Effect of Abdominal Ultrasound on Clinical Care, Outcomes, and Resource Use Among Children With Blunt Torso Trauma: A Randomized Clinical Trial.

Importance: The utility of the focused assessment with sonography for trauma (FAST) examination in children is unknown. Objective: To determine if the FAST examination during initial evaluation of injured children improves clinical care. Design, Setting, and Participants: A randomized clinical trial (April 2012-May 2015) that involved 975 hemodynamically stable children and adolescents younger than 18 years treated for blunt torso trauma at the University of California, Davis Medical Center, a level I trauma center. Interventions: Patients were randomly assigned to a standard trauma evaluation with the FAST examination by the treating ED physician or a standard trauma evaluation alone. Main Outcomes and Measures: Coprimary outcomes were rate of abdominal computed tomographic (CT) scans in the ED, missed intra-abdominal injuries, ED length of stay, and hospital charges. Results: Among the 925 patients who were randomized (mean [SD] age, 9.7 [5.3] years; 575 males [62%]), all completed the study. A total of 50 patients (5.4%, 95% CI, 4.0% to 7.1%) were diagnosed with intra-abdominal injuries, including 40 (80%; 95% CI, 66% to 90%) who had intraperitoneal fluid found on an abdominal CT scan, and 9 patients (0.97%; 95% CI, 0.44% to 1.8%) underwent laparotomy. The proportion of patients with abdominal CT scans was 241 of 460 (52.4%) in the FAST group and 254 of 465 (54.6%) in the standard care-only group (difference, -2.2%; 95% CI, -8.7% to 4.2%). One case of missed intra-abdominal injury occurred in a patient in the FAST group and none in the control group (difference, 0.2%; 95% CI, -0.6% to 1.2%). The mean ED length of stay was 6.03 hours in the FAST group and 6.07 hours in the standard care-only group (difference, -0.04 hours; 95% CI, -0.47 to 0.40 hours). Median hospital charges were $46 415 in the FAST group and $47 759 in the standard care-only group (difference, -$1180; 95% CI, -$6651 to $4291). Conclusions and Relevance: Among hemodynamically stable children treated in an ED following blunt torso trauma, the use of FAST compared with standard care only did not improve clinical care, including use of resources; ED length of stay; missed intra-abdominal injuries; or hospital charges. These findings do not support the routine use of FAST in this setting. Trial Registration: clinicaltrials.gov Identifier: NCT01540318.

Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas.

Angiogenesis sustains tumor growth and metastasis, and recent studies indicate that the vascular endothelium regulates tissue mass. In the prostate, androgens drive angiogenic inducers to stimulate growth, whereas androgen withdrawal leads to decreased vascular endothelial growth factor, vascular regression and epithelial cell apoptosis. Here, we identify the angiogenesis inhibitor pigment epithelium-derived factor (PEDF) as a key inhibitor of stromal vasculature and epithelial tissue growth in mouse prostate and pancreas. In PEDF-deficient mice, stromal vessels were increased and associated with epithelial cell hyperplasia. Androgens inhibited prostatic PEDF expression in cultured cells. In vivo, androgen ablation increased PEDF in normal rat prostates and in human cancer biopsies. Exogenous PEDF induced tumor epithelial apoptosis in vitro and limited in vivo tumor xenograft growth, triggering endothelial apoptosis. Thus, PEDF regulates normal pancreas and prostate mass. Its androgen sensitivity makes PEDF a likely contributor to the anticancer effects of androgen ablation.

Serum vascular endothelial growth factor as a surveillance marker for cellular rejection in pediatric cardiac transplantation.

BACKGROUND: Early detection and treatment of acute rejection in cardiac transplant recipients significantly improves long-term survival. Endomyocardial biopsy is used routinely for diagnosing allograft rejection; however, in young children, this procedure carries some risk. We evaluated serum vascular endothelial growth factor (VEGF) as a potential surveillance marker of acute cellular rejection. METHODS: Blood samples (n=62) were analyzed from 23 patients and compared with controls (n=18) using an ELISA for VEGF. Results were correlated with endomyocardial biopsy rejection grades. RESULTS: Mean baseline VEGF levels of the transplant population were consistently higher than controls. Serum VEGF levels were significantly higher during acute cellular rejection when compared with the non-rejecting transplant group (700.7+/-154 pg/ml vs. 190.5+/-29 pg/ml). VEGF decreased two- to eightfold after immunosuppressive therapy in 9 of 11 rejection episodes. CONCLUSIONS: These data suggest that VEGF may play a role in the pathogenesis of acute allograft rejection and it may serve as a reliable serologic surveillance marker.

Congenital pulmonary capillary hemangiomatosis: Report of two cases and review of the literature.

Pulmonary capillary hemangiomatosis (PCH) is a rare disease characterized by pulmonary hypertension and excessive neovascularization within the pulmonary interstitium, vasculature, and airways. We describe two unusual cases of congenital PCH. Both cases had concurrent anomalies, including renal and urinary bladder agenesis and hypertropic cardiomyopathy. In one case, capillary proliferation caused significant impingement of the proximal bronchial airways. A review of the current literature is described.

Presentation and management of late-onset duodenomegaly in a teenager with chronic obstruction from malrotation.

Anomalies of intestinal rotation typically present in infancy and early childhood. The diagnosis in older children and adults may be vague and delayed. We discuss a case and management of a patient with late-onset duodenomegaly with chronic obstruction from malrotation.

Evolution of the CT imaging findings of accessory spleen infarction.

We report the case of a 12-year-old girl presenting with multiple episodes of left upper-quadrant pain caused by torsion of an accessory spleen.We present the CT findings of progression of accessory spleen infarction over the course of 7 days.

Pigment epithelium-derived factor targets endothelial and epithelial cells in Wilms' tumor.

PURPOSE: Loss of pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, has been linked to progression of angiogenesis-dependent diseases. We postulated that decreased levels of endogenous PEDF in the kidney creates a tumor permissive environment for Wilms' tumor. METHODS: Fresh and frozen Wilms' tumor (n = 28), adjacent (n = 3), and normal kidney (n = 8) were immunostained and graded. The Wilms' tumor cells (SK-NEP-1), renal epithelial cells (NRK-52), and fresh tumor samples were grown in culture. Condition media were collected and analyzed by an in vitro angiogenesis assay and Western blot. The SK-NEP-1 cells were treated with PEDF and cell viability assessed. RESULTS: Wilms' tumors expressed less PEDF than normal and adjacent kidney. Pigment epithelium-derived factor protein secretion was abundant in NRK-52 cells but significantly decreased in Wilms' tumor. Pigment epithelium-derived factor acted as blockade to angiogenesis and it had a dose-dependent cytotoxic effect on Wilms' tumor epithelial cells. CONCLUSION: Renal tubular epithelial cells are a rich source of PEDF in the normal kidney. Reduced levels of PEDF in Wilms' tumor remove a critical endogenous renal barrier to angiogenesis and tumor cell survival. Therapeutic replacement of PEDF may prove to be an effective strategy to combat Wilms' tumor progression.

Gene transfer of pigment epithelium-derived factor suppresses tumor growth and angiogenesis in a hepatoblastoma xenograft model.

Normal hepatocytes express pigment epithelium-derived factor (PEDF), an endogenous antiangiogenic factor. We hypothesized that decreased PEDF expression may be one mechanism driving hepatoblastoma growth, and in vivo gene transfer of PEDF could suppress neovascularization and limit tumor growth. PEDF functional activity was determined in vitro using endothelial cell migration assays and in vivo using a subcutaneous tumor model. HUH-6 human hepatoblastoma tumors were treated with hybrid adenoviral/adeno-associated viral expression vectors for PEDF (Hyb-PEDF, n = 4) or beta-galactosidase (Hyb-betagal, n = 4) daily for 4 d. Mitotic figures, microvascular density (MVD), PEDF, and VEGF expression were assessed. Hyb-PEDF treatment inhibited in vivo tumor growth (p < 0.008) and decreased MVD (p < 0.001), the number of mitotic figures (p < 0.001), and VEGF expression when compared with Hyb-betagal-treated tumors. HUH-6 expression of PEDF was dramatically reduced when cultured under hypoxic conditions and also when grown in vivo, and the addition of neutralizing anti-PEDF antibody increased the already high baseline angiogenic activity of the HUH-6 cell secretions in vitro (p < 0.04). PEDF is an important endogenous regulator of the liver vasculature. Augmenting intra-tumoral PEDF levels inhibits tumor growth by reducing angiogenesis and VEGF expression. Potent inhibitors of angiogenesis, such as PEDF, may be an effective alternative treatment for children with hepatoblastoma.

Successful orthotopic liver transplantation for treatment of a hepatic yolk sac tumor.

Yolk sac tumors (YSTs) represent 3% of malignancies in childhood and most commonly arise in the gonads. Hepatic YSTs are rare and previous reported cases were treated with resection and/or chemotherapy with mixed results. We present the first case of an unresectable hepatic YST in a 2-year-old boy treated successfully with liver transplantation.

Fetal constrictive pericardial defect with pulmonary capillary hemangiomatosis.

Pericardial defect is a rare anomaly that has a variable presentation. Prompt recognition and early surgical intervention are associated with a favorable outcome. The authors present an unusual case of unexpected fetal demise in a 31-week-gestational-age girl who had a large pericardial defect forming a constrictive ring around both ventricular chambers. The defect coexisted with pulmonary capillary hemangiomatosis, an association that has not been reported in cases of pericardial defect.

Wilms' tumor growth is suppressed by antiangiogenic pigment epithelium-derived factor in a xenograft model.

BACKGROUND/PURPOSE: Pigment epithelium-derived factor (PEDF), a potent endogenous inhibitor of angiogenesis, is highly expressed in the kidney. The authors postulated that systemic administration of PEDF would decrease Wilms' tumor growth in a xenograft model, and increased renal vascularity would result in a mouse null for PEDF. METHODS: Tumors were induced in athymic mice using human anaplastic Wilms' tumor cells. Purified PEDF protein or vehicle was administered for 7 days beginning 2 to 3 weeks after inoculation. Tumors were stained with anti-PEDF and anti-Factor VIII antibodies. Mitoses and microvascular density (MVD) were counted per high-power field (hpf). PEDF-null mice were generated on a SV129/C57Bl6 background. Wild-type and null kidneys were assessed for MVD. RESULTS: Mean tumor weight in the 2-week group was 60% less than controls (P <.05). The MVD and mitotic count in treated tumors were significantly less than controls (P <.05). PEDF stained strongly in normal kidneys but was minimal to absent in Wilms' tumor. PEDF-null kidneys had increased MVD compared with wild-type (P <.05). CONCLUSIONS: PEDF is expressed strongly in normal murine kidney, and loss of its angioinhibitory activity may contribute to pathologic angiogenesis in Wilms' tumor. Systemic PEDF suppresses WT growth by targeting both the tumor cells and its associated vasculature.

Inflammatory myofibroblastic tumor (inflammatory pseudotumor) of the neck infiltrating the trachea.

Inflammatory myofibroblastic tumor (IMT), popularly known as inflammatory pseudotumor, is a slow growing quasi-neoplastic lesion with a distinct histologic appearance and benign clinical course. A case of a neck IMT with infiltration into the trachea causing asthmalike symptoms in a 12-year-old girl is described. Both tracheal and neck IMT have been described, but no other case has displayed this infiltration. A review of the pertinent literature and the etiology, diagnosis, treatment, and outcomes of this tumor are discussed. It is important to consider IMT in a differential diagnosis because it can be easily misdiagnosed as a malignancy. A surgeon must not perform radical surgery, radiation, or chemotherapy until a final pathologic diagnosis is made because of the nature of this lesion.

Increased microvascular density predicts relapse in Wilms' tumor.

BACKGROUND/PURPOSE: Tumor stage and histology are the most important prognostic criteria in Wilms' tumors; however, a subset of patients remains who have favorable histology tumors and unexpectedly relapse. The authors postulated that increased microvascular density (MVD), a hallmark for angiogenesis, could identify patients at risk for relapse. METHODS: A case-control study was used to compare relapse (n = 15) with nonrelapse tumors (n = 35). Tumor MVD was counted in 5 random high-powered fields (hpf) using anti-Factor VIII antibody and expressed as mean vessel count/hpf +/- SEM. MVD and clinical data were evaluated using univariate analysis and student's t test. RESULTS: The relapse group had higher MVD than the nonrelapse group (34.9 +/- 2.9 v 22.4 +/- 2; P <.05). When evaluating the favorable histology (FH) group alone, there was higher MVD in the relapse group (32.4 +/- 2.7 v 19 +/- 1.8; P <.05). MVD was found to be the only predictor of relapse when compared with age, sex, tumor weight, and histology. CONCLUSIONS: These results suggest that increased MVD can identify Wilms' tumor patients at high risk for relapse, especially those patients with favorable histology tumors. A larger study is warranted to determine the potential utility of MVD in stratification of Wilms' tumor patients.