Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

Surgical management of acute life-threatening events affecting esophageal atresia and/or tracheoesophageal fistula patients.

BACKGROUND: Following surgical correction, many patients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) present to the emergency department (ED) with acute airway complications. We sought to determine the incidence and risk factors for severe acute life-threatening events (ALTEs) in pediatric patients with repaired congenital EA/TEF and the outcomes of operative interventions. METHODS: A retrospective cohort chart review was performed on patients with EA/TEF with surgical repair and follow-up at a single centre from 2000 to 2018. Primary outcomes included 5-year ED visits and/or hospitalizations for ALTEs. Demographic, operative, and outcome data were collected. Chi-square tests and univariate analyses were performed. RESULTS: In total, 266 EA/TEF patients met inclusion criteria. Of these, 59 (22.2%) had experienced ALTEs. Patients with low birth weight, low gestational age, documented tracheomalacia, and clinically significant esophageal strictures were more likely to experience ALTEs (p < 0.05). ALTEs occurred prior to 1 year of age in 76.3% (45/59) of patients with a median age at presentation of 8 months (range 0-51 months). Recurrence of ALTEs after esophageal dilatation was 45.5% (10/22), mostly due to stricture recurrence. Patients experiencing ALTEs received anti-reflux procedures (8/59, 13.6%), airway pexy procedures (7/59, 11.9%), or both (5/59, 8.5%) within a median age of 6 months of life. The resolution and recurrence of ALTEs after operative interventions are described. CONCLUSION: Significant respiratory morbidity is common among patients with EA/TEF. Understanding the multifactorial etiology and operative management of ALTEs have an important role in their resolution. TYPE OF STUDY: Original Research, Clinical Research. LEVEL OF EVIDENCE: Level III Retrospective Comparative Study.

Unanticipated consequences of COVID-19 pandemic policies on pediatric acute appendicitis surgery.

BACKGROUND: Global pandemics may limit access to specialized care, delaying diagnosis and treatment of common acute surgical diseases. We analyzed the impact of the novel coronavirus disease 2019 (COVID-19) pandemic on acute appendicitis at an urban tertiary care center. We hypothesize that pandemics are associated with delayed presentation and worsened clinical sequelae, specifically, higher incidences of perforation in children. METHODS: We retrospectively assessed patients admitted to our institution with acute appendicitis in pre-pandemic control (February 2018-June 2019) and COVID-19 (February 2020-June 2021) cohorts. Primary outcomes included complicated appendicitis rates (perforation/abscess/bowel obstruction), COVID-19 status, complications and travel distance to our institution. 1107 patients met inclusion criteria: 491 (44.4%) during the control period and 616 (55.6%) in the COVID-19 cohort. Statistical analysis involved t-tests, contingency tables and logistic regression modelling for key variables. RESULTS: A larger proportion of complicated appendicitis occurred during COVID-19 compared to controls (28.3% vs 38.8%, p < 0.001). Symptom duration at presentation and length of stay were not significantly different. Duration of antibiotic treatment, surgery length, readmission rate and travel distances were significantly higher during COVID-19. The pre-pandemic cohort had a significantly younger age distribution. CONCLUSION: Pediatric appendicitis was significantly impacted during COVID-19, demonstrated by increased rates of complicated appendicitis, surgery duration and antibiotic duration. This may be an unintended secondary consequence of patients avoiding healthcare facilities for non-pandemic related illnesses or lockdown policies. Government policies directing all provincial pediatric appendicitis cases to pediatric institutions increased travel distances for our patients and had unanticipated consequences and resource requirements on tertiary healthcare. LEVEL OF EVIDENCE: Level III for "Treatment Studies".

The long-term outcomes of symptomatic congenital lobar emphysema patients.

INTRODUCTION: Surgical (OP) management for symptomatic congenital lobar emphysema (CLE) is the standard of care with nonoperative (NOP) approach applied for asymptomatic cases. The aim of this study is to report the outcomes for NOP approach to the care of symptomatic CLE infants. METHODS: A retrospective study of CLE patients treated 2000-2021 at a single institution. Patients with CLE and respiratory symptoms were included. RESULTS: Overall, 23 children had symptomatic CLE, and 12 had NOP management. The median age at diagnosis was 38.5 days (50) in the NOP group versus 25 days (20) in the OP group (p = 0.31). There was no significant difference in the location of the involved lobe, term birth, postnatal diagnosis and gender, and both groups required noninvasive support in 33% of the cases. There was a trend towards higher frequency of oxygen support in the OP group preoperatively (89% vs. 42%, p = 0.07). The median length of stay was 14 days in the NOP group compared to a median postsurgery stay of 7.5 days in the OP group. In follow-up, there was no significant difference in respiratory readmission in first year of life, growth delay, treatment with asthma medication or body mass index in the NOP versus OP group. None of the children in the NOP group required surgery during follow-up. CONCLUSIONS: A NOP approach for symptomatic CLE infants can have favorable long-term outcomes. Further studies will be required to identify markers to aid in clinical decision-making.

Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group.

BACKGROUND/PURPOSE: A small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients. METHODS: Retrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale. RESULTS: There were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD. CONCLUSION: More than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment. LEVEL OF EVIDENCE: Level 4.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Interhospital variability in localization techniques for small pulmonary nodules in children: A pediatric surgical oncology research collaborative study.

BACKGROUND: Pulmonary nodules that are deep within lung parenchyma and/or small in size can be challenging to localize for biopsy. This study describes current trends in performance of image-guided localization techniques for pulmonary nodules in pediatric patients. METHODS: A retrospective review was performed on patients < 21 years of age undergoing localization of pulmonary nodules at 15 institutions. Localization and resection success, time in interventional radiology (IR), operating room (OR) and total anesthesia time, complications, and technical problems were compared between techniques. RESULTS: 225 patients were included with an average of 1.3 lesions (range 1-5). Median nodule size and depth were 4 mm (range 0-30) and 5.4 mm (0-61), respectively. The most common localization techniques were: wire + methylene blue dye (MBD) (28%), MBD only (25%), wire only (14%), technetium-99 only (11%), coil + MBD (7%) and coil only (5%). Localization technique was associated with institution (p < 0.01); technique and institution were significantly associated with mean IR, OR, and anesthesia time (all p < 0.05). Comparing techniques, there was no difference in successful IR localization (range 92-100%, p = 0.75), successful resection (94-100%, p = 0.98), IR technical problems (p = 0.22), or operative complications (p = 0.16). CONCLUSIONS: Many IR localization techniques for small pulmonary nodules in children can be successful, but there is wide variability in application by institution and in procedure time. LEVEL OF EVIDENCE: Retrospective review, Level 3.

I-PASS enhances effectiveness and accuracy of hand-off for pediatric general surgery patients.

BACKGROUND: I-PASS is a validated and standardized hand-off protocol shown to reduce medical error and improve hand-off efficiency in the pediatric medical population. Our aim was to evaluate the feasibility, effectiveness, accuracy and resident satisfaction of implementing I-PASS on a pediatric surgery service. METHODS: A prospective intervention Quality Improvement (QI approved) study was utilized to evaluate resident written and verbal hand-offs before and after implementation of I-PASS on a pediatric surgery service at a tertiary center. Anonymous surveys were completed by residents following each observation. Results were analyzed using T or Mann-Whitney U Tests and Chi Square. RESULTS: A total of 49 written tools and 50 verbal hand-offs were compared pre-and post I-PASS implementation. With I-PASS, increased written accuracy was observed in the documentation of the patient summary (p < 0.05). Accuracy in the verbal hand-off of illness severity, patient summary, contingency plan, action list and synthesis also improved (p < 0.05); but duration of hand-off increased (p < 0.01). Post implementation surveys of residents demonstrated an increased understanding of patient management (p < 0.05). CONCLUSION: Implementing I-PASS on a pediatric surgery service with modifications catered to surgical patients, improved the effectiveness and accuracy of written and verbal patient hand-offs and increased provider satisfaction and preparedness. LEVEL OF EVIDENCE: Level II.

Appendectomy Versus Observation for Appendicitis in Neutropenic Children With Cancer.

BACKGROUND: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration. METHODS: Sites from the Pediatric Surgery Oncology Research Collaborative performed a retrospective review of children with NA over a 6-year period. RESULTS: Sixty-six children, with a median age of 11 years (range 1-17), were identified with NA while undergoing cancer treatment. The most common cancer diagnoses were leukemia (62%) and brain tumor (12%). Upfront appendectomy was performed in 41% of patients; the remainder had initial nonoperative management. Rates of abscess or perforation at diagnosis were equivalent in the groups (30% vs 24%; P = .23). Of patients who had initial nonoperative management, 46% (17 of 37) underwent delayed appendectomy during the same hospitalization. Delayed appendectomy was due to failure of initial nonoperative management in 65% (n = 11) and count recovery in 35% (n = 6). Cancer therapy was delayed in 35% (n = 23). Initial nonoperative management was associated with a delay in cancer treatment (46% vs. 22%, P = .05) and longer LOS (29 vs 12 days; P = .01). Patients who had initial nonoperative management and delayed appendectomy had a higher rate of postoperative complications (P < .01). CONCLUSIONS: In pediatric patients with NA from oncologic treatment, upfront appendectomy resulted in lower complication rates, reduced LOS, and fewer alterations in chemotherapy regimens compared to initial nonoperative management.

Reducing Underdiagnosis of Hirschsprung-Associated Enterocolitis: A Novel Scoring System.

BACKGROUND: Hirschsprung-Associated Enterocolitis (HAEC) is a life-threatening and difficult to diagnose complication of Hirschsprung Disease (HSCR). The goal of this study was to evaluate existing HAEC scoring systems and develop a new scoring system. METHODS: Retrospective, multi-institutional data collection was performed. For each patient, all encounters were analyzed. Data included demographics, symptomatology, laboratory and radiographic findings, and treatments received. A "true" diagnosis of HAEC was defined as receipt of treatment with rectal irrigations, antibiotics, and bowel rest. The Pastor and Frykman scoring systems were evaluated for sensitivity/specificity and univariate and multivariate logistic regression performed to create a new scoring system. RESULTS: Four centers worldwide provided data on 200 patients with 1450 encounters and 369 HAEC episodes. Fifty-seven percent of patients experienced one or more episodes of HAEC. Long-segment colonic disease was associated with a higher risk of HAEC on univariate analysis (OR 1.92, 95% CI 1.43-2.57). Six variables were significantly associated with HAEC on multivariate analysis. Using published diagnostic cutoffs, sensitivity/specificity for existing systems were found to be 38.2%/96% for Pastor's and 56.4%/86.9% for Frykman's score. A new scoring system with a sensitivity/specificity of 67.8%/87.9% was created by stepwise multivariate analysis. The new score outperformed the existing scores by decreasing underdiagnosis in this patient cohort. CONCLUSIONS: Existing scoring systems perform poorly in identifying episodes of HAEC, resulting in significant underdiagnosis. The proposed scoring system may be better at identifying those underdiagnosed in the clinical setting. Head-to-head comparison of HAEC scoring systems using prospective data collection may be beneficial to achieve standardization in the field.

Outcomes of multi-gestational pregnancies affected by esophageal atresia - tracheoesophageal fistula.

BACKGROUND: Contemporary outcomes of infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) from multi-gestational pregnancies compared to those of singleton pregnancies have not been reported. METHODS: A single-center retrospective review of EA/TEF patients born from 1999 to 2013 was performed. Patient demographics, gestational age (GA), birth weight, associated anomalies, requirement for gastrostomy tube and mortality were reviewed. RESULTS: Singleton EA/TEF patients outnumbered those from multi-gestational pregnancies nearly 10:1 (214 vs 22 patients). EA/TEF patients from multi-gestational pregnancies were more likely to be premature (77% vs. 32%), have lower birth weight (mean 1766 g vs. 2695 g), have associated duodenal atresia (18% vs. 6%) and require gastrostomy tube (41% vs. 33%) for feeding challenges compared to EA/TEF singletons. Mortality was also significantly greater for multi-gestational EA/TEF patients compared to singleton EA/TEF patients (18% vs. 6%). CONCLUSION: EA/TEF infants from multi-gestational pregnancies have greater clinical complexity and mortality than singleton EA/TEF patients. Parents of EA/TEF multi-gestational infants should be appropriately counseled and supported.

Requirement and Duration of Tube Feed Supplementation among Congenital Diaphragmatic Hernia Patients.

PURPOSE: Oral feeds pose a challenge for congenital diaphragmatic hernia (CDH) infants. Tube feed (TF) supplementation may be required to support the achievement of normal growth. The aim of this study was to determine the duration and factors associated with TF use in CDH infants at our institution. METHODS: A single centre retrospective chart review was performed for CDH-born infants who underwent repair between 2000 to 2013 (REB #1000053124). Patient demographics, perinatal management, and feeding status of infants with at least 1-year follow-up were reviewed. RESULTS: Of 160 CDH infants, 32 (20%) were discharged on partial or complete TF, and an additional 5 (3.1%) patients started TF post discharge. CDH infants with TF were more likely to have initial arterial blood pH < 7.25, patch repair, ECMO support, and prolonged ICU stay (p < 0.05). Time to TF discontinuation did not differ significantly between those partially or fully TF at discharge. Twelve patients (33.3%) remained TF at their last known follow-up. CONCLUSION: High risk CDH patients are likely to require TF to support their nutritional intake. Parents and caregivers need to be informed and properly supported. Long-term monitoring of CDH patient oral intake, growth, and development will be required. LEVEL OF EVIDENCE/TYPE OF STUDY: Level III Retrospective Study.

Vocal cord dysfunction following esophageal atresia and tracheoesophageal fistula (EA/TEF) repair.

BACKGROUND: The purpose of this study was to determine risk factors and long-term outcomes in patients with esophageal atresia +/-tracheoesophageal fistula (EA/TEF) with vocal cord dysfunction (VCD) owing to recurrent laryngeal nerve (RLN) injury. METHOD: A retrospective chart review was performed for EA/TEF patients repaired at our institution from 1999 to 2014 (REB #1000032265). RESULTS: Of 197 patients, 22 (11.2%) were diagnosed with VCD by indirect laryngoscopy following EA/TEF repair. Aspiration was documented on video swallow study for 21 patients, and as a result, 13 required thickened feeds and 8 required gastrostomy tube feeds. Of the 16 H-type TEF patients, 8 (50%) had VCD. Following discharge, 20 (90.9%) patients with VCD eventually tolerated full feeds orally without aspiration but only 8 (36.4%) had documented recovery of vocal cord movement at long-term follow up (mean 452 days). Overall, patients with VCD were more likely to have feeding modifications, increased exposure to radiological studies, and increased frequency of Otolaryngology follow-up compared to EA/TEF patients without VCD. CONCLUSION: EA/TEF patients are at risk for VCD. Clinical improvement did not always correlate with recovery of VC motion. Strategies to minimize RLN damage will improve outcomes and quality of life for EA/TEF patients. LEVEL OF EVIDENCE: Level III.

Pulmonary hypertension in congenital diaphragmatic hernia patients: Prognostic markers and long-term outcomes.

Prenatal observed/expected lung-to-head ratio (O/E LHR) by ultrasound correlates with postnatal mortality for congenital diaphragmatic hernia (CDH) patients. The aim of this study is to determine if O/E LHR correlates with pulmonary hypertension (PH) outcomes for CDH patients. METHODS: A single center retrospective chart review was performed for CDH neonates from January 1, 2006, to December 31, 2015, (REB #1000053124) to include prenatal O/E LHR, liver position, first arterial blood gas, repair type, echocardiogram (ECHO), and lung perfusion scan (LPS) results up to 5years of age. RESULTS: Of 153 newborns, 123 survived (80.4%), 58 (37.9%) had prenatal O/E LHR, and 42 (27.5%) had postnatal ECHO results. High mortality risk neonates (O/E LHR ≤45%) correlated with higher right ventricular systolic pressure (RVsp) at birth. Generally PH resolved by age 5years. LPS results did not change over time (p>0.05) regardless of initial PH severity, suggesting that PH resolution did not correlate with increased ipsilateral lung perfusion to offload the right ventricle. CONCLUSION: Prenatal prognostic markers correlated with initial PH severity for CDH newborns, but PH resolved over time despite fixed perfusion bias to the lungs. These results suggest favorable PH outcomes for CDH patients who survive beyond infancy. TYPE OF STUDY: Retrospective Cohort Study. LEVEL OF EVIDENCE: 3b.

Neurodevelopmental outcomes of infants with esophageal atresia and tracheoesophageal fistula.

BACKGROUND: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a complex disorder, and most outcome data are confined to mortality and feeding-related morbidities. Our objective was to examine mortality, growth and neurodevelopmental outcomes in a large recent cohort of infants with EA/TEF. METHODS: Single center study of EA/TEF infants referred from January 2000 to December 2015. Data collected included associated defects, neonatal morbidity and mortality and growth and neurodevelopmental outcomes at age 12-36months. Multiple regression analysis was used to determine variables associated with adverse outcome. RESULTS: Of the 253 infants identified, 102 infants (40%) were preterm. Overall mortality was 8.3%, the majority from major cardiac malformations (p<0.001) Neurodevelopmental assessments (n=182) showed that 76% were within normal, while some delay was seen in 24%, most often in expressive and receptive language. Nine infants had hearing impairment and 5 had visual impairment. Gastrostomy tubes were required in 47 patients and 15% continued to have weight growth velocities less than the 10th centile. A number of specialist interventions were required, Speech/Language being frequent. CONCLUSION: Mortality in EA/TEF is primarily related to concomitant anomalies, especially cardiac. Multidisciplinary follow up is important for early identification and intervention for growth failure and developmental delay. TYPE OF STUDY: Retrospective study LEVEL OF EVIDENCE: Level II.

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. METHODS: Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5-16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. DISCUSSION: The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. TRIAL REGISTRATION NUMBER: clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016.

Effect of gestational age at birth on neonatal outcomes in gastroschisis.

INTRODUCTION: Induced birth of fetuses with gastroschisis from 34weeks gestational age (GA) has been proposed to reduce bowel damage. We aimed to determine the effect of birth timing on time to full enteral feeds (ENT), length of hospital stay (LOS), and sepsis. METHODS: A retrospective analysis (2000-2014) of gastroschisis born at ≥34weeks GA was performed. Associations between birth timing and outcomes were analyzed by Mann-Whitney test, Cox regression, and Fisher's exact test. RESULTS: 217 patients were analyzed. Although there was no difference in ENT between those born at 34-36+6weeks GA (median 28 range [6-639] days) compared with ≥37weeks GA (27 [8-349] days) when analyzed by Mann-Whitney test (p=0.5), Cox regression analysis revealed that lower birth GA significantly prolonged ENT (p=0.001). LOS was significantly longer in those born at 34-36+6weeks GA (42 [8-346] days) compared with ≥37weeks GA 34 [11-349] days by both Mann-Whitney (p=0.02) and Cox regression analysis (p<0.0005). Incidence of sepsis was higher in infants born at 34-36+6weeks (32%) vs. infants born at ≥37weeks (17%; p=0.02). CONCLUSIONS: Early birth of fetuses with gastroschisis was associated with delay in reaching full enteral feeds, prolonged hospitalization, and a higher incidence of sepsis.

Laparoscopy in pediatric surgery: Implementation in Canada and supporting evidence.

BACKGROUND/PURPOSE: The purpose of this study was to assess the diffusion of laparoscopy usage in Canadian pediatric centers and the relationship between uptake of laparoscopic surgery and the level of evidence supporting its use. METHODS: National data on four pediatric laparoscopic operations (appendectomy, pyloromyotomy, cholecystectomy, splenectomy) were analyzed using the Canadian Institute for Health Information Discharge Database (2002-2013). The highest level of evidence to support the use of each procedure was identified from Cochrane, Embase, and Pubmed databases. Chi-square test for trend was used to determine significance and time to plateau. RESULTS: There were 28,843 operations (open: 12,048; laparoscopic: 16,795). Use of laparoscopic procedures increased over time (p<0.0001). A plateau was reached for cholecystectomy (2006), splenectomy (2007), and appendectomy (2012), but not for pyloromyotomy. Laparoscopic pyloromyotomy in 2013 remains less diffused than the other procedures (p<0.0001). Laparoscopic appendectomy and pyloromyotomy are supported by level-1a evidence in children, whereas cholecystectomy and splenectomy are supported by level-1a evidence in adults but level-3 in children. CONCLUSIONS: In Canada, it has taken a long time to reach high-level implementation of laparoscopic surgery in children. Laparoscopic cholecystectomy first reached plateau, whereas laparoscopic pyloromyotomy continues to increase but remains low despite high level of evidence in support of its usage compared to open surgery.

Are paediatric operations evidence based? A prospective analysis of general surgery practice in a teaching paediatric hospital.

BACKGROUND/AIM: Paediatric surgical practice should be based upon solid scientific evidence. A study in 1998 (Baraldini et al., Pediatr Surg Int) indicated that only a quarter of paediatric operations were supported by the then gold standard of evidence based medicine (EBM) which was defined by randomized controlled trials (RCTs). The aim of the current study was to re-evaluate paediatric surgical practice 16 years after the previous study in a larger cohort of patients. METHODS: A prospective observational study was performed in a tertiary level teaching hospital for children. The study was approved by the local research ethics board. All diagnostic and therapeutic procedures requiring a general anaesthetic carried out over a 4-week period (24 Feb 2014-22 Mar 2014) under the general surgery service or involving a general paediatric surgeon were included in the study. Pubmed and EMBASE were used to search in the literature for the highest level of evidence supporting the recorded procedures. Evidence was classified according to the Oxford Centre for Evidence Based Medicine (OCEBM) 2009 system as well as according to the classification used by Baraldini et al. Results was compared using Χ (2) test. P < 0.05 was considered statistically significant. RESULTS: During the study period, 126 operations (36 different types) were performed on 118 patients. According to the OCEBM classification, 62 procedures (49 %) were supported by systematic reviews of multiple homogeneous RCTs (level 1a), 13 (10 %) by individual RCTs (level 1b), 5 (4 %) by systematic reviews of cohort studies (level 2a), 11 (9 %) by individual cohort studies, 1 (1 %) by systematic review of case-control studies (level 3a), 14 (11 %) by case-control studies (level 3b), 9 (7 %) by case series (type 4) and 11 procedures (9 %) were based on expert opinion or deemed self-evident interventions (type 5). High level of evidence (OCEBM level 1a or 1b or level I according to Baraldini et al. PSI 1998) supported 75 (60 %) operations in the current study compared to 18 (26 %) in the study of 1998 (P < 0.0001). CONCLUSION: The present study shows that nowadays a remarkable number of paediatric surgical procedures are supported by high level of evidence. Despite this improvement in evidence-based paediatric surgical practice, more than a third of the procedures still lack sufficient evidence-based literature support. More RCTs are warranted to support and direct paediatric surgery practice according to the principals of EBM.