Neonatal esophageal perforation: nonoperative management.

BACKGROUND: Esophageal perforation is a rare complication of enteric instrumentation in neonates. Enteric tube placement in micro-preemies poses a particular hazard to the narrow lumen and thin wall of the developing esophagus. The complication may be difficult to recognize or misdiagnosed as esophageal atresia, and is associated with considerable mortality. Historically, management of this life-threatening iatrogenic disease was operative, but trends have shifted toward nonoperative treatment. Here, we review neonatal esophageal perforation at our own institution for management techniques, risk factors, and outcomes. MATERIALS AND METHODS: Seven neonatal patients with esophageal perforation were identified and charts reviewed for demographics, comorbidities, etiology of perforation, diagnostic modalities, management decisions, complications, and outcomes. RESULTS: Mean gestational age was 27.2 ± 4.0 wk, and weight at diagnosis was 892 ± 674 g. All seven patients had esophageal perforation resulting from endotracheal or enterogastric intubation and were managed nonoperatively. Treatment included removal of the offending tube, nil per os, and antibiotics. Five patients required additional interventions: four tube thoracostomies for pneumothoraces and one peritoneal drain for pneumoperitoneum. Three patients died because of sequelae of prematurity (intraventricular hemorrhage, necrotizing enterocolitis, and sepsis). One patient was diagnosed as having esophageal atresia; esophagoscopy before surgical repair established the correct diagnosis. CONCLUSIONS: Neonates, particularly those under 1500 g, are at substantial risk for iatrogenic esophageal perforation during enterogastric intubation. Nonoperative management may be a safe initial strategy in the neonatal setting, but more aggressive interventions may ultimately be required. Despite recent improvement in early recognition of this injury, misdiagnosis still occurs.

Celecoxib inhibits Ewing sarcoma cell migration via actin modulation.

BACKGROUND: Ewing sarcoma (ES) is an aggressive childhood solid tumor in which 30% of cases are metastatic at presentation, and subsequently carry a poor prognosis. We have previously shown that treatment with celecoxib significantly reduces invasion and metastasis of ES cells in a cyclooxygenase-2-independent fashion. Celecoxib is known to downregulate ß-catenin independently of cyclooxygenase-2. Additionally, the actin cytoskeleton is known to play an important role in tumor micrometastasis. We hypothesized that celecoxib's antimetastatic effect in ES acts via modulation of one of these two targets. METHODS: ES cells were treated with celecoxib, and the levels of ß-catenin and total actin were examined by Western blot and quantitative polymerase chain reaction. Cells were transfected with small interfering RNA targeting ß-catenin, and invasion assays were performed. Immunofluorescence staining for ß-catenin and F-actin was performed on treated and untreated cells. Additionally, cells were subjected to a wound healing assay to assess migration. RESULTS: Celecoxib had no effect on the messenger RNA or protein levels of ß-catenin but did significantly decrease the amount of total actin within ES cells. Reduction of ß-catenin by small interfering RNA had no effect on invasion, and celecoxib treatment of the ß-catenin depleted cells continued to inhibit invasion. Immunofluorescence staining demonstrated no change in ß-catenin with treatment but did show a significant reduction in the amount of F-actin, as well as morphologic changes of the cells. Wound healing assays demonstrated that celecoxib significantly inhibited migration. CONCLUSIONS: Celecoxib does not exert its antimetastatic effects in ES through alteration of ß-catenin but does significantly modulate the actin cytoskeleton.

Acute Gastric Dilatation Complicated by Necrosis and Perforation Following a Binge Eating Episode.

Acute gastric dilatation is a rare entity limited to case reports in the literature. It is characterized by significant distention of the stomach beyond physiologic parameters. The sequelae of this phenomenon are life-threating, as it can lead to gastric perforation. It is frequently reported in patients who suffer from eating disorders, particularly binge eating disorder and bulimia nervosa. We present a case of a 28-year-old female who suffered from acute gastric dilatation following significant food intake. Her long hospital course was complicated by gastric necrosis and perforation, requiring multiple laparotomies prior to the restoration of a functional gastrointestinal tract. We aim to demonstrate the true gravity of this diagnosis and raise its awareness.

Bike helmets prevent pediatric head injury in serious bicycle crashes with motor vehicles.

BACKGROUND: Approximately 75% of all bicycle-related mortality is secondary to head injuries, 85% of which could have been prevented by wearing a bicycle helmet. Younger children appear to be at greater risk than adults, yet helmet use is low despite this risk and legislation and ordinances requiring helmet use among younger riders. We sought to determine whether bicycle helmets are associated with the incidence and severity of head injury among pediatric bicyclists involved in a bicycle crash involving a motor vehicle. METHODS: We performed a retrospective review of patients age ≤ 18 years hospitalized at a level I pediatric trauma center between January 1, 2008, and December 31, 2018. Data were abstracted from the institutional trauma registry and electronic medical record. International Classification of Diseases 9th and 10th editions and external causes of injury codes were used to identify MV related bicycle crashes and determine the abbreviated injury severity (AIS) for head injury severity. Injury narratives were reviewed to determine helmet use. We calculated the incidence of head injury from bicycle vs. MV crashes utilizing descriptive statistics. We analyzed the risk and severity of injury utilizing univariate and multivariate logistic regression. RESULTS: Overall, 226 bicyclists were treated for injuries from being struck by a MV. The median age was 11 (interquartile range (IQR): 8 to 13) years. Helmeted bicyclists (n = 26, 27%) were younger (9.4 years versus 10.8 years, p = 0.04), and were less likely (OR 0.21, 95% CI 0.09 to 0.49) to be diagnosed with a head injury compared to unhelmeted bicyclists (n = 199). Of those with a head injury, helmeted bicyclists were less likely (OR 0.57, 95% CI 0.11-2.82) to sustain severe or higher injury using AIS. When adjusting for demographics (age, sex, race) and injury severity, helmet use predicted a reduction in head injury (OR 6.02, 95% CI 2.4-15.2). CONCLUSIONS: Bicycle helmet use was associated with reduced odds of head injury and severity of injury.. These results support the use of strategies to increase the uptake of bicycle helmets wearing as part of a comprehensive youth bicycling injury prevention program.

Characteristics and outcomes of extracorporeal life support in pediatric trauma patients.

BACKGROUND: Extracorporeal life support utilizing extracorporeal membrane oxygenation (ECMO) techniques has been used in the pediatric population for numerous indications, but its use in trauma has been understudied. We sought to examine the indications, characteristics, and outcomes of children placed on ECMO for trauma and hypothesized that outcomes would be equivalent to those of patients placed on ECMO for other indications. METHODS: We performed a retrospective review of all pediatric trauma patients in the Extracorporeal Life Support Organization registry from 1989 to 2018. Patient characteristics, indications for ECMO, pre- and post-ECMO ventilator settings and blood chemistry, complications, and survival rates were examined. Categories were stratified by mode: venovenous (VV), veno-arterial (VA), or conversion. Data were analyzed using SPSS software, with significance considered at p value less than 0.05. RESULTS: We identified 573 patients with a median age of 4.82 years. The majority of patients (62.3%) were male and on VA support (54.5%). Drowning (38.7%) was the most common mechanism, followed by burns (21.1%) and thoracic trauma (17.8%). Complication rates were high (81.9%), with the most frequent types being cardiovascular, mechanical, and hemorrhagic. Incidences of complications (overall and by type) were similar to those reported in other Extracorporeal Life Support Organization cohorts. Overall survival was 55.3% and was significantly higher (p = 0.00) for patients on VV (74.3%) compared with those on VA (41.7%), even when controlling for mechanism. CONCLUSION: Survival and complication rates of pediatric trauma patients on ECMO are comparable to those reported for other indications. Trauma should not be considered a contraindication for ECMO. LEVEL OF EVIDENCE: Therapeutic, level V.

Minimally invasive surgery for pediatric renal tumors: A systematic review by the APSA Cancer Committee.

Minimally invasive nephrectomy is performed routinely for adult renal tumors and for many benign pediatric conditions. Although open radical nephroureterectomy remains the standard of care for Wilms tumor and most pediatric renal malignancies, there are an increasing number of reports of minimally invasive surgery (MIS) for those operations as well. The APSA Cancer Committee performed a systematic review to better understand the risks and benefits of MIS in pediatric patients with renal tumors. METHODS: The search focused on MIS for renal tumors in children and followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist. The initial database search identified 491 published articles, and after progressive review of abstracts and full-length articles, 19 were included in this review. RESULTS: There were two direct comparison studies where open surgery and MIS were compared. The remaining studies reported only on minimally invasive nephrectomy. Across all studies, there were a total of 151 patients, 126 of which had Wilms tumor and 10 patients had RCC. 104 patients had MIS, with 47 patients having open surgery. In the two studies in which open surgery and MIS were directly compared, more lymph nodes were harvested during open surgery (median = 2 (MIS) vs 5 (open); mean = 2.47 (MIS) vs 3.8 (open)). Many noncomparison studies reported the harvest of 2 of fewer lymph nodes for Wilms tumor. Several MIS patients were also noted to have intraoperative spill or positive margins. Survival between groups was similar. CONCLUSIONS: There is a lack of evidence to support MIS for pediatric renal tumors. This review demonstrates that lymph node harvest has been inadequate for MIS pediatric nephrectomy and there appears to be an increased risk for intraoperative spill. Survival data are similar between groups, but follow-up times were inconsistent and patient selection was clearly biased, with only small tumors being selected for MIS. TYPE OF STUDY: Review article. LEVEL OF EVIDENCE: III.

The incidence of Marfan syndrome and cardiac anomalies in patients presenting with pectus deformities.

PURPOSE: The incidence of Marfan syndrome in the general population is 0.3%. Two-thirds of patients with Marfan syndrome have concurrent pectus deformity. However, incidence of Marfan syndrome and cardiac abnormalities in patients presenting with an isolated pectus deformity remains unknown. We sought to establish the degree of association between pectus deformities and these abnormalities, and whether referral of these patients for cardiac and genetic workup is warranted. METHODS: Our pediatric surgery group refers patients with pectus deformities for genetic and cardiac evaluation. We examined 415 records from 2009 to 2016, and identified 241 patients with a chief complaint of a pectus deformity. Patient characteristics, echocardiogram results, Haller indices, and genetic results were analyzed. RESULTS: The frequency of Marfan syndrome in our study was 5.3%. The incidence of Marfan was highest among patients with combined type pectus deformity (20%). Cardiac anomalies showed an overall incidence of 35%. Of those diagnosed with Marfan, 84% had cardiac abnormalities. CONCLUSION: More than 5% of patients presenting with a chief complaint of pectus deformity will have a diagnosis of Marfan syndrome, compared to 0.3% in the general population. Approximately a third of this population will have cardiac abnormalities. Referral of patients with pectus deformities for evaluation for Marfan syndrome and cardiac abnormalities is appropriate. LEVEL OF EVIDENCE: Level IV.

Recent trends in the operative experience of junior pediatric surgical attendings: a study of APSA applicant case logs.

PURPOSE: Pediatric surgical education and workforce have changed significantly in the past decade. To document trends in the operative experiences of junior pediatric surgeons, we examined case logs submitted by applicants for membership to APSA. METHODS: Case logs for 164 APSA membership applicants from 2006 to 2013 were reviewed. Total case volume, categories, and specific operations were analyzed. Negative binomial regression assessed for significant associations between the number of cases and the application year, presence of a pediatric surgery training program, region of the country, and years since fellowship completion. RESULTS: Overall case numbers decreased initially after 2006/2007, but have remained stable since. Decreasing trends were seen in a number of specific cases/categories. The number of newborn cases did not change. Significant variations in operative experience were identified depending upon region, presence of a pediatric surgery training program, and years since fellowship completion. Median reported value for several important cases was ≤4 per year, and for some was zero. CONCLUSION: These data describing the experience of young pediatric surgeons supplement recent observations regarding pediatric surgery fellows and general surgery residents. The limited exposure of surgeons to particularly rare conditions appears to be an unresolved problem. This information will be useful in developing future workforce proposals.

The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation.

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma.