Changes of smooth muscle contractile filaments in small bowel atresia

AIM: To investigate morphological changes of intestinal smooth muscle contractile fibres in small bowel atresia patients. METHODS: Resected small bowel specimens from small bowel atresia patients (n = 12) were divided into three sections (proximal, atretic and distal). Standard histology hematoxylin-eosin staining and enzyme immunohistochemistry was performed to visualize smooth muscle contractile markers α-smooth muscle actin (SMA) and desmin using conventional paraffin sections of the proximal and distal bowel. Small bowel from age-matched patients (n = 2) undergoing Meckel's diverticulum resection served as controls. RESULTS: The smooth muscle coat in the proximal bowel of small bowel atresia patients was thickened compared with control tissue, but the distal bowel was unchanged. Expression of smooth muscle contractile fibres SMA and desmin within the proximal bowel was slightly reduced compared with the distal bowel and control tissue. There were no major differences in the architecture of the smooth muscle within the proximal bowel and the distal bowel. The proximal and distal bowel in small bowel atresia patients revealed only minimal differences regarding smooth muscle morphology and the presence of smooth muscle contractile filament markers. CONCLUSION: Changes in smooth muscle contractile filaments do not appear to play a major role in postoperative motility disorders in small bowel atresia

Adenomyoma of the small intestine a rare pathological lead point for intussusception in an infant

INTRODUCTION: Intussusception is a typical abdominal emergency in early childhood. CASE DESCRIPTION: We report a case of an infant in the typically affected age group with an intussusception triggered by a rare benign intramural intestinal adenomyoma as a pathological lead point. The infant had the typical symptoms of a recurrent idiopathic ileocolic intussusception. DISCUSSION AND EVALUATION: Idiopathic intussusception is frequent in the infant age group. Contrary to that, reports on pathological lead points for intussusceptions are sparse in the toddler age. CONCLUSIONS: That case illustrates that even in intussusceptions in the typically affected age group, it is important to be aware of pathological lead points, especially if the intussusceptions are recurrent

Injury incidence in elite youth field hockey players at the 2016 European Championships

Despite being an essential consideration when deciding rule changes, injury prevention strategies, and athlete development models, there is little epidemiological data of U18 field hockey player injuries–something explicitly referred to in the 2015 International Olympic Committee’s Consensus Statement on Youth Athlete Development. The aim of this study was to quantify incidence and characteristics of injuries in elite youth field hockey players during a major international tournament. Standardized reporting forms detailing time, location on pitch, mechanism and anatomical location of injury were completed for new musculoskeletal conditions resulting in a time stoppage by the umpire and where a player was noticeably affected by an injury for up to 20 s regardless of time stoppage. Injury incidence was 1.35 and 2.20 injuries/match or 53 and 86 injuries per 1000 player match hours for boys (B) and girls (G) respectively; girls were over three times more likely to have a minor injury. Most injuries were contusions due to being hit by the ball or stick (B: 12, G: 27), with high numbers of injuries to the torso (B: 8) and head/face (G: 7). Injuries during the penalty corner (B: 3, G: 4) were to the lower limb and hand, and boys were less likely to wear facial protection (B: 65.9%, G: 86.4%). Results form an essential initial dataset of injuries in U18 field hockey players. Current reporting protocols under-report injuries and must be addressed by the international governing body. The high number of head/face injuries, particularly in females, requires further investigation

Decentralized surgery of abdominal wall defects in Germany

Purpose: Neonatal surgery for abdominal wall defects is not performed in a centralized manner in Germany. The aim of this study was to investigate whether treatment for abdominal wall defects in Germany is equally effective compared to international results despite the decentralized care. Methods: All newborn patients who were clients of the major statutory health insurance company in Germany between 2009 and 2013 and who had a diagnosis of gastroschisis or omphalocele were included. Mortality during the first year of life was analysed. Results: The 316 patients with gastroschisis were classified as simple (82%) or complex (18%) cases. The main associated anomalies in the 197 patients with omphalocele were trisomy 18/21 (8%), cardiac anomalies (32%) and anomalies of the urinary tract (10%). Overall mortality was 4% for gastroschisis and 16% for omphalocele. Significant factors for non-survival were birth weight below 1500 g for both groups, complex gastroschisis, volvulus and anomalies of the blood supply to the intestine in gastroschisis, and female gender, trisomy 18/21 and lung hypoplasia in omphalocele. Conclusions: Despite the fact that paediatric surgical care is organized in a decentralized manner in Germany, the mortality rates for gastroschisis and omphalocele are equal to those reported in international data

Global Initiative for Children’s Surgery (GICS) Pediatric Trauma Care Initiative: A Call for a Comprehensive Approach to a Global Problem

Introduction: Trauma is a major problem which has a significant health, social, and economic impact. Particularly, pediatric trauma carries substantial mortality and morbidity. This is a great concern for subspecialized general and pediatric surgeons. Therefore, a global initiative for pediatric trauma care is warranted and should be initiated. Aim: The international association “Global Initiative for Children’s Surgery” (GICS) would like to propose and organize a children’s trauma care (CTC) initiative. This initiative should comprehensively address pediatric trauma management globally, especially in low- and middle-income countries (LMICs). The initiative seeks to achieve a structured cooperation and collaboration with respective sister organizations and local stakeholders. Methods: The initiative will address these relevant aspects: 1. first aid; 2. prehospital primary trauma care; 3. hospital primary trauma care; 4. advanced care (ATLS); 5. diagnostic facilities; 6. operation room (OR) equipment; 7. specialized surgical services; 8. rehabilitation; 9. registry, research, and auditing; 10. specialization in pediatric trauma; 11. capacity and confidence building in pediatric trauma; 12. prevention. The GICS CTC provided activities have been recorded and evaluated in a structured manner. This statement paper is based on data of a narrative review as well as expert opinions. Results: The Trauma Working Group of GICS provided specialized trauma prevention leaflets available for translation to different languages. A one-day children’s primary trauma course has been designed to be delivered at the physical GICS meetings. Exercising advocacy, the group addressed several meetings on prevention of pediatric trauma, which included the 75th United Nations General Assembly (UNGA) (2020), GICS IVth meeting in Johannesburg (2020), Norwich (UK) Joint SPRINT Symposium on Pediatric Surgery for Pediatricians (2021), the second online Pan African Pediatric Surgical Association (PAPSA) meeting (2021), the seventh World Congress of the World Federation of Associations of Pediatric Surgeons (WOFAPS) in Prague (2022), and GICS pediatric trauma webinar (2023). Additionally, the working group participated in the preparations of a pediatric trauma module for the World Health Organization (WHO) and published several related studies. The contents of the selected articles added relevant information to the categories stated above. Conclusions: The CTC initiative of GICS is proposed as a mean to address pediatric trauma comprehensively through a process of collaboration and advocacy with existing organizations to achieve awareness, health education, prevention, health, and training. Further, it will support the provision of suitable facilities to health institutions. The establishment of a specialization in pediatric trauma is encouraged. GICS CTC initiative aims to improve pediatric trauma care in LMICs by developing injury prevention strategies; optimizing the use of locally available resources; obtaining commitment by LMICs governments; improvement in all fields of hospital care; improvements in infrastructure, education and training, and attention to data registry and research

ERNICA guidelines for the management of rectosigmoid Hirschsprung's disease

Background Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. Aims This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. Methods Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. Results Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. Conclusion In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.Peer reviewe

ERNICA guidelines for the management of rectosigmoid Hirschsprung's disease

Background Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. Aims This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. Methods Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. Results Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. Conclusion In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.Peer reviewe

Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven by Different p53 Mutants

UNLABELLED: Missense mutations in the DNA binding domain of p53 are characterized as structural or contact mutations based on their effect on the conformation of the protein. These mutations show gain-of-function (GOF) activities, such as promoting increased metastatic incidence compared with p53 loss, often mediated by the interaction of mutant p53 with a set of transcription factors. These interactions are largely context specific. To understand the mechanisms by which p53 DNA binding domain mutations drive osteosarcoma progression, we created mouse models, in which either the p53 structural mutant p53R172H or the contact mutant p53R245W are expressed specifically in osteoblasts, yielding osteosarcoma tumor development. Survival significantly decreased and metastatic incidence increased in mice expressing p53 mutants compared with p53-null mice, suggesting GOF. RNA sequencing of primary osteosarcomas revealed vastly different gene expression profiles between tumors expressing the missense mutants and p53-null tumors. Further, p53R172H and p53R245W each regulated unique transcriptomes and pathways through interactions with a distinct repertoire of transcription factors. Validation assays showed that p53R245W, but not p53R172H, interacts with KLF15 to drive migration and invasion in osteosarcoma cell lines and promotes metastasis in allogeneic transplantation models. In addition, analyses of p53R248W chromatin immunoprecipitation peaks showed enrichment of KLF15 motifs in human osteoblasts. Taken together, these data identify unique mechanisms of action of the structural and contact mutants of p53. SIGNIFICANCE: The p53 DNA binding domain contact mutant p53R245W, but not the structural mutant p53R172H, interacts with KLF15 to drive metastasis in somatic osteosarcoma, providing a potential vulnerability in tumors expressing p53R245W mutation

Genome-wide identification of disease-causing copy number variations in 450 individuals with anorectal malformations

Anorectal malformations (ARM) represent a spectrum of rare malformations originating from a perturbated development of the embryonic hindgut. Approximately 60% occur as a part of a defined genetic syndrome or within the spectrum of additional congenital anomalies. Rare copy number variations (CNVs) have been associated with both syndromic and non-syndromic forms. The present study represents the largest study to date to explore the contribution of CNVs to the expression of ARMs. SNP-array-based molecular karyotyping was applied in 450 individuals with ARM and 4392 healthy controls. CNVs were identified from raw intensity data using PennCNV. Overlapping CNVs between cases and controls were discarded. Remaining CNVs were filtered using a stringent filter algorithm of nine filter steps. Prioritized CNVs were confirmed using qPCR. Filtering prioritized and qPCR confirmed four microscopic chromosomal anomalies and nine submicroscopic CNVs comprising seven microdeletions (del2p13.2, del4p16.2, del7q31.33, del9p24.1, del16q12.1, del18q32, del22q11.21) and two microduplications (dup2p13.2, dup17q12) in 14 individuals (12 singletons and one affected sib-pair). Within these CNVs, based on their embryonic expression data and function, we suggest FOXK2 , LPP , and SALL3 as putative candidate genes. Overall, our CNV analysis identified putative microscopic and submicroscopic chromosomal rearrangements in 3% of cases. Functional characterization and re-sequencing of suggested candidate genes is warranted.Deutsche Forschungsgemeinschaft (German Research Foundation) https://doi.org/10.13039/501100001659BONFOR grant O-120.0001 and Herbert-Reeck foundation (2019).Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation) https://doi.org/10.13039/501100003042Eva Luise und Horst Köhler Stiftung https://doi.org/10.13039/501100007952BONFOR grant O-149.012

Malignant transformation and tumour recurrence in sacrococcygeal teratoma: a global, retrospective cohort study

Introduction: Sacrococcygeal teratoma (SCT) is a rare congenital tumour. The risk of malignancy and recurrence is not well defined. Previous studies are small and report differing conclusions about the timing of surgery and the duration of follow-up. The authors studied the risk of malignant transformation and SCT recurrence after surgery to address these gaps. Methods: This was a global retrospective cohort study. Data of consecutive SCT patients was obtained from 145 institutes in 62 countries. Malignant transformation, defined as malignancy at initial resection, malignant recurrence or death due to malignancy, and its risk factors were analysed. Results: Of the 3612 included patients, 3407 entered analysis. The risk of malignant transformation of the initial tumour was 3.3, 5.1, 10.1, and 32.9% at age 3 months, 6 months, 1 year, and 2 years, respectively. After 6 years, the censored risk of malignancy (64%) did not further increase. Recurrent SCT was diagnosed in 349 (10.2%) children with 126 (36.1%) malignant recurrences. Risk factors for recurrence were Altman type II [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.2-2.2], Altman type III (OR: 1.6, 95% CI: 1.2-2.3), initial immature histology (OR: 1.9, 95% CI: 1.4-2.6), and initial malignant histology (OR: 4.0, 95% CI: 2.9-5.4). Conclusion: The risk of malignancy at initial resection in SCT increases with age reaching a plateau at 6 years of age. Recurrence after resection occurred in 10% of patients and 36% of these were malignant at that time. Altman type II or type III, and immature or malignant histology were associated with recurrence. Level of evidence: Level III