Appendectomy and Cholecystectomy Outcomes for Pediatric Cancer Patients with Leukopenia: A NSQIP-Pediatric Study.

BACKGROUND: Children with cancer often develop leukopenia which may impair wound healing and increase surgical complication rates. When leukopenic children with cancer develop an acute surgical condition, the optimal management strategy remains unclear. This study examined the effect of preoperative leukopenia on postoperative outcomes in children with cancer who underwent an appendectomy or cholecystectomy. METHODS: We retrospectively identified cancer patients undergoing an appendectomy or cholecystectomy from the National Surgical Quality Improvement Program-Pediatric database from 2012-2018. Demographics and perioperative characteristics were compared by leukopenia status (WBC <4 vs. ≥4 × 10^3/mL). Postoperative length of stay (LOS) and 30-day composite complications, including infections, reoperations, and readmissions, were analyzed for each procedure using multivariate regression. RESULTS: There were 227 children who underwent an appendectomy and 101 children who underwent a cholecystectomy. Leukopenia was seen in 93 (41.0%) appendectomy and 57 (56.4%) cholecystectomy cases. Nineteen (8.4%) appendectomy patients and six (5.9%) cholecystectomy patients developed a postoperative complication. The median postoperative LOS was 2 days (IQR 1-6 days) for appendectomy and 1 day (IQR 1-2.5 days) for cholecystectomy cases. After multivariate analyses, leukopenia was not associated with increased postoperative complications after an appendectomy (OR 0.55, P = 0.36) or cholecystectomy (OR 0.39, P = 0.37). There was no significant difference in postoperative LOS based on leukopenia status for children who underwent an appendectomy (P = 0.82) or cholecystectomy (P = 0.37). CONCLUSION: In pediatric cancer patients, leukopenia was not associated with increased short-term postoperative complications or longer postoperative LOS after either an appendectomy or cholecystectomy. These results support that operative management can be performed safely in pediatric appendicitis and cholecystitis in leukopenic cancer patients.

Pediatric traumatic abdominal wall hernia as a component of the seatbelt syndrome: a case series and review of the literature.

BACKGROUND: Blunt impact-induced traumatic abdominal wall hernia (TAWH) is an uncommon pediatric surgical problem classically associated with handlebar injury but increasingly seen with seatbelt use in motor vehicle collisions (MVC). Herein we describe the largest case series of pediatric TAWH to date and review the literature to establish the unique syndromic characteristics of MVC-associated TAWH. METHODS: In this single-institution series, we discuss four pediatric patients, all with seatbelt-associated TAWH after high-speed MVC characterized by full-thickness disruption of the lateral abdominal wall. We then performed a review of the literature to identify additional pediatric MVC-associated TAWH and define the characteristics of patients who sustained this unique injury. RESULTS: In addition to the four patients in our case series, five additional pediatric patients presenting with TAWH after restrained MVC were identified in the literature. Of these nine patients, eight (89%) presented with an obvious seatbelt sign (bruising/laceration to the abdominal wall). Six (67%) had associated injuries typical of the seatbelt syndrome, including four spinal flexion injuries (44%) and five bowel injuries requiring repair or resection (56%). Overall, 56% of seatbelt-associated TAWH occurred in children with a BMI percentile > 95%. CONCLUSIONS: In this case series and literature review, we note a high rate of seatbelt syndrome injuries in pediatric patients presenting with TAWH after restrained MVC. Suspicion for TAWH should be high in children presenting with a seatbelt sign and should trigger a low threshold for pursuing additional axial imaging. LEVEL OF EVIDENCE: Level IV; case series.

Extrapulmonary sequestration with a left internal thoracic arterial feeding vessel in an infant treated with video-assisted Thoracoscopic resection: a case report.

BACKGROUND: Congenital lung malformations exist along a spectrum of pathogenesis and disease severity. Extrapulmonary sequestration (EPS), in which nonfunctional lung tissue develops without connection to the tracheobronchial tree, is one rare manifestation of this disease. Atypical vascular anatomy with a systemic feeding vessel characterizes these lesions. CASE PRESENTATION: A 3 day old, 37 week gestation infant underwent chest X-ray for confirmation of umbilical catheter placement and was found to have an elevated left hemidiaphragm consistent with eventration versus congenital diaphragmatic hernia. He remained asymptomatic and was evaluated as an outpatient at the age of 9 months, where CT angiogram demonstrated extrapulmonary versus intrapulmonary sequestration with a systemic feeding vessel from the left internal mammary artery. CONCLUSIONS: It is exceedingly rare for the feeding artery to arise from the internal mammary; two such cases have been reported to date, both in adult patients. Here we present a third case of EPS with arterial supply from the internal mammary successfully treated with video-assisted thoracoscopic resection in a 9 month old infant.

Extracorporeal cardiopulmonary resuscitation in a neonate after air embolism during insufflation for laparoscopic peritoneal dialysis catheter placement.

Laparoscopy is increasingly utilized in neonatal surgery with safe and effective outcomes. Air embolism from insufflation for pneumoperitoneum is a rare but known risk of laparoscopy. Here we present a rare case of air embolism during insufflation for laparoscopic peritoneal dialysis catheter placement treated with extracorporeal cardiopulmonary resuscitation.

Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis?

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGFß-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 - 8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFß-1 (rs2241712) were associated with NEC- related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC.

Genomics in premature infants: a non-invasive strategy to obtain high-quality DNA.

We used a cost-effective, non-invasive method to obtain high-quality DNA from buccal epithelial-cells (BEC) of premature infants for genomic analysis. DNAs from BEC were obtained from premature infants with gestational age ≤ 36 weeks. Short terminal repeats (STRs) were performed simultaneously on DNA obtained from the buccal swabs and blood from the same patient. The STR profiles demonstrated that the samples originated from the same individual and exclude any contamination by external DNAs. Whole exome sequencing was performed on DNAs obtained from BEC on premature infants with and without necrotizing enterocolitis, and successfully provided a total number of reads and variants corroborating with those obtained from healthy blood donors. We provide a proof of concept that BEC is a reliable and preferable source of DNA for high-throughput sequencing in premature infants.

Endothelial monocyte activating polypeptide II interferes with VEGF-induced proangiogenic signaling.

Endothelial monocyte activating polypeptide II (EMAP II) is a proinflammatory cytokine with antiangiogenic properties. EMAP II functions as a potent inhibitor of primary and metastatic tumor growth, has strong inhibitory effects on endothelial cells (ECs), and can reduce intratumoral expression of the angiogenesis inducer vascular endothelial growth factor (VEGF). VEGF influences EC functions such as proliferation, migration, survival and tube formation. Therapeutic strategies that target VEGF have been demonstrated to reduce the tumor growth. We investigated the effects of EMAP II on VEGF-induced angiogenesis signaling. Primary human fetal lung ECs (HFLECs) and human umbilical vein ECs (HUVECs) were grown in E-Stim medium. Protein binding was analyzed using enzyme-linked immunosorbent assay (ELISA). Protein expression was determined by western blot analysis. EC proliferation and migration was determined using WST-1 reagent and transwell membrane, respectively. EMAP II efficiently and dose dependently binds to VEGF receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2) as observed by ELISA. B(max) values for VEGFR1 and VEGFR2 were 0.45 and 0.17, respectively. In addition, EMAP II inhibited binding of VEGF to VEGFR1 and VEGFR2. EMAP II significantly reduced VEGF-induced expression of phosphorylated VEGFR1 (in HFLEC and HUVEC) by >50%, and of phosphorylated VEGFR2 (in HUVEC) by 66%. EMAP II also inhibited downstream VEGF signaling. Although VEGF-induced phosphorylation of Akt, Erk1/2, p38 and Raf 2.8-, 1.5-, 2.2- and 3.6-fold, respectively, EMAP II preincubation blocked this induction in phosphorylation to control levels. VEGF-induced EC proliferation 2.5-fold, and EMAP II pretreatment abrogated this effect. Similarly, VEGF-induced EC migration (2.5-fold) was significantly inhibited by EMAP II. These finding suggest that inhibition of VEGF signaling is one possible antiangiogenic mechanism of EMAP II, which may explain its in vivo antitumor activity and delineate therapeutic strategies to enhance anti-VEGF therapy to inhibit tumor growth.

Functional characterization of a putative aquaporin from Encephalitozoon cuniculi, a microsporidia pathogenic to humans.

The microsporidia are a group of obligate intracellular parasitic protists that have been implicated as both human and veterinary pathogens. The infectious process of these organisms is believed to be dependent upon the rapid influx of water into spores, presumably via aquaporins (AQPs), transmembrane channels that facilitate osmosis. An AQP-like sequence of the microsporidium Encephalitozoon cuniculi (EcAQP), when cloned and expressed in oocytes of Xenopus laevis, rendered these oocytes highly permeable to water. No permeability to the solutes glycerol or urea was observed. Pre-treatment of EcAQP-expressing oocytes with HgCl(2) failed to inhibit their osmotic permeability, as predicted from EcAQP's lack of mercury-sensitive cysteine residues near the NPA motifs which line the AQP aqueous pore. EcAQP exhibits sequence identity to AQP A of Dictyostelium discoideum (26%) and human AQP 2 (24%). Further study of AQPs in microsporidia and their potential inhibitors may yield novel therapeutic agents for microsporidian infections.