Pediatric Surgery International

Administration of heavy metal cadmium (Cd) after 60-h incubation induces omphalocele spectrum in the chick embryo. Although previous studies have shown that the earliest detectable histological changes in the chick Cd model occurs commencing at 4-h post-treatment (4H). However, the molecular mechanism by which Cd acts in the critical period of early embryogenesis still remains unclear. Zic3, a Gli superfamily transcription factor, is expressed in somites and plays an important role in vertebrate development, including somitogenesis and thus ventral body wall formation. Gli3 is also expressed in somites and interacts with Zic3 physically and functionally. It has been reported that Gli3 homozygous double mutants display omphalocele. Zic3 mutant mice have also been known to result in omphalocele phenotype. We designed this study to test the hypothesis that Gli3 and Zic3 gene expression is downregulated during the critical period of very early embryogenesis in the Cd-induced omphalocele in the chick model. After 60-h incubation, chick embryos were exposed to either saline or 50 μM cadmium and divided into two groups: control and Cd (n = 24 for each group). Real-time reverse transcription polymerase chain reaction was performed to evaluate the relative mRNA expression levels of Gli3 and Zic3 in the Cd-induced omphalocele chick model. Differences between the two groups at each time point were analyzed statistically and the significance was accepted at p < 0.05. Immunohistochemistry was also performed to evaluate the expression/distribution of those proteins in chick embryo. The relative mRNA expression level of Gli3 and Zic3 was significantly decreased in the Cd group at 4H when compared with controls (p < 0.05). However, there were no significant differences at the other time points. At 4H, immunoreactivity of GLI3 and ZIC3 was also markedly decreased in Cd-treated embryos, whereas strong expression of them was seen in the somite in controls. We provide evidence, for the first time, that Gli3 and Zic3 gene expression is downregulated during the narrow window of very early embryogenesis in Cd chick model. Disruption of Gli3–Zic3 interaction in the critical period for ventral body wall formation may contribute to omphalocele phenotype in Cd chick model.

To evaluate the perioperative risk factors for 30-day complications of the Kasai procedure in a large, cross-institutional, modern dataset. The 2012–2015 National Surgical Quality Improvement Program Pediatric database was used to identify patients undergoing the Kasai procedure. Patients’ characteristics were compared by perioperative blood transfusions and 30-day outcomes, including complications, reoperations, and readmissions. Multivariable logistic regression was used to identify risk factors predictive of outcomes. Propensity matching was performed for perioperative blood transfusions to evaluate its effect on outcomes. 190 children were included with average age of 62 days. Major cardiac risk factors were seen in 6.3%. Perioperative blood transfusions occurred in 32.1%. The 30-day post-operative complication rate was 15.8%, reoperation 6.8%, and readmission 15.3%. After multivariate analysis, perioperative blood transfusions (OR 3.94; p < 0.01) and major cardiac risk factors (OR 7.82; p < 0.01) were found to increase the risk of a complication. Perioperative blood transfusion (OR 4.71; p = 0.01) was associated with an increased risk of reoperation. Readmission risk was increased by prematurity (OR 3.88; p = 0.04) and 30-day complication event (OR 4.09; p = 0.01). After propensity matching, perioperative blood transfusion was associated with an increase in complications (p < 0.01) and length of stay (p < 0.01). Major cardiac risk factors and perioperative blood transfusions increase the risk of post-operative complications in children undergoing the Kasai procedure. Further research is warranted in the perioperative use of blood transfusions in this population. IV.

Inflammatory pseudotumor (IP) is an unusual cause of chronic abdominal pain in children. The management of these lesions is complicated by controversies surrounding their appropriate classification and the numerous alternate names with which they are described. Successful treatment requires careful radiologic and pathologic evaluation to distinguish IPs from other lesions, along with complete surgical resection. We present the case of a 15-year-old boy with IP and review the literature in an attempt to simplify the description of these tumors.

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

Extralobar pulmonary sequestration (EPS) can occasionally be found incidentally in congenital diaphragmatic hernia (CDH). Extralobar pulmonary sequestration usually arises in the chest or the abdomen; rarely in the diaphragm. We report a neonatal case of antenatally diagnosed CDH associated with intradiaphragmatic EPS.

Hemolytic uremic syndrome (HUS) consists of an acute onset of microanglopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. HUS-associated colitis can be seen in up to 100% of patients and is usually associated with severe abdominal pain and distention. Colonic perforation is a complication of HUS that has a reported incidence of 1%–2%, and although there are several case reports in the literature describing perforation of the colon, it is still very difficult to discern the abdominal symptoms associated with HUS colitis from perforation. Four cases of colonic perforation are reported here from a consecutive series of 57 patients, in which a trend in the length of time from the onset of symptoms of HUS to colonic perforation was determined. A review of the literature for cases of HUS-associated colonic perforation was also performed. The time from the onset of HUS symptoms to colonic perforation in our series was similar to that found in the literature review (11 ± 5 vs 14 ± 8 days). Awareness that this complication has a tendency to occur towards the end of the 2nd week during the course of HUS is essential to avoid an unnecessary and untimely surgical intervention.

Normal development of the fetal diaphragm requires muscularization of the diaphragm as well as the structural integrity of its underlying connective tissue components. Developmental mutations that inhibit the formation of extracellular matrix (ECM) have been shown to result in congenital diaphragmatic hernia (CDH). Copper (Cu) is an important element during diaphragm morphogenesis by participating in cross-linking of collagen and elastin fibers. Cu transport is strictly regulated by two membrane proteins: Cu-uptake transporter 1 (CTR1) and the Cu-efflux pump ATP7A. Animals lacking Cu-dependent enzymes exhibit abnormal connective tissue with diaphragmatic defects. However, the molecular basis of disruptions in Cu-mediated ECM formation in CDH remains unclear. We designed this study to investigate the hypothesis that diaphragmatic expression of CTR1 and ATP7A is decreased in the nitrofen-induced CDH model. Timed-pregnant rats were exposed to either nitrofen or vehicle on gestational day 9 (D9), and fetuses were harvested on selected time-points D15 and D18. Microdissected fetal diaphragms (n = 48) were divided into control and nitrofen-induced CDH samples (n = 12 per experimental group and time-point). Diaphragmatic gene expression levels of CTR1 and ATP7A were analyzed by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed to evaluate CTR1 and ATP7A protein expression in fetal diaphragms, which was combined with specific rhodanine staining to determine diaphragmatic Cu content. Relative mRNA levels of CTR1 and ATP7A were significantly reduced in diaphragms of nitrofen-exposed fetuses on D15 (0.06 ± 0.02 vs. 0.18 ± 0.08; p < 0.05 and 0.04 ± 0.02 vs. 0.08 ± 0.02; p < 0.05) and D18 (0.10 ± 0.03 vs. 0.17 ± 0.02; p < 0.05 and 0.09 ± 0.03 vs. 0.16 ± 0.04; p < 0.05) compared to controls. Immunoreactivity of CTR1 and ATP7A was markedly decreased in the malformed diaphragmatic ECM of nitrofen-exposed fetuses on D15 and D18, which was associated with a significantly decreased diaphragmatic Cu content on D15 (7.22 ± 2.91 vs. 17.50 ± 3.09; p < 0.05) and D18 (17.60 ± 3.54 vs. 28.20 ± 4.63; p < 0.05) compared to controls. Reduced diaphragmatic expression of CTR1 and ATP7A during morphogenesis may impair the activity of Cu-dependent enzymes and thus contribute to defective ECM during diaphragmatic development.

Patients with sickle cell disease (SCD) are predisposed to infections. There is a paucity of recent information on the incidence of post-splenectomy infectious complications in these patients. The purpose of this study was to determine whether splenectomy increases infectious complications in SCD. Twenty-nine patients with SCD had splenectomy for sequestration crises at our hospital between 1988 and 1992; 16 of them received all of their follow-up care at our institution. These 16 charts were reviewed for infectious-related admissions, hospital days, days of IV antibiotics, positive cultures, and episodes of sepsis. For each patient, these parameters in the pre- and postoperative period were compared and expressed as number per year. The mean age at time of splenectomy was 2.5 ± 0.4 years and the mean follow-up was 4.5 ± 0.4 years. There was no significant difference in the pre- and postoperative periods for admissions, hospital days, days of IV antibiotics, positive cultures, or episodes of sepsis per year. There were also no operative deaths. The incidence of pre-splenectomy sepsis was 0.04 ± 0.03 episodes per year compared to 0.09 ± 0.04 (P = ns) episodes/year after splenectomy. Sepsis occurred at an average of 20.8 (range 2–30) months postoperatively; Streptococcus pneumoniae was the most common causative organism. The total mortality after splenectomy in SCD patients was 3.4% (1/29) over a nearly 5-year period. Although infections are common in children with SCD, there was no increase in infections or episodes of sepsis in SCD patients who underwent splenectomy.

We report our experience with cutaneous vesicostomies performed in 55 children aged less than 3 months to 8 years as a means of temporary diversion. Renal function improved or remained normal in 53 patients and hydronephrosis improved in 53 of 54 in whom it was present pre-operatively. Mucosal prolapse requiring revision occurred in 3 children. Spontaneous vesicostomy closure and stomal stenosis occurred in 2 patients each. Significant cellulitis occurred in 1 patient. Five children have required higher diversion; 35 have undergone undiversion an average of 24 months after vesicostomy creation. A vesicostomy is simple to construct and easy to manage, with minimal complications. The operation does not compromise future continence and is easily reversible.