The Outcome of A Centralization Program in Biliary atresia: 20 years and beyond.

OBJECTIVE: Biliary atresia (BA) is a rare disease and reported outcomes of surgical management, typically a Kasai portoenterostomy (KPE), vary considerably across the world. Centralization has been proposed to improve this. SUMMARY BACKGROUND DATA: A national centralization programme was started in Jan. 1999, involving 3 English units with co-located liver transplant facilities. As the program has now reached the 20-year point, the main aim was to update outcome statistics and identify trends. METHODS: Prospective registry and database. The main measures of outcome were (i) time to KPE, (ii) Clearance of Jaundice (CoJ), defined as reaching a bilirubin value of <20µmol/L (≈1.5 mg/dL), and (iii) actuarial native liver survival (NLS) and overall survival (OS). Data are quoted as median (IQR) and non-parametric statistical comparison used with P<0.05 regarded as significant. RESULTS: 867 infants were born with BA and managed between January 1999 and December 2019. Death occurred without intervention (n=10, 1.1%) or were subject to primary transplant (n=26, 3.0%); leaving 831 (95.9%) infants who underwent KPE at median age of 51 (IQR 39-64) days. Age at KPE reduced over the period (P=0.0001) becoming 48(35-57) days in the last 5-year era. CoJ was achieved in 505/831 (60.6%), also increasing over the period (P=0.002). 42 (5.0%) died post-KPE and 384 were transplanted, leaving 405 alive with their native livers at last follow-up. Of the 412 children transplanted, there were 23 (5.6%) deaths, leaving 387 alive. 5-year and 10-year native liver survival were 51.3% (95% CI 54.8-47.8) and 46.5% (95% CI 50.1 - 42.9) and overall survival were 91.5% (95% CI 93.2 - 89.4) and 90.5% (95% CI 92.3 - 88.2%) respectively. CONCLUSIONS: There have been continued improvements in efficiency over the period of centralization with a significant reduction in time to KPE and improved CoJ following KPE. Overall survival in this disease remains >90%.

Hepatic benign and malignant masses in children: a single UK tertiary centre experience.

PURPOSE: The aim of this study was to review the incidence, spectrum and investigation of liver masses presenting to our tertiary liver unit. METHODS: A retrospective single-centre cohort study of paediatric patients (age < 16 years) diagnosed with a liver mass who were investigated at a UK paediatric hepatobiliary tertiary referral centre. Data relating to the clinical findings at presentation, source of referral, diagnostic investigations and histopathology findings were recorded and analysed. RESULTS: 107 patients were identified between July 2012 and July 2019 (55 females). 69 (64%) patients had benign liver lesions, whereas the remaining 38 (36%) were found to have malignant masses. The liver lesions were most commonly detected incidentally (33%) with the second most common presentation being with palpable mass (29%). 82 (77%) patients were referred from other hospitals. All patients underwent USS, 74% MRI, 36% CT, 5% CEUS, 1% PET and 5% HIDA scan with 47% ultimately undergoing biopsy. 72% of patients had AFP measured. The most common benign liver masses were haemangioma 33 (48%), hepatic cyst 17 (25%) and FNH 12 (19%). Amongst the malignant lesions, 29 (76%) were hepatoblastoma and 3 (8%) were hepatocellular carcinoma. CONCLUSIONS: This large review series demonstrates that just over 1/3 of patients presenting to a paediatric tertiary referral centre with a focal liver lesion had neoplastic liver lesions, despite the published literature commonly stating that 2/3 of paediatric liver masses are malignant.

Inspissated bile syndrome; Safe and effective minimally invasive treatment with percutaneous cholecystostomy in neonates and infants.

PURPOSE: Inspissated bile syndrome (IBS) is a rare cause of obstructive jaundice in neonates and infants with several treatment options reported. We present our experience with the use of minimally invasive ultrasound-guided percutaneous cholecystostomy drain catheter placement with ongoing saline lavage in neonates and infants. METHODS: Retrospective chart review of patients treated with percutaneous cholecystostomy, from February 2010 till June 2015. We reviewed the technical and clinical success along with complications of the procedure. RESULTS: There were 6 patients, mean age 17weeks (range 4-40). Most had significant risk factors for IBS presenting with biliary obstruction. A total of 7 procedures performed on the 6 patients, with a technical success rate of 6/7. One patient required cannulation of the intrahepatic biliary system. Drains were flushed for a median of 26days (10-70). Clinical success was achieved in all patients. 3 had displacement of the drain, one of which required re-insertion. Another developed a small sub-hepatic collection post procedure with pyrexia. On long term follow up one was found to have a forme fruste choledochal cyst. CONCLUSION: Centers with suitable interventional radiology services ultrasound-guided percutaneous cholecystostomy drain catheter placement with ongoing saline lavage is a safe and effective minimally invasive treatment for IBS in neonates and infants.

Renal Transplantation From Pediatric Donors in the United Kingdom.

BACKGROUND: Significant disparity exists in the United Kingdom between the need for organ transplant and supply of deceased donor organs. In the recent years, efforts to increase donation has improved the rate of mainly deceased donors after circulatory death and from older donors. The rate of donation from pediatric population has remained low and those younger than 2 years including neonatal donation has remained largely unexplored. METHODS: A retrospective review of the outcome of renal transplantation from pediatric donor (<18 years) kidneys in the United Kingdom. RESULTS: Our results show a poor referral and conversion rate, and high discard rate (43%) of kidneys procured from donors younger than 2 years. During the 15-year study period (1997-2011), 47 donors younger than 2 years were referred (3 per year). Of these, 26 proceeded to donation resulting in 17 transplants (65% utilization). The referral rate for donors 2 years or older to younger than 5 years also remains low (76 in 15 years), but the conversion (88%) and utilization rates (73%) are better in this group. There was better utilization in donors aged 5 years or older to younger than 18 years. Overall graft and patient survival remains excellent in all 3 groups; with comparable survival of 82%, 85%, and 77% (P = 0.29) with mean follow-up periods of 9, 12.5, and 11.8 years, respectively. CONCLUSIONS: Despite excellent outcome, the referral, donation, and utilization of kidneys from donors younger than 5 years and particularly those younger than 2 years remain low. We suggest implementing improved strategies to increase donation from this group of population.

Omental infarct in a hernia: an unusual cause of paediatric acute scrotum.

We report a case of paediatric acute scrotum due to segmental haemorrhagic infarct of the omentum secondary to strangulation in the left inguinal hernia in a toddler as initial presentation after hernia being noticed by mother once earlier. A 4-year-old boy with non-traumatic acute left scrotum who had a history of left inguinal swelling once earlier presented with massively swollen, painful and discoloured left hemiscrotum extending into the groin simulating acute testicular torsion. Interestingly, there was a segmental omental infarct which precipitated the emergency and had ipsilateral testicular ascent and atrophy as long-term sequelae. Strangulated segmental omental infarct is a rare cause of acute abdomen/scrotum in children. Omentum is a very rare content of inguinal hernia in a toddler and infarct is exceptional. The diagnosis is usually not established before surgery in children. It should be included in the differential diagnoses of acute scrotum, especially in patients with untreated inguinal hernia.

Robot-assisted resection of choledochal cysts and hepaticojejunostomy in children.

PURPOSE: Choledochal cysts have traditionally been treated as an open procedure. However, recent publications from some large volume centres show that minimally invasive surgery has become their standard approach. Robotic surgical systems facilitate a surgeon's ability to undertake complex procedures. We present our experience of using robot assistance to treat choledochal cysts. METHODS: Children admitted with a choledochal cyst from March 2009 to Nov 2012 were included. There were 27 patients (20 females). Mean age 5.4 years (range 0.3-15.9). Mean weight 21.9 kg (range 5.9-78.8); 10 weighed <10 kg. The choledochal cysts were types 1c(12), 1f(10) and 4(5). The da vinci Surgical System was used for the robot-assisted resection of the choledochal cyst and hepaticojejunostomy. Roux loop was fashioned extra-corporeally. Mean follow-up is 2.7 years (range 0.9-4.7). RESULTS: 22 cases were completed successfully with robotic assistance. Five open conversions were for anatomical concerns or technical reasons. One child had three complications (omental hernia, anastomotic stricture and subsequent bile leak). Patients were on full feeds by a median of 5 days (range 3-6) and discharged after 6 days (range 4-7). CONCLUSION: Robotic-assisted resection of choledochal cysts in children is safe. They made a rapid recovery with a good cosmetic outcome.

Implantable versus cuffed external central venous catheters for the management of children and adolescents with acute lymphoblastic leukaemia.

PURPOSE: The aim of this study was to determine if there is a difference between complications for totally implantable central venous catheters (ports) and tunnelled external central venous catheters (external CVCs) that result in early removal of the central venous catheter (CVC) in children and adolescents with acute lymphoblastic leukaemia (ALL). METHODS: All children hospitalised between November 1996 and December 2007 with ALL who had a CVC were included retrospectively. We analysed data regarding the patient's first CVC. RESULTS: We included 322 patients. 254 received a port and 68 received an external CVC. There were 102 CVC complications that required removal of the CVC prior to the completion of chemotherapy (65 in patients with ports, 37 in patients with external CVCs). Overall complications requiring CVC removal were significantly less likely to occur in the patient's with ports (p < 0.001). Ports were significantly less likely to require removal prior to the end of treatment overall (p < 0.001) and for specific complications such as infection (p < 0.001) and dislodgement (p = 0.001). However, when adjusted for disease severity there is no difference in premature CVC removal rates. CONCLUSION: When patients are risk-stratified for disease severity there is no difference in rates of CVC removal prior to completion of treatment.

Robot-assisted resection of choledochal cysts and hepaticojejunostomy in children less than 10 kg.

BACKGROUND/PURPOSE: Laparoscopic resection of choledochal cysts and hepaticojejunostomy have been described in children since 1995, but these can be technically demanding procedures. Robotic surgical systems can facilitate complex minimal-access procedures. In 2009, we made the transition from conventional laparoscopic to robotic-assisted choledochal cyst excision with hepaticojejunostomy. We present our experience in children weighing less than 10 kg. METHODS: During 2009, 5 children weighing less than 10 kg underwent robotic resections of choledochal cysts and hepaticojejunostomy using the da Vinci surgical system. The Roux loop was fashioned extracorporeally. Mean age was 1 year (range, 0.5-1.4), and mean weight was 8.5 kg (range, 7.6-9.5). All 5 had type 1c cysts, and 3 were very large. RESULTS: All 5 cases were treated successfully by robotic resection of the cyst and hepaticojejunostomy. Feeding was established by a median of 4 days (range, 3-6), and patients were discharged after a median of 6 days (range, 5-7) with no postoperative complications. CONCLUSION: The technique is safe and effective in children weighing less than 10 kg. The authors found ergonomic advantages in using robotic-assisted surgery for this complex minimal-access procedure.

Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia managed with extracorporeal membrane oxygenation: experience and outcome.

OBJECTIVE: Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia, an infection that affects predominantly young people, has a mortality rate of > 70% despite aggressive conventional management. Little information is available on the management of patients with Panton-Valentine leukocidin expressing S. aureus pneumonia with extracorporeal membrane oxygenation support. As a large extracorporeal membrane oxygenation center, we reviewed our experience and outcomes with Panton-Valentine Leukocidin expressing S. aureus pneumonia. DATA SOURCES: Locally held register of all extracorporeal membrane oxygenation patients at Glenfield Hospital. STUDY SELECTION: Retrospective study including all patients with sputum-positive Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation support at a single extracorporeal membrane oxygenation center. DATA SYNTHESIS: On review of our database held from September 1989 until date, there were four patients with sputum-confirmed Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation. Refractory hypoxemia and/or uncompensated hypercapnia despite optimal conventional management were the indications for extracorporeal membrane oxygenation. After varying periods on extracorporeal membrane oxygenation with appropriate antibiotic and ancillary care, all four patients were discharged home. CONCLUSIONS: Panton-Valentine leukocidin expressing S. aureus pneumonia can cause severe, necrotizing pneumonia associated with acute respiratory distress syndrome, which can be particularly challenging to manage. Extracorporeal membrane oxygenation support permits low pressure lung ventilation, avoiding barotrauma to lungs made friable by Panton-Valentine leukocidin expressing S. aureus infection. Although this is a small number of patients, the results are encouraging.

A unique case of a congenital diaphragmatic hernia in a boy with albinism.

Congenital diaphragmatic hernia and oculocutaneous albinism are both rare birth defects that can be diagnosed in the newborn period. However, they have not been previously reported to have occurred together. This report describes a unique case of a male Asian baby with oculocutaneous albinism and a right-sided congenital diaphragmatic hernia.

Adriamycin produces a reproducible teratogenic model of gastrointestinal atresia in the mouse.

Gastrointestinal atresia is a major cause of bowel obstruction in the newborn. Experimental models and clinical observations have demonstrated the heterogeneous nature of its pathogenesis. A proportion is due to late intra-uterine vascular insults and some are genetic in nature. Epidemiological studies have found gastrointestinal atresia to occur with other birth defects, in particular VACTERL anomalies, suggesting that a subset of cases may result from an early disturbance to intestinal morphogenesis. Adriamycin is teratogenic in rats, producing gastrointestinal atresia and VACTERL anomalies. The mouse is the foremost mammal studied by developmental biologists, offering an expanding wealth of knowledge and scientific research techniques. The aim of this study was to create an Adriamycin mouse model for investigating the development of gastrointestinal atresia. CBA/Ca mice were accurately time-mated (n = 30). Four different doses of Adriamycin (0-saline control, 4, 5 and 6 mg/kg) at three different timings of injections were compared (12 groups). Dams received two intraperitoneal injections, 24 h apart, commencing on day 7, 7.5 or 8. Foetuses were harvested on day 18. Gastrointestinal atresia and VACTERL anomalies were examined using a dissecting microscope. Adriamycin produced type IIIa gastrointestinal atresia in six treatment groups. The effect of Adriamycin depended on the timing and dose of the injections. VACTERL anomalies were only found in four treatment groups, proposing overlapping critical embryological windows for these malformations. Gastrointestinal atresia can be induced by the teratogen Adriamycin, occurring with and without VACTERL anomalies. This produces a reproducible mouse model in which the molecular pathogenesis of gastrointestinal atresia may be studied.

Adriamycin produces a reproducible teratogenic model of vertebral, anal, cardiovascular, tracheal, esophageal, renal, and limb anomalies in the mouse.

BACKGROUND/PURPOSE: The Adriamycin rat model is an established model for vertebral, anal, cardiac, tracheal, esophageal, renal, and limb (VACTERL) anomalies and gastrointestinal atresias. Mice are the foremost mammal studied by developmental biologists, providing greater availability of molecular probes, antibodies, and transferable knowledge with transgenic studies. Only tracheoesophageal malformations have been previously described in the Adriamycin mouse model. The aim of this study was to carry out a dose-response analysis of the teratogenicity of Adriamycin in the mouse to determine the effect of the dose and timing of exposure in producing tracheoesophageal malformations and show if it causes other VACTERL anomalies. METHODS: CBA/Ca mice were accurately time mated (n = 30). Four different doses (0 [saline], 4, 5, and 6 mg/kg) of Adriamycin (EBEWE Pharma Ges.m.b.H. Nfg.KG, A-4866 Unterach, Austria) at 3 different timings of injections were compared. Dams received 2 intraperitoneal injections, 24 hours apart, commencing on day 7, 7.5, or 8. Fetuses were harvested on day 18. Anomalies were examined using a dissecting microscope and serial transverse sections. RESULTS: Administering Adriamycin at 6 mg/kg on days 7 and 8 had the most teratogenic effect, with 80% of fetuses having 3 or more VACTERL anomalies: anorectal malformation, 100%; tracheoesophageal malformation, 50%; right-sided aortic arch, 58.3%; bladder agenesis/bilateral hydronephrosis, 100%. CONCLUSION: This study establishes a mouse model that should provide insights into the cellular and molecular mechanisms underlying VACTERL anomalies.

Abnormal separation of the respiratory primordium in the adriamycin mouse model of tracheoesophageal malformations.

BACKGROUND/PURPOSE: Organogenesis relies on temperospatially coordinated signaling systems. The adriamycin rat model provided insights into the dysmorphogenesis of tracheoesophageal malformations. An adriamycin mouse model (AMM) would facilitate the investigation of their molecular pathogenesis. To transfer the knowledge gained from the rat, we describe a histological account of the critical period of organogenesis of these malformations in the AMM. METHOD: CBA/Ca mice were accurately time-mated (n = 18). Dams received intraperitoneal injections of adriamycin (6 mg/kg) (n = 12) or saline control (n = 6) on days 7 and 8. Fetuses were harvested on days 9, 9.5, 10, 11, 12, and 13, resin embedded, and 1-mum sections of the developing foregut were examined. RESULTS: Day 11 control fetuses showed normal separation of the respiratory primordium, with apoptotic bodies at the point of separation. A more caudal point of separation of the distal foregut without apoptotic bodies was found in 4 of 10 AMM fetuses. Day 13 AMM fetuses had dorsal or ventral outpouchings of the foregut, indicating which malformation they would develop. Abnormal branching of the notochord was seen from day 9.5 in AMM fetuses. This was not always associated with abnormal tracheoesophageal development. CONCLUSION: This study confirms that the abnormal observations made in the rat model apply to the mouse.

Adriamycin mouse model: a variable but reproducible model of tracheo-oesophageal malformations.

A spectrum of tracheo-oesophageal malformations is seen in humans: oesophageal atresia, tracheal agenesis and laryngotracheo-oesophageal clefts. They are thought to share a common but unknown aetiology. These birth defects are frequently associated with other VACTERL anomalies. The adriamycin rat model (ARM) has proved to be a valuable model of the VACTERL anomalies, illustrating the dysmorphogenesis of oesophageal atresia and tracheal agenesis. As organogenesis relies on temporaspatially co-ordinated signalling systems, the next step would be to study the molecular pathogenesis of tracheo-oesophageal malformations. However, the mouse is the foremost mammal studied by developmental biologists, offering an expanding wealth of knowledge and scientific research techniques with which to investigate these anomalies. A limited dose response analysis of the teratogenicity of adriamycin in the mouse has identified a dose and timing of injections that produced tracheo-oesophageal malformations and other VACTERL anomalies. A clear account of the types and variability of the tracheo-oesophageal malformations produced by this dose is essential in order to be able to plan and interpret any future investigations of early gestation fetuses. CBA/Ca mice were accurately time-mated (n = 10). Nine dams received intraperitoneal injections of adriamycin (6 mg/kg) and one control dam received saline injections, on days 7 and 8. Fetuses were harvested on day 18, near term. Tracheo-oesophageal malformations were examined by dissecting microscope and serial transverse sections. Results are reported in the standard teratological manner as mean percentage per litter (+/-SEM). The resorption rate of the adriamycin treated fetuses was 50.4%. There were 29 adriamycin treated fetuses for inspection. Tracheo-oesophageal malformations were found in 29.2% (+/-10.3), affecting five out of nine litters. Oesophageal atresia occurred in 15.6% (+/-8.1), laryngotracheo-oesophageal cleft in 10.4% (+/-7) and tracheal agenesis in 3.1% (+/-3.1). All of these malformations occurred with a tracheo-oesophageal fistula. Unlike the ARM, the AMM can produce fetuses with complete laryngotracheo-oesophageal cleft as well as oesophageal atresia or tracheal agenesis. Their occurrence was found to be reproducible but variable. These are important considerations when planning and interpreting experiments using this model.

Endoscopic treatment for high grade vesicoureteral reflux in infants.

PURPOSE: Minimally invasive endoscopic treatment for vesicoureteral reflux has become an established alternative to long-term antibiotic prophylaxis and surgical intervention in children. We determined the long-term efficacy and safety of this treatment for high grade reflux in infants. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 411 consecutive infants who underwent endoscopic treatment of grade III to V vesicoureteral reflux between June 1985 and October 2004. A total of 29 patients (7%) were excluded from study because they were lost to followup or the medical records were incomplete. Of the remaining 382 infants, including 203 males, 274 had bilateral and 108 had unilateral vesicoureteral reflux. This represented 642 high grade refluxing units with grade III to V disease in 232, 339 and 71, respectively. A dimercapto-succinic acid scan performed in 312 infants revealed renal scarring in 88 (28%). The tissue augmenting substance used for endoscopic injection was polytetrafluoroethylene and dextranomer/hyaluronic acid copolymer in 432 and 210 ureters, respectively. Endoscopic treatment was done at a median age of 7 months (range 2 months to 1 year). Median followup in these patients was 7 years (range 6 months to 20 years). RESULTS: Complete resolution of vesicoureteral reflux after a single injection occurred in 443 ureters (69%), including 73% with dextranomer/hyaluronic acid copolymer and 65% with polytetrafluoroethylene. Of the 642 ureters 127 (20%) required more than 1 injection to correct vesicoureteral reflux. In 60 ureters vesicoureteral reflux was downgraded to grade I or II and no further treatment was given, while 12 ureters that failed to respond to endoscopic treatment required open surgical intervention. Only 1 ureter required reimplantation to treat vesicoureteral obstruction. CONCLUSIONS: Endoscopic correction is a safe, effective, minimally invasive outpatient procedure for high grade vesicoureteral reflux in infants. Early correction of vesicoureteral reflux may provide protection from reflux associated renal damage and prolonged antibiotic use.

Definitive surgical management of antenatally diagnosed exomphalos.

BACKGROUND/PURPOSE: The management of exomphalos is controversial with many centers in the United Kingdom and elsewhere advocating a conservative nonsurgical approach for the larger examples. Nevertheless, this approach is not without problems or complication. The aim of the study was to ascertain the outcome of all infants with an antenatally diagnosed exomphalos treated recently at our institution using a policy of aggressive abdominal wall closure. METHODS: This is a retrospective review of all infants with exomphalos treated from January 1995 to September 2002. RESULTS: There were 35 infants, all of whom underwent surgery. These were separated into 3 groups: group A (all exomphalos minor) underwent primary closure (n = 11), group B (exomphalos major) underwent primary closure (n = 13), and group C (exomphalos major) underwent staged closure involving a silo (n = 11). Infants in group C had a lower birth weight (P = .05) and were less mature (P = .06). They required longer periods of ventilation (P < .001), a longer hospital stay (P = .001), and a longer period to achieve full enteral feeds (P < .001). Overall survival was 34 (97%) of 35 infants. One premature infant who was born with a ruptured exomphalos sac (birth weight, 862 g) died of nonsurgical complications (sepsis and respiratory failure) early after the creation of a silo. CONCLUSIONS: An aggressive surgical approach in infants with exomphalos is a safe option resulting in effective abdominal wall closure. This requires a skilled multidisciplinary approach and possibly greater resources than other options.