Yimo Lin

Predictors of survival in patients with spinal ependymoma

Abstract 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.

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.

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.

Eosinophilic granuloma/Langerhans cell histiocytosis: Pediatric neurosurgery update

Case 1 A 23‐month‐old female was admitted to the neurosurgery service with a 3‐month history of a progressively enlarging neck mass. There was associated redness, swelling, and tenderness to palpation, but no neurological deficits on examination. A noncontrast computed tomography (CT) scan of the neck and magnetic resonance imaging (MRI) with contrast showed an osteolytic contrast‐enhancing lesion primarily involving the C2 posterior elements, with a compressive circumferential epidural component extending from C2 to C5 [Figure 1]. A skeletal survey was negative for any other osseous lesions. She underwent C2 to C5 laminectomy with partial resection of the lesion without complication. Pathology was consistent with Langerhans cell (LC) histiocytosis (LCH). She was discharged home several days after her operation and subsequently started outpatient chemotherapy with cytarabine.

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.

Prognostic factors and survival in primary adult high grade brainstem astrocytoma: a population based study from 1973-2008.

Adult brainstem astrocytomas are a rare and heterogeneous group of malignancies. Most reports represent low-grade gliomas. This study used the Surveillance, Epidemiology and End Results (SEER) database to analyze the association between survival and demographic factors, tumor histology, and treatment characteristics among adult patients with high-grade brainstem astrocytoma (HGBSA). Adult patients with histologically confirmed diagnoses of primary HGBSA were studied. In univariate and multivariate analysis, we investigated the effect of demographics, tumor histology and treatment modality on survival. Overall median survival in the cohort of 240 adult patients was 7months, with 1, 2, 5 and 10year survival rates of 33.2%, 19.7%, 10.1%, and 8.3%, respectively. Age >50years (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.45-2.70, p<0.001) and grade IV versus grade III tumor (HR 1.61, 95% CI 1.15-2.26, p=0.006) were associated with statistically significant increased mortality in multivariate analyses. Surgical intervention trended toward association with lower mortality (HR 0.68, 95% CI 0.47-1.01, p=0.055). Our findings suggest that in patients with HGBSA, younger age and lower-grade histology are associated with better prognosis. Surgical intervention trended towards a significant association with better outcome, while radiation treatment was not associated with a statistically significant benefit in survival.

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 (β = -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.

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.

Is there a “July effect” in pediatric neurosurgery?

PurposeThe 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.MethodsData 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.ResultsThree 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.ConclusionFor the majority of morbidity and mortality events, no significant difference was found in occurrence rates between the first and last quarters.

Treatment options for pediatric craniopharyngioma.

Case 1 A 13‐year‐old female with intermittent headaches evaluated by an ophthalmologist was noted to have a retinal abnormality, prompting a magnetic resonance imaging (MRI) scan and referral to the neurosurgery service. On initial exam, the patient was neurologically intact and without headache. Imaging revealed a complex heterogeneous cystic mass, arising from a suprasellar location, invading into the third ventricle, and closely apposed to the hypothalamus bilaterally. There was mild contrast enhancement peripherally and inferiorly. Of note, the initial MRI and clinical presentation [Figure 1] showed no hydrocephalus. Likewise, initial endocrine evaluation was normal. On follow‐up imaging, however, the ventricular system was noted to be enlarging. After extensive discussion of the risks, benefits, and alternatives to surgery, a right frontal endoscopic transventricular resection was planned with a goal of gross total resection (GTR). Intraoperatively, the tumor was found to be densely adherent to the walls of the third ventricle. Approximately 50% of the tumor could be safely debulked. Postoperatively, she was noted to have hypopituitarism and required hormonal replacement with desmopressin, hydrocortisone, and levothyroxine. The patient was discharged in stable condition but returned soon after with symptoms and imaging consistent with a trapped right ventricle for which she underwent a septostomy and eventual ventriculoperitoneal shunt placement. She subsequently completed proton radiation for the residual tumor, which has remained stable over 4‐year follow‐up. After radiation, she developed hypothalamic obesity and suffered a gradual decline in her vision bilaterally. At last follow‐up, she could count fingers on the right and could only detect motion on the left. Since completing her treatments, she has required 24‐h care. The patient has had multiple emergency room visits and hospital admissions for sodium fluctuations. She has also suffered multiple bone fractures secondary to osteoporosis from chronic steroid use.