC. No demographic characteristics (age, sex, race, date of diagnosis) were significantly associated with mortality. CONCLUSIONS: Analysis of a pediatric cohort of choroid plexus tumors in children in the SEER database shows that tumor grade is predictive of survival. In cases of CPC, the extent of surgical resection, especially GTR, is significantly associated with increased survival. Radiation did not confer survival benefit.

Analysis of risk factors and survival in pediatric high-grade spinal cord astrocytoma: a population-based study.

BACKGROUND/AIMS: Primary pediatric high-grade spinal cord astrocytomas are rare neoplasms with poor prognoses. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed prognostic factors and survival. METHODS: Pediatric patients with histologically confirmed diagnoses of primary high-grade spinal cord astrocytoma (WHO grade III-IV) from 1973 to 2008 in the SEER database were studied. Univariate and multivariate Cox proportional hazards models were used to analyze the relationship between demographic, tumor grade, and treatment factors on survival. RESULTS: Median survival in the 48 patient cohort was 10 months. Increasing age and higher tumor grade were found to be significantly associated with higher mortality. For children aged <7, 7-12, and 13-18 years, median survival was 22, 11, and 8 months, respectively. For children with anaplastic astrocytoma (WHO grade III), median survival was 12 months, compared with 7 months for those with glioblastoma multiforme (WHO grade IV). This study did not find a statistically significant relationship between sex, race, presence of radiation therapy or extent of surgical resection and mortality. CONCLUSION: Survival in primary pediatric high-grade spinal cord astrocytomas was positively associated with younger age and lower tumor grade. Survival was not associated with other demographic or treatment modality factors.

Safety assessment of intraparenchymal central nervous system biopsies: Single institution healthcare value review.

The study objective was to evaluate a single institution experience with adult stereotactic intracranial biopsies and review any projected cost savings as a result of bypassing intensive care unit (ICU) admission and limited routine head computed tomography (CT). The authors retrospectively reviewed all stereotactic intracranial biopsies performed at a single institution between February 2012 and March 2019. Primary data collection included ICU length of stay (LOS), hospital LOS, ICU interventions, need for reoperation, and CT use. Secondarily, location of lesion, postoperative hematoma, neurological deficit, pathology, and preoperative coagulopathy data were collected. There were 97 biopsy cases (63% male). Average age, ICU LOS, and total hospital stay were 58.9 years (range; 21-92 years), 2.3 days (range; 0-40 days), and 8.8 days (range 1-115 days), respectively. Seventy-five (75 of 97) patients received a postoperative head CT. No patients required medical or surgical intervention for complications related to biopsy. Eight patients required transfer from the ward to the ICU (none directly related to biopsy). Nine patients transferred directly to the ward postoperatively (none required transfer to ICU). Of the patients who did not receive CT or went directly to the ward, none had extended LOS or required transfer to ICU for neurosurgical concerns. Eliminating routine head CT and ICU admission translates to approximately $584,971 in direct cost savings in 89 cases without a postoperative ICU requirement. These practice changes would save patients' significant hospitalization costs, decrease healthcare expenditures, and allow for more appropriate hospital resource use.

Publisher Correction: α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Patient and treatment factors associated with survival among pediatric glioblastoma patients: A Surveillance, Epidemiology, and End Results study.

Glioblastoma (GBM) is a rare malignancy in children. The United States Surveillance, Epidemiology, and End Results (SEER) database allows large-scale analyses of clinical characteristics and prognostic features. We used it to study patients aged <20 years with histologically confirmed GBM (2000-2010) and examined the relationship between patient demographics, tumor characteristics, patterns of treatment, and outcomes. The primary outcome was disease-specific survival. 302 subjects were identified, with median age 11 years. Median follow-up was 32 months (95% CI 27-39). 34.4% had gross total resection (GTR). 61% underwent radiation after surgery (17% of subjects <3 years, 67% of those aged 4-19 years). Median survival and 2-year survival rates were 20 months and 46.9%, respectively. In multivariate analyses, age, tumor location, extent of resection, and year of diagnosis were significantly associated with the primary outcome. Compared to those aged 0-4 years, subjects aged 5-9 years and 10-14 years had higher risk of mortality. Infratentorial tumor location (HR 2.0, 95% CI 1.2-3.3, p = 0.007) and subtotal resection (HR 2.04, 95% CI 1.4-3.0, p < 0.001) were associated with increased mortality. Later year of diagnosis was significantly associated with decreased risk of death (HR 0.93, 95% CI 0.9-0.99, p = 0.031). There was no association between sex, race, region, or tumor size and the primary outcome. Repeat analyses examining all-cause mortality identified the same risk factors as for CNS cancer-specific mortality. Younger age, supratentorial location, GTR, and later year of diagnosis were associated with improved survival.

α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility.

The balance between ovarian folliculogenesis and follicular atresia is critical for female fertility and is strictly regulated by a complex network of neuroendocrine and intra-ovarian signals. Despite the numerous functions executed by granulosa cells (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordinate/modulate several cellular pathways is unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (α-SNAP) is a multifunctional protein that participates in SNARE-mediated membrane fusion events. In addition, it regulates cell-to-cell adhesion, AMPK signaling, autophagy and apoptosis in different cell types. In this study we examined the expression pattern of α-SNAP in ovarian tissue and the consequences of α-SNAP (M105I) mutation (hyh mutation) in folliculogenesis and female fertility. Our results showed that α-SNAP protein is highly expressed in GCs and its expression is modulated by gonadotropin stimuli. On the other hand, α-SNAP-mutant mice show a reduction in α-SNAP protein levels. Moreover, increased apoptosis of GCs and follicular atresia, reduced ovulation rate, and a dramatic decline in fertility is observed in α-SNAP-mutant females. In conclusion, α-SNAP plays a critical role in the balance between follicular development and atresia. Consequently, a reduction in its expression/function (M105I mutation) causes early depletion of ovarian follicles and female subfertility.

Revision surgeries following vagus nerve stimulator implantation.

The vagus nerve stimulator (VNS) has been shown to provide a safe, albeit costly, treatment for intractable epilepsy. We aimed to analyze the incidence, timing, and clinical/demographic associations of revision surgery post-VNS implantation in epilepsy patients. The Thomson Reuters MarketScan database, containing data from 23-50million individuals, was used. Epilepsy patients receiving VNS implantations from 2003 to 2009 were identified by Current Procedural Terminology and International Classification Of Diseases Ninth Revision codes. Incidence and timing of subsequent implant-related surgeries were recorded. Events were described using time-to-event methodology, with Kaplan-Meier failure estimation/Cox proportional hazard models adjusted for clinical/demographic factors. In 1234 patients, average incidence of revision surgeries over 6years of follow-up were <1%, <3%, 4-10%, and <1% for VNS electrode revision, battery revision/removal, battery replacement/implantation, and infection washout, respectively. For electrode revision and battery revision/replacement, the incidence was higher in the first year and for battery replacement in later years. Age, sex, insurance type, or geographic region did not significantly impact event occurrence. Implant-related revision surgeries are rare. Some events occur more often in certain follow-up years than others; none are significantly impacted by age, sex, insurance type, or geographic region. The most common reason for revision was battery replacement several years after VNS placement.

Outcomes of endoscopic third ventriculostomy in adults.

Endoscopic third ventriculostomy (ETV) is an alternative to ventriculoperitoneal shunting for treatment of hydrocephalus. Studies have reported favorable outcomes for up to three-quarters of adult patients. We performed the first ETV outcomes study using an administrative claims database, examining current practice for adult patients in the United States. We interrogated the Truven Health MarketScan® database for Current Procedural Terminology codes corresponding to ETV and ventriculoperitoneal shunt from 2003- to 2011, including patients over 18years and data from initial and subsequent hospitalizations. ETV failure was defined as any subsequent ETV or shunt procedure. Five hundred twenty-five patients underwent ETV with 6months minimum follow-up. Mean age was 45.9years (range: 18-86years). Mean follow-up was 2.2years (SD: 1.6years, range: 0.5-8.4years). Etiology of hydrocephalus was 21.3% tumor, 9.0% congenital/aqueductal stenosis, 15.8% hemorrhage, and 53.9% others. ETV was successful in 74.7% of patients. Of 133 who failed, 25 had repeat ETV; 108 had shunt placement. Longer length of stay for index surgery was associated with higher risk of failure (hazard ratio (HR): 1.03, p<0.001), as was history of previous shunt (HR: 2.45, p<0.001). Among patients with repeat surgeries, median time to failure was 25days. This study represents a longitudinal analysis of nationwide ETV practice over 9years. Success rate in this large cohort is similar to that published by other single-center retrospective studies. Age and geographic variation may be associated with surgeon choice of ETV or shunt placement after failure of the initial ETV.

Analysis of survival in pediatric high-grade brainstem gliomas: A population-based study.

BACKGROUND: The purpose of this study was to use the National Cancer Institutes' Surveillance, Epidemiology, and End Results (SEER) database to perform a large-scale analysis of brainstem anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Use of the SEER database gave us a larger sample size of this rare tumor type, allowing for the analysis of the relationship between prognostic factors and survival. MATERIALS AND METHODS: We selected pediatric patients (<18 years old) from the SEER database with histologically confirmed diagnoses of primary high-grade gliomas (World Health Organization Grade III/IV) of the brainstem. In univariate and multivariate analysis, we analyzed the relationship between demographic (age, gender, race, diagnosis date), histologic (AA, GBM), and treatment (surgery, radiation) factors on survival. RESULTS: In our cohort of 124 patients, those with AA had a median survival of 13 months and those with GBM 9 months. Higher-grade tumors were associated with statistically significantly increased mortality (hazard ratio [HR]: 1.74, confidence intervals [CIs]: 1.17-2.60). Surgical intervention was associated with a significantly lower mortality, either alone (HR: 0.14, CI: 0.04-0.5) or in combination with radiation (HR: 0.35, CI: 0.15-0.82). Radiation therapy alone was significantly associated with decreased mortality within the first 9 months after diagnosis but not with overall mortality. No demographic characteristics were significantly associated with mortality. CONCLUSIONS: Outcome remains poor in the pediatric high-grade brainstem glioma population. Survival is correlated with lower-grade tumor histology, radiation therapy only in the first 9 months after diagnosis, and surgical resection.

Treatment of pediatric Grade II spinal ependymomas: a population-based study.

OBJECT: Grade II spinal cord ependymomas occurring in pediatric patients are exceptionally rare neoplasms. In this paper the authors use a national cancer database to determine patient demographics, treatment patterns, and associated outcomes of this cohort. METHODS: The Surveillance Epidemiology and End Results (SEER) database was used to analyze subjects younger than 18 years with histologically confirmed diagnoses of Grade II spinal cord ependymoma from the years 1973 to 2008. Descriptive data on the demographic characteristics of this cohort and the associated treatment patterns are shown. The Kaplan-Meier method was used to estimate overall survival at 1, 2, 5, and 10 years. RESULTS: This cohort comprised 64 pediatric subjects with Grade II spinal ependymoma. The median age was 13 years, nearly half of the patients were male, and most were white (84%). The median follow-up was 9.2 years. Overall survival at 5 and 10 years was 86% and 83%, respectively. Gross-total resection was achieved in 57% of subjects, and radiation therapy was administered to 36%. Radiation therapy was administered to 78% of subjects after subtotal resection but only to 19% of patients after gross-total resection; this difference was significant (p < 0.001). In a multivariate regression model analyzing sex, age at diagnosis, year of diagnosis, radiotherapy, and extent of resection, female sex was found to be an independent predictor of decreased mortality (HR 0.15 [95% CI 0.02-0.94], p = 0.04). CONCLUSIONS: These data show long-term outcomes for pediatric patients with Grade II spinal ependymoma. Radiotherapy was more likely to be administered in cases of subtotal resection than in cases of gross-total resection. Female sex is associated with decreased mortality, while other demographic or treatment modalities are not.

Predictors of survival in patients with spinal ependymoma.

OBJECTIVES: We aimed to examine the impact of demographic and treatment factors on overall survival among spinal ependymoma patients. METHODS: Using data from Surveillance, Epidemiology, and End Results (SEER) from 1990-2008, we evaluated subjects with histologically confirmed spinal cord ependymoma. RESULTS: We identified 1,353 patients with spinal ependymoma (mean age 43.5 years). Among these, 26 had anaplastic ependymoma (AE), 374 had myxopapillary ependymoma (MPE), and 953 had other low-grade ependymoma (non-MPE). Median follow-up was 61 months. Overall survival at 5 years was 97% for MPE, 92% for low-grade non-MPE, and 73% for AE. Gross total resection (GTR) was achieved in 58% of subjects with MPE, 51% with low-grade non-MPE, and 50% with AE. Radiation occurred more often after subtotal resection (STR) than after GTR, and more often among those with anaplastic histology. Histology and extent of surgical resection were significant prognostic factors in multivariate analyses. Compared to MPE, subjects with low-grade non-MPE had a higher risk of mortality at 5 years (HR 2.35, P = 0.03), as did subjects with AE (HR 8.63, P < 0.01). Compared to GTR, STR was associated with an increased risk of mortality at 5 years (HR 2.2, P = 0.01), as was biopsy only (HR 2.05, P = 0.03) and no surgery (HR 4.97, P < 0.01). Among patients with either STR or GTR, adjuvant radiotherapy did not confer a survival benefit at 5 years (STR: HR 2.29, P = 0.07, and GTR: HR 2.2, P = 0.12). DISCUSSION: We found that lower grade histology and higher extent of surgical resection were significant prognostic factors for more favourable survival outcomes for spinal ependymoma patients.

Permeability imaging in pediatric brain tumors.

While traditional computed tomography (CT) and magnetic resonance (MR) imaging illustrate the structural morphology of brain pathology, newer, dynamic imaging techniques are able to show the movement of contrast throughout the brain parenchyma and across the blood-brain barrier (BBB). These data, in combination with pharmacokinetic models, can be used to investigate BBB permeability, which has wide-ranging applications in the diagnosis and management of central nervous system (CNS) tumors in children. In the first part of this paper, we review the technical principles underlying four imaging modalities used to evaluate BBB permeability: PET, dynamic CT, dynamic T1-weighted contrast-enhanced MR imaging, and dynamic T2-weighted susceptibility contrast MR. We describe the data that can be derived from each method, provide some caveats to data interpretation, and compare the advantages and disadvantages of the different techniques. In the second part of this paper, we review the clinical applications that have been reported with permeability imaging data, including diagnosing the nature of a lesion found on imaging (neoplastic versus non-neoplastic, tumor type, tumor grade, recurrence versus pseudoprogression), predicting the natural history of a tumor, monitoring angiogenesis and tracking response to anti-angiogenic agents, optimizing chemotherapy agent selection, and aiding in the development of new antineoplastic drugs and methods to increase local delivery of chemotherapeutics.