Faculty Bibliography

Most children with neuroblastoma presenting after infancy have metastatic, chemoresistant disease. Amplification of the MYCN proto-oncogene is a significant marker of these poor-prognosis neuroblastoma tumors. Recent studies suggest that MYCN may function in part by promoting angiogenesis via vascular endothelial growth factor (VEGF). VEGF blockade has been validated as a therapeutic strategy in adult cancers. In these studies, we asked whether inhibition of VEGF signaling via VEGFR2 blockade in established MYCN-amplified neuroblastoma xenografts would: 1) restrict tumor growth; 2) induce hypoxia; and 3) alter tumor vasculature. The MYCN-amplified neuroblastoma human cell line NGP was implanted intrarenally in athymic female mice. After 5 weeks, mice with established tumors were selected, a cohort euthanized to provide day 0 controls, and the rest assigned to receive biweekly injections of DC101 (anti-murine VEGFR2 antibody) or vehicle. DC101 treatment did not inhibit progressive tumor growth in established NGP xenografts. Although tumor vasculature was not significantly disrupted, a modest increase in tumor hypoxia was demonstrated by pimonidazole staining, and expression of a previously described hypoxia metagene was increased by gene set enrichment analysis (GSEA) in DC101-treated tumors. DC101 treatment elicited increased: 1) expression of VEGFR1 and its ligand placental growth factor; and 2) increased Notch activation in tumor vasculature concurrent with expression of the Notch ligand Jagged1. This result suggests that established MYCN-amplified neuroblastoma tumors are relatively VEGF-independent, and display the ability to rapidly up-regulate hypoxia-responsive alternative proangiogenic mechanisms that may stabilize vasculature when VEGF is deficient.

PURPOSE: Intestinal abnormalities are sometimes seen during antenatal testing; however, the postnatal importance of these findings has not been well established. We evaluated whether abnormal intestinal appearance on fetal ultrasound (US) was ultimately related to neonatal outcome. METHODS: Fetal US examinations from 2003 to 2006 were evaluated. Hyperechogenic bowel was defined as having the echogenicity comparable to bone, and dilated bowel was identified based on the sonographer's assessment. Persistence or resolution of US findings on subsequent US examinations and eventual outcomes were assessed. Cases were categorized as hyperechogenic or dilated and then subgrouped based on whether the US finding resolved. RESULTS: Sixty-eight fetuses had either hyperechogenic (n = 48) or dilated bowel (n = 20) on antenatal US. In 56 cases, complete data were available for analysis. Of 44 liveborn infants, 11 (25.0%) had an abdominal abnormality, and 33 (75.0%) were normal at birth. Compared to those with dilated bowel, fetuses with hyperechogenic bowel had a higher rate of prenatal demise (20.8% vs 10%) but a lower rate of abnormality at birth (10.3% vs 53.3%). Hyperechogenic bowel resolved on subsequent US more frequently than dilated bowel (65.5% vs 20.0%). In both groups, all fetuses with sonographic resolution were normal at birth. Of 9 fetuses that had persistently hyperechogenic bowel, 3 (33.3%) were born with an abnormality, and all were found to have meconium peritonitis or meconium ileus. In the 12 cases where dilated bowel did not resolve, 8 (66.7%) were eventually born with an abnormality, most commonly intestinal atresia. CONCLUSIONS: Hyperechogenic and dilated bowel are associated with a significant rate of fetal demise. Hyperechogenicity is more common than dilation and is more likely to be transient. Dilated bowel is more often associated with neonatal abnormality than hyperechogenic bowel. Persistence of fetal US findings predicts a higher likelihood of abnormality in the neonate.

PURPOSE: After a successful course of extracorporeal membrane oxygenation (ECMO), patients can deteriorate and a second ECMO course may be contemplated. When a second ECMO course becomes necessary in pediatric patients, survival rates comparable to the first ECMO course are possible. The perceived difficulties involved in recannulation after an initial ECMO course can prevent clinicians from reliably offering a second ECMO run to an eligible pediatric patient. We hypothesized that national ECMO registry data could provide cannulation templates for pediatric patients requiring a second ECMO course. METHODS: We obtained data from the Extracorporeal Life Support Organization registry (1981-2007) on patients 1 to 18 years old who required single-run ECMO (SRE) or multiple-run ECMO (MRE). Primary outcome measures were complications and survival. Cannulation-specific variables were compared using chi(2) methods (Fisher exact, McNemar's). Statistical significance was assumed at P < .05. RESULTS: A total of 3810 (96.8%) children underwent SRE and 127 (3.2%) required MRE. Survival was similar in both groups (49% vs 44%; P = .28). Cannulation data were available in 2539 SRE (67%) and 88 MRE (69%) cases. Compared with SRE, first ECMO courses in MRE patients consisted of fewer cervical (52.3% vs 71.7%; P < .001) but more femoral (20.5% vs 10.7%; P = .01) and central (27.3% vs 17.6%; P = .02) cannulations. In MRE patients, central cannulation was more frequent in second vs first ECMO courses (43.0% vs 27.3%; P = .03). Multiple-run ECMO survival was unaffected by cannulation strategy. Multiple-run ECMO patients with unchanged cannulation sites between first and second ECMO courses had fewer total complications than those requiring new cannulation sites (3.7 vs 5.1; P = .04). CONCLUSIONS: Second ECMO courses in pediatric patients can achieve survival comparable to the first course, but more often require central cannulation. Reusing cannulation sites for a second ECMO course is associated with fewer total complications than cannulating at new sites. These data provide guidance when considering cannulation strategies for second ECMO courses in pediatric patients.

Environmental sensor networks offer a powerful combination of distributed sensing capacity, real-time data visualization and analysis, and integration with adjacent networks and remote sensing data streams. These advances have become a reality as a combined result of the continuing miniaturization of electronics, the availability of large data storage and computational capacity, and the pervasive connectivity of the Internet. Environmental sensor networks have been established and large new networks are planned for monitoring multiple habitats at many different scales. Projects range in spatial scale from continental systems designed to measure global change and environmental stability to those involved with the monitoring of only a few meters of forest edge in fragmented landscapes. Temporal measurements have ranged from the evaluation of sunfleck dynamics at scales of seconds, to daily CO2 fluxes, to decadal shifts in temperatures. Above-ground sensor systems are partnered with subsurface soil measurement networks for physical and biological activity, together with aquatic and riparian sensor networks to measure groundwater fluxes and nutrient dynamics. More recently, complex sensors, such as networked digital cameras and microphones, as well as newly emerging sensors, are being integrated into sensor networks for hierarchical methods of sensing that promise a further understanding of our ecological systems by revealing previously unobservable phenomena.

BACKGROUND: Minimally invasive treatments for nonparasitic splenic cysts are well described. Recent evidence suggests that laparoscopic splenic cystectomy is associated with high recurrence rates in children. Because these cysts are uncommon, no large series is available. We reviewed our clinical data focusing on cyst recurrences and their management. METHODS: All children who underwent laparoscopic excision of a nonparasitic splenic cyst from January 2002 to December 2006 were identified. Medical and surgical records were reviewed for perioperative details, hospital course, and outcome. RESULTS: Eight children (median age, 13 years; range, 7-16 years) who underwent laparoscopic splenic cystectomy were identified. The most common presenting complaint was left upper quadrant pain or mass (n = 6; 75%). Median cyst size was 13 cm (range, 4-20 cm). There were no conversions to an open technique, completion splenectomies, or perioperative complications. Cysts were identified pathologically as epidermoid (n = 6) or posttraumatic (n = 2). Median hospital stay was 1.5 days. One child required partial splenectomy because of cyst anatomy and remains recurrence-free at 12 months. Cyst recurrence occurred in 7 patients (88%) at a median of 9.4 months (range, 3-18 months) after initial surgery. Median recurrent cyst size was 5.6 cm (range, 3-11 cm). Of 7 recurrences, 4 (57%) were symptomatic. Percutaneous ultrasound-guided cyst drainage and sclerosis were performed in 2 children with symptomatic recurrences, one of whom required 4 separate interventions. There were no complications during management of cyst recurrences. Five children with recurrence (71%) have been followed conservatively and are free of morbidity at a median of 23 months (range, 8-55 months). CONCLUSIONS: Laparoscopic excision of nonparasitic splenic cysts in children is associated with a high recurrence rate and may be insufficient treatment. Partial splenectomy may decrease recurrence rates. Conservative management of splenic cyst recurrence after laparoscopic excision is associated with good short-term outcomes. If necessary, image-guided management of symptomatic recurrences can be performed safely.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is accepted therapy for cardiorespiratory failure. Even after a successful ECMO course, patient deterioration may occur and a second course of ECMO may be contemplated. Although data regarding second ECMO courses exist in neonates, there are no reports describing second ECMO courses in pediatric patients. We hypothesized that data from a national ECMO registry would be useful in identifying which pediatric patients would be optimal candidates for a second course of ECMO. METHODS: We obtained data from the national Extracorporeal Life Support Organization registry from 1981 to 2007 on all patients 1-18 years old who required single-run ECMO (SRE) or multiple-run ECMO (MRE). Primary outcome measures were complications and survival. Continuous variables were assessed for distribution normality by using a Shaprio-Wilk statistic to guide nonparametric testing. SRE and MRE patients were compared by using chi2 tests (Fisher's exact and McNemar's) to assess differences in categorical variables; continuous data were assessed by using Mann-Whitney U or Wilcoxon signed-rank testing. Two multivariate regression models were constructed to identify independent predictors of survival and complications in MRE patients. Statistical significance was assumed at P < 0.05. RESULTS: A total of 3937 pediatric patients received ECMO for cardiac or respiratory failure. Of them, 3810 (96.8%) children underwent a single course of ECMO, whereas 127 (3.2%) required multiple ECMO runs. Compared with SRE patients, the first ECMO course in MRE patients was notable for higher rates of cardiac ECMO (61% versus 44%, P < 0.001), venoarterial ECMO (88% versus 78%, P = 0.04), and central cannulation (28% versus 17%, P = 0.007). There was no survival difference between MRE and SRE patients (44% versus 49%, P = 0.28). Median time between MRE courses was 9.0 days (interquartile range = 5-20 days). The mean number of complications per MRE patient was higher in the second ECMO run compared with the first (3.93 versus 3.12, P = 0.008). Multivariate regression identified 2 variables as independent predictors of survival in MRE patients: (1) renal complications during first ECMO run (P = 0.04); and (2) total number of complications during second ECMO run (P = 0.005). A separate multivariate analysis identified 3 variables independently predictive of complications in MRE patients: (1) age (P < 0.001); (2) duration of second run (P < 0.001); and (3) total number of complications during first ECMO run (P < 0.001). CONCLUSIONS: ECMO therapy achieves 49% survival in children 1-18 years of age. When a second ECMO course becomes necessary, survival rates comparable to the first ECMO course are possible. Patients developing renal complications during their first ECMO course have worse outcome with a second ECMO course. Patients are at greater risk for complications during a second ECMO course if they experience a high number of first-run complications, are >3 years old, or undergo a prolonged second ECMO course. These data are useful when deciding whether to offer a second ECMO course to an eligible pediatric patient.

PURPOSE: Available data comparing the management and outcome of right-sided (R-CDH) vs left-sided congenital diaphragmatic hernia (L-CDH) are inconsistent. Large-volume CDH studies are limited by small numbers of R-CDH or are confounded by compilations from multiple institutions with multiple treatment strategies. Consequently, they are underpowered to draw conclusions. To define the behavior and outcomes of R-CDH better, we report the largest single-institution series of R-CDH and ask if factors traditionally linked to poor prognosis in L-CDH were applicable to R-CDH. METHODS: We reviewed a single institution's experience with 267 consecutive evaluable neonates with unilateral CDH repaired from 1990 to 2006, with specific focus on R-CDH. chi(2) tests were performed for disease-related categorical variables. Two-tailed unpaired t tests were used for continuous variables. Factors associated with morbidity and survival were determined by univariate regression. Statistical significance was set at P < .05. RESULTS: Forty right-sided (15%) and 227 (85%) left-sided cases of CDH were identified. Prenatal diagnosis was made in 20 right-sided vs 170 left-sided defects (50% vs 75%, P < .01). Survival was 22 of 40 in R-CDH compared with 175 of 227 in L-CDH (55% vs 77%, P < .01). Extracorporeal membrane oxygenation was required in 16 right-sided and 33 left-sided cases (40% vs 15%, P < .001). A diaphragmatic patch was used in 22 of 29 right-sided compared with 82 of 199 left-sided repairs (76% vs 41%, P < .01); rates of abdominal wall prosthesis were also higher in right-sided hernias (38% vs 19%, P < .05). No differences were detected in right-sided vs left-sided recurrences (14% vs 8%, P = .38), mean time from birth to operation (5.3 vs 4.8 days, P = .80), or presence of cardiac anomalies (15% vs 12%, P = .63). Morbidity persisting beyond 6 months of age was present in 16 of 22 R-CDH survivors compared with 76 of 175 L-CDH survivors (73% vs 43%, P > .05). Among R-CDHs, prenatal diagnosis was the only factor to predict survival by univariate regression (P < .01). Use of a prosthesis in the diaphragm (P < .05) for R-CDH repair correlated with morbidity. CONCLUSION: Although previous reports suggest that associated anomalies, need for extracorporeal membrane oxygenation, and time to repair can influence L-CDH survival, these data do not support extrapolation to R-CDH survival. Right-sided CDH carries a disproportionately high morbidity and mortality. Prenatal diagnosis was the only factor predictive of R-CDH survival. Morbidity may correlate with use of prosthetic material for R-CDH repair. Right-sided CDH is a unique disease that may require a modified antenatal consultation.

Right-sided diaphragmatic defects represent less than 20% of all congenital diaphragmatic hernias (CDH). Recent data suggest that right CDH (R-CDH) may carry a disproportionately high morbidity as well as increased rates of extracorporeal support when compared with left CDH. Treatment of infants with R-CDH may be further complicated by anatomical distortion unique to right-sided defects. We report 2 cases of azygous vein cannulation in neonates with large isolated R-CDH. Both infants had postnatal deteriorations within 48 hours, met our criteria for extracorporeal membrane oxygenation (ECMO), and underwent venoarterial cannulations through the right neck. In each case, the venous cannula passed directly into the azygous vein and failed to provide adequate ECMO support. Echocardiography confirmed both cases of azygous cannulation. In one child, the right atrium was successfully cannulated after 90 minutes of extensive cannula manipulation. This child survived a 5-day ECMO course and is alive at 22-month follow-up. In the second child, despite prolonged efforts at cannula repositioning, cannulation of the right atrium was not achieved. We did not offer central cannulation because of a rapidly deteriorating clinical course, with expiration in several hours. At autopsy, a dilated azygous vein was evident as a result of inferior vena cava compression by a malpositioned liver. The possibility of azygous vein cannulation may be increased in neonates with R-CDH and has not been previously reported. When evaluating infants with R-CDH for ECMO, clinicians must recognize the possibility of azygous cannulation and its potentially lethal consequences, and should anticipate alternative venous cannulation

Therapeutic thoracentesis may be preferable over tube thoracostomy in select clinical scenarios in which a symptomatic pleural effusion develops after an isolated and limited physiologic insult. Notable risks in patients undergoing bedside thoracentesis include parenchymal lung injury, abdominal organ injury, and incomplete pleural drainage. These risks are driven in part by inexperienced house officers performing the technique, coupled with technical limitations imparted by hospital-provided thoracentesis kits. To address these concerns, we present a modification to the technique of bedside thoracentesis whereby a triple-lumen catheter is placed into the pleural space over a guidewire. This approach overcomes shortcomings of the packaged thoracentesis kits, improves patient comfort, minimizes the risk of lung injury, and provides more complete drainage of the pleural cavity in patients requiring therapeutic thoracentesis. This approach carries a small risk of air entry into the pleural space, which can be minimized with meticulous technique. Furthermore, by using a Seldinger approach, our technique can improve resident comfort with thoracentesis by drawing on a more robust skill set that likely already has developed during their training in central line placement.

Children requiring surgical intervention for pancreatic disease may be at risk long term for exocrine insufficiency and glucose intolerance. Pediatric surgeons must balance the need to perform adequate surgical resection while preserving as much normal pancreatic parenchyma as possible. Neoplasms of the middle pancreatic segment with low malignant potential and isolated trauma to the pancreatic body or neck represent 2 conditions where extensive pancreatic resection is unnecessary. Central pancreatectomy for such lesions is well described in adults. Reconstruction of the distal pancreatic remnant is traditionally performed via Roux-en-Y pancreaticojejunostomy. Pancreaticogastrostomy is an alternative approach that has been used to reconstruct the distal pancreas in the adults. Pancreaticogastrostomy offers several technical advantages over pancreaticojejunostomy. Because children may be uniquely susceptible to the long-term consequences of excessive pancreatic resection, 2 cases using this technique of central pancreatectomy with pancreaticogastrostomy are described