Jonathan Karpelowsky

Definitive abdominal wall closure using a porcine intestinal submucosa biodegradable membrane in pediatric transplantation

Abstract:  Abdominal closure in children less than 10 kg following liver or kidney transplantation can be challenging. Excessive pressure attained from a tight closure can result in abdominal compartment syndrome, graft compromise and loss. Concerns over using prosthetic patches are that of infection and dehiscence. We report a series of definitive abdominal wall closure using a biodegradable membrane from porcine intestinal submucosa (Surgisis®; Cook Biotech Incorporated, West Lafayette, IN, USA). A prospective collection and follow up of liver and kidney transplant patients weighing less than 10 kg who required abdominal wall augmentation with Surgisis® in order to achieve satisfactory closure. There were 10 liver and two renal transplant patients. The average weight of the liver transplant patients was 6.6 kg (5.4–8.5 kg) and the renal 9.8 kg. The average area of Surgisis® used was 71.2 cm2 (25–160 cm2) and length of follow up was 15.3 months (1–27 months). Concomitant measures to aid abdominal closure included bilateral recipient nephrectomy for the renal patients and reduction by 33% of the lateral segmental grafts in two liver transplant patients. Delayed closure occurred in all patients except one and the average days to closure from the first surgery was 3.75 days (0–6 days). Following liver transplantation one patient died from multiple organ failure at one month secondary to hemophagocytosis from underlying combined immune deficiency syndrome and one patient with hepatic artery thrombosis was salvaged at re‐exploration. There were two wound complications, one patient developed two small sinuses and some skin dehiscence which healed over four months and the second developed a skin sinus following trans‐patch liver biopsy which healed in three wk. Both had positive microbial cultures but neither necessitated removal of the graft. There were no incisional hernias. Surgisis® is a safe method for facilitating abdominal closure in pediatric transplant patients. It appears to have long‐term durability with no incisional hernias on short‐ and medium‐term follow up, and is fairly resistant to infection.

Growth in children with congenital diaphragmatic hernia during the first year of life

PURPOSE Infants with congenital diaphragmatic hernia (CDH) have high rates of mortality and long-term morbidity, including poor growth and failure to thrive. The aim of this study was to describe growth patterns during the first year of life in infants with congenital diaphragmatic hernia in a non-ECMO cohort. METHODS Medical records of infants with CDH admitted to our center between January 2005 and December 2011 were reviewed. Infants with anthropometric measurements at 3, 6 and 12months were included. Anthropometric measurements were obtained for the first year of life. Logistic regression analyses were performed to find predictive associations with failure to thrive (FTT). RESULT Of the 45 survivors, 38 were seen twice (84%) and 24 (53%) were seen on three occasions to age 12months. Poor growth was observed with weight being most affected. FTT was present in 63% during the first six months of life. Days of mechanical ventilation were the only predictor of FTT. Besides poor weight gain, height and head circumference were also reduced. However, catch-up growth occurred during the second half of infancy and at age 12months failure to thrive had reduced by two thirds to 21%. CONCLUSIONS Poor growth is a common early finding in CDH patients, which improves during infancy. This emphasizes the importance of close follow-up and aggressive nutritional management in CDH patients.

Recurrent diaphragmatic hernia: Modifiable and non-modifiable risk factors.

The risk of recurrence of Congenital Diaphragmatic Hernia (CDH) in an era of thoracoscopic surgery is unclear.

Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis

Introduction This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. Design A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. Participants Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. Interventions Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. Analysis Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. Ethics and dissemination The research has been approved by the Human Research Ethics Committee of the Sydney Childrens Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. Trial registration numbers NCT02795793; ACTRN12616000788471.

Nonoperative management in children with early acute appendicitis: A systematic review

PURPOSE Appendectomy has remained the gold standard treatment of acute appendicitis for more than 100years. Nonoperative management (NOM) has been shown to be a valid treatment alternative for acute uncomplicated appendicitis in adults. A systematic review of available evidence comparing operative management (OM) and NOM in children with acute uncomplicated appendicitis was performed. METHODS Systematic searches of MedLine, Embase, and a clinical trial register (https://clinicaltrials.gov/) were performed in March 2016. Only articles that studied NOM for uncomplicated appendicitis in children were included. Data generation was performed independently by two authors, and quality was assessed using the rating schema by the Oxford Centre for Evidence-Based Medicine. RESULTS 15 articles were selected: four retrospective analyses, four prospective cohort studies, four prospective nonrandomized comparative trials and one randomized controlled trial (RCT). Initial success of the NOM groups (a cure within two weeks of intervention) ranged from 58 to 100%, with 0.1-31.8% recurrence at one year. CONCLUSION Although present literature is scarce, publications support the feasibility of further studies investigating NOM of acute uncomplicated appendicitis in children. Higher quality prospective RCTs with larger sample sizes and robust randomization methods, studying the noninferiority of NOM with antibiotics compared with OM are required to establish its utility. LEVEL OF EVIDENCE This manuscript is a systematic review and thus assigned the lowest evidence used from the manuscripts analyzed which is a Level IV.

Outcomes of pulmonary metastases in hepatoblastoma — is the prognosis always poor?

BACKGROUND Hepatoblastoma is a rare tumour accounting for approximately 1% of all paediatric malignancies. Hepatoblastoma complicated by pulmonary metastatic disease continues to cause management difficulties due to a lack of robust evidence and treatment guidelines. METHOD This series is the experience of a tertiary paediatric referral centre. Patients were prospectively enlisted, and their charts were retrospectively reviewed. RESULTS Thirty-seven patients were treated for hepatoblastoma from 1995 to 2012 inclusive. The overall survival was 34/37(91.9%). Eight patients had lung metastases at diagnosis (LMD) and twenty-nine did not (NLMD). Two-year EFS was 62.5% in the LMD group and 89.3% in the NLMD group (p=0.078). Overall survival in the LMD and NLMD groups was 100% and 89.7%, respectively (p=0.389). Two patients in the LMD group required multiple thoracic resections to achieve cure. Within the NLMD group, two patients developed lung metastases whilst on treatment, and both of these patients died. CONCLUSION In this series, children presenting with lung metastases had a higher risk of relapse but excellent overall survival. However, children who developed pulmonary disease during treatment had a poor prognosis. We advocate aggressive surgical treatment of pulmonary hepatoblastoma to achieve cure.

Reducing the incidence of hepatic artery thrombosis in pediatric liver transplantation: Effect of microvascular techniques and a customized anticoagulation protocol

We aimed to assess the incidence of HAT over three eras following implementation of microvascular techniques and a customized anticoagulation protocol in a predominantly cadaveric split liver transplant program. We retrospectively reviewed pediatric liver transplants performed between April 1986 and 2016 and analyzed the incidence HAT over three eras. In E1, 1986‐2008, each patient received a standard dose of 5 U/kg/h of heparin and coagulation profiles normalized passively. In E2, 2008‐2012, microvascular techniques were introduced. In E3, 2012‐2016, in addition, a customized anticoagulation protocol was introduced which included replacement of antithrombin 3, protein C and S, and early heparinization. A total of 317 liver transplants were completed during the study period, with a median age of 31.7 months. In E1, 22% of grafts were cadaveric in situ split grafts, while the second and third eras used split grafts in 59.0% and 64.9% of cases, respectively. HAT occurred in 9.5% in the first era, 11.5% (P=.661) in the second, and dropped to 1.8% in the third era (P=.043). A routine anticoagulation protocol has significantly reduced the incidence of HAT post‐liver transplantation in children in a predominantly cadaveric in situ split liver transplant program.

Outcomes of oesophageal atresia and tracheo-oesophageal fistula repair.

Oesophageal atresia and tracheo‐oesophageal fistula are congenital anomalies of the oesophagus requiring surgical repair in infancy, either by open or thoracoscopic approach. Although mortality rates associated with this procedure are low, children may go on to have complications throughout childhood and into adulthood, most commonly related to ongoing gastrointestinal and respiratory symptoms. This review outlines the early, mid and long‐term outcomes for these children in terms of quality of life and incidence of symptoms.

Delayed primary closure and the incidence of surgical complications in pediatric liver transplant recipients

PURPOSE The purpose of this study was to analyze the general surgical complications in pediatric liver transplant recipients and the safety of delayed primary closure at a single tertiary center. METHODS A retrospective review of all liver transplant recipients between April 1986 and May 2014 was performed. All general and gastrointestinal complications were recorded and analyzed. The incidence and risk of these complications were compared between children who had a primary versus those who had a delayed closure, with or without the use of Surgisis®, of their abdomen. RESULTS 242 patients underwent 281 liver transplants. The median age of the children was 31months. Whole (77), reduced size (91), split (96), and living related grafts (17) were used. General surgical complications were observed in 33 cases (11.7%). 135 cases underwent delayed primary closure (DPC) of their abdomen, 35 with Surgisis®. Patients with biliary atresia had a higher rate (4.6%) of bowel perforation (p=0.013). The majority of complications occurred within 3months of transplantation. CONCLUSION General surgical complications postpediatric liver transplantation were common but usually not life threatening. Delayed primary closure was safe, had no significant long-term issues, and was not associated with higher incidence of wound related complications.

Surgical management of oesophageal atresia.

There have been major advances in the surgery for oesophageal atresia (OA) and tracheo-oesophageal fistula(TOF) with survival now exceeding 90%. The standard open approach to OA and distal TOF has been well described and essentially unchanged for the last 60 years. Improved survival in recent decades is most attributable to advances in neonatal anaesthesia and perioperative care. Recent surgical advances include the use of thoracoscopic surgery for the repair of OA/TOF and in some centres isolated OA, thereby minimising the long term musculo-skeletal morbidity associated with open surgery. The introduction of growth induction by external traction (Foker procedure) for the treatment of long-gap OA has provided an important tool enabling increased preservation of the native oesophagus. Despite this, long-gap OA still poses a number of challenges, and oesophageal replacement still may be required in some cases.