Identification of an MLL4-GPS2 fusion as an oncogenic driver of undifferentiated spindle cell sarcoma in a child.

Undifferentiated spindle cell sarcoma (UDS) is a poorly defined or understood entity, essentially a waste-basket for cases failing to fulfill criteria for better-established diagnoses based on combined histology, immunohistochemistry, and tumor genetic assays. We identified a novel chromosomal translocation t(17;19)(p13;q13) in a pediatric UDS and have characterized this alteration to show rearrangement of the MLL4 and GPS2 genes, resulting in an in-frame fusion gene MLL4-GPS2, the expression of which promotes anchorage-independent growth. MLL4 was previously reported to be similarly rearranged in hepatocellular carcinomas, notably those positive for hepatitis B virus. Isolated reports of individual rearrangements of GPS2 in a prostate carcinoma cell line and in glioblastoma multiforme, each with different partner genes, recently emerged from high-throughput sequencing studies but have not been further evaluated for biological effect.

CSF complications following intradural spinal surgeries in children.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a complication of intradural spinal surgery and is associated with poor wound healing and infection. The incidence of CSF leak is reported at ∼16% in adults, but little information is available in children. PURPOSE: The aim of this study is to determine the CSF leak rate and predisposing factors after intradural pediatric spinal surgeries. METHODS: This study was a retrospective chart review of 638 intradural spinal operations at BC Children's Hospital. CSF leak was defined as pseudomeningocele or CSF leak through incision. Primary operations to untether lipomyelomeningoceles, myelomeningocele/meningocele closure, and Chiari decompressions were excluded. RESULTS: CSF leaks occurred in 7.1%, with 3% having overt CSF leaks through skin (OCSF leak). CSF leaks, specifically OCSF leaks, were associated with postoperative wound infection (P = 0.0016). Sixteen of 45 cases of CSF leak required reoperation. The type of dural suture used, site of operation, or use of fibrin glue did not affect CSF leak rates. Previous spinal surgery (P < 0.0001), use of dural graft (P = 0.0043), method of dural suturing (P = 0.0023), and procedure performed (P < 0.001) were associated with postoperative CSF leakage. Patients with CSF leak were older than those without leak (98 vs. 72 months, P = 0.002). CONCLUSIONS: Our results provide evidence on intraoperative factors that may predispose to CSF leaks after spinal intradural surgery and may help guide surgical practice. This study confirms that the pediatric population shares many of the same risk factors for CSF leak as in adult populations. Further research is needed to explain how specific factors are associated with CSF leaks.

Neurological morbidity of surgical resection of pediatric cerebellar astrocytomas.

BACKGROUND: Review of children with low-grade cerebellar astrocytoma (LGCA) prior to 1992 showed a 98% rate of gross total resection (GTR) but a concerning incidence of permanent neurological dysfunction. The purpose of this study was to determine the rate of GTR of LGCA since 1992 and frequency of neurologic injury. METHODS: Retrospective review of children with LGCA was performed. CT/MR scans were rereviewed to assess extent of resection. Primary outcomes included incidence of GTR and incidence of permanent new neurological deficits. Other outcomes included late effects severity score (LESS), Bloom score for functional status, and educational assessment. RESULTS: Of 50 LGCA, GTR was achieved in 38 (76%) compared to 43 of 44 (98%) prior to 1992 (p < 0.004). Permanent new neurologic deficits from surgery occurred in 16% compared to 18% in the prior era (p = 0.61). For 35 patients operated on by the 2 surgeons in the prior study, 74% had GTR, with permanent neurological deficits in 8.6%. At latest follow-up, all patients were alive, 16% with residual tumor. LESS was two or less (mild or no deficit) in 94%. Bloom score was one or two (no or mild disability) in 90%. Eighty-six percent attended normal school. CONCLUSIONS: Less aggressive resection of LGCA in children may reduce postoperative neurologic deficits in the hands of the same surgeons as in the prior study but not overall at our institution. The good long-term outcomes suggest that it may be appropriate to do incomplete resection rather than risk additional neurological deficit.

Ring apophysis fracture in pediatric lumbar disc herniation: a common entity.

BACKGROUND/AIMS: Lumbar disc herniation (LDH) can be associated with ring apophysis fracture (RAF), which is found in 6% of adult cases. However, the incidence and management of RAF in pediatric LDH is not well documented. The purpose of this study is to determine the prevalence of RAF in pediatric LDH, identify risk factors and explore the influence of RAF on the surgical management and outcome of LDH patients. METHODS: Hospital records and images were retrospectively reviewed for all pediatric patients (<18 years old) who underwent CT scanning for LDH at BC Children's Hospital from 1985 to 2010. RESULTS: Forty-two patients met the study inclusion criteria. RAF was present in 38% of the pediatric patients with LDH. There was a significant correlation with gender (p = 0.021; 55% of the males had RAF, and 20% of the females) and association with central herniations (p = 0.003). At the last follow-up, 58% of the patients with RAF were symptom free, compared with 68% of the patients with no RAF. CONCLUSION: RAF is more frequently associated with LDH in children than in adults. Gender and central disc herniation are associated with RAF. Given the frequency of RAF, to properly identify these fractures and anticipate their treatment, preoperative CT would be necessary.

BC Patient Safety & Quality Council: using network and social movement theory to improve healthcare.

The BC Patient Safety & Quality Council has a mandate to bring health system stakeholders together in a collaborative partnership to improve quality of care. Our experience has demonstrated the value of networks to provide a forum for individuals to "think like a system," considering the perspectives of others in addressing system issues. This transition from silo-based thinking is important as we move to improve the quality of care at the pace that is required.

Improving care for British Columbians: the critical role of physician engagement.

Canadian provinces are addressing quality of care and patient safety in a systemic way, but obtaining physician involvement in system improvement continues to be a challenge. To address this issue, individual physicians, physician groups, the British Columbia Medical Association, the health authorities, the BC Patient Safety & Quality Council (BCPSQC) and the Ministry of Health have come together to support physician involvement and foster physician satisfaction. Building on earlier work on patient safety, in 2010 the ministry developed a comprehensive strategy for system-wide improvement, focusing on achieving critical population, patient and sustainability outcomes. Central to this plan is the acknowledged need to involve healthcare providers of all disciplines, in particular physicians. Today, BC physicians are leading large-scale provincial clinical improvement in three interdependent areas: Clinical Care Management, Integrated Primary and Community Care, and the National Surgical Quality Improvement Program. To further physicians' key contributions to BC's healthcare system, the BCPSQC, physician-ministry committees, health authorities and the Ministry will continue to engage physicians through practice support, feedback, financial recognition and information exchange, and by supporting improvements in the care provided to patients.

Natural history of untreated syringomyelia in pediatric patients.

OBJECT: The natural history of syringomyelia in pediatric patients remains uncertain. Although symptomatic and operative cases of syringomyelia are well studied, there are fewer articles in the literature on the nonoperative syrinx and its clinical and radiological course. The purpose of this research was to analyze the natural history of untreated syringomyelia in pediatric patients presenting with minimal neurological symptoms. METHODS: A review of the neurosurgery database at British Columbia's Children's Hospital identified all pediatric patients (< 18 years of age) with syringes identified on MR imaging. Patients were included in this study if they had at least 2 MR images of the spine, at least 1 year apart, while receiving nonoperative treatment. Magnetic resonance imaging was used to determine changes in the size of the syrinx over time. Clinic notes were analyzed to establish demographic and clinical features and to determine any clinical changes over time. RESULTS: A total of 17 patients were included in the study. Symptoms at presentation were often mild and included limb numbness (3 cases), headaches (2 cases), mild sensory deficits (2 cases), mild motor deficits (3 cases), and intermittent incontinence (7 cases). The consultant neurosurgeon believed that the syrinx was not contributing to the symptoms in these 17 patients. The syrinx either remained unchanged (7 cases) or diminished in size (8 cases) in a total of 15 patients (88%). In the remaining 2 patients the authors noted an increase in syrinx size, in 1 of whom the clinical course also worsened. Both of these patients had a Chiari malformation and subsequently underwent craniocervical decompression. Overall, the mean change was -0.7 mm of maximal axial diameter (range -2.6 to +2.7 mm). Sixteen patients (94%) exhibited no worsening of symptoms over time. CONCLUSIONS: Syringomyelia often remains stable in patients receiving nonoperative treatment. However, given that 2 (12%) of 17 syringes in this series enlarged, it is likely appropriate to include periodic imaging in the follow-up of these cases.

A randomized, controlled trial of the impact of early and rapid diagnosis of viral infections in children brought to an emergency department with febrile respiratory tract illnesses.

OBJECTIVES: Acute respiratory tract infections represent a significant burden on pediatric emergency departments (ED) and families. We hypothesized that early and rapid diagnosis of a viral infection alleviates the need for ancillary testing and antibiotic treatment. STUDY DESIGN: We conducted a randomized, controlled trial of children 3 to 36 months of age with febrile acute respiratory tract infections at a pediatric ED. Two hundred four subjects were randomly assigned to receive rapid respiratory viral testing on admission or a routine ED admission protocol. Outcome measures were: mean length of visits, rate of ancillary tests, and antibiotic prescription in the ED. A follow-up call was made to all study subjects to inquire about further healthcare visits, ancillary testing, and antibiotic prescription after ED discharge. RESULTS: We did not find a statistically significant difference in ED length of visits, rate of ancillary testing, or antibiotic prescription rate in the ED between the study groups. There was, however, a significant reduction in antibiotic prescription after ED discharge (in the group who had rapid viral testing RR = 0.36; 95% CI = 0.14, 0.95). CONCLUSIONS: Rapid multi-viral testing in the ED did not significantly affect ED patient treatment but may reduce antibiotic prescription in the community after discharge from the ED, suggesting a novel strategy to alter community physician antibiotic prescription patterns.

Conventional and diffusion-weighted magnetic resonance imaging findings in a pediatric patient with a posterior fossa brain tumor and papilledema.

We present a case report of a 21-month-old female patient to highlight magnetic resonance (MR) imaging findings associated with papilledema in a pediatric patient with an intracranial tumor. The MR findings included optic disc elevation, dilated perioptic subarachnoid spaces, optic nerve tortuosity and restricted diffusion in the optic nerve heads, all of which resolved upon resolution of raised intracranial pressure (ICP) and papilledema. The case demonstrates that both conventional and diffusion-weighted MR imaging findings can detect the presence, and follow posttreatment resolution, of increased ICP and papilledema in a pediatric tumor patient. The postoperative resolution of optic disc elevation clearly indicates the intracranial tumor etiology.

Establishing a provincial patient safety and learning system: pilot project results and lessons learned.

An effective safety event reporting system is an essential part of a comprehensive patient safety program. In British Columbia, we are implementing a provincial web-based event reporting tool and learning system called the BC Patient Safety and Learning System (PSLS). In this paper, we describe and report the results of our pilot study in a neonatal intensive care unit at BC Women's Hospital in Vancouver. Our approach aimed to foster a culture of safety by using the technology implementation to facilitate organizational learning about patient safety and to promote sustainable reporting behaviours. Results showed that PSLS was enthusiastically adopted by staff and enabled efficient reporting, promoted timely and complete follow-up activities and facilitated quality improvement. Our lessons learned laid the foundation for the provincial rollout of PSLS and may be of interest to those implementing similar systems elsewhere.

Pediatric patients with poor neurological status and arteriovenous malformation hemorrhage: an outcome analysis.

OBJECT: In general, patients who present with low Glasgow Coma Scale (GCS) scores and/or fixed and dilated pupils are not expected to do well following arteriovenous malformation (AVM) hemorrhage. However, there is a sense among neurosurgeons that pediatric patients may make a better recovery than adults following such an event. There have been few studies focusing on the outcome of pediatric patients with poor neurological status following AVM hemorrhage. The purpose of this study was to characterize functional outcome in pediatric patients with severe disability after AVM hemorrhage. METHODS: This was a retrospective analysis of clinical presentation and outcome in 15 patients seen at the authors' pediatric hospital presenting with low GCS scores (defined as GCS ≤ 8) following AVM hemorrhage. RESULTS: Initial GCS scores ranged from 3 to 6, and 11 of 14 patients had fixed pupils on clinical examination (data were not available in 1 patient). Eight of 15 patients suffered primarily a lobar hemorrhage, 3 suffered primarily infratentorial bleeding, 2 suffered primarily hemorrhages of the basal ganglia, and 2 suffered intraventricular hemorrhage. The overall mortality rate was 20% (3 of 15 patients). The clinical outcome of survivors was defined by the Pediatric Cerebral Performance Category (PCPC) and Pediatric Overall Performance Category (POPC) scores at follow-up. One year after AVM hemorrhage, 7 (58%) of the 12 surviving patients showed normal or mild disability (PCPC Score 1 or 2), whereas 5 (42%) of 12 patients had moderate or severe disability (PCPC Score 3 or 4). No patients were in a coma or vegetative state, and 11 (92%) of the 12 patients were functioning independently (POPC Score 1, 2, or 3) 1 year after AVM hemorrhage. All patients were functionally independent by last follow-up, with 8 patients (67%) in the normal or mild disability PCPC category, and 4 in the moderate category (PCPC Score 3). All 12 survivors made a meaningful recovery and went on to live independent lives. CONCLUSIONS: Pediatric patients suffering AVM hemorrhage have a good outcome and are able to function independently, despite a poor neurological state initially.

Microfibrillar collagen hemostat-induced necrotizing granulomatous inflammation developing after craniotomy: a pediatric case series.

OBJECT: Microfibrillar collagen hemostat (MCH; trade name Avitene) is a partially water-insoluble acid salt of purified bovine corium collagen. This agent has been widely used to control hemorrhage at surgery, and especially during pediatric neurosurgeries at the authors' institution. Despite its effectiveness, rare case reports detailing adverse inflammatory reactions to MCH have been documented. Based primarily on MR imaging, postoperative reactions have most commonly elicited clinical differential diagnoses of tumor recurrence or abscess. According to the literature, MCH induces a very characteristic mixed inflammatory response that is rich in eosinophils; in light of these observations, many authors have suggested an allergy-based pathogenesis. METHODS: The authors retrospectively reviewed 3 pediatric neurosurgical cases treated at their institution, wherein a common histomorphological inflammatory reaction to MCH was elicited at the site of prior craniotomy. RESULTS: Case 1 is that of a 10-year-old girl whose diagnosis was a right temporal lobe ganglioglioma, classified as WHO Grade I. Case 2 is that of a 9-year-old boy whose diagnosis was a left parietal lobe anaplastic ependymoma, classified as WHO Grade III. Finally, Case 3 is that of a 15-year-old girl whose diagnosis was focal cortical dysplasia Type IIA affecting the left occipital lobe. Each patient presented with new or recurrent seizures 5­6 weeks after the initial resection. The postsurgical reactions incited by MCH mimicked the radiological appearance of either an abscess (Cases 2 and 3) or recurrent tumor (Case 1). Histologically, the mixed inflammatory infiltrate was typified by the presence of MCH-centric necrotizing granulomas that were surrounded by a palisade of macrophages and often several eosinophils. CONCLUSIONS: The findings are in keeping with previous case reports describing the clinicopathological features of adverse reactions occurring due to MCH. Based on the authors' observations, the possibility of an idiopathic inflammatory reaction to MCH should be considered when either seizures, a typical radiological appearance (that is, consistent with tumor recurrence or abscess formation), or both arise shortly after initial surgery. A conservative treatment approach to this type of inflammatory lesion appears to be the most appropriate management strategy.