Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy.

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (-1.09 ± 1.53 versus -1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (-0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (-1.77 ± 1.22) compared to those without (-1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip -0.98 ± 0.95 versus -0.28 ± 1.06, p = 0.010; TB -1.36 ± 1.10 versus -0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15-2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02-4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study.

PURPOSE: Infant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy. METHODS: We assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors. RESULTS: The 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P = .0187), respectively. In multivariable analysis, localized relapse (P = .0073), SHH molecular subgroup (P = .0103), CSI use after relapse (P = .0161), and age ≥ 36 months at initial diagnosis (P = .0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P = .007). CONCLUSION: A substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.

Implementation of a clinical pathway to screen and treat medical inpatients for opioid withdrawal.

Background: Opioid-related inpatient hospital stays are increasing at alarming rates. Unidentified and poorly treated opioid withdrawal may be associated with inpatients leaving against medical advice and increased health care utilization. To address these concerns, we developed and implemented a clinical pathway to screen and treat medical service inpatients for opioid withdrawal. Methods: The pathway process included a two-item universal screening instrument to identify opioid withdrawal risk (Opioid Withdrawal Risk Assessment [OWRA]), use of the validated Clinical Opiate Withdrawal Scale (COWS) to monitor opioid withdrawal symptoms and severity, and a 72-h buprenorphine/naloxone-based treatment protocol. Implementation outcomes including adoption, fidelity, and sustainability of this new pathway model were measured. To assess if there were changes in nursing staff acceptability, appropriateness, and adoption of the new pathway process, a cross-sectional survey was administered to pilot four hospital medical units before and after pathway implementation. Results: Between 2016 and 2018, 72.4% (77,483/107,071) of admitted patients received the OWRA screening tool. Of those, 3.0% (2,347/77,483) were identified at risk for opioid withdrawal. Of those 2,347 patients, 2,178 (92.8%) were assessed with the COWS and 29.6% (645/2,178) were found to be in active withdrawal. A total of 49.5% (319/645) patients were treated with buprenorphine/naloxone. Fifty-seven percent (83/145) of nurses completed both the pre- and post-pathway implementation surveys. Analysis of the pre/post survey data revealed that nurse respondents were more confident in their ability to determine which patients were at risk for withdrawal (p = .01) and identify patients currently experiencing withdrawal (p < .01). However, they cited difficulty working with the patient population and coordinating care with physicians. Conclusions: Our study demonstrates a process for successfully implementing and sustaining a clinical pathway to screen and treat medical service inpatients for opioid withdrawal. Standardizing care delivery for patients in opioid withdrawal can also improve nursing confidence when working with this complex population.

Escalation of Opioid Withdrawal Frequency and Subsequent AMA Rates in Hospitalized Patients From 2017 to 2020.

OBJECTIVE: To measure trends for the emergence of opioid withdrawal (OW) and leaving against medical advice (AMA) among hospitalized patients. METHOD: Retrospective time-series of hospitalized patients with OW, defined by a Clinical Opioid Withdrawal score >8, using electronic health record data at a tertiary health system and of patients with a discharge status of AMA from January 1, 2017 to December 31, 2020. RESULTS: The average number of monthly hospitalizations with OW showed a year-to-year increment of 15% in 2018, 21% in 2019, and 34% from 2019 to 2020, whereas the total monthly hospitalizations remained stable. The segmented regression analysis showed that the upward trend in hospitalizations with OW became significant after January 2019 (slope: 1.14, 95% confidence interval [CI]: 0.70, 1.57). After August 2019, Fentanyl was added to the hospital urine drug testing panel and was identified in most OW patients. The monthly proportion of patients who left AMA was significantly higher among the OW patients than among all other admitted patients. There was a significant increase of 0.39 (95% CI: 0.29-0.49, P < 0.001) per month in %AMA among patients with OW. The estimated difference in %AMA among OW patients versus all other patients was 7.25 (95% CI: 5.12-9.38) in January 2017, and 16.92 (95% CI: 14.60-19.24) in December 2020. CONCLUSIONS: The number of hospitalized patients either presenting with or developing OW increased between 2017 and 2020 with a significant rise occurring after January 2019. The percentage of patients who left AMA among those who developed OW steadily worsened during the entire study period.

Comparative Effectiveness of Pediatric Integrative Medicine: A Pragmatic Cluster-Controlled Trial.

Symptoms of pain, nausea/vomiting, and anxiety (PNVA) are highly prevalent in pediatric inpatients. Poorly managed symptoms can lead to decreased compliance with care, and prolonged recovery times. Pharmacotherapy used to manage PNVA symptoms is of variable effectiveness and carries safety risks. Complementary therapies to manage these symptoms are gaining popularity due to their perceived benefits and low risk of harm. Pediatric integrative medicine (PIM) is the combination of complementary therapies with conventional medicine in pediatric populations. A two-arm, cluster-controlled, pragmatic clinical trial was carried out to compare the effectiveness of a PIM service in conjunction with usual care, versus usual care only to treat PNVA symptoms in hospitalized pediatric patients. The primary outcome was the improvement of PNVA symptom severity using a 10-point numerical rating scale. Participant enrollment occurred between January 2013 and January 2016. A total of 872 participants (usual care n = 497; PIM n = 375) were enrolled. The PIM therapies significantly reduced PNVA symptom severity (p < 0.001). This study found that a hospital-based PIM service is both safe and effective for alleviating PNVA symptoms. Future research should carry out this work in other pediatric inpatient divisions, and in other sites to determine the reproducibility of findings.

Effortful control moderates the relation between negative emotionality and socially appropriate behavior.

The current study investigated the relation between negative emotionality and socially appropriate behavior in a diverse sample of preschool and kindergarten children (N = 74). More specifically, we tested whether effortful control would moderate this relation. A computerized task measured children's effortful control by assessing their accuracy in shifting attention between different emotionally valenced faces (happy and angry) while inhibiting their responses to neutral faces. Teachers completed the Affect Intensity Scale-Child Version to assess child negative emotionality as well as the Preschool and Kindergarten Behavior Scales to assess two aspects of socially appropriate behavior (social cooperation and inhibition of externalizing behavior). Regression analyses indicated that children with high negative emotionality and strong effortful control had fewer externalizing problems and greater social cooperation compared with their counterparts with weaker effortful control. These findings support and extend previous research suggesting that effortful control may protect children, particularly those with high negative emotionality, from poor social outcomes. A novel contribution of this study is its use of an attention shifting task that incorporates emotionally salient stimuli. These findings have important implications for educators working with young children who encounter increased expectations for regulating their behavior during preschool and kindergarten.

Hsp70 acts as a fine-switch that controls E3 ligase CHIP-mediated TAp63 and ΔNp63 ubiquitination and degradation.

The major clinical problem in human cancer is metastasis. Metastases are the cause of 90% of human cancer deaths. TAp63 is a critical suppressor of tumorigenesis and metastasis. ΔNp63 acts as a dominant-negative inhibitor to block the function of p53 and TAp63. Although several ubiquitin E3 ligases have been reported to regulate p63 stability, the mechanism of p63 regulation remains partially understood. Herein, we show that CHIP, an E3 ligase with a U-box domain, physically interacts with p63 and promotes p63 degradation. Notably, Hsp70 depletion by siRNA stabilizes TAp63 in H1299 cells and destabilizes ΔNp63 in SCC9 cells. Loss of Hsp70 results in a reduction in the TAp63-CHIP interaction in H1299 cells and an increase in the interaction between ΔNp63 and CHIP in SCC9 cells. Our results reveal that Hsp70 acts as a molecular switch to control CHIP-mediated ubiquitination and degradation of p63 isoforms. Furthermore, regulation of p63 by the Hsp70-CHIP axis contributes to the migration and invasion of tumor cells. Hence, our findings demonstrate that Hsp70 is a crucial regulator of CHIP-mediated ubiquitination and degradation of p63 isoforms and identify a new pathway for maintaining TAp63 or ΔNp63 stability in cancers.

Pontine gliomas a 10-year population-based study: a report from The Canadian Paediatric Brain Tumour Consortium (CPBTC).

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG) are midline gliomas that arise from the pons and the majority are lethal within a few months after diagnosis. Due to the lack of histological diagnosis the epidemiology of DIPG is not completely understood. The aim of this report is to provide population-based data to characterize the descriptive epidemiology of this condition in Canadian children. PATIENTS AND METHODS: A national retrospective study of children and adolescents diagnosed with DIPG between 2000 and 2010 was undertaken. All cases underwent central review to determine clinical and radiological diagnostic characteristics. Crude incidence figures were calculated using age-adjusted (0-17 year) population data from Statistics Canada. Survival analyses were performed using the Kaplan-Meier method. RESULTS: A total of 163 patients with pontine lesions were identified. Central review determined one-hundred and forty-three patients who met clinical, radiological and/or histological criteria for diagnosis. We estimate an incidence rate of 1.9 DIPG/1,000,000 children/year in the Canadian population over a 10 years period. Median age at diagnosis was 6.8 years and 50.3% of patients were female. Most patients presented with cranial nerve palsies (76%) and ataxia (66%). Despite typical clinical and radiological characteristics, histological confirmation reported three lesions to be low-grade gliomas and three were diagnosed as CNS embryonal tumor not otherwise specified (NOS). CONCLUSIONS: Our study highlights the challenges associated with epidemiology studies on DIPG and the importance of central review for incidence rate estimations. It emphasizes that tissue biopsies are required for accurate histological and molecular diagnosis in patients presenting with pontine lesions and reinforces the limitations of radiological and clinical diagnosis in DIPG. Likewise, it underscores the urgent need to increase the availability and accessibility to clinical trials.

Intracranial growing teratoma syndrome (iGTS): an international case series and review of the literature.

PURPOSE: Intracranial growing teratoma syndrome (iGTS) is a rare phenomenon of paradoxical growth of a germ cell tumor (GCT) during treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of iGTS in Western countries. METHODS: Pediatric patients from 22 North American and Australian institutions diagnosed with iGTS between 2000 and 2017 were retrospectively evaluated. RESULTS: From a total of 777 cases of central nervous system (CNS) GCT, 39 cases of iGTS were identified for an overall frequency of 5%. Pineal region was a more frequent location for iGTS as compared to cases of GCT without iGTS (p < 0.00001). In patients with an initial tissue diagnosis of GCT, immature teratoma was present in 50%. Serum AFP or ßhCG was detectable in 87% of patients (median values 66 ng/mL and 44 IU/L, respectively). iGTS occurred at a median of 2 months (range 0.5-32) from diagnosis, in the majority of patients. All patients underwent surgical resection, leading to gross total resection in 79%. Following surgery, all patients resumed adjuvant therapy or post treatment follow-up for GCT. At a median follow-up of 5.3 years (range 0.2-11.8), 37 (95%) of patients are alive, including 5 with stable residual mass. CONCLUSION: iGTS occurs in 5% of patients with GCT in Western countries. Tumors of the pineal region and GCT containing immature teratoma appear to be associated with a higher risk of developing iGTS. Complete surgical resection is the mainstay of treatment. Overall survival of patients developing iGTS remains favorable.

Canadian Pediatric Neuro-Oncology Standards of Practice.

Primary CNS tumors are the leading cause of cancer-related death in pediatrics. It is essential to understand treatment trends to interpret national survival data. In Canada, children with CNS tumors are treated at one of 16 tertiary care centers. We surveyed pediatric neuro-oncologists to create a national standard of practice to be used in the absence of a clinical trial for seven of the most prevalent brain tumors in children. This allowed description of practice across the country, along with a consensus. This had a multitude of benefits, including understanding practice patterns, allowing for a basis to compare in future research and informing Health Canada of the current management of patients. This also allows all children in Canada to receive equivalent care, regardless of location.

Impact of Vertebral Fractures and Glucocorticoid Exposure on Height Deficits in Children During Treatment of Leukemia.

Objective: To assess the effect of vertebral fractures (VF) and glucocorticoid (GC) exposure on height deficits in children during treatment of acute lymphoblastic leukemia (ALL). Methods: Children with ALL treated without cranial radiation therapy (n = 160; median age, 5.1 years; 58.1% male) were followed prospectively for 6 years. Spinal deformity index (SDI) was used to quantify VF status. Results: Baseline height z score ± SD was 0.3 ± 1.2. It fell by 0.5 ± 0.4 in the first 6 months for boys and by 0.4 ± 0.4 in the first 12 months for girls (P < 0.01 for both) and then subsequently recovered. The prevalence of VF peaked at 1 year (17.6%). Among those with VF, median SDI rose from 2 [interquartile range (IQR): 1, 7] at baseline to 8 (IQR: 1, 8) at 1 year. A mixed model for repeated measures showed that height z score declined by 0.13 (95% CI: 0.02 to 0.24; P = 0.02) for each 5-unit increase in SDI during the previous 12 months. Every 10 mg/m2 increase in average daily GC dose (prednisone equivalent) in the previous 12 months was associated with a height z score decrement of 0.26 (95% CI: 0.20 to 0.32; P < 0.01). Conclusions: GC likely plays a major role in the observed height decline during therapy for ALL. Because only a minority of children had VF, fractures could not have contributed significantly to the height deficit in the entire cohort but may have been important among the subset with VF.

Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study.

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research.

Survival Following Tumor Recurrence in Children With Medulloblastoma.

Medulloblastoma is the most common malignant brain tumor in children. Published survival rates for this tumor are ∼70%; however, there is limited published information on outcome after disease recurrence. This was an observational study which included all persons under the age of 18 years diagnosed with medulloblastoma from 1990 to 2009 inclusive in Canada. Data collected included date of diagnosis, age at diagnosis, sex, stage, pathology, treatment, recurrence, and current status. Survival rates were determined. In total, 550 cases were ascertained meeting the study criteria. The overall survival rate at 1 year was 83.6%±1.7%, at 3 years 77.2%±1.9%, and at 5 years 72.5%±20%. The progression-free survival rates were 78%±1.9%, 70%±2.1%, and 69±2.1% at 1, 3, and 5 years from initial diagnosis. In total, 173 (31.2%) were reported to have had tumor recurrence and 23 (11.4%) of them were alive at the time of survey with an overall survival rate at 1 year of 38.3%±4%, at 2 years of 16.9%±3.3%, and at 5 years of 12.4%±2.8%. Our data confirm that children with recurrent medulloblastoma have a poor prognosis, supporting the need for novel treatment approaches for this group.

Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.

Atypical teratoid rhabdoid tumor in the first year of life: the Canadian ATRT registry experience and review of the literature.

While 2/3 of patients with ATRT are less than 3 years at diagnosis, the literature suggests younger children present with more aggressive disease and poorer outcome. However, little data exist on characteristics and outcome of patients diagnosed with ATRT in the first year of life. In particular, it is unclear whether they access similar treatments as do older children. We compared the cohort of patients ≤12 months from the Canadian ATRT registry to all cases extracted from the literature reported between 1996 and 2014 to describe their clinical and treatment characteristics, and potential prognostic factors. Twenty-six (33.7%) patients from the Canadian registry were ≤12 months at diagnosis as were 120 cases identified in the literature. Post-operatively, 46% of the registry's patients underwent palliation as opposed to 10.8% in the literature cohort. Palliative patients were significantly younger than those who received active therapy (3.3 vs. 6.6 months). While the use of high-dose chemotherapy (HDC) was relatively similar in both cohorts (42.9 and 35.5% respectively), radiotherapy (RT) use was significantly lower in the Canadian cohort (14.3 vs 44.9%). Children ≤6 months, who received active therapy, had a worst outcome than older ones. Gross total resection, HDC and adjuvant RT were associated with better outcomes. Eighty percent of the tested patients had evidence of germline mutation of INI1. While 1/3 of ATRT occurs within the first year of life, a large proportion only received palliative therapy. Even when actively treated, children ≤6 months fare worse. Some selected patients benefit from HDC.

Survival of children with medulloblastoma in Canada diagnosed between 1990 and 2009 inclusive.

The treatment of medulloblastoma, the most common malignant brain tumor in children, has evolved over the last few decades. The objectives of this paper were to determine the survival of pediatric medulloblastoma in Canada, to determine if there has been an improvement in the survival rates between the years of 1990 and 2009, inclusive, and to determine prognostic factors for survival. All patients under the age of 18 years diagnosed with medulloblastoma from 1990 to 2009, inclusive, in Canada were included. Data collected included date of diagnosis, age at diagnosis, gender, stage, pathology, treatment, recurrence and current status. From these, survival rates were determined. Data were obtained on 628 eligible patients. The overall 5-year survival rate for the study time period was 69.2 ± 3.3 %. The survival rate increased during the interval of 1996-2000, then remained stable; 1990-1994: 60.2 ± 4.3 %; 1995-1999: 73.2 ± 3.5 %; 2000-2004: 68.8 ± 3.7 %; and 2005-2009: 72.1 ± 4.9 %, p = 0.05. Children over 14 years of age had a significantly better overall survival than those age 5-14 and those under 5 (85.7 ± 5.5 % vs 76.1 ± 2.7 % and 60.8 ± 3 % respectively, p = 0.001). Histologic medulloblastoma subtype and M stage of disease did not result in significant differences in survival. Despite changes in approaches to therapy, we demonstrate a steady survival rate for children with medulloblastoma after 1996. In our analyses, age over 14 years was associated with a higher survival rate.

Low-grade ependymoma with late metastasis: autopsy case study and literature review.

INTRODUCTION: Ependymoma metastasis occurs usually along with local recurrence within 7 years after the initial diagnosis. Later spinal metastasis without local recurrence after the surgical resection has been rarely reported in patients with low-grade ependymomas but not with high-grade ependymomas. Here, we present a case with autopsy revealing late extensive supratentorial metastasis of a fourth ventricle classic WHO grade II ependymoma with no local recurrence or spinal metastasis. METHODS: A 4-year-old boy underwent a gross total resection (GTR) of the fourth ventricle ependymoma and postoperative radiation therapy. Follow-up MRI showed no recurrence for the next 7 years, but a half year later, extra-axial tumors in the left cerebellopontine angle and right frontal lobe were observed. GTR of the left cerebellopontine angle ependymoma was performed, followed by additional radiation therapy. RESULTS: He was stable for the following 2 years before MRI revealed growth of the right frontal tumor and new lesions. GTR of the right frontal tumor demonstrated similar pathologic features of ependymoma. Despite chemotherapy, follow-up MRIs exhibited increasing numbers and sizes of supratentorial tumors but no infratentorial or spinal tumors. He died 15 years after the initial diagnosis. Postmortem brain examination confirmed the supratentorial subarachnoid dissemination with multifocal metastases of classic ependymomas but no recurrence at the infratentorial sites. CONCLUSION: Our case study and literature review suggest that low-grade ependymomas under the current WHO classification have the risk of late metastasis. Therefore, long-term follow-up of the whole neuroaxis is more important for the patients with low-grade ependymomas even in the absence of local recurrence.

Low grade astrocytoma in children under the age of three years: a report from the Canadian pediatric brain tumour consortium.

In children under the age of 3 years, the most common solid tumors are brain tumors. Low grade astrocytomas represent 30-40 % of brain tumours in this age group. This study reviewed the incidence, characteristics, therapy, and outcome of children less than 36 months of age diagnosed with a low grade astrocytoma from 1990 to 2005 in Canada. A data bank was established using data collected from Canadian pediatric oncology centers on children less than age 3 diagnosed with brain tumors between 1990 and 2005. Cases of low grade astrocytoma were extracted from this data bank and their characteristics summarized. From the 579 cases in the data bank, 153 cases of low grade astrocytoma (26 %) were identified. The mean duration of symptoms prior to presentation was 13 weeks, and 53 % of patients underwent a greater than 90 % resection of their tumor, while 30 % underwent 10-90 % resection. Seventy-one percent of patients received no further therapy after surgery and of the 45 who received therapy following surgery, 43 received chemotherapy, and 5 received radiation therapy. Sixty-eight patients had recurrence or progression of their tumor. Eighty-seven percent of patients were alive at the time of the survey with a 2 year survival rate of 95.3 ± 1.8 %, 5 year survival rate of 93.1 ± 2.1 % and 10 year survival rate of 89.1 ± 2.8 %. The 5 year survival rate for Canadian children less than 36 months of age with a low grade astrocytoma was 93.0 ± 2.8 % which is similar to that for older children with this tumor.