SUCCESSFUL TREATMENT OF A SOLITARY SKULL METASTASIS IN A CHILD WITH WILMS' TUMOR.

This report presents the successful treatment of a child with a solitary metastatic lesion to the calvarium following treatment for Stage III anaplastic Wilms' Tumor.

Reduction in Overt and Silent Stroke Recurrence Rate Following Cerebral Revascularization Surgery in Children with Sickle Cell Disease and Severe Cerebral Vasculopathy.

BACKGROUND: Children with sickle cell disease (SCD) and moyamoya may benefit from indirect cerebral revascularization surgery in addition to chronic blood transfusion therapy for infarct prevention. We sought to compare overt and silent infarct recurrence rates in children with SCD undergoing revascularization. METHODS: This was a retrospective cohort study of all children with SCD and moyamoya treated at two children's hospitals. Clinical events and imaging studies were reviewed. RESULTS: Twenty-seven children with SCD and confirmed moyamoya receiving chronic transfusion therapy were identified, of whom 12 underwent indirect cerebral revascularization. Two subjects had postoperative transient ischemic attacks and another had a subarachnoid blood collection, none of which caused permanent consequences. Two subjects had surgical wound infections. Among these 12 children, the rate of overt and silent infarct recurrence decreased from 13.4 infarcts/100 patient-years before revascularization to 0 infarcts/100 patient-years after revascularization (P = 0.0057); the postrevascularization infarct recurrence rate was also significantly lower than the overall infarct recurrence of 8.87 infarcts/100 patient-years in 15 children without cerebral revascularization (P = 0.025). CONCLUSIONS: The rate of overt and silent infarct recurrence was significantly lower following indirect cerebral revascularization. A prospective study of cerebral revascularization in children with SCD is needed.

Clinical course of postthrombotic syndrome in children with history of venous thromboembolism.

Postthrombotic syndrome (PTS) is a chronic morbidity of venous thromboembolism (VTE) in children. Information about the evolution of PTS is lacking in children. Present study was aimed to evaluate the time-course of extremity PTS in children who were serially followed in a hematology clinic. This retrospective cohort study included 69 consecutive children with documented VTEs that presented with symptoms of extremity VTE: 67 extremity VTEs with or without extension to vena cava, 2 inferior vena cava VTEs. Severity of PTS was assessed using modified Villalta scale. Median age of the cohort was 12.6 years (interquartile range 1.6-15 years) while median follow-up was 28.7 months (interquartile range 13.3-33.4 months. PTS prevalence was 46.8% [95% confidence interval (CI) 37.9-57.7%]. Lower extremity VTE was associated with development of PTS compared to upper extremity VTE regardless of catheter use (P = 0.002). The time-course of PTS fluctuated in 11 of 33 children (33%; 95% CI 20-47%) at a median interval of 12 months from diagnosis of VTE (range 4-14 months): three progressed from mild/moderate to severe, one improved from moderate to mild, seven fluctuated between mild and moderate. Recurrence and incomplete resolution of VTE were associated with variability in PTS severity (P < 0.05). In summary, this study suggested that almost 50% of study cohort developed PTS, and the time-course of PTS was not static in one third of children. Future research should focus on identifying the predictors contributing to the worsening of PTS and developing risk-stratified treatment interventions so as to improve the outcome of children with VTE.

Characterizing microbial diversity in production water from an Alaskan mesothermic petroleum reservoir with two independent molecular methods.

The phylogenetic diversity of Bacteria and Archaea within a biodegraded, mesothermic petroleum reservoir in the Schrader Bluff Formation of Alaska was examined by two culture-independent methods based on fosmid and small-subunit rRNA gene PCR clone libraries. Despite the exclusion of certain groups by each method, there was overall no significant qualitative difference in the diversity of phylotypes recovered by the two methods. The resident Bacteria belonged to at least 14 phylum-level lineages, including the polyphyletic Firmicutes, which accounted for 36.2% of all small-subunit rRNA gene-containing (SSU(+)) fosmid clones identified. Members of uncultured divisions were also numerous and made up 35.2% of the SSU(+) fosmid clones. Clones from domain Archaea accounted for about half of all SSU(+) fosmids, suggesting that their cell numbers were comparable to those of the Bacteria in this microbial community. In contrast to the Bacteria, however, nearly all archaeal clones recovered by both methods were related to methanogens, especially acetoclastic methanogens, while the plurality of bacterial fosmid clones was affiliated with Synergistes-like acetogenic Firmicutes that possibly degrade longer-chain carboxylic acid components in the crude oil to acetate. These data suggest that acetate may be a key intermediary metabolite in this subsurface anaerobic food chain, which leads to methane production as the primary terminal electron sink.

Abnormal rib number in childhood malignancy: implications for the scoliosis surgeon.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine if rib anomalies are present in pediatric malignancies in the United States. SUMMARY OF BACKGROUND DATA: Scoliosis surgeons view radiographs of the entire spine, counting the number of ribs. A European study noted that rib anomalies were more common in certain malignancies. We wished to determine if this is also true in the United States. If so, the potential for screening, early detection of malignancy, and a better understanding of tumor biology is possible. METHODS: A retrospective review of 218 children with malignancy and a control group of 200 children with polytrauma or suspected child abuse was performed. Chest radiographs were reviewed to determine the number of ribs, and the presence of rib anomalies. 24 ribs was considered normal, <24 or >24 was considered abnormal. P < 0.05 was considered significant. RESULTS: The average age was 6.8 +/- 5.5 years and number of ribs was 23.8 +/- 0.6. Rib number was normal in 86.8%. There were significant differences between the malignancy and control groups in age (control, 5.7 +/- 5.1 years; malignancy, 7.8 +/- 5.7 years, P = 0.00007), rib number (control, 23.9 +/- 0.5; malignancy, 23.7 +/- 0.7, P = 0.001), and normal/abnormal rib counts (control, 92% normal; malignancy, 82% normal, P = 0.003). In the malignant group, 50% had a lymphoproliferative malignancy, 33% a solid tumor, and 17.0% a neural tumor. Neural malignancies had a higher incidence of rib abnormalities compared with lymphoproliferative or solid malignancies (P = 0.01). Relative to the control group, those with a neural and lymphoproliferative malignancy were 6.23 (95% CI, 2.7-14.5) and 2.0 (95% CI, 1.0-4.1) times more likely to have an abnormal rib count. CONCLUSIONS: Homeobox genes, important in vertebral and rib sequencing, are abnormally expressed in many different malignancies. This association is a question of great interest. What is the potential for rib number being used as a predictor of childhood malignancy? Can these findings be expanded to adults? These questions require further research. The association noted in this study is interesting but should not yet be used to alarm parents regarding an increased risk of malignancy in their children.

Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia.

A retrospective cohort study of children with sickle cell anemia (SCA) and strokes was used to test the hypothesis that exchange transfusion at the time of stroke presentation more effectively prevents second strokes than does simple transfusion. Children receiving simple transfusion had a 5-fold greater relative risk (95% confidence interval = 1.3 to 18.6) of second stroke than those receiving exchange transfusion.

Long-term outcomes in patients with stage IV neuroblastoma.

AIM OF STUDY: Long-term outcome studies in survivors with stage IV neuroblastoma (NB) are sparse. This review evaluates late complications and long-term outcomes in stage IV NB survivors. METHODS: A retrospective review of stage IV NB survivors was performed to analyze outcomes, including long-term morbidity, recurrence, and survival. MAIN RESULTS: Of 153 patients with stage IV NB, 52 (34%) survived (male-female, 26:26). Age at diagnosis was 29.1 +/- 31.7 months in survivors. Eighteen were 1 year or younger and 34 were older than 1 year compared with 10 nonsurvivors 1 year or younger and 91 older than 1 year (P = .0003, Fisher's Exact test). Primary tumor sites were adrenal (35), retroperitoneal (11), mediastinal (3), pelvic (2), and no primary with tumor metastases identified (1). Ten survivors had favorable and 16 had unfavorable histology compared with 1 favorable and 18 unfavorable in nonsurvivors (P = .01). Four survivors had MYCN amplification (> or = 10 copies) and 2 deletions of 1p and 11q. Sites of metastasis in survivors and nonsurvivors were similar. Treatment in survivors included surgery in 51 (75% [39/51] complete tumor resection [CTR]); chemotherapy, 50; radiation, 17; stem cell transplantation, 20; and bone marrow transplant, 1. In nonsurvivors, 13 (25%) of 53 (P < < .0001) had CTR, 18 stem cell transplantation, and 12 bone marrow transplant. Six patients had tumor recurrence but survived (mean, 9.3 +/- 8.3 years; range, 6 months-24 years). Recurrence was local (1), distant (2), and both (3) and was treated by resection, chemotherapy, and radiation. The mean age of survivors was 12.4 +/- 8.3 years (range, 2-34 years). In all stage IV cases, event-free survival was 30% and overall survival was 34%. Long-term complications occurred in 23 (44%) survivors, including endocrine disturbances (7), orthopedic (5), cataracts (2), adhesive bowel obstruction (2), hypertension (1), bronchiolitis (1), blindness (1), peripheral neuropathy (1), nonfunctioning kidney (1), cholelithiasis (1), and thyroid nodule (1). CONCLUSION: Only 34% of patients with stage IV NB survived despite aggressive multimodal therapy. Age of younger than 1 year, favorable pathology, CTR, and no recurrence were the only statistically significant factors that favored survival. Forty-four percent of survivors experienced late morbidity, and tumor recurred in 6 (11.5%) of 52. Patients should be monitored for tumor recurrence and long-term sequelae. New methods of treatment are required to achieve better outcomes.

Heterologous cells cooperate to augment stem cell migration, homing, and engraftment.

T-lymphocyte depletion of bone marrow grafts compromises engraftment, suggesting a facilitating mechanism provided by the T cells that has been shown to associate with CD8(+) but not CD4(+) T cells. Explanations for this phenomenon have focused on immune targeting of residual host cells or cytokine production. We provide evidence for an alternative mechanism based on cooperative effects on cell motility. We observed that engraftment of CD34(+) cells in a beta(2)-microglobulin-deficient nonobese diabetic/severe combined immunodeficiency (beta(2)m(-/-) NOD/SCID) mouse model paralleled clinical observations in humans, with an enhancing effect noted from the addition of CD8(+) cells but not CD4(+) cells. This correlated with CD8(+) augmentation of CD34(+) cell homing to the bone marrow in vivo and CD8(+) cell-associated increases of CD34(+) cell transmigration through a bone marrow endothelial cell line in vitro. The cooperative interaction was not sensitive to brefeldin A inhibition of protein secretion. However, cytochalasin D-induced inhibition of CD8(+) cytoskeletal rearrangements abrogated CD34(+) transendothelial migration and impaired CD34(+) cell homing in vivo. CD8(+) cells did not migrate in tandem with CD34(+) cells or alter endothelial barrier integrity; rather, they affected phosphotyrosine-mediated signaling in CD34(+) cells in response to the chemokine stromal derived factor-1alpha (SDF-1alpha). These data demonstrate cell-cell cooperativity between different cell types in mediating chemotactic events and provide one potential explanation for the clinically observed effect of CD8(+) cells on bone marrow transplantation. This modification of cell migration by neighboring cells provides broad possibilities for combinatorial effects between cells of different types to influence cell localization.

Esthesioneuroblastoma in children.

Esthesioneuroblastoma (olfactory neuroblastoma) is a rare tumor of the olfactory epithelium. Approximately 1,000 cases have been described in the literature since the original description in 1924. It occurs in older individuals and is rare in children. The authors describe the clinicopathologic presentation in a series of five children treated with neoadjuvant/adjuvant chemotherapy and review the English literature for previously described patients younger than 18 years to assess clinical presentation, mode of treatment, and outcome in this age group.

Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke.

OBJECTIVE: To test the hypothesis that children with sickle cell disease (SCD) who have an initial stroke temporally unrelated to another medical event are at higher risk for recurrent stroke than are children who had strokes temporally related to medical events. METHODS: A retrospective cohort study of children with SCD and stroke who received regularly scheduled blood transfusions for a minimum of 5 years was conducted. Medical records were examined for the documentation of antecedent or concurrent medical events (hypertension, acute chest syndrome, aplastic crisis, fever associated with infection, exchange transfusion) associated with physician contact within 14 days before the initial stroke. RESULTS: A total of 137 pediatric patients from 14 centers were studied. Mean age at first stroke was 6.3 years (1.4 to 14.0 years) with mean follow-up of 10.1 years (5 to 24 years). Thirty-one (22%) patients had a second stroke (2.2 per 100 patient years); 26 patients had an identified medical or concurrent event associated with their initial stroke. None of these patients had recurrent stroke 2 or more years after the initial event. The remaining 111 patients had an ongoing risk of recurrent stroke (1.9 per 100 patient-years) despite long-term transfusions (P =.038). CONCLUSIONS: The absence of an antecedent or concurrent medical event associated with an initial stroke is a major risk factor for subsequent stroke while receiving regular transfusions.