Pediatric Surgery International最新文献

Purpose: This study aimed to investigate the expression of cluster of differentiation 7 (CD7) in hepatoblastoma (HB) and its potential use as a novel biomarker of HB.

Methods: CD7 expression was investigated in human HB samples at the gene level by bulk, single-cell RNA sequencing, and spatial transcriptomic analyses, in addition to the protein level by immunohistochemical (IHC) staining. CD7 gene expression-based survival analysis was also conducted, along with gene set enrichment analysis (GSEA) of the CD7-SECTM1 receptor-ligand gene pair.

Results: CD7 was differentially expressed in human HB at both the gene level by various bioinformatics analyses, and the protein level by IHC, with remarkably higher expression levels in embryonal HB. Conversely, CD7 was not expressed in other primary adult liver tumors. CD7^high HB cases showed poorer 5-year event-free survival (P = 0.016), and GSEA demonstrated that CD7 is linked to the embryonal MYCN transcription factor, as were protumor kinases such as JAK3, and marginally MAPK14 and MAPK3.

Conclusion: CD7 is expressed in human HB, especially the embryonal histological subtype, and appears to be linked to tumor progression and poor clinical outcomes. Nevertheless, CD7-targeted chimeric antigen receptor T cells could be proposed as a promising immunotherapy for embryonal HB.

Purpose: To investigate vasoactive intestinal peptide (VIP) expression and distribution in fetal Sprague-Dawley (SD) rat lung with congenital diaphragmatic hernia (CDH). Assess the impact of VIP analog Aviptadil on CDH-associated lung hypoplasia.

Methods: CDH was induced in pregnant SD rats by nitrofen gavage on E9.5. The CDH + VIP group received Aviptadil via tail vein from E10.5. Lung development was assessed by hematoxylin and eosin (HE) staining. VIP, α-SMA, and CD31 were evaluated by immunofluorescence (IF). VIP mRNA and protein levels were quantified by RT-qPCR and Western blotting.

Results: The CDH group exhibited a significantly lower lung index compared to the control group (P < 0.001), with no significant difference observed between the CDH and CDH + VIP groups. Compared to controls, VIP expression in CDH lungs was significantly downregulated at both the mRNA (P = 0.049) and protein levels (P = 0.049). HE staining revealed mature alveolar structures in the control group, whereas the CDH group showed disrupted pulmonary architecture. Partial improvement was observed in the CDH + VIP group. IF analysis indicated that VIP was predominantly localized in the bronchi. VIP fluorescence intensity was significantly decreased in the CDH group compared to both the control group (P = 0.002) and the CDH + VIP group (P = 0.005), while no significant difference was found between the CDH + VIP and control groups. α-SMA fluorescence was primarily localized to pulmonary arterioles and bronchial smooth muscle. Compared to the control group, α-SMA expression was significantly upregulated in the CDH group (P < 0.001). The CDH + VIP group showed a significant reduction in α-SMA expression compared to the CDH group (P = 0.026), with no significant difference from the control group. CD31 was mainly localized to the vascular endothelium. CD31 fluorescence intensity was markedly increased in the CDH group compared to both the control (P < 0.001) and CDH + VIP groups (P < 0.001). The CDH + VIP group also had significantly higher CD31 levels than the control group (P = 0.005).

Conclusion: This study revealed that VIP is downregulated in CDH lungs. In this nitrofen-induced SD rat model, Aviptadil partially restored VIP levels and was associated with attenuation of vascular remodeling and alveolar dysplasia, suggesting a possible therapeutic role in CDH-related pulmonary hypoplasia that warrants further investigation.

Purpose: Necrotizing enterocolitis (NEC) is a severe neonatal disease marked by intestinal injury, and epithelial damage has been linked to ferroptosis. This study aimed to determine the protective effect of Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, on NEC-associated intestinal injury.

Methods: NEC was induced in mouse pups via formula feeding, hypoxia, and lipopolysaccharide exposure. Fer-1 (5 mg/kg) was administered intraperitoneally on postnatal days 6 and 8. Intestinal tissues were analyzed for morphological injury, epithelial proliferation (Ki67), ferroptosis markers (Gpx4 and Tfr1), and lipid peroxidation (4-HNE). Human NEC intestinal organoids derived from surgical samples were treated with Fer-1 (2 µM) for 48 h. Levels of ferrous ion (FerroOrange), lipid peroxide (BODIPY), and reactive oxygen species (DCFDA) were measured.

Results: Fer-1 significantly reduced NEC-induced epithelial injury in mice, leading to improved intestinal morphology and increased epithelial proliferation, as indicated by elevated Ki67 expression. The protective effect was associated with reduced ferroptosis, demonstrated by upregulated Gpx4 expression and decreased levels of Tfr1 and 4-HNE. Similarly, in human NEC organoids, Fer-1 significantly reduced the accumulation of ferrous ions, lipid peroxides, and ROS.

Conclusion: Fer-1 effectively protects against NEC-induced intestinal injury by inhibiting ferroptosis and reducing oxidative stress. These findings highlight its potential as a novel therapeutic strategy for managing intestinal damage in NEC.

Purpose: Intestinal neuronal dysplasia (IND) features abnormal enteric nervous system (ENS) development and symptom overlap with Hirschsprung's disease, yet fetal-stage mechanisms remain unclear. We established a Sox10-Venus⁺/Ncx^⁻/⁻ mouse model of IND, enabling fluorescent labeling of enteric neural crest cells (ENCCs) to test the hypothesis whether neuronal/glial differentiation abnormalities arise during early fetal stages.

Methods: ENCCs were isolated from embryonic day 13.5 (E13.5) fetal gut of Sox10-Venus⁺/Ncx^⁻/⁻ (n = 6) and Sox10-Venus⁺/Ncx^⁺/⁺ (n = 6) embryos, dissociated, and cultured under non-adherent conditions for 14 days to generate neurospheres. Neurosphere diameter and the proportion of SOX10⁺ cells were measured using epifluorescence microscopy. Differentiation on day 14 was assessed by immunofluorescence for TUJ1 (neuronal) and S100β (S100B, glial) markers.

Results: Ncx^⁻/⁻ neurospheres were significantly larger than controls on days 5 and 10, with no significant difference on day 14. The proportion of SOX10⁺ cells remained higher through day 10. On day 14, Ncx^⁻/⁻ neurospheres exhibited a lower proportion of TUJ1⁺ cells, preserved S100β⁺ cell proportions, and disrupted spheroid organization with heterogeneous marker distribution.

Conclusion: These findings demonstrate that Ncx deficiency leads to abnormal ENS development beginning during the fetal period, providing a mechanistic basis for postnatal hyperganglionosis and validating this model for studying IND pathogenesis.

Objective: To investigate the efficacy and safety of ultrasound-guided hydrostatic enema reduction in treating recurrent intussusception in children.

Methods: Medical records of patients with recurrent intussusception treated by ultrasound-guided hydrostatic enema reduction at Wuhan Children's Hospital from July 2019 to May 2024 were retrospectively analyzed. Patient gender, age, recurrence frequency, and reduction success rates were observed.

Results: From July 2019 to May 2024, a total of 3,084 children underwent ultrasound-guided hydrostatic reduction at Wuhan Children's Hospital. Of these, 2,961 cases achieved successful reduction (success rate: 96.0%) and 123 cases experienced reduction failure (failure rate: 4.0%). During hospitalization, 215 patients developed recurrence (recurrence rate: 7.3%). These 215 patients with recurrence were enrolled in the present study, including 156 males and 59 females, aged 0.59-10.42 years (mean 3.04 years). The number of recurrences during hospitalization ranged from 1 to 9 times (average 1.73 times). The distribution of recurrence frequency was as follows: 143 patients (66.5%) experienced 1 recurrences, 32 patients (14.9%) had 2 recurrences, 19 patients (8.8%) had 3 recurrences, and 21 patients (9.8%) had 4 or more recurrences. All patients underwent successful ultrasound-guided hydrostatic enema reduction without significant secondary factors identified, and none required surgical exploration.

Conclusion: Ultrasound-guided hydrostatic enema reduction is safe and effective for recurrent intussusception in children. In the absence of obvious secondary factors, enema reduction may be considered as a preferred first-line treatment for recurrent intussusception to avoid unnecessary surgical exploration.

Purpose: This study aimed to develop a nomogram to predict the risk of postoperative anastomotic stricture (AS) after choledochal cyst excision in pediatric patients.

Methods: A retrospective analysis was conducted on pediatric patients who underwent choledochal cyst excision with Roux-en-Y hepaticojejunostomy between March 2014 and December 2023. Eligible patients were divided into training and validation cohorts (8:2 ratio). Key predictors were identified using LASSO regression and multivariable logistic regression. The nomogram's performance was evaluated using the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). The model was validated in the validation cohort.

Results: A total of 1700 patients were included, of whom 32 had AS. The LASSO regression identified four independent predictors: perioperative biliary infection, anastomotic location, anastomotic diameter, and Roux-en-Y limb length (all P < 0.05). The nomogram demonstrated excellent discrimination in both the training (C-index = 0.826, 95% CI: 0.724-0.912) and the validation cohorts (C-index = 0.884, 95% CI: 0.791-0.977). Calibration curves (Hosmer-Lemeshow test, P = 0.221) and DCA confirmed its calibration and clinical utility.

Conclusion: This nomogram provides a reliable tool for predicting the risk of AS in children after choledochal cyst surgery, thereby facilitating intraoperative decision-making and optimizing postoperative surveillance to mitigate stricture-related complications. Further validation in prospective multicenter cohorts is warranted.

Purpose: Pulmonary hypertension secondary to congenital diaphragmatic hernia (CDH-PH) is a major determinant for poor outcomes and high mortality patients with CDH. Identifying risk factors for PH is critical to improve clinical management and optimize treatment approaches. The aim of this study was to investigate factors associated with the development of CDH-PH.

Methods: A systematic review of the literature was registered on PROSPERO and performed according to the PRISMA guidelines. PubMed and Medline were searched for studies published until February 2025 reporting the incidence, mortality and/or risk factors of CDH-PH in human. Studies with overlapping patient populations not meeting inclusion criteria were excluded. CDH-PH incidence was estimated using a proportional meta-analysis. Risk ratios (RRs) for risk factors were calculated using the Mantel-Haenszel method with a randoms effect model in RevMan 5.4. Results are presented as proportions or RRs with 95% confidence intervals (CIs).

Results: Of 11,618 studies, 193 full-text articles were screened, and a total of 59 articles were included. The overall incidence of CDH-PH in infants was 45% (95%CI: 40-50%), with higher risk of death in comparison to CDH newborns without PH [RR 5.04 (3.43-7.39); p < 0.05]. Risk factors for CDH-PH were: pre-operative liver herniation [RR 1.75 (1.48-2.08; p < 0.05], non-left CDH (bilateral and Right-CDH) [RR 1.20 (1.08-1.33); p < 0.05], female sex [RR 1.07 (1.04-1.09); p < 0.05], and congenital heart disease [RR 2.15 (1.48-3.12); p < 0.05].

Conclusions: We found that almost half patients with CDH suffer from PH and that CDH-PH patients have a fivefold higher risk of death in comparison to CDH patients without PH. Although the etiology of CDH-PH remains elusive, the risk factors identified may indirectly indicate that a high degree of mechanical compression on the fetal lungs contributes to vascular remodeling and predisposes to CDH-PH.