World Journal of Pediatric Surgery最新文献

Abstract:

Background: Necrotizing enterocolitis (NEC) is associated with increased neurodevelopmental impairment. Gut-brain interactions through the brainstem may be central to NEC-related microglia-driven neuroinflammation. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has intestinal protective properties and is a potential therapy for NEC. The aim of this study is to test the hypothesis that HB-EGF in pregnant rats reduces both NEC incidence and proinflammatory changes in the brainstem microglia of newborn rats.

Methods: We compared four experimental groups, HB-EGF⁺/NEC^-, HB-EGF^-/NEC^-, HB-EGF⁺/NEC⁺ and HB-EGF^-/NEC⁺, depending on whether HB-EGF was given prenatally, and whether the newborn rats underwent the NEC induction protocol. We stained brainstem microglia and performed fractal analyses to provide objective measures of morphological changes.

Results: NEC incidence was lower in the HB-EGF⁺/NEC⁺ group (n=64, p<0.005) than in the HB-EGF^-/NEC⁺ group. Brainstem microglia of breastfed rats had a larger cell area, perimeter, roughness, and less circularity compared with smaller, denser, compact cells in the NEC⁺ pups (p<0.0001, n=320 cells). HB-EGF⁺/NEC⁺ and HB-EGF^-/NEC⁺ pups had similar-appearing microglia.

Conclusions: Prenatal HB-EGF treatment reduces NEC incidence in neonatal rats. NEC-related proinflammatory changes are seen in microglial cells present in crucial centers controlling the gut-brain pathway. HB-EGF has a growth-promoting effect on healthy microglia in the offspring but does not avert microglial activation in the brainstem of newborn rats with NEC.

The practice, art and science of surgical pathology for disease entities evolves continuously. Standards for diagnosis and management of Hirschsprung disease (HSCR), variants and related dysmotility disorders are no exception. Morphologic parameters that withstand the test of time still fulfill aims for 'personalized' and precision medicine. The expert management of these patients relies on critical points of interaction between pathologists, gastroenterologists and pediatric surgeons for: (1) diagnosis or exclusion within the HSCR spectrum, (2) intraoperative determination of the extent of aganglionosis and HSCR transition zone features, (3) validation of optimal proximal margin for primary pull-through or ostomy site and (4) confirmation of specimen adequacy and diagnoses in the event of postoperative dysfunction or need of outside case material review for referred patients. Additional roles in pathologists' scope include specimen triage for HSCR specialized ancillary procedures and other intestinal motility disorders, and in contributing surgical specimens for research collaboratives. This review highlights the cumulative experience of the authors' integrated practice model for patients with HSCR and explores the approach for patients with prototypical or challenging presentations and management. It is intended primarily for pediatric surgeons and gastroenterologists who seek to assimilate surgical pathology practice based on available relevant HSCR literature, recognizing that each patient poses a unique constellation of functional manifestations and histopathologic expression of Hirschsprung Disease.

10.1136/wjps-2025-001032.video016376273975112BMJ Journals Video Playerwjps2025001032media1.

Background: Hirschsprung's disease (HSCR) is a functional obstruction of the gastrointestinal tract characterized by abdominal distension, constipation, and vomiting. The protein zonulin serves as a biomarker for intestinal permeability. We sought to explore the changes in plasma zonulin levels in patients with HSCR and to assess its predictive role in the development of postoperative Hirschsprung-associated enterocolitis (HAEC).

Methods: There are 60 patients with HSCR were recruited for this study, categorized into short-segment disease (S-HSCR) (n=33), long-segment disease (L-HSCR) (n=15), and total colonic aganglionosis (TCA) (n=12). Venous blood samples were taken from all participants before and after pull-through surgery. Plasma concentrations of zonulin were determined using an ELISA. Immunohistochemistry (IHC) analysis was conducted to evaluate the expression of zonula occludens-1 (ZO-1) and occludin in colonic tissues. Hematoxylin and Eosin stained (H&E-stained) sections were used to evaluate the degree of inflammation in the dilated (ganglionic) segment. Postoperative outcomes were assessed through a combination of online questionnaires and telephone interviews. Diagnostic threshold for HAEC was based on clinical symptom sets and the HAEC scoring system developed previously.

Results: Preoperative zonulin levels in patients with TCA were statistically lower than those in patients with S-HSCR (p=0.008) and L-HSCR (p=0.028). The incidence of postoperative HAEC was 16.7%, 57.1%, and 14.3% in TCA, L-HSCR, and S-HSCR groups, respectively. Patients who experienced an increase in plasma zonulin levels of more than 1.5 times those on the first day after surgery had a higher risk of developing HAEC (p=0.005). IHC staining further confirmed decreased expression of ZO-1 and occludin in colonic tissues of patients with HSCR who experienced postoperative HAEC.

Conclusion: Preoperative zonulin levels were lowest in the TCA group. The change in zonulin levels on the first day after surgery can serve as a useful indicator for predicting the risk of postoperative HAEC occurrence.

Biliary atresia (BA) is a rare and devastating cholangiopathy with an incidence of 1:15 000-20 000 in Europe. There is a consensus that BA and related rare diseases should be managed at centers of expertise. However, current BA care in Europe is heterogeneous, with decentralized treatment in the majority of European countries. The varying outcomes in Europe, referring to overall and native liver survival following Kasai procedure, have led to an ongoing discussion on international clinical and scientific collaborations. In 2017, the European Reference Networks (ERN) have been launched by the European Commission to improve the treatment of rare diseases. The ERNs bring together centers of expertise, which undergo qualification and monitoring processes. The European Reference Network on Rare Hepatological Diseases (ERN RARE-LIVER) represents a network of medical practitioners and patient representatives with the goal of improving care for rare liver diseases with BA as one key disorder. Exchange programs, digital case discussions and the endorsement of clinical studies are part of the RARE-LIVER agenda, including the prospective European Biliary Atresia Registry (EBAR), which has recently been launched. Such sustainable joint European efforts and strategies are crucial to improve BA outcomes in the short term and long term.

Objective: This study investigates the tumor-suppressive role of microRNA (miR)-205-5p in neuroblastoma (NB) and evaluates exosome-mediated delivery of miR-205-5p as a therapeutic strategy.

Methods: miR-205-5p expression in NB cells was quantified via quantitative reverse transcription PCR. Functional assays (CCK-8, colony formation, wound healing, Transwell) assessed proliferation, migration, and invasion. Bioinformatic tools and dual-luciferase assays identified miR-205-5p/Runt-related transcription factor 2 (RUNX2) binding. RUNX2 rescue experiments reversed miR-205-5p effects. Exosomes from SH-SY5Y cells transfected with miR-205-5p mimics/NC (negative control) lentiviruses were isolated, characterized, and co-cultured with recipient cells. In vivo, subcutaneous NB xenografts in nude mice were established using OE-miR-205-5p, sh-miR-205-5p, or NC lentiviral cells, followed by exosome injections to evaluate tumor growth.

Results: miR-205-5p was downregulated in NB cells. Its overexpression suppressed proliferation, migration, invasion, and tumor growth in vitro and in vivo. RUNX2 was confirmed as a direct target; its restoration reversed miR-205-5p-mediated inhibition. Exosomes efficiently delivered miR-205-5p to recipient cells, downregulating RUNX2 and impairing malignant behaviors. In mice, miR-205-5p-enriched exosomes significantly inhibited tumor progression.

Conclusions: Exosome-encapsulated miR-205-5p inhibits NB progression by targeting RUNX2, highlighting its potential as a novel therapeutic modality.

Background: Hepatoblastoma (HB) is the most common malignant liver tumor in children. However, the optimal duration of preoperative chemotherapy remains unclear, particularly regarding its impact on tumor size and proximity to critical blood vessels.

Methods: This retrospective study analyzed 24 patients with HB treated at Shanghai Xinhua Hospital from 2006 to 2022. All patients underwent neoadjuvant chemotherapy. Tumor size and distances to key vasculature, including the confluence of hepatic veins (COHV) and the portal vein bifurcation (PVB), were measured using CT scans after two and four chemotherapy cycles. Statistical analyses assessed changes in these parameters.

Results: The maximum tumor diameter decreased significantly after two cycles of chemotherapy (11.9±2.5 cm to 8.3±2.0 cm, p<0.0001) and further to 7.1±1.9 cm after four cycles. The distance to COHV (DSTCOHV) increased from 0.5±0.9 cm to 1.4±1.2 cm after two cycles (p<0.001) and to 1.6±1.4 cm after four cycles (p<0.0001). However, for distance to PVB (DSTPVB), the increase was more modest, from 0.1±0.3 cm to 0.6±0.5 cm after two cycles (p<0.001) and to 0.8±0.6 cm after four cycles (p<0.0001). Patients with limited response after two cycles gained minimal benefit from additional chemotherapy.

Conclusions: Preoperative chemotherapy significantly reduces tumor size and improves surgical margins, particularly during the first two cycles. For tumors near PVB, prolonged chemotherapy may offer limited benefit, emphasizing the need for individualized treatment planning.

Biliary atresia (BA) may be characterized as an obliterative cholangiopathy presenting in the newborn period with conjugated jaundice, pale stools, and dark urine. It is usually thought of as an isolated anomaly in otherwise normal infants. However, in a minority, other anomalies may be present, some as defined syndromes, others as a non-random association. The most fully characterized is that of the biliary atresia splenic malformation syndrome seen in about 10% of European and North American series with a typical array of unusual extrahepatic anomalies (e.g., situs inversus, polysplenia, absence of the inferior vena cava, and a preduodenal portal vein). Its underlying genetic background is obscure in most cases. There are other syndromes with a definite link to BA, such as Cat-Eye syndrome and Kabuki syndrome, and still others that may have a link, such as Zimmerman-Laband syndrome.

Background: Wound dehiscence is a known complication after anorectal malformations (ARMs) surgery. The aim was to evaluate if a standardized post-posterior sagittal anorectoplasty (PSARP) treatment program decreased wound dehiscence rates.

Methods: Wound dehiscence rates within 30 days post-PSARP were compared in a case-control single-center study between patients with a standardized post-PSARP treatment 2017-2023, and a cohort with a non-standardized management 2001-2016. The standardized post-PSARP program comprised a minimum of 3 days of: intravenous antibiotics imipenem+cilastatin (with optional subsequent oral amoxicillin+clavulanic acid+metronidazole), fasting after primary PSARP (no stoma), urinary catheter and regular wound cleansing.

Results: A total of 149 patients (61% males) with various ARM subtypes were included of which 51% were reconstructed with stomas. Overall, wound dehiscence developed in 8 of 59 patients (14%) in the standardized post-PSARP program group versus 28 of 90 patients (31%) in the control group (p=0.014). In primary PSARPs (no stoma, 59% males), wound dehiscence developed in 6 of 33 patients (18%) in the standardized post-PSARP program group versus 17 of 40 patients (43%) in the control group (p=0.026).

Conclusion: Wound dehiscence rates may be reduced using a standardized post-PSARP treatment program.

Biliary atresia (BA) is a lethal hepatobiliary disorder in infants characterized by progressive destruction of intrahepatic and extrahepatic bile ducts and obstructive biliary fibrosis. Although hepatic portoenterostomy (Kasai procedure) can temporarily reconstruct bile drainage, persistent postoperative inflammation and hepatic fibrosis still lead to over half of the patients requiring liver transplantation for survival. Epidemiological studies reveal significant geographical and ethnic disparities in BA incidence, suggesting that genetic susceptibility plays an indispensable role in its pathogenesis. This article is based on the multidimensional interactive pathogenic hypothesis of BA of 'embryonic developmental abnormalities, perinatal injury, and dysregulated immune microenvironment' in addition to progressive hepatobiliary fibrosis. We review advances in the genetic and epigenetic regulatory networks of BA with the aim of providing ideas for future genetic research on this disease.