Necrotizing enterocolitis (NEC) is an inflammatory bowel disease of preterm human newborns with yet unresolved etiology. An established neonatal murine model for NEC employs oral administration of lipopolysaccharides (LPS) combined with hypoxia/hypothermia. In adult mice, feeding dextran sodium sulfate (DSS) represents a well-established model for experimental inflammatory bowel disease. Here we investigated the effect of DSS administration on the neonatal murine intestine in comparison with the established NEC model. 3-day-old C57BL/6J mice were either fed formula containing DSS or LPS. LPS treated animals were additionally stressed by hypoxia/hypothermia twice daily. After 72 h, mice were euthanized, their intestinal tissue harvested and analyzed by histology, qRT-PCR and flow cytometry. For comparison, adult C57BL/6J mice were fed with DSS for 8 days and examined likewise. Untreated, age matched animals served as controls. Adult mice treated with DSS exhibited colonic inflammation with significantly increased Cxcl2 mRNA expression. In contrast, tissue inflammation in neonatal mice treated with DSS or LPS plus hypoxia/hypothermia was present in colon and small intestine as well. Comparative analysis of neonatal mice revealed a significantly increased lesion size and intestinal Cxcl2 mRNA expression after DSS exposure. Whereas LPS administration mainly induced local neutrophil recruitment, DSS treated animals displayed increased monocytes/macrophages infiltration. Our study demonstrates the potential of DSS to induce NEC-like lesions accompanied by a significant humoral and cellular immune response in the small and large intestine of neonatal mice. The new model therefore represents a good alternative to LPS plus hypoxia/hypothermia administration requiring no additional physical stress.

Background: Pediatric minimally invasive surgery (MIS) is a standard technique worldwide. We aimed to analyze the research activity in this field. Methods: Articles on pediatric MIS (1991–2020) were analyzed from the Web of Science™ for the total number of publications, citations, journals, and impact factors (IF). Of these, the 50 most cited publications were evaluated in detail and classified according to the level of evidence (i.e., study design) and topic (i.e., surgical procedure). Results: In total, 4464 publications and 53,111 citations from 684 journals on pediatric MIS were identified. The 50 most cited papers were published from 32 institutions in the USA/Canada (n = 28), Europe (n = 19), and Asia (n = 3) in 12 journals. Four authors (USA/Europe) contributed to 26% of the 50 most cited papers as first/senior author. Hot topics were laparoscopic pyeloplasty (n = 9), inguinal hernia repair (n = 7), appendectomy, and pyloromyotomy (n = 4 each). The majority of publications were retrospective studies (n = 33) and case reports (n = 6) (IF 5.2 ± 3.2; impact index 16.5 ± 6.4; citations 125 ± 39.4). They were cited as often as articles with high evidence levels (meta-analyses, n = 2; randomized controlled trials, n = 7; prospective studies, n = 2) (IF 12.9 ± 22.5; impact index 14.0 ± 6.5; citations 125 ± 34.7; p > 0.05). Conclusions: Publications on laparoscopic pyeloplasty, inguinal hernia repair, appendectomy, and pyloromyotomy are cited most often in pediatric MIS. However, the relevant number of studies with strong evidence for the advantages of MIS in pediatric surgery is missing.

Introduction Adequate patient volume is essential for the maintenance of quality, meaningful research, and training of the next generation of pediatric surgeons. The role of university hospitals is to fulfill these tasks at the highest possible level. Due to decentralization of pediatric surgical care during the last decades, there is a trend toward reduction of operative caseloads. The aim of this study was to assess the operative volume of the most relevant congenital malformations at German academic pediatric surgical institutions over the past years. Methods Nineteen chairpersons representing university-chairs in pediatric surgery in Germany submitted data on 10 index procedures regarding congenital malformations or neonatal abdominal emergencies over a 3-year period (2015 through 2017). All institutions were categorized according to the total number of respective cases into “high,” “medium,” and “low” volume centers by terciles. Some operative numbers were verified using data from health insurance companies, when available. Finally, the ratio of cumulative case load versus prevalence of the particular malformation was calculated for the study period. Results From 2015 through 2017, a total 2,162 newborns underwent surgery for congenital malformations and neonatal abdominal emergencies at German academic medical centers, representing 51% of all expected newborn cases nationwide. The median of cases per center within the study period was 101 (range 18–258). Four institutions (21%) were classified as “high volume” centers, four (21%) as “medium volume” centers, and 11 (58%) as “low volume” centers. The proportion of patients operated on in high-volume centers varied per disease category: esophageal atresia/tracheoesophageal fistula: 40%, duodenal atresia: 40%, small and large bowel atresia: 39%, anorectal malformations: 40%, congenital diaphragmatic hernia: 56%, gastroschisis: 39%, omphalocele: 41%, Hirschsprung disease: 45%, posterior urethral valves: 39%, and necrotizing enterocolitis (NEC)/focal intestinal perforation (FIP)/gastric perforation (GP): 45%. Conclusion This study provides a national benchmark for neonatal surgery performed in German university hospitals. The rarity of these cases highlights the difficulties for individual pediatric surgeons to gain adequate clinical and surgical experience and research capabilities. Therefore, a discussion on the centralization of care for these rare entities is necessary.

Antenatal administration of extracellular vesicles from amniotic fluid stem cells (AFSC-EVs) reverses features of pulmonary hypoplasia in models of congenital diaphragmatic hernia (CDH). However, it remains unknown which lung cellular compartments and biological pathways are affected by AFSC-EV therapy. Herein, we conducted single-nucleus RNA sequencing (snRNA-seq) on rat fetal CDH lungs treated with vehicle or AFSC-EVs. We identified that intra-amniotically injected AFSC-EVs reach the fetal lung in rats with CDH, where they promote lung branching morphogenesis and epithelial cell differentiation. Moreover, snRNA-seq revealed that rat fetal CDH lungs have a multilineage inflammatory signature with macrophage enrichment, which is reversed by AFSC-EV treatment. Macrophage enrichment in CDH fetal rat lungs was confirmed by immunofluorescence, flow cytometry, and inhibition studies with GW2580. Moreover, we validated macrophage enrichment in human fetal CDH lung autopsy samples. Together, this study advances knowledge on the pathogenesis of pulmonary hypoplasia and further evidence on the value of an EV-based therapy for CDH fetuses.

Single-incision pediatric endosurgery (SIPES) allows operation through one access site, eliminating the multiple sites traditionally used. There are few large series evaluating the versatility of SIPES. The purpose of this study is to review a 5-year single-institution experience with routine SIPES use. This is an Institutional Review Board-approved retrospective analysis of prospectively collected data. All SIPES cases from March 2009 to December 2013 were included. Our database contains demographics, procedure type, operative duration, estimated blood loss, instance of added ports or conversion to open, complications, and follow-up duration. Of 1322 SIPES operations performed, most (82.1%) were appendectomies and cholecystectomies. Of 871 (66%) patients seen in follow-up, with a median duration of 26 days, 53 (6.1%) experienced postoperative complications. Forty-two cases (4.8%) were surgical-site infections, of which 4 required drainage. Less frequent complications that required operative intervention include recurrent inguinal hernia (n=4), umbilical hernia (n=3), intraabdominal abscess (n=1), bleeding (n=1), abdominal compartment syndrome (n=1), bowel obstruction (n=1), stitch granuloma (n=1), and persistent postoperative pain (n=1). Operative times and complication rates are comparable to those in prior reported multiport laparoscopic series, allowing safe integration of SIPES into the routine of a surgical practice for most common procedures.

The surgical management of patients with congenital diaphragmatic hernia (CDH) is challenging and ever changing. It requires the highest expertise not only on the surgical level but also of neonatologists and anesthesiologists. In selected patients traditional open surgery is increasingly replaced by thoracoscopic CDH repair in many centers worldwide. Despite obvious and well-described advantages of the minimally invasive approach like a shorter ventilatory time, less pain, a shorter hospital length of stay, and a better cosmesis, important controversies remain. This review discusses hot topics of minimally invasive CDH repair, such as extracorporeal membrane oxygenation, hypercapnia/acidosis, patch repair, surgical training, and recurrence.