Faculty Bibliography

Thrombotic disease is rare in neonates. Many of the cases reported in literature are attributed to the placement of central catheters. We report on a case of aortic thrombosis in a newborn infant with significant respiratory distress due to meconium aspiration, necessitating intubation and placement of central catheters. Due to the location and size of the thrombus in our case, various subspecialties were involved, which ultimately guided therapy to anti-coagulate the patient

Laparascopic repair of inguinal hernias in female children can be achieved using the inversion and ligation technique in which the hernia sac is inverted into the peritoneal cavity and ligated using endoloops. This technique has been shown to reduce operative time and post-operative complications such as missed contralateral hernia, wound infection and hernia recurrence. We describe a case of a 3-month old female who underwent laparoscopic repair of bilateral inguinal hernias, and presented one year post-operatively with bilateral groin bulges. On re-operation the bulges were determined not to be true hernia recurrences, but rather pseudorecurrences of accumulated fluid distal to the ligation point after incomplete inversion. They were successfully repaired in an open fashion, without subsequent development of groin bulges. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

Appendicitis remains the most common cause for emergency abdominal surgery in children. Immediate appendectomy in complicated, perforated appendicitis can be hazardous and nonoperative therapy has been gaining use as an initial therapy in children. Previous studies have reported failure rates in nonoperative therapy in such cases ranging from 10% to 41%. Factors leading to treatment failures have been studied with various and disparate results. We reviewed our institutional experience in treated complicated appendicitis, with focus on those initially managed nonoperatively. METHODS: Records of all children admitted with the diagnosis of perforated appendicitis to NYU Langone Medical Center and Bellevue Hospital Center from January 1, 2003 to December 31, 2013 were reviewed. The diagnosis was made with ultrasound and/or computed tomography scan. Those with abscesses amenable to drainage underwent aspiration and drain placement by an interventional radiologist. Broad spectrum intravenous (IV) antibiotics were given until the patient became afebrile, pain free and tolerating a regular diet. Oral antibiotics were continued for an additional week and interval appendectomy was done eight weeks later. The primary outcome measure was treatment response with failure defined as those who did not improve or required readmission for additional IV antibiotics and/or early appendectomy. Multiple patient and treatment related variables, including those previously reported as predicting failure in nonoperative therapy, were studied. Continuous variables were reported as means +/- standard error and compared using 2-tailed unpaired t tests; nonparametric variables were analyzed by Mann-Whitney U tests. Categorical variables were reported as medians +/- interquartile ranges and compared using Chi-square testing. Statistical significance was accepted for p<.05. RESULTS: Sixty-four patients were identified as undergoing initial nonoperative therapy. Fifty-two (81%) were categorized as treatment successes being treated nonoperatively and 12 (19%) were failures. Variables showing no significance in predicting treatment failures included duration of symptoms, presence of appendicolith, presence of phlegmon, presence of abscess, initial white blood cell count, and SIRS (Systemic Inflammatory Response Syndrome) positive. The variables that predicted failure of nonoperative therapy vs. successes were presence of bandemia (75% vs. 40%, p=0.052) and small bowel obstruction on imaging (42% vs. 15%, p=0.052) and presence of bandemia >/=15% which was highly predictive of failure (67% vs. 4%, p<0.01). CONCLUSIONS: Predicting which patients with complicated perforated appendicitis will respond well to nonoperative therapy may allow us to more effectively treat patients with complicated perforated appendicitis. In our study the presence of small bowel obstruction and bandemia, especially >/=15% correlated with treatment failure; this suggests that these select patients may need a modified treatment strategy.

PURPOSE: Quality improvement (QI) bundles have been widely adopted to reduce surgical site infections (SSI). Improvement science suggests when organizations achieve high-reliability to QI processes, outcomes dramatically improve. However, measuring QI process compliance is poorly supported by electronic health record (EHR) systems. We developed a custom EHR tool to facilitate capture of process data for SSI prevention with the aim of increasing bundle compliance and reducing adverse events. METHODS: Ten SSI prevention bundle processes were linked to EHR data elements that were then aggregated into a snapshot display superimposed on weekly case-log reports. The data aggregation and user interface facilitated efficient review of all SSI bundle elements, providing an exact bundle compliance rate without random sampling or chart review. RESULTS: Nine months after implementation of our custom EHR tool, we observed centerline shifts in median SSI bundle compliance (46% to 72%). Additionally, as predicted by high reliability principles, we began to see a trend toward improvement in SSI rates (1.68 to 0.87 per 100 operations), but a discrete centerline shift was not detected. CONCLUSION: Simple informatics solutions can facilitate extraction of QI process data from the EHR without relying on adjunctive systems. Analyses of these data may drive reductions in adverse events. Pediatric surgical departments should consider leveraging the EHR to enhance bundle compliance as they implement QI strategies.

Objective: 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. Methods: Prenatal LHR and liver position were obtained from 2002 to 2009. The primary endpoint was survival. Results: LHR was greater in survivors after adjusting for gestational age (median 1.40 versus 0.81; p < 0.001). 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). LHR > 0.85 predicted survival after adjustment for gestational age (OR = 33.6, 95% CI = 5.4-209.5). Liver position did not predict survival. Conclusions: Prenatal LHR >0.85 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.

ABSTRACT: Vascular endothelial growth factor (VEGF) blockade is an effective therapy for human cancer, yet virtually all neoplasms resume primary tumor growth or metastasize during therapy. Mechanisms of progression have been proposed to include genes that control vascular remodeling and are elicited by hypoperfusion, such as the inducible enzyme cyclooxygenase-2 (COX-2). We have previously shown that COX-2 inhibition by the celecoxib analog SC236 attenuates perivascular stromal cell recruitment and tumor growth. We therefore examined the effect of combined SC236 and VEGF blockade, using the metastasizing orthotopic SKNEP1 model of pediatric cancer. Combined treatment perturbed tumor vessel remodeling and macrophage recruitment, but did not further limit primary tumor growth as compared to VEGF blockade alone. However, combining SC236 and VEGF inhibition significantly reduced the incidence of lung metastasis, suggesting a distinct effect on prometastatic mechanisms. We found that SC236 limited tumor cell viability and migration in vitro, with effects enhanced by hypoxia, but did not change tumor proliferation or matrix metalloproteinase expression in vivo. Gene set expression analysis (GSEA) indicated that the addition of SC236 to VEGF inhibition significantly reduced expression of gene sets linked to macrophage mobilization. Perivascular recruitment of macrophages induced by VEGF blockade was disrupted in tumors treated with combined VEGF- and COX-2-inhibition. Collectively, these findings suggest that during VEGF blockade COX-2 may restrict metastasis by limiting both prometastatic behaviors in individual tumor cells and mobilization of macrophages to the tumor vasculature.

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 chi(2) testing (Fisher's Exact). Statistical significance was assumed at P < .05. 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.

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.

Clear cell sarcoma of the kidney (CCSK) is uncommon pediatric renal tumor and can present a significant therapeutic challenge in those patients whose tumors spread beyond the kidney. Thus, identifying potential novel targets for treatment may be clinically important. Clear cell sarcoma of the kidney is characterized by a unique vascular pattern, in which nests of tumor cells are separated by regularly-spaced, fine fibrovascular septa. This distinctive histopathology raises the possibility that understanding the factors which drive angiogenesis in CCSK tumors may suggest new therapeutic targets. Here, we describe a case of CCSK and present immunohistochemical studies of its vasculature.