British Association of Paediatric Surgeons International Affairs Committee: A report of international fellowships

Objective This paper describes the fellowship programme of the International Affairs Committee of the British Association of Paediatric Surgeons.Patients and methods The selection of low-income and middle-income country (LMIC) fellows from 2005 to 2016, their funding, experience, and current roles are described. Qualitative and quantitative analysis was performed. Results Thirty-eight trainees from 21 LMIC were awarded fellowships over the 11-year period. Thirty-two have completed the fellowship at time of writing, all are now in consultant positions. Obtaining a visa was the single most cited barrier to starting the fellowship. Twenty completed the questionnaire. Hundred percent felt the  fellowship had contributed to personal development and 71% had altered clinical practice subsequent to their experience. Thirty-three percent have gained research opportunities.Conclusion This evaluation supports LMIC-high-income country partnerships and highlights the benefits of fellowships to both the individual surgeon, their department and patient population.  Keywords: BAPS, fellowship, low- and middle-income country, partnershi

Management and outcomes of gastrointestinal congenital anomalies in low, middle and high income countries: Protocol for a multicentre, international, prospective cohort study

Introduction: Congenital anomalies are the fifth leading cause of death in children globally, contributing an estimated half a million deaths per year. Very limited literature exists from low and middle income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research Collaboration aims to undertake the first multicentre, international, prospective cohort study of a selection of common congenital anomalies comparing management and outcomes between low, middle and high income countries (HICs) globally.Methods and Analysis: The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung\u27s disease).Patient recruitment will be for a minimum of 1 month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre.The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of post-operative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors.Ethics and Dissemination: At the host centre, this study is classified as an audit not requiring ethical approval. All participating collaborators have gained local approval in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for open access publication in a peer reviewed journal.Trial Registration Number: NCT03666767

Developing and implementing an interventional bundle to reduce mortality from gastroschisis in low-resource settings [version 1; peer review: 1 approved, 2 approved with reservations]

Background: Gastroschisis is associated with less than 4% mortality in high-income countries and over 90% mortality in many tertiary paediatric surgery centres across sub-Saharan Africa (SSA). The aim of this trial is to develop, implement and prospectively evaluate an interventional bundle to reduce mortality from gastroschisis in seven tertiary paediatric surgery centres across SSA. Methods: A hybrid type-2 effectiveness-implementation, pre-post study design will be utilised. Using current literature an evidence-based, low-technology interventional bundle has been developed. A systematic review, qualitative study and Delphi process will provide further evidence to optimise the interventional bundle and implementation strategy. The interventional bundle has core components, which will remain consistent across all sites, and adaptable components, which will be determined through in-country co-development meetings. Pre- and post-intervention data will be collected on clinical, service delivery and implementation outcomes for 2-years at each site. The primary clinical outcome will be all-cause, in-hospital mortality. Secondary outcomes include the occurrence of a major complication, length of hospital stay and time to full enteral feeds. Service delivery outcomes include time to hospital and primary intervention, and adherence to the pre-hospital and in-hospital protocols.  Implementation outcomes are acceptability, adoption, appropriateness, feasibility, fidelity, coverage, cost and sustainability. Pre- and post-intervention clinical outcomes will be compared using Chi-squared analysis, unpaired t-test and/or Mann-Whitney U test. Time-series analysis will be undertaken using Statistical Process Control to identify significant trends and shifts in outcome overtime. Multivariate logistic regression analysis will be used to identify clinical and implementation factors affecting outcome with adjustment for confounders. Outcome: This will be the first multi-centre interventional study to our knowledge aimed at reducing mortality from gastroschisis in low-resource settings. If successful, detailed evaluation of both the clinical and implementation components of the study will allow sustainability in the study sites and further scale-up. Registration: ClinicalTrials.gov Identifier NCT03724214

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Glycosaminoglycans and inflammatory cells in the pathophysiology of neonatal necrotizing enterocolits

Fulminant neonatal necrotizing enterocolitis (NEC), is characterised by temperature instability, hypotension, disseminated intravascular coagulopathy and oliguria, all clinical manifestations of multi-system organ dysfunction. The capillary leak syndrome (CLS) is common, poses a particularly difficult management problem and is directly and indirectly responsible for many of the complications suffered by infants with this intestinal disorder. Glycosaminoglycans (GAGs) are key components of the extra-cellular matrix (ECM) and are important for structural stability, the regulation of vascular permeability and trans-endothelial inflammatory cell migration. The capillary leak phenomenon might be explained in part by matrix degradation. The primary aim of this thesis was to examine the nature and distribution of GAGs in NEC. A secondary aim was to describe the inflammatory cell infiltrate (ICI) in relation to GAGs in this disease. Histochemical experiments were performed on intestine from infants who underwent surgical resection for NEC. GAGs were detected using a cationic gold (CG) method; a 5nm gold conjugated poly-L-lysine probe at a pH of 1.5 was applied to tissue sections then developed with silver enhancer. Glycanases were employed to determine specific GAG families; sections were incubated with chondroitinase ABC or heparinase III. Control specimens from well-preserved resection margins were incubated with phosphate buffered saline. Matrix and cell surface degradation of GAGs was evident and proportionate to NEC severity. With chondroitinase ABC, GAGs in all layers of the bowel wall were digested, leaving the vascular stain intact. Whilst vascular GAGs were reduced with heparinase III, basement membrane and baso-lateral GAGs were unaffected. Inflammatory cells produce glycanases, therefore, to explore one possible mechanism of GAG degradation the cellular infiltrate in NEC was examined. The alkaline phosphatase anti-alkaline phosphatase (APAAP) method was employed. Neutrophil elastase, MAC 387, HLA-DR, CD3, CD20 and Ki67 monoclonal antibodies were used. Expression of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and E-Selectin was also determined following high temperature citration. Neutrophils were found to be restricted to the serosa in early NEC, and did not appear in the mucosa in substantial numbers until mucosal ulceration had occurred. The pattern of activation of lymphocytes and up- regulation of adhesion molecules was consistent with an immune response to antigenic stimulation in the early stages of the disease. The hypothesis was put forward that urinary GAG levels would be elevated in NEC in proportion to disease severity. Urinary GAGs were measured in both an experimental ischaemia/reperfusion (IR) model and in human new-borns with advanced NEC. Urine from human infants was assayed using a modification of this technique. In addition, the urine from infants was subjected to two-dimensional gel electrophoresis to determine specific GAG subgroups present. In the experimental model, there was no difference between animals in the IR group and controls. Similarly in human new-borns with gangrenous bowel secondary to NEC and mechanical intestinal ischaemia, there was no significant difference in the GAG/Cr when compared with controls. However, infants with intestinal ischaemia, and in particular those with confluent intestinal gangrene had abnormal quantities of heparan sulphate (HS) relative to chondroitin sulphate (CS) detected in the urine. Our immunohistochemical results support evidence of a lymphocyte driven immunopathy as an important part of the mechanisms that underlie disease progression in NEC. Furthermore, in vivo assays of urinary GAGs demonstrated abnormal HS elevation in the presence of gangrenous bowel, suggesting that this may be a useful adjunct in detecting infants with advanced disease

Flexible-Tip Laparo-Endoscopic Surgery:A Bridge to Single Port Appendicectomy in Children

Single port surgery (SPS) has been demonstrated to have some advantages over conventional laparoscopy. However, currently available port sizes may limit the application in younger children or those with a small umbilicus. Moreover, the consultant learning curve required to master single port surgery may have a negative impact on surgical training. We report the first series of children who were treated with a reduced incision technique for appendicectomy using flexible-tip laparo-endoscopic surgery (FLES). FLES was set up using one 11-mm and 2 × 5-mm bladeless ports (Ethicon XCEL™) via umbilical and low left iliac fossa incisions. A 10-mm flexible-tip laparo-endoscope was utilized. Tip angulation ensured visibility while minimising instrument clashing. A database of children undergoing FLES was kept prospectively. Demographic and peri-operative information and complications were recorded. Data are presented as medians with ranges. Between March and June 2010, 5 children (4 females) aged 9 (4-13) years underwent FLES for right iliac fossa pain. 2 procedures were performed by the admitting consultant, 3 by a supervised inexperienced laparoscopic trainee. 4 children had acute appendicitis including 1 with an inflammatory mass. Another had a haemorrhagic ovarian cyst. Appendicectomy was performed in all. The duration of surgery was 104 (93-130) min, and postoperative hospital stay was 2 (1-6) days. At 7 (5-8) months' follow-up no complications have been recorded. At follow-up, the cosmetic results were judged to be excellent in all by the children, their parents and the reviewing surgeon. FLES is an alternative to standard laparoscopy and SPS in children, and be performed effectively and safely by junior trainees. Cosmetic results are excellent. It may represent a bridge technology, particularly for younger children, until single port products and techniques more suitable for appendicectomy in this age group are available. Finally, flexible-tip technology may play a useful role as SPS evolves. © Georg Thieme Verlag KG Stuttgart · New York

GABBY: An <i> ex vivo </i> model for learning and refining the technique of preformed silo application in the management of gastroschisis

Background: Gastroschisis (GS) is a congenital full-thickness defect of the anterior abdominal wall, whose incidence is increasing. Traditional postnatal management options include primary reduction and closure under general anaesthetic or operative silo construction for defects judged to be unsuitable for immediate repair. The cot-side application of the preformed silo (PFS) with delayed abdominal wall closure has recently been advocated as the management method of choice for infants with GS. We report a novel trainer designed to facilitate acquisition and refinement of the skills to apply the PFS. Materials and Methods: A model of an infant with GS was constructed to allow application of a PFS. Each step of the clinical application of a PFS could be simulated. Paediatric surgeons at a regional meeting participated in evaluating the model. This cohort was surveyed with regards to previous clinical experience applying the PFS, invited to apply the silo on the model and then resurveyed with regard to the technique, ease of the application of the PFS on the model, its robustness and potential use as a training tool. Results: Seventeen paediatric surgeons completed the surveys and applications of the PFS on the model. Under supervision, each step of the procedure was completed by all participants. Feedback was enthusiastic and positive and participants judged the model to be realistic and potentially very useful as a training tool (median score 8 out of 10). Conclusions: We have developed and evaluated a reproducible, low-cost model of an infant with GS. This ex vivo trainer may be a useful adjunct in the acquisition and refinement of the skills of surgeons who manage GS using a PFS

Epidemiology, management and outcome of gastroschisis in Sub-Saharan Africa: Results of an international survey

Background: The aim was to compare gastroschisis (GS) epidemiology, management and outcome in low-income countries (LIC) in Sub-Saharan Africa (SSA) with middle- (MIC) and high-income countries (HIC). Materials and Methods: A 10-question survey was administered at the 2012 Pan-African Paediatric Surgery Association Congress. Results are presented as median (range); differences were analysed using contingency tests. Results: A total of 82 delegates (28 countries [66 institutions]) were divided into LIC (n = 11), MIC (n = 6) and HIC (n = 11). In LIC, there were fewer surgeons and more patients. LIC reported 22 cases (1-184) GS/institution/year, compared to 12 cases (3-23)/institution/year in MICs and 15 cases (1-100)/institution/year in HICs. Antenatal screening was less readily available in LIC. Access to parenteral nutrition and neonatal intensive care in LIC was 36% and 19%, compared to 100% in HIC. Primary closure rates were similar in LIC and HIC at 58% and 54%, respectively; however, the majority of staged closure utilised custom silos in LIC and preformed silos in HIC. In LIC, mortality was reported as >75% by 61% delegates and 50-75% by 33%, compared to <25% by 100% of HIC delegates (P < 0.0001). Conclusions: Gastroschisis is a problem encountered by surgeons in SSA. Mortality is high and resources in many centres inadequate. We propose the implementation of a combined epidemiological research, service delivery training and resource provision programme to help improve our understanding of GS in SSA whilst attempting to improve outcome