Pediatric trauma at an adult trauma center.

BACKGROUND: Accidental traumatic injury is the number 1 cause of morbidity and mortality in the pediatric population. In this study, we aim to prove that certain pediatric patients can be treated with good outcomes at an adult level 1 trauma center. METHODS: Retrospective analysis using the Howard University Hospital trauma registry identified 71 patients treated at Howard University Hospital between the ages of 1 and 17 years old. Specific variables were identified and collected for each patient. RESULTS: The majority of pediatric traumas treated at Howard University Hospital between June 2004 and May 2005 had high survival rates (93%). The patients who did not survive (7%) included 3 patients who were dead on arrival and 2 who died shortly after arrival to the hospital. CONCLUSIONS: Certain pediatric populations who present with minor and/or isolated injuries can be treated in an adult level 1 trauma center with similar outcomes to treatment in a pediatric level 1 trauma center.

The Bianchi procedure: a 20-year single institution experience.

BACKGROUND/PURPOSE: The emergence of improved outcomes for small bowel (SB) transplantation has raised questions regarding the utility of autologous intestinal lengthening for patients with short bowel syndrome (SBS). Chronic immunosuppression, multiple hospitalizations, and posttransplant lymphoproliferative disease are significant adverse factors. The purpose of this study is to evaluate the 20-year single institution experience with the Bianchi procedure and analyze its role in the management of pediatric SBS. METHODS: Medical records for 19 consecutive patients who underwent the Bianchi procedure from 1984 to 2004 were reviewed. Patients were categorized into 3 groups: less than 5 years, 5 to 9.9 years, and 10 years or more after surgery. Various outcome variables were evaluated. Data are presented in tabular format as the number of patients (%) or average (range). RESULTS: Nineteen patients were included in the study. Of 16 patients weaned from total parenteral nutrition (TPN), 7 (44%) responded to Bianchi procedure alone and 9 patients (56%) required SB transplant at an average of 4.09 years (range, 0.7-13.64 years) post-Bianchi. Four patients (21%) died, 1 received SB transplant and died of unrelated causes, and 3 were still on TPN and had not received SB transplantation. CONCLUSION: The Bianchi procedure facilitated weaning from TPN and eliminated the need for supplemental nutrition in select patients. Although the role of surgery is primarily adjunctive in the treatment of SBS, it offers therapeutic benefit in decreasing parenteral nutrition requirements and promoting intestinal adaptation. In particular, the Bianchi procedure has significant potential to improve the prognosis of pediatric patients with SBS.

Neuroblastoma impairs chemokine-mediated dendritic cell migration in vitro.

BACKGROUND/PURPOSE: Chemokine receptor (CCR7 [cysteine chemokine receptor 7]) and ligand (CCL19) interactions trigger dendritic cell (DC) recruitment from sites of antigen uptake to secondary lymphoid organs for T-cell priming and tumor lysis. Inhibition of this interaction may allow some aggressive tumors to evade immune detection. Although we have shown dysfunctional DC migration in murine neuroblastoma (NB) in vivo, the molecular mechanisms of impairment are unknown. We hypothesize that NB-induced aberrant CCR7-CCL19 signaling impairs DC migration. METHODS: Bone marrow-derived DCs were isolated from A/J mice (n = 24), matured, and cocultured with murine NB (TBJ) or media (control) for 7 days. CCR7 and CCL19 protein and RNA expressions by control and NB-exposed DC were measured by flow cytometry, Western blot analysis, and polymerase chain reaction. Migration assays using Transwell plates (Corning Incorporated, Corning, NY, via Fisher Scientific, Pittsburgh, Pa) were performed with matured DC and CCL19. Furthermore, to determine if these changes in DC migration could be overcome, superphysiological concentrations of CCL19 (100 ng/mL) were used. Results are reported as the average percentage +/- SD. RESULTS: No significant differences in CCR7 or CCL19 protein expression between tumor and control were seen at 7 days. However, NB significantly decreased CCL19-induced migration by more than 50%: control (26.48% +/- 1.52%) vs DC cocultured with TBJ (12.7% +/- 0.3%) (P < .05). Superphysiological doses up to 100 ng/mL CCL19 showed no significant upregulation in migration in DC cocultured with tumor cells. CONCLUSIONS: Although in vitro coculture with NB does not induce significant changes in either CCR7 or CCL19 expression, profound functional impairments in CCR7/CCL19-mediated migration occurs. These findings suggest that intracellular signal transduction pathways for these chemokines may be impaired by tumor. Targeting this chemokine-receptor pathway may provide a novel therapeutic strategy.

Murine neuroblastoma attenuates dendritic cell cysteine cysteine receptor 7 (CCR7) expression.

BACKGROUND/PURPOSE: Dendritic cell (DC) migration from tumors to T-cell priming sites is critical in developing antitumor cytotoxicity. Cysteine cysteine receptor 7 (CCR7), a promigratory chemokine receptor, regulates DC recruitment to secondary lymphoid organs. Tumors may inhibit CCR7 expression to evade immunodetection. Previous work implicates impaired DC migration as a critical defect in immunity to neuroblastoma (NB). However, the mechanism has yet to be defined. We hypothesize that NB abrogates DC CCR7 expression and signaling, leading to decreased antitumor immunity. METHODS: A/J mice (N = 36) were injected with saline (control) or murine NB (TBJ) and bone marrow-derived DC were isolated at 7, 14, and 28 days. CCR7 expression was analyzed by polymerase chain reaction, Western blot, and flow cytometry. Cytometry data were analyzed using the paired Student's t test. RESULTS: Dendritic cells isolated from mice with NB had a 60% increase in CCR7 protein expression by flow cytometry compared with control mice at day 7. However, there was a 43% downregulation of CCR7 expression by DC from tumor-bearing mice compared with controls 2 weeks postinoculation (P < .005). These observations were confirmed by polymerase chain reaction and Western blot analysis. CONCLUSION: Neuroblastoma initially upregulates CCR7 expression by DC. However, with tumor progression, this chemokine is downregulated, likely leading to impaired DC migration. Immunotherapeutic strategies to bypass or augment CCR7-dependent DC trafficking may improve survival for patients with aggressive disease.

Neuroblastoma-induced inhibition of dendritic cell IL-12 production via abrogation of CD40 expression.

BACKGROUND/PURPOSE: CD40 expression by dendritic cells (DCs) critically regulates their maturation/antitumor activity. CD40-CD40 ligand (CD40L) signaling stimulates DC-mediated IL-12 production/cytotoxicity. Recent studies suggest that neuroblastoma (NB)-derived gangliosides impair DC maturation, IL-12 secretion, and NK/T-cell activity. Neuroblastoma ganglioside-mediated abrogation of CD40 expression by DC and tumor-induced tolerance has not been studied. The purpose of this study is to determine if NB inhibits DC IL-12 production via CD40. The contributory role of the NB-derived ganglioside GM3 in this process is also examined. METHODS: Dendritic cells were generated from bone marrow of mice injected with saline (control) or murine NB. Control DCs were matured with or without GM3. Dendritic cells were cocultured with NB cells treated with or without a ganglioside synthesis inhibitor. Dendritic cell groups were analyzed for maturation/costimulatory markers. Control and tumor-derived DC were stimulated with CD40L or Staphylococcus aureus and studied for IL-12 expression. RESULTS: CD40 expression on DC generated from NB bearing mice decreased by 64% (P < .001). GM3 down-regulated DC maturation and CD40 expression. Only CD40-dependent IL-12 production was abrogated (60%, P < .01) in DC derived from NB-bearing mice. Dendritic cell capacity to synthesize IL-12 remained intact. CONCLUSIONS: Neuroblastoma-induced inhibition of DC function may result from ganglioside-mediated CD40 signaling deficiency. Strategies to bypass/augment CD40-CD40L signaling may improve current NB immunotherapies.