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Purpose Previous studies comparing extracorporeal membrane oxygenation (ECMO) modality for congenital diaphragmatic hernia (CDH) have not accounted for confounding by indication. We therefore hypothesized that using a propensity score (PS) approach to account for selection bias may identify outcome differences based on ECMO modality for infants with CDH. Methods We utilized ELSO Registry data (2000–2016). Patients with CDH were divided to either venoarterial (VA) or venovenous (VV) ECMO. Patients were matched by PS to control for nonrandom treatment assignment. Subgroup analyses were conducted based on timing of CDH repair relative to ECMO. Primary analysis was the “intent-to-treat” cohort based on the initial ECMO mode. Mortality was the primary outcome, and severe neurologic injury (SNI) was a secondary outcome. Results PS matching (3:1) identified 3304 infants (VA = 2470, VV = 834). In the main group, mortality was not different between VA and VV ECMO (OR = 1.01, 95% CI: 0.86–1.18) and there was no difference in SNI between VA and VV (OR = 0.80; 95% CI: 0.63–1.01). For the pre-ECMO CDH repair subgroup, 175 VA cases were matched to 70 VV. In these neonates, mortality was higher for VV compared to VA (OR = 2.10, 95% CI: 1.19–3.69), without any difference in SNI (OR = 1.48; 95% CI: 0.59–3.71). For the subgroup that did not have pre-ECMO CDH repair, 2030 VA cases were matched to 683 VV cases. In this subgroup, VV was associated with 27% lower risk of SNI relative to VA (OR = 0.73, 95% CI: 0.56–0.95) without any difference in mortality (OR = 0.94, 95% CI: 0.79–1.11). Conclusion This study revalidates that ECMO mode does not significantly affect mortality or SNI in infants with CDH. In the subset of infants who require pre-ECMO CDH repair, VA favors survival, whereas, in the subgroup of infants that did not have pre-ECMO CDH repair, VV favors lower rates of SNI. We conclude that neither mode appears consistently superior across all situations, and clinical judgment should remain a multifactorial decision. Level of evidence Level III.

We present a term infant with the unusual findings of malrotation in combination with both duodenal and pyloric webs of windsock type, thus masquerading as postoperative bowel dysfunction and ultimately requiring three laparotomies. To the best of our knowledge these three findings in combination have not been previously reported. The dilemma of whether to perform a duodenotomy or not during malrotation repair and the importance of instrumenting the intestine from the duodenotomy site in both retrograde and antegrade directions are discussed.

This study evaluates the safety and efficacy of thoracoscopic lobectomy in infants and children.From January 1994 to November 2013, 347 patients underwent video-assisted thoracoscopic lobe resection at two institutions. All procedures were performed by or under the direct guidance of a single surgeon. Patients' ages ranged from 1 day to 18 years, and weights ranged from 2.8 to 78 kg. Preoperative diagnosis included sequestration/congenital pulmonary airway malformation (n=306), severe bronchiectasis (n=24), congenital lobar emphysema (n=13), and malignancy (n=4).Of the 347 procedures, 342 were completed thoracoscopically. Operative times ranged from 35 minutes to 240 minutes (average, 115 minutes). Average operative time when a trainee was the primary surgeon was 160 minutes. There were 81 upper, 25 middle, and 241 lower lobe resections. There were four intraoperative complications (1.1%) requiring conversion to an open thoracotomy. The postoperative complication rate was 3.3%, and 3 patients required re-exploration for a prolonged air leak. Hospital length of stay (LOS) ranged from 1 to 16 days (average). In patients5 kg and3 months of age, the average operative time was 90 minutes, and the LOS was 2.1 days.Thoracoscopic lung resection is a safe and efficacious technique. With proper mentoring it is an exportable technique, which can be performed by pediatric surgical trainees. The procedures are safe and effective even when performed in the first 3 months of life. Early resection avoids the risk of later infection and malignancy.

Background Congenital diaphragmatic hernia (CDH) is a common birth defect affecting 1 in 3000 births. It is characterised by herniation of abdominal viscera through an incompletely formed diaphragm. Although chromosomal anomalies and mutations in several genes have been implicated, the cause for most patients is unknown. Methods We used whole exome sequencing in two families with CDH and congenital heart disease, and identified mutations in GATA6 in both. Results In the first family, we identified a de novo missense mutation (c.1366C>T, p.R456C) in a sporadic CDH patient with tetralogy of Fallot. In the second, a nonsense mutation (c.712G>T, p.G238*) was identified in two siblings with CDH and a large ventricular septal defect. The G238* mutation was inherited from their mother, who was clinically affected with congenital absence of the pericardium, patent ductus arteriosus and intestinal malrotation. Deep sequencing of blood and saliva-derived DNA from the mother suggested somatic mosaicism as an explanation for her milder phenotype, with only approximately 15% mutant alleles. To determine the frequency of GATA6 mutations in CDH, we sequenced the gene in 378 patients with CDH. We identified one additional de novo mutation (c.1071delG, p.V358Cfs34*). Conclusions Mutations in GATA6 have been previously associated with pancreatic agenesis and congenital heart disease. We conclude that, in addition to the heart and the pancreas, GATA6 is involved in development of two additional organs, the diaphragm and the pericardium. In addition, we have shown that de novo mutations can contribute to the development of CDH, a common birth defect.

Purpose Information regarding initial employment of graduating pediatric surgery fellows is limited. More complete data could yield benchmarks of initial career environment. Methods An anonymous survey was distributed in 2011 to 41 pediatric surgery graduates from all ACGME training programs interrogating details of initial positions and demographics. Results Thirty-seven of 41 (90%) fellows responded. Male to female ratio was equal. Graduates carried a median debt of $220,000 (range: $0–$850,000). The majority of fellows were married with children. 70% were university/hospital employees, and 68% were unaware of a business plan. Median starting compensation was $354,500 (range: $140,000–$506,000). Starting salary was greatest for >90% clinical obligation appointments (median $427,500 vs. $310,000; p=0.002), independent of geographic location. Compensation had no relationship to private practice vs. hospital/university/military position, coastal vs. inland location, and practice sites number. Median clinical time was 75% and research time 10%. 49% identified a formal mentor. Graduates covered 1–5 different offices (median 1) and 1–5 surgery sites (median 2). 60% were satisfied with their compensation. Conclusion Recent pediatric surgery graduates are engaged mainly in clinical care. Research is not incentivized. Compensation is driven by clinical obligations. Graduates have limited knowledge of the business plan supporting their compensation, nature of malpractice coverage, and commitments to resources including research. Graduates have important fiscal and parenting obligations.

Purpose Lung-to-head ratio (LHR) has been used for antenatal evaluation of infants with congenital diaphragmatic hernia (CDH). We hypothesized that LHR was predictive of acute and chronic pulmonary hypertension in infants with CDH. Methods Echocardiograms on all inborn infants with CDH (December 2001–March 2011) were reviewed. Echocardiograms at 1 and 3months post-repair and most recent follow-up were assessed for presence of pulmonary hypertension (PAH). LHR, gestational age, birth weight, extracorporeal membrane oxygenation (ECMO), and death rate were obtained. Bivariate and multivariate analyses were performed. Results 106 infants with CDH had LHR obtained at median 28weeks gestation (median LHR=1.25 [range 0.4–5.3]). Median follow-up was 26.6months (range 4.6–97.5). The long-term incidence of pulmonary hypertension was 16%. LHR was significantly associated with pulmonary hypertension at one month (p=0.0001) but not at 3months (p=0.22) or long-term (p=0.54). LHR was predictive of ECMO use (p=0.01) and death (p=0.001). Conclusions The overall incidence of PAH in infants with CDH decreases over time. Prenatal LHR predicts PAH at one month but not long-term in infants with CDH. The ability for LHR to predict PAH at one month but not long term may suggest remodeling of the pulmonary vasculature over time.

Ventilation practices have changed significantly since the initial reports in the mid 1980 of successful use of permissive hypercapnia and spontaneous ventilation [often called gentle ventilation (GV)] in infants with congenital diaphragmatic hernia (CDH). However, there has been little standardization of these practices or of the physiologic limits that define GV. We sought to ascertain among Diaphragmatic Hernia Research and Exploration; Advancing Molecular Science (DHREAMS) centers' GV practices in the neonatal management of CDH. Pediatric surgeons and neonatologists from DHREAMS centers completed an online survey on GV practices in infants with CDH. The survey gathered data on how individuals defined GV including ventilator settings, blood gas parameters and other factors of respiratory management. A total of 87 respondents, from 12 DHREAMS centers completed the survey for an individual response rate of 53% and a 92% center response rate. Approximately 99% of the respondents defined GV as accepting higher carbon dioxide (PCO2) and 60% of the respondents also defined GV as accepting a lower pH. There was less consensus about the use of sedation and neuromuscular blocking agents in GV, both within and across the centers. Acceptable pH and PCO2 levels are broader than the goal ranges. Despite a lack of formal standardization, the results suggest that GV practice is consistently defined as the use of permissive hypercapnia with mild respiratory acidosis and less consistently with the use of sedation and neuromuscular blocking agents. GV is the reported practice of surveyed neonatologists and pediatric surgeons in the respiratory management of infants with CDH.

Congenital diaphragmatic hernia (CDH) is characterized by incomplete formation of the diaphragm, occurring as either an isolated defect or in association with other anomalies. Genetic factors including aneuploidies and copy number variants are important in the pathogenesis of many cases of CDH, but few single genes have been definitively implicated in human CDH. In this study, we used whole exome sequencing (WES) to identify a paternally inherited novel missense GATA4 variant (c. 754C>T, p. R252W) in a familial case of CDH with incomplete penetrance. Phenotypic characterization of the family included magnetic resonance imaging (MRI) of the chest and abdomen demonstrating asymptomatic defects in the diaphragm in the two “unaffected” missense variant carriers. Screening 96 additional CDH patients identified a de novo heterozygous GATA4 variant (c.848G>A; p.R283H) in a non-isolated CDH patient. In summary, GATA4 is implicated in both familial and sporadic CDH, and our data suggests that WES may be a powerful tool to discover rare variants for CDH.

Infants affected with congenital diaphragmatic hernias (CDH) suffer from some degree of respiratory insufficiency arising from a combination of pulmonary hypoplasia and pulmonary hypertension. Respiratory care strategies to optimize blood gasses lead to significant barotrauma, increased morbidity, and overuse of extracorporeal membrane oxygenation (ECMO). Newer permissive hypercapnia/spontaneous ventilation protocols geared to accept moderate hypercapnia at lower peak airway pressures have led to improved outcomes. High-frequency oscillatory ventilation can be used in infants who continue to have persistent respiratory distress despite conventional ventilation. ECMO can be used successfully as a resuscitative strategy to minimize further barotrauma in carefully selected patients.

Extracorporeal membrane oxygenation (ECMO) support is often used to support infants and children with hemodynamic or respiratory failure. One of the major obstacles of safely treating a child with ECMO is balancing the risk of hemorrhage with the potential for thrombus development. Managing thrombosis in the setting of ECMO is challenging and has no defined algorithm. The use of recombinant tissue-type plasminogen activator (tPA) for thrombolysis has been previously described in cases where thrombi have developed despite adequate anticoagulation. In such situations, the risk of hemorrhage must be carefully balanced with the benefit of dissolving the clot and reestablishing flow. We present a case of an infant who required ECMO because of severe primary pulmonary hypertension and subsequently developed a right atrial thrombus adjacent to the ECMO cannula. The patient was treated with tPA with immediate improvement but had fatal intracranial hemorrhage almost 3 days after the tPA was administered. In this report, we review the current literature on tPA use during ECMO support and suggest a rational approach.

Thoracoscopic lobectomy for congenital cystic lung lesions is an accepted technique in pediatric surgery. Since an increasing number of these lesions are detected prenatally, the safety and efficacy of infant resections have been questioned. We reviewed our experience over a 10-year period to evaluate early resection of these lesions.From January 2001 to August 2009, 75 patients under 1 year of age and weighing10 kg underwent thoracoscopic lobectomy at two institutions. Patients carried the following diagnoses: 52 had congenital cystic adenomatoid malformation, 20 had bronchopulmonary sequestration, and 3 had congenital lobar emphysema. All lesions were confirmed after birth by computed tomography scan. Patient age at operation ranged from 4 days to 11 months and patient weight from 3.1 to 10 kg.Seventy-four of 75 lobectomies were thoracoscopically completed. There were 16 upper lobectomies, 1 middle lobectomy, and 55 lower lobectomies. Operative time ranged from 45 to 225 minutes. Hospital length of stay ranged from 1 to 5 days. A subset of 26 patients had surgery younger than 3 months of age and5 kg, despite being asymptomatic. Their operative time averaged 90 minutes, and mean length of hospital stay was 1.5 days.Thoracoscopic lobectomy is safe for infants10 kg and avoids the morbidity associated with thoracotomy. Operating early on younger patients may avoid the inflammatory changes associated with both clinically apparent and subclinical infections, even in patients weighing5 kg. This may make the procedures less technically challenging and may result in lower complication and conversion rates.

Accurate measurement of gap length is useful for operative planning in cases of esophageal atresia (EA) without distal fistula. This paper demonstrates how fiberoptic endoscopy of the distal esophagus enables measurement of the gap in the case of isolated EA, and compares other commonly practiced techniques.

Hepatic pulmonary fusion is extremely rare with only 9 previous cases reported in the literature. In typical cases, the clinician should be alerted to the possibility of hepatic pulmonary fusion if the chest radiograph shows a large opacity on the right side without a contralateral mediastinal shift. The authors present a case of right-sided diaphragmatic hernia and hepatic pulmonary fusion with associated contralateral mediastinal shift discovered beyond the neonatal period. The 9 previous cases were retrospectively reviewed with special attention to mediastinal shift on preoperative chest radiograph, operative procedure, and mortality. Only one previous case demonstrated a contralateral mediastinal shift. The most common procedure performed was partial separation of the hepatic pulmonary fusion and approximation of the diaphragmatic defect. Four of the previous 9 patients died. In our case, reduction of bowel and approximation of the diaphragmatic defect around the fused liver and lung have been successful.

The many ways monies enter and leave a university pediatric section are as poorly understood as the value and relationship to the parent hospital or university. This blinded confidential financial performance survey of similar university pediatric surgery sections begins to benchmark performance and define those relationships.

Pectus deformities arise from overgrowth of the cartilagenous portion of the ribs. Traditional resective/open procedures have been almost entirely replaced by video assisted retrosternal bar placement with excellent outcomes. This review considers the comprehensive evaluation and care of a pectus patinet as well as technical details regarding conduct of the surgery.

Femoral cannulation in pediatric patients requiring extracorporeal membrane oxygenation (ECMO) is commonly associated with distal limb ischemia. Authors have previously reported successful lower limb perfusion using various open techniques to cannulate a distal lower extremity artery at the time of initial ECMO cannulation. These procedures include open femoral artery antegrade cannulation and distal posterior tibial artery retrograde cannulation in older children and adults. Such approaches require ample vessel diameters to accommodate an arteriotomy and catheter insertion and, therefore, are of limited use in smaller children. We hypothesized that after femoral artery cannulation for ECMO, a percutaneous technique of distal limb perfusion might offer unique advantages when treating lower extremity ischemia in small pediatric patients. We report a technique for percutaneous antegrade cannulation in a 4-year-old patient shortly after her primary cannulation for venoarterial ECMO via the femoral artery.

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 χ 2 methods (Fisher exact, McNemar's). Statistical significance was assumed at P 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 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.

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.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 P0.05.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%, P0.001), 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 (P0.001); (2) duration of second run (P0.001); and (3) total number of complications during first ECMO run (P0.001).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, are3 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.

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.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.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.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.

We asked if fetal lung-to-head ratio (LHR) of 1.0 or lower or liver herniation had a statistical effect on survival or need for extracorporeal membrane oxygenation (ECMO), compared with LHR above 1.0 in patients with congenital diaphragmatic hernia (CDH). Methods Antenatal records of all patients diagnosed with CDH from January of 2002 to June of 2005 were examined. Inclusion criteria were isolated left-sided CDH and absence of significant cardiac or other anomalies/syndromes, treated solely at this institution. Lung-to-head ratio values were compared based on the value currently proposed for fetal intervention: LHR of 1.0 or lower vs LHR above 1.0. Outcome was assessed as survival (discharge to home) or need for ECMO. Results Twenty-eight patients met inclusion criteria. Overall survival was 86% (24/28). Postnatal survival in fetuses with LHR of 1.0 or lower (8/11) was not statistically different from LHR above 1.0 (16/17) (73% vs 94%, P = .114). The need for ECMO in the group with LHR of 1.0 or lower (3/11) was not significantly different from those with LHR above 1.0 (1/17) (27% vs 6%, P = .114). Herniation of the fetal liver into the chest did not affect survival or need for ECMO (P = .228). Conclusion Neither LHR of 1.0 or lower nor liver herniation identified a risk factor significant enough to warrant fetal intervention. Multicenter studies may be more appropriate to investigate this clinical problem.

Background: The initial clinical presentation and radiographic finding of microcolon in children with long-segment intestinal aganglionosis involving the entire colon, ileum and sometimes the jejunum can mimic meconium ileus. This makes the diagnosis difficult for the radiologist and surgeon. Objective: To document and describe the clinical and radiographic findings in children with long-segment intestinal aganglionosis who are initially thought to have meconium ileus. Materials and methods: We reviewed the cases of six neonates with long-segment intestinal aganglionosis presenting as meconium ileus at our institutions between 1978 and 2002. We examined the clinical presentation and the radiographic, surgical, and pathologic findings. In addition, 17 cases from the literature were identified and are included in the discussion. Results: A total of 23 cases were reviewed. Right lower quadrant intraluminal calcifications were noted on abdominal radiographs in all six neonates of our series and were described in 13 of the 17 neonates reported in the literature. Similarly, a microcolon was present in five of the six neonates of our series and in 14 of 16 historical neonates (one not reported). Conclusion: In a neonate with small-bowel obstruction and a microcolon, the presence of right lower quadrant intraluminal calcifications should raise the suspicion of long-segment intestinal aganglionosis even if the operative findings are typical of meconium ileus and a biopsy should be performed.

Patterns of lung growth and function were studied retrospectively in 103 patients (73 male and 30 female) with idiopathic pectus excavatum in order to determine: 1) the prevalence of restrictive lung defect and/or other lung function abnormalities; 2) the possible association between type of lung function abnormalities and age of the patient; and 3) whether the type of lung function is associated with other clinical conditions. Forty-three patients (42%) were between 5-9 years of age; 36 (35%) were between 10-14 years; and 24 (23%) were between 15-19 years. Restrictive lung disease was detected only in 5 patients (5%), whereas 42 patients (41%) had evidence of obstructive pattern, and the remaining 56 patients (54%) had a normal pattern. The mean values for lung volume (total lung capacity (TLC) and/or forced vital capacity (FVC)) were lowest in the 10-14-year group, whereas the mean values of the indices of lower airway function (forced expiratory volume at 1 sec (FEV(1)), FEV(1)/FVC, forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75)), and FEF(25-75)/FVC) were higher in the younger group. Residual volume (RV) and RV/TLC were elevated in all age groups, but they declined toward normalization with increasing age. There were no significant differences between groups (stratified either by pattern of lung function or by age) with regard to their demographics or clinical characteristics (scoliosis, direction of sternal rotation, history of asthma/reactive airways disease, or exercise intolerance). We conclude that idiopathic pectus excavatum may be associated with a variety of lung function abnormalities (in particular, lower airway obstruction) even in the absence of overt clinical symptoms. There was no evidence of significant worsening of lung function with increasing age.

Background/Purpose: Unfavorable histology (UH) in Wilms tumor has been linked to malfunction of the p53 tumor suppressor gene, which regulates (1) the endogenous angiogenesis suppressor thrombospondin-1 (TSP-1) and (2) vascular endothelial growth factor (VEGF). The authors hypothesized that clinically aggressive favorable histology Wilms tumor (FH), like UH, but distinct from standard-risk FH disease, would display altered p53/TSP-1 function and upregulated angiogenesis. Methods: Three Wilms tumor specimens manifesting different histology and clinical behavior were obtained: clinically aggressive UH, clinically aggressive FH, and standard-risk FH disease. Xenografts were induced intrarenally in athymic mice. P53, TSP-1, and VEGF status and neovascularity were assessed in tumor tissues. Lungs were evaluated for metastasis. Results: Clinically aggressive FH Wilms tumor displayed progressive alteration in p53/TSP-1 status and upregulation of VEGF. Such alteration was observed in the UH tumor, but was absent from the standard-risk FH tumor. Xenografts from clinically aggressive tumors displayed brisk neoangiogenesis and yielded lung metastases. Conclusions: This is the first report of altered p53/TSP-1 function in association with clinically aggressive behavior in FH Wilms tumor. These characteristics were not observed in parallel studies of a nonaggressive FH tumor. Loss of wild-type p53 function may contribute to disease progression in FH Wilms tumor, in part by upregulation of VEGF.

Background/Purpose: Antiangiogenic agents offer a new approach to the treatment of aggressive neoplasms, yet very few agents are available for current use. The authors have shown previously the efficacy of antiangiogenic therapy in experimental Wilms tumor, using an investigative antibody. They hypothesized that topotecan, administered in a regimen targeting endothelial cells, would suppress tumor growth and angiogenesis in experimental Wilms tumor. Methods: Experimental tumors were induced in the left kidneys of athymic mice by injection of cultured Wilms tumor cells. Topotecan (0.36, 0.6, 1.0, 2.0, and 3.0 mg/kg) or vehicle was injected intraperitoneally in 2 cycles over a 6-week period. Fluorescein angiograms and platelet endothelial cell adhesion molecule-1 staining of primary tumors were performed to ascertain vascular architecture. Endothelial apoptosis was assessed by TdT-mediated dUTP nick end labeling assay. Results: Tumor weights were reduced significantly in treated versus control animals, even in the lowest-dose group. Endothelial cell staining and angiography results showed relatively sparse vascularity in treated xenografts. Endothelial apoptosis was observed in treated but not control tumors. Conclusions: Topotecan, delivered in an “antiangiogenic” regimen, even at very low doses, significantly inhibited growth of experimental Wilms tumors. No adverse effects were noted at low doses. Thus, the established chemotherapy agent topotecan may be useful in a novel role: as antiangiogenic therapy. J Pediatr Surg 36:1781-1784. Copyright © 2001 by W.B. Saunders Company.

A full-term baby girl who was sent home day of life 2 was admitted to the hospital on day of life 7 for respiratory distress and poor feeding. The child was found to be hypertensive and in heart failure. Further workup led to the diagnosis of a suprarenal abdominal aortic aneurysm, but the infant had deteriorated clinically with heart failure, modest renal failure, renovascular hypertension, and no operative cure. The child died on day of life 20. Early diagnosis and prompt surgical resection are essential to managing this rare and lethal condition.

Background/Purpose: Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor. Methods: VEGF isoform expression in clinical (n = 2) and experimental tumors were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10 6 cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle (n = 16) treatment was started and continued daily for 5 weeks. Results: At 6 weeks tumors weighed 84% less in treated versus control animals (0.69 v 4.41 g; P Conclusions: Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients. J Pediatr Surg 36:357-361. Copyright © 2001 by W.B. Saunders Company.

Background/Purpose: Neuroblastoma is the most common tumor of the abdomen in children. Consistently effective treatments are lacking for aggressive disease. The authors previously reported that therapy with anti-vascular endothelial growth factor (VEGF) antibodies suppresses both growth and metastasis in an experimental model of Wilms' tumor. The authors hypothesized that, in a parallel model of neuroblastoma, anti-VEGF treatment would inhibit (1) growth and (2) metastasis. Methods: Primary tumors were established in the kidneys of nude mice. In cohort 1 (n = 42), mice were killed at 3 time-points, and tissues were evaluated histologically. Tumors were assayed for VEGF. In cohort 2 (n = 28), anti-VEGF antibody or vehicle was administered. Tumor weights and the incidence of metastases in the 2 groups were compared. VEGF deposition was evaluated by immunohistochemistry. Results: Mice displayed large tumors with liver and lung metastases. VEGF levels in tumors increased over time. Antibody-treated animals displayed significantly smaller tumors, but incidence and size of metastases were unaffected. VEGF was localized to tumor stroma immunohistochemically, with no difference in pattern observed in control and antibody-treated tumors. Conclusions: Anti-VEGF antibodies inhibit primary tumor growth in experimental neuroblastoma, but not metastasis. This may contrast with the effect of the same antibody in a parallel model of Wilms' tumor. J Pediatr Surg 35:977-981. Copyright © 2000 by W.B. Saunders Company.

Vascular endothelial growth factor (VEGF) has been shown previously to correlate with tumor growth and metastasis in an experimental model of anaplastic Wilms' tumor. The authors hypothesized that treatment with anti-VEGF antibodies would suppress both primary tumor growth and metastasis in this model.Tumors were induced in the right kidneys of nude mice by the injection of cultured Wilms' tumor cells. After 1 week, anti-VEGF treatment was begun with injection of either vehicle or an anti-VEGF antibody intraperitoneally. Mice were killed after 4.5 weeks of treatment and tumor weights and the incidence of metastases evaluated.Anti-VEGF treatment resulted in a greater than 95% reduction in tumor weight (P.0001). Anti-VEGF treatment also abolished the establishment of lung metastases (40% in control animals, P.003). Cessation of treatment resulted in rebound tumor growth.Anti-VEGF therapy can suppress both primary tumor growth and the establishment of metastases in experimental anaplastic Wilms' tumor.

Background/Purpose : Pathological vascular architecture is a feature of neoangiogenic processes such as diseases of the retina and tumor growth. The authors hypothesized that experimental human Wilm's tumors would display a vascular architecture similar to retinal diseases that are driven by vascular endothelial growth factor (VEGF). Methods : Human Wilms' tumors were established in the right kidneys of nude mice. After 4.5 weeks of tumor growth, fluorescein angiograms were performed before death. Representative sections of tumors and contralateral, control kidneys were evaluated by fluorescent microscopy. Results : Fluorescein angiograms demonstrated a characteristic pathological architecture. Vascular tortuosity, capillary tufting, and hemorrhage were noted. These features were not present in normal kidneys. Conclusions : Vascular architecture of Wilms' tumor displays the specific features previously described in diseases of the retina, which have been shown to be driven by VEGF, suggesting that neoangiogenesis in this model is also VEGF driven.

Background/Purpose : The growth and spread of solid tumors are critically dependent on the induction of angiogenesis. We hypothesized that vascular endothelial growth factor (VEGF) would be detected in Wilms' tumors, and that both growth and metastasis would parallel VEGF levels in a murine model. Methods : Primary tumors were established in the right kidneys of nude mice (n = 21). Mice were killed at 3, 4.5, or 6 weeks. Tumor-bearing and control kidneys were subjected to enzyme-linked immunosorbent assay (ELISA) for VEGF. Representative sections were assessed by histology and immunohistochemistry. Lungs were examined for metastases. Clinical specimens of Wilms' tumor (n = 12) also were assayed for VEGF. Results : The authors detected VEGF by ELISA with increasing frequency, and in increasing quantity, as experimental Wilms' tumors were grown over time. Immunohistochemistry demonstrated accumulation of VEGF in areas of viable tumor. Lung metastases occurred in 8 of 10 animals with VEGF-positive tumors, but in only 3 of 11 animals with VEGF-negative tumors, an association that was statistically significant. VEGF was found in 10 of 12 clinical Wilms' tumor specimens tested. Conclusions : VEGF is present in both clinical and experimental Wilms' tumors. In a murine model, absolute VEGF levels increase as primary tumors grow, and VEGF production is significantly associated with tumor metastasis.

Pediatric germ cell tumors (n = 135) with a major component of immature teratoma (IT) registered on Pediatric Oncology Group/Children's Cancer Group treatment protocols from 1990 to 1995 were reviewed. Sixty cases were pure IT with no malignant component and 75 were mixed tumors with a major component of IT. Foci of yolk sac tumor (YST) were present in all 75 mixed tumors; additional malignant components were present in 15. The IT component was as follows: 47% grade 3, 29% grade 2, 24% grade 1. There were no significant correlations between tumor grade and patient age by specific subsets or overall (all p > 0.10). Significant correlations were detected between stage and the presence of foci of YST (p = 0.0145) and grade and the presence of foci of YST (p < 0.001). Serum alpha-fetoprotein concentrations were elevated at diagnosis in 96% of ovarian tumors with foci of YST and were mildly elevated (< 60 ng/dL) in only 16% of tumors without YST. Overall 2- to 6-year survival rate was 96% and was related to the presence of YST. Central pathologic review revealed aspects of morphologic diagnosis that were most frequently misinterpreted by contributing pathologists. These included the classification of differentiating tissues as immature and the failure to recognize two well-differentiated patterns of YST (the hepatoid pattern resembling fetal liver and the well-differentiated glandular pattern resembling fetal lung or intestine). Such foci were often overlooked. The authors conclude that the presence of microscopic foci of YST, rather than the grade of IT, per se, is the only valid predictor of recurrence in pediatric IT at any site.

Background/Purpose: If the goal of partial liquid ventilation (PLV) with perfluorocarbons in the management of respiratory failure is to improve dynamic lung compliance (C dyn ) and pulmonary vascular resistance (PVR) while sustaing O 2 delivery, the optimal ventilatory management is unclear. The authors asked if volume-cycled or pressure-limited ventilation had different effects on PVR, cardiac index (CI), and C dyn in uninjured and injured neonatal piglet lungs. Methods: Anesthetized piglets (6 to 8 kg) were ventilated after tracheostomy. C dyn was measured by in-line Fleisch pneumotach/PC data acquisition terminal. Thermodilution instrumentation allowed determination of both Cl and PVR. Volume-control or pressure-limited ventilation was established in uninjured or injured (surfactant deficiency induced by saline lavage at 18 mL/kg) animals. After a stable 30-minute baseline, animals were assigned randomly to one of four groups: group I (n = 9), uninjured animals plus volume-cycled ventilation (intermittent mandatory ventilation [IMV], 10 bpm; tidal volume [TV], 15 mL/kg, positive end-expiratory pressure [PEEP], 5 cm H 2 O; Fio 2 , 1.0; and PLV for 150 minutes); group II (n = 9), uninjured animals plus pressure-limited ventilation (IMV, 10 bpm; peak inspiratory pressure (PIP), 25 cm H 2 O, PEEP, 5 cm H 2 O, Fio 2 , 1.0; and PLV for 150 minutes); group III (n = 7), injured animals plus volume-cycled ventilation (IMV, 10 bpm; TV, 15 mL/kg; PEEP, 5 cm H 2 O; Fio 2 , 1.0 for 30 minutes, followed by saline injury for 30 minutes, followed by PLV rescue for 120 minutes); group IV (n = 7), injured animals plus pressure-limited ventilation (IMV, 10 bpm; PIP, 25 cm H 2 O; PEEP, 5 cm H 2 O; Fio 2 , 1.0 for 30 minutes, followed by saline injury, and PLV rescue). Comparison within and between groups was accomplished by repeated measures analysis of variance (ANOVA) with Tukey correction. Results: There was no significant difference between volumecycled or pressure-limited ventilation in healthy lungs; however, in the setting of lung injury, dynamic compliance was 1.44 ± 0.15 after 180 minutes in the volume-cycled group and 0.91 ± 0.10 in the pressure-limited group after the same interval (mL/cm H 2 O · kg ± SEM). Similarly, PVR was 100 ± 6 in the volume-cycled group and 145 ± 12 in the pressurelimited group after 180 minutes of lung injury (mm Hg/L/kg · min ± SEM). Cardiac index declined significantly in all groups independent of ventilatory mode. Conclusions: These results suggest that in the setting of lung injury, C dyn and PVR improved significantly when volume-cycled, compared with pressure-limited ventilation was used. Although no difference existed between ventilatory modes in healthy lungs, pressure-limited ventilation, when combined with PLV in injured lungs, had adverse effects on lung compliance and pulmonary vascular resistance. Volume-cycled ventilation may optimize the ability of perfluorocarbon to recruit collapsed or atelectatic lung regions.

Sacrococcygeal teratomas (SCTs) can present a challenging problem and can be associated with significant perinatal morbidity and mortality. A female child was born at 36 weeks' gestation with a large, vascular Type 1 SCT originally identified by prenatal ultrasound. A CT scan showed two large feeding vessels arising from both internal iliac arteries that were successfully embolized during angiography. A radiofrequency probe was then used to ablate a zone between normal tissue and the tumor. The SCT was subsequently surgically excised with minimal blood loss. This case is presented to illustrate two useful and previously unreported postnatal adjuncts to the surgical treatment of massive, hypervascular sacrococcygeal tumors.

Purpose To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at 2 years of age. Methods This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at 2 years of age. Results BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 ± 15, 95 ± 16, and 95 ± 11. Ten percent (5/47) scored more than 2 standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 ± 14, 94 ± 16, 93 ± 13, 97 ± 10, and 94 ± 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At 2 years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. Conclusion CDH patients on average have lower developmental scores at 2 years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays.

In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO.Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), Pco2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (PPA), left atrial pressure (PLA), and circuit flow (QPA) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm(-5)) x 1,000] = [(PPA-PLA/(QPA x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; SPA02, 100%) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; SPA02, 50%). Endogenous NO was suppressed with L-arginine-N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance.Baseline normoxic PVR (3,403 +/- 1,169) was increased significantly by hypoxia (6,524 +/- 1,018, P.01) and was fully resorted to baseline by normoxia (3,497 +/- 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 +/- 1,441, P.01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 +/- 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 +/- 1,642, P.01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 +/- 1,796, P = NS).In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.

Background Congenital diaphragmatic hernia (CDH) is a common birth defect with significant morbidity and mortality. Although the aetiology of CDH remains poorly understood, studies from animal models and patients with CDH suggest that genetic factors play an important role in the development of CDH. Chromosomal anomalies have been reported in CDH. Methods In this study, the authors investigated the frequency of chromosomal anomalies and copy number variants (CNVs) in 256 parent–child trios of CDH using clinical conventional cytogenetic and microarray analysis. The authors also selected a set of CDH related training genes to prioritise the genes in those segmental aneuploidies and identified the genes and gene sets that may contribute to the aetiology of CDH. Results The authors identified chromosomal anomalies in 16 patients (6.3%) of the series including three aneuploidies, two unbalanced translocation, and 11 patients with de novo CNVs ranging in size from 95 kb to 104.6 Mb. The authors prioritised the genes in the CNV segments and identified KCNA2 , LMNA , CACNA1S , MYOG , HLX , LBR , AGT , GATA4 , SOX7 , HYLS1 , FOXC1 , FOXF2 , PDGFA , FGF6 , COL4A1 , COL4A2 , HOMER2 , BNC1 , BID , and TBX1 as genes that may be involved in diaphragm development. Gene enrichment analysis identified the most relevant gene ontology categories as those involved in tissue development (p=4.4×10−11) or regulation of multicellular organismal processes (p=2.8×10−10) and ‘receptor binding’ (p=8.7×10−14) and ‘DNA binding transcription factor activity’ (p=4.4×10−10). Conclusions The present findings support the role of chromosomal anomalies in CDH and provide a set of candidate genes including FOXC1 , FOXF2 , PDGFA , FGF6 , COL4A1 , COL4A2 , SOX7 , BNC1 , BID , and TBX1 for further analysis in CDH.

Purpose Expansion of the number of training programs in pediatric surgery occurred from 2003 through 2010. We sought to determine the effect of program expansion on case volume and distribution of operative experience. Methods Public domain data on pediatric surgery resident summary statistics available from the Accreditation Council for Graduate Medical Education (ACGME) from July 2003 through June 2010 were analyzed. Total case volume as primary surgeon or teaching assistant, mean case volume per resident, standard deviation, mode, minimum, and maximum number of cases per resident were evaluated. Mean total cases per resident, minimally invasive laparoscopic and thoracoscopic cases, and requisite cases as defined by the ACGME categories of: tumor, important pediatric surgical, and neonatal cases were analyzed by a Cuzick Wilcoxon-type nonparametric trend statistic using a significance level of 0.05. Skew was assessed by Pearson coefficient with levels of −0.5 to 0.5 defining a parametric distribution. Results The number of pediatric surgical training residents increased by 42% during the years reported, from 24 to 34. No statistically significant difference was found in the mean number of total cases or requisite cases per resident. The mean volume of minimally invasive procedures increased significantly. Case volume per resident was non-parametrically distributed with increasing positive skew over time. Conclusions The increase in number of pediatric surgical resident training positions has not adversely affected overall operative experience or exposure to highly specialized requisite cases, on average. The increasing positive skew of total and index cases, however, suggests that variability between programs in case exposure is increasing over time.

The head ultrasound (US) is used extensively at most extracorporeal membrane oxygenation (ECMO) centers to screen for intracranial pathology in the ECMO candidate. Daily head US examinations are obtained in patients on ECMO to detect the emergence of intracranial hemorrhage (ICH). The authors asked whether these serial studies could be correlated with more definitive diagnostic studies, such as computed tomography (CT) and magnetic resonance imaging (MRI) scans, autopsy data, or the long-term neurodevelopmental status, to discern the predictive value of these daily examinations. Seventy-four consecutively treated neonates with reversible respiratory failure refractory to conventional support met institutional criteria for placement on ECMO. In addition to a pre-ECMO US, daily real-time portable head US images were evaluated for changes in echotexture, ventricular configuration, and extraaxial fluid. Follow-up CT and MRI scans were evaluated for the presence of hemorrhagic or ischemic lesions. Autopsy data were obtained from nonsurvivors. Survivors were examined by a neurodevelopmental specialist at regular intervals and classified as normal or delayed for chronological age. In this series of 74 patients, CT MRI scanning and autopsy data demonstrated structural injury in 19 patients; there were 16 ischemic infarctions and three hemorrhages. The incidence of hemorrhage in this series was considerably lower than that previously reported. Ten of the 19 patients had serial head US findings demonstrating a progression from focal increases in echotexture to diffuse effacement of cerebral architecture. In the remaining nine, serial head US examinations did not show injury. An additional 10 children had a clear delay in neurological development despite no evidence of anatomic injury on serial head US examinations or CT MRI scanning. The mortality was 42% for neonates who had either an abnormal head US result or an abnormal result on the follow-up neuroimaging study. In the 43 patients without evidence of such injury, the mortality was 16%.

The literature suggests that lung-head ratio (LHR) and liver position may inconsistently predict outcome for congenital diaphragmatic hernia (CDH). We reviewed our inborn neonates with isolated left-sided CDH to determine whether these variables predicted survival and to estimate the optimal LHR threshold.Prenatal LHR and liver position were obtained from 2002 to 2009. The primary endpoint was survival.LHR was greater in survivors after adjusting for gestational age (median 1.40 versus 0.81; p0.001). LHR demonstrated excellent diagnostic discrimination, with area under receiver operating characteristic (ROC) curve 0.93 (95% CI 0.86-0.99). LHR threshold of 1.0 was 83% sensitive and 91% specific in predicting survival. An optimal LHR threshold of 0.85 predicted survival with 95% sensitivity and 64% specificity, reducing false negatives (survivors with low LHR). LHR0.85 predicted survival after adjustment for gestational age (OR = 33.6, 95% CI = 5.4-209.5). Liver position did not predict survival.Prenatal LHR0.85 predicts survival for infants with isolated left-sided CDH without compromising discrimination of survivors from non-survivors. The diagnostic utility of LHR may be confounded by gestational age at measurement. Stringent LHR threshold may minimize false-negative attribution and improve utility of this measurement as predictor of survival.

Both seasonal and novel (pH1N1-09) influenza commonly present with fever, cough, sore throat, and myalgias, a constellation of symptoms known as influenza-like illness. Pulmonary complications, pneumonia and acute respiratory distress syndrome, are the major reported causes of morbidity and mortality associated with seasonal and novel (pH1N1) influenza. Patients with these complications require intensive care with mechanical ventilation and possibly extracorporeal life support. Between April and December 2009, five patients at our institution required extracorporeal membrane oxygenation (ECMO) for treatment of confirmed or suspected pH1N1-09 influenza infection. The indication for ECMO in four of these patients was acute respiratory distress syndrome. The fifth patient was treated for cardiogenic shock from fulminant pH1N1-09 influenza-associated myocarditis. Five additional pediatric patients with severe pH1N1-09 influenza infections were evaluated for ECMO: four with pulmonary complications and one with cardiogenic shock. One patient declined ECMO and died, whereas the other four stabilized with aggressive medical therapy and recovered without ECMO support. Fulminant myocarditis secondary to seasonal influenza infection has been well described but has not been reported with pH1N1-09 influenza virus. In this report we summarize the clinical characteristics of two patients who presented in cardiogenic shock secondary to fulminant pH1N1-09 influenza myocarditis. Neither child had a significant medical history, and both presented after 1 week of fever, abdominal pain, and lethargy but no respiratory complaints or diagnosis of influenza-like illness. Echocardiography revealed pericardial effusion with tamponade in both patients. Neither child underwent endomyocardial biopsy, but their acute clinical presentation, echocardiography findings, and positive serology results were highly suggestive of a clinical diagnosis of fulminant myocarditis.

This is the annual report of the Extracorporeal Life Support Organization. It concerns the aggregate experience of all reported patients treated with extracorporeal membrane oxygenation as of April 1993. The patients are either neonatal, pediatric pulmonary, or neonatal/pediatric cardiac. A survival rate of 81% (neonatal), 48% (pediatric), and 45% (cardiac) is reported in patients thought to have at least an 80% mortality likelihood.

Fetal upper respiratory tract function was studied in five cases of antenatally diagnosed congenital diaphragmatic hernia and in 16 cases of uncomplicated pregnancy at gestational ages ranging from 27 to 38 weeks. The evaluation of fetal upper respiratory tract function was performed using ultrasonography combined with color-flow and spectral Doppler analysis. In all cases with uncomplicated pregnancy, fetal breathing-related nasal and oropharyngeal fluid flow was seen at the level of the nose. The five cases with congenital diaphragmatic hernia all demonstrated fetal breathing activity by thoracic wall movement. In four of the fetuses, perinasal fluid flow was seen by the Doppler technique. The fetus with no demonstrated perinasal flow during breathing movements died in the early neonatal period and had pulmonary hypoplasia. Observation of the fetal breathing-related nasal and oropharyngeal fluid flow in cases of antenatally diagnosed congenital diaphragmatic hernia provides a rationale to hypothesize that the absence of this phenomenon is a useful marker for prenatal prediction of pulmonary hypoplasia.

Thoracic volume relationships supported by the diaphragm are important mechanical components of neonatal lung growth. Alterations modify regional lung growth. We used stereologic morphometry to study effects of altered diaphragm function on alveolar growth in neonatal pigs. Nine piglets (1 mo) were divided into three groups: unilateral phrenectomy, noncompliant patch replacement of diaphragm, and sham. Seven days later lungs were fixed in situ with 2.5% glutaraldehyde by airway installation at 20 cm H2O. Five 1-mm cubes were cut from lung corresponding to apex/RUQ(A), base/RLQ(B), apex/LUQ(C), and base/LLQ(D) and prepared for light microscopy (n = 25/quad/animal). Stereologic morphometry involved point counting for air volume density and point intersect to determine the surface area density of the alveolar spaces. Results were analyzed for variance and by Tukey range testing. Variance of air volume % between groups-quadrants B, C, D had decreased air volume % in phrenectomy group compared with patch and sham group (P.05). Variance of air volume % within groups, for phrenectomy group A (81.5%), is different from all others (B = 70.6%, C = 75.5%, D = 66.7%); C is different from D (P.05). For patch and sham group, D (P = 74.8%, S = 80.7%) is different from A (P = 84.1%, S = 86.6%) and C (P = 86.2%, S = 84.4%). Variance of surface area density between groups--quadrant D had increased surface area density % in phrenectomy group compared to sham group (P.05). Variance of surface area density % within groups, for phrenectomy group, A (37.9 mm-1) is different from D (55.7 mm-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction Experience in thoracoscopic congenital diaphragmatic hernia (CDH) repair has expanded, yet efficacy equal to that of open repair has not been demonstrated. In spite of reports suggesting higher recurrent hernia rates after thoracoscopic repair, this approach has widely been adopted into practice. We report a large, single institutional experience with thoracoscopic CDH repair with special attention to recurrent hernia rates. Methods We reviewed the records of neonates with unilateral CDH repaired between January 2006 and February 2010 at Morgan Stanley Children's Hospital. Completely thoracoscopic repairs were compared to open repairs of the same period. In addition, successful thoracoscopic repairs were compared with thoracoscopic repairs that developed recurrence. Data were analyzed by Mann-Whitney U and Fisher exact tests. Results Thirty-five neonates underwent attempted thoracoscopic repair, with 26 completed. Concurrently, 19 initially open CDH repairs were performed. Preoperatively, patients in the open repair group required more ventilatory support than the thoracoscopic group. Recurrence was higher after thoracoscopic repair (23% vs 0%; P = .032). In comparing successful thoracoscopic repairs to those with recurrence, none of the factors analyzed were predictive of recurrence. Conclusions Early recurrence of hernia is higher in thoracoscopic CDH repairs than in open repairs. Technical factors and a steep learning curve for thoracoscopy may account for the higher recurrence rates, but not patient severity of illness. In an already-tenuous patient population, performing the repair thoracoscopically with a higher risk of recurrence may not be advantageous.

Purpose Extracorporeal Life Support Organization Registry data confirm that the number of pediatric patients being supported by extracorporeal membrane oxygenation (ECMO) is increasing. To minimize the potential neurologic effects of carotid artery ligation, the common femoral artery (CFA) is frequently being used for arterial cannulation. The cannula has the potential for obstructing flow to the lower limb, thus increasing ischemia and possible limb loss. We present a single institution's experience with CFA cannulation for venoarterial (VA) ECMO and ask whether any precannulation variables correlate with the development of significant limb ischemia. Methods We reviewed all pediatric patients who were supported by VA ECMO via CFA cannulation from January 2000 to February 2010. Limb ischemia was the primary variable. The ischemia group was defined as the patients requiring an intervention because of the development of lower extremity ischemia. The patients in the no-ischemia group did not develop significant ischemia. Continuous variables were reported as medians with interquartile ranges and compared using Mann-Whitney U tests. Differences in categorical variables were assessed using χ 2 testing (Fisher's Exact). Statistical significance was assumed at P Results Twenty-one patients (age, 2-22 years) were cannulated via the CFA for VA ECMO. Significant ischemia requiring intervention (ischemia group) occurred in 11 (52%) of 21. In comparing the 2 groups (ischemia vs no ischemia), no clinical variables predicted the development of ischemia (Table 1). In the ischemia group, 9 (81%) of 11 had a distal perfusion catheter (DPC) placed. Complications of DPC placement included one case of compartment syndrome requiring a fasciotomy and one patient requiring interval toe amputation. Of the 2 patients in the ischemia group who did not have a DPC placed, 1 required a vascular reconstruction of an injured superficial femoral artery and 1 underwent a below-the-knee amputation. Mortality was lower in the ischemia group (27% vs 60%). Conclusions Limb ischemia remains a significant problem, as more than half of our patients developed it. The true incidence may not be known as a 60% mortality in the no-ischemia group could mask subsequent ischemia. Although children are at risk for developing limb ischemia/loss, no variable was predictive of the development of significant limb ischemia in our series. Because of the inability to predict who will develop limb ischemia, early routine placement of a DPC at the time of cannulation may be warranted. However, DPCs do not completely resolve issues around tissue loss and morbidity. Prevention of limb ischemia/loss because of CFA cannulation for VA ECMO continues to be a problem that could benefit from new strategies.