Surgical management and outcomes of 12 cases of Wilms tumour with intracardiac extension from a single centre.

PURPOSE: To review demographics, effect of preoperative chemotherapy on tumour thrombus, imaging, operative strategy, and outcomes of 12 patients presenting with intracardiac extension of Wilms tumour thrombus. METHODS: A retrospective audit was undertaken on patients with intracardiac extension of Wilms tumour. Patients were identified from the oncology database and information obtained on clinical presentation, stage, preoperative treatment, surgical procedures and complications, histology, and survival status. Ethics approval was obtained from the University of Cape Town Human Research Ethics Committee. RESULTS: From 1984 to 2016, 337 children with Wilms tumour were treated. Twelve (3.6%) had intracardiac extension of tumour thrombus, nine into the right atrium, and three into the right ventricle. Ultrasound, computerized tomography, magnetic resonance imaging, and echocardiograms were used to assess thrombus level. Patients were staged as stage III(8) and IV(4). All patients received preoperative chemotherapy. Thrombus retracted from the heart in two cases. One patient died preoperatively. Eleven underwent laparotomy, median sternotomy, and cardiopulmonary bypass (CPB). Four underwent cavectomy. Five required cavoatrial patches. Thrombus extending into the hepatic veins was extracted in five patients. There was one intraoperative complication and one perioperative death. Thrombus histology showed viable tumour in 9 of 11 patients. Three patients died of progressive disease. Seven patients are currently disease free. CONCLUSION: A combination of imaging is required to determine thrombus extent, and this facilitates surgical planning. Preoperative chemotherapy may cause thrombus regression, thus avoiding CPB. CPB offers appropriate conditions for safe tumour thrombus excision. Full management in centres with appropriately experienced staff and facilities for CPB is recommended.

Local anesthetic wound infusion versus standard analgesia in paediatric post-operative pain control.

INTRODUCTION: Local anesthetic wound infusion has shown promising results in adults. Its use in children is limited to some centers and there are only a few prospective trials in this group of patients. METHODS: Sub-fascial continuous local anaesthetic wound infusion (CLAWI) (0.2% Bupivacaine) plus intravenous paracetamol and rescue intravenous morphine was compared to: (a) Epidural bupivacaine (EPI) plus paracetamol and rescue intravenous morphine for patients undergoing laparotomy. (b) Intravenous morphine and paracetamol (standard post-operative analgesia-SAPA) in children undergoing Lanz incision laparotomy for complicated appendicitis. 'InfiltralLong', PANJUNK(®) catheters were placed sub-fascially after peritoneal closure for post-operative bupivacaine infusion. Pain scores were recorded regularly by the same blinded pain specialist. The primary outcomes were pain control and total morphine. The secondary outcomes were time to full feeds, mobilization requirement for urinary catheter and complications. RESULTS: Sixty patients (18 laparotomy-CLAWI, 17 laparotomy-EPI and 12 appendectomy-CLAWI, and 13 appendectomy-SAPA) were analyzed. The average pain score was 2.5 (1-4) in the CLAWI groups, 3.0 (1-5) in the EPI group and 3.5 (2-5) in the SAPA group. Morphine requirements were markedly less for CLAWI. SAPA and EPI groups required urinary catheters for longer and took longer to mobilize (average 4 days compared to 2 days for CLAWI). There were no wound or bupivacaine complications in the CLAWI group. CONCLUSION: Continuous subfascial bupivacaine infusion is reliable, safe and effective in paediatric post-operative pain control with considerably reduced opiate requirements.

Liver tumours in children: current surgical management and role of transplantation.

This article reviews the current surgical management of liver tumours in children in the light of improved chemotherapy, surgical techniques and outcomes from transplantation. It is a principle of management that complete removal of a tumour must be achieved for cure. Neoadjuvant chemotherapy may downstage advanced local disease to enable safe curative tumour resection. When this is not achievable, transplant is indicated. Conventional indications for transplant are unresectable stages 3 and 4 tumours confined to the liver. With the realisation that lifelong immunosuppressive therapy has considerable adverse consequences, there has been a recent trend towards extreme and 'acrobatic' liver resection to avoid transplantation, but still obtain a cure. The current literature is reviewed in the light of these trends and our own experience.

The Input Signal Step Function (ISSF), a standard method to encode input signals in SBML models with software support, applied to circadian clock models.

Time-dependent light input is an important feature of computational models of the circadian clock. However, publicly available models encoded in standard representations such as the Systems Biology Markup Language (SBML) either do not encode this input or use different mechanisms to do so, which hinders reproducibility of published results as well as model reuse. The authors describe here a numerically continuous function suitable for use in SBML for models of circadian rhythms forced by periodic light-dark cycles. The Input Signal Step Function (ISSF) is broadly applicable to encoding experimental manipulations, such as drug treatments, temperature changes, or inducible transgene expression, which may be transient, periodic, or mixed. It is highly configurable and is able to reproduce a wide range of waveforms. The authors have implemented this function in SBML and demonstrated its ability to modify the behavior of publicly available models to accurately reproduce published results. The implementation of ISSF allows standard simulation software to reproduce specialized circadian protocols, such as the phase-response curve. To facilitate the reuse of this function in public models, the authors have developed software to configure its behavior without any specialist knowledge of SBML. A community-standard approach to represent the inputs that entrain circadian clock models could particularly facilitate research in chronobiology.

The domestication of fire: the relationship between biomass fuel, fossil fuel and burns.

Primitive man's discovery and use of fire had a tremendous impact on modern development. It changed lifestyles, and brought with it new fuel sources and cooking methods. It also introduced devastation, injury, pain, disfigurement, and loss of life, and the need to continuously develop management, training and prevention programs.

Mapping the core of the Arabidopsis circadian clock defines the network structure of the oscillator.

In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators. In Arabidopsis, oscillator coupling relies on a core loop in which the evening oscillator component TIMING OF CAB EXPRESSION 1 (TOC1) was proposed to activate a subset of morning-expressed oscillator genes. Here, we show that TOC1 does not function as an activator but rather as a general repressor of oscillator gene expression. Repression occurs through TOC1 rhythmic association to the promoters of the oscillator genes. Hormone-dependent induction of TOC1 and analysis of RNA interference plants show that TOC1 prevents the activation of morning-expressed genes at night. Our study overturns the prevailing model of the Arabidopsis circadian clock, showing that the morning and evening oscillator loops are connected through the repressing activity of TOC1.

Staged abdominal closure after small bowel or multivisceral transplantation.

Following paediatric SBMT, size discrepancy between the recipient's abdomen and the graft may lead to ACS, graft dysfunction, and death. We report our experience with SAC in these patients. Between 04/1993 and 03/2009, 57 children underwent 62 SBMTs. When abdominal wall tension seemed excessive for safe PAC, SAC was performed, using a Silastic® sheet and a vacuum occlusive dressing. Transplantations with SAC (23 combined liver and small bowel [CLB]) were compared with those with PAC [14 ISB and 25 CLB]. Indications for transplantation, preoperative status (after stratification for ISB/CLB transplants), age at transplantation, donor-to-recipient weight ratio, reduction in bowel and/or liver, and incidence of wound complications were not different in both groups. Post-operative intubation, stay in intensive care unit, and hospital stay were prolonged after SAC. Two deaths were related to ACS after PAC, none after SAC. Since 2000, one-yr patient survival is 73% after ISB transplantation and 57% vs. 75% after CLB transplantation with PAC vs. SAC, respectively (NS). SAC safely reduces severe ACS after paediatric SBMT and can be combined with graft reduction for transplantation of small recipients.

Intussusception as a presenting feature of Burkitt lymphoma: implications for management and outcome.

PURPOSE: Intussusception is a recognised but unusual presenting feature of Burkitt lymphoma. We sought to identify the clinical features associated with intussusception in this setting, and assess the outcome following protocol directed chemotherapy. METHODS: A retrospective case note review was performed on patients treated for Burkitt lymphoma at our institution between 1976 and 2010. Cases presenting with intussusception were identified from hospital records and oncology database. RESULTS: Fourteen of the 210 children seen with a diagnosis of Burkitt lymphoma during the study period (6.7%) developed intussusception. Median age was 6.1 years (range 2.5-10.9). Twelve patients presented with recurrent abdominal pain, and two patients with a jaw mass associated with endemic Burkitt lymphoma. Nine patients underwent a right hemicolectomy with ileo-colic anastomosis, and five had segmental small-bowel resections. Three patients had bone marrow involvement at diagnosis, two of whom died. All patients received chemotherapy. Median follow-up was 6.07 years (range 0.1-28.8). CONCLUSIONS: Small bowel lymphoma should be considered in children presenting with intussusception above the normal infantile peak age range. The presentation is often insidious, and complete obstruction may not be apparent. However, when surgically resected, the majority can achieve a good outcome with additional chemotherapy.

Pregnancy following liver transplantation during childhood and adolescence.

More than 80% of pediatric transplant recipients will survive to reach adulthood, and many will consider having children. We report on outcomes and management of five pregnancies in four women undergoing orthotopic liver transplantation during childhood or adolescence and followed up at our Transplant Center. A retrospective clinical folder audit was performed. Mean age at transplantation was 13.3 ± 3.4 yr (range, 10-18 yr). Mean interval between transplantation and pregnancy was 15.4 ± 4.9 yr (range, 10-22 yr). Mean maternal age at conception was 28 ± 3.5 yr (range, 23-32 yr). Mean gestational age was 36.6 ± 1.7 wk. Mean birth weight was 2672 ± 249 g. Immunosuppression was cyclosporin based in three women and tacrolimus based in one woman. Pregnancy complications necessitating the induction of labor included fetal distress and rising maternal liver enzymes in two women, cholestasis of pregnancy and impaired renal graft function in one woman, fetal distress and preeclampsia in one woman. Modes of delivery were normal vaginal delivery in three women and cesarean section in one woman. No maternal or fetal deaths and no congenital malformations occurred. No episodes of rejection occurred during pregnancy. Two women experienced acute cellular rejection requiring an increase in baseline immunosuppression in the first year, following delivery. No graft losses occurred during a mean follow-up of 44 ± 17.9 months post-delivery. With careful management, pregnancy post-liver transplantation can have a successful outcome.

Nephron-sparing surgery for bilateral Wilms' tumours: a single-centre experience with 23 cases.

INTRODUCTION: The challenge of management with bilateral Wilms' tumours is the eradication of the neoplasm, while at the same time preserving renal function. Surgical management with a variety of nephron-sparing techniques, combined with chemotherapy and occasionally supplemented by transplantation has evolved over the last 30 years to achieve remarkable success. We document the experience of a single centre in a developing country. MATERIAL AND METHODS: Twenty-three bilateral Wilms' tumours were seen in our service between 1981 and 2007. Treatment was, in most cases, according to National Wilms' Tumour Study Group protocols, with initial bilateral biopsy, neoadjuvant chemotherapy, and tumourectomy. Technique of nephrectomy included full mobilization of the tumour-involved kidney, topical cooling with slush ice, vascular exclusion, tumour resection and reconstruction of the remnant kidney. RESULTS: Twelve patients are alive and free of disease one to 15 years after treatment, all with well-preserved renal function (lowest glomerular filtration rate was 65 ml/min per (1.73 m 2 ). None of the survivors have hypertension. Eleven have died (two of unrelated disease) including six of the seven with spread outside the kidney. All three with unfavourable histology are alive. Four of the five metachronous presentations are alive, as are eight of 12 patients with synchronous bilateral tumours who presented since 2000. CONCLUSIONS: Appropriate chemotherapy and nephron-sparing surgery can achieve good results with preservation of adequate renal function in nearly all cases. Unfavourable histology did not have a reduced survival in our series. Metastatic spread outside the kidney had a poor prognosis.

The use of TachoSil in children undergoing liver resection with or without segmental liver transplantation.

INTRODUCTION: Local haemostatic agents are used for the control of surgical haemorrhage when standard techniques are inadequate, but there are few studies of these products in children. PATIENTS AND METHODS: This was a prospective, open-label study in which children (aged 4 weeks to 6 years) undergoing liver resection with or without segmental liver transplantation were treated with TachoSil, a collagen patch coated with a dry layer of human fibrinogen and human thrombin, if minor (i. e., oozing) or moderate bleeding was present after primary haemostatic treatment. Time to haemostasis after TachoSil application was the primary endpoint. Safety was assessed by adverse events (AEs), including post-operative infections, symptoms of graft rejection and re-operations. RESULTS: Enrolment was stopped early after 16 children had entered the study. 13 children underwent whole liver resection and transplantation and 3 patients underwent segmental resection. Satisfactory haemostasis was achieved in 13 children (81.3%; 95% CI: 61.8-100%) at 3 min and in 1 child at 8 min. Occurrence of AEs was as expected, with most being known complications of the underlying disease, surgical procedure, or use of immunosuppressive medication. No AEs were considered to be related to the use of TachoSil. CONCLUSIONS: The use of TachoSil for haemostasis after primary haemostatic treatment appears to be safe and effective in children undergoing liver resection.

Can fireworks-related injuries to children during festivities be prevented?

OBJECTIVE: To determine the epidemiological features and outcome of fireworks-related injuries among children 0 - 13 years old. DESIGN: A retrospective study from the trauma registry of a children's hospital from 2001 - 2009. RESULTS: Fifty-five children were treated for injuries from fireworks. The mean age was 8.8 years, 78% were boys, and the largest age group was 5 - 9 years old. Firecrackers accounted for 95% of the injuries; the most commonly injured body sites were hands (44%), eyes (42%) and face (31%); 47% of the patients had more than one injury. The most common injury type was burns (67%); 25 children were admitted, mostly to the burns and ophthalmology units. The mean length of hospital stay was 3.5 days. Surgical intervention was required in 38% of the patients. Most of the fireworks accidents occurred in or around the patients' homes. There were more fireworks-related injuries around Guy Fawkes Day (85%) than New Year's Eve (9%). CONCLUSION: Consumer fireworks cause serious but preventable injuries to children, either as users or bystanders. Children and their families should be encouraged to enjoy pyrotechnical displays conducted by professionals at designated areas. All fireworks for individual private use should either be supervised by an adult or banned. Current legislation should be more strictly enforced, especially the sale to under-age children.

Hepatic venous outflow obstruction in paediatric liver transplantation.

INTRODUCTION: Vascular complications after orthotopic split liver transplantation in children result in significant post-operative complications. MATERIALS AND METHODS: A review of children undergoing liver transplantation from 2004 to 2006 was undertaken. The data was obtained based on a proforma-based analysis. RESULTS: Seven of 106 transplants were identified to have hepatic venous outflow obstruction (HVOO) of whom five were males and two were females. Median age at transplant was 8 years (range 3 years 4 months-15 years). The median donor-to-recipient weight ratio was 2.78 (range 0.97-6.15). ANASTOMOTIC TECHNIQUE: Hepatic vein-IVC in four, Hepatic vein-hepatic vein (HV-IVC) confluence in two and cavo hepatic in one. Ascites was the commonest post op manifestation of HVOO. Although Doppler USG was useful in identifying the venous outflow obstruction, venography confirmed the exact site of obstruction aiding in therapeutic dilatation. Three of seven cases had early onset (<1 month) while 4/7 had late onset (>1 month). 5/7 underwent venography and dilatation, of whom three are well and one is awaiting a repeat venography and dilatation. 2/7 died without intervention and 1/7 died in the waiting list for retransplantation. CONCLUSION: The diagnosis of HVOO requires a high index of suspicion, prompting early venography to manage HVOO successfully. Technical steps to avoid HVOO are to keep the hepatic vein-caval anastomosis short and wide with triangulation and to avoid graft rotation at the hepato caval junction.

Isolated liver transplant in infants with short bowel syndrome: insights into outcomes and prognostic factors.

OBJECTIVE: Selected infants with short bowel syndrome (SBS) and progressive intestinal failure associated liver disease (IFALD) may benefit from isolated liver transplantation (iLTx). The aim of the study is to identify risk factors for unfavourable outcome in iLTx. PATIENTS AND METHODS: A retrospective review of medical records from 1998 to 2005 was undertaken. Risk factors were assessed by comparing long-term survivors with those who died after iLTx. RESULTS: Fifteen iLTx were performed in 14 infants with IFALD. All were parenteral nutrition (PN) dependent, but had tolerated enterally 54% (38-100) of energy intake before iLTx. Median residual bowel was 60 cm (30-200). Eight out of 14 had intact ileocaecal valve (ICV). Median bilirubin was 298 micromol/L (87-715) and all had portal hypertension. Eight out of 9 survivors were weaned from PN after median 15 months. In 4 out of 9 children, nontransplant surgery after iLTx facilitated intestinal adaptation. Growth velocity had improved at 3 years after iLTx (P=0.001). Five children who died had poor enteral tolerance following iLTx (P<0.002), which correlated with pretransplant dysmotility seen in 4 out of 5 children shown by contrast studies (P=0.02)and increased frequency of line infections before (>6/year P<0.04) and after (P<0.001) iLTx. CONCLUSIONS: Isolated liver transplantation is a lifesaving option for selected children with SBS and IFALD. Revised criteria are proposed: progressive IFALD; 50 cm functional bowel in absence of ICV or 30 cm with ICV; 50% daily energy intake tolerated enterally for 4 weeks with satisfactory growth; and children with dysmotile bowel should be assessed for combined liver/bowel transplant unless the dysmotility is resolved and associated with minimal line infections.

Challenges associated with paediatric pain management in Sub Saharan Africa.

The African child is particularly vulnerable to disease and injury, and subsequently, to pain and suffering. Factors such as inadequate training, language barriers, cultural diversity, limited resources and the burden of disease prevents sick and injured children from receiving basic pain care. This situation can only be rectified by providing pre and post graduate training on the safe use of analgesic preparations, the availability of drugs and government support.

Ashes to ashes: thermal contact burns in children caused by recreational fires.

Recreational open fires are an important and preventable cause of burn. In contrast to adults, who often sustain flame burns, children are at higher risk of thermal contact burns caused by hot embers many hours after the fire was first lit. Cases of thermal contact injury in children due to recreational fires were reviewed and the potential of a small charcoal fire to cause burns over a prolonged period was tested. Between 1993 and 2007, 67 children were admitted for treatment, with a median age of 1.6 years. Total burn surface area ranged from 0.5% to 19.5% (median 4%) with burns most commonly affecting the hands and feet. The average length of stay was 7 days and a total of 81 surgical procedures were carried out. Injury was most commonly sustained after falling into (40%), or accidentally crawling or walking on (30%), the remnants of an unextinguished fire. Small charcoal fires retain sufficient heat to cause injury at least 16h after lighting. Strategies for prevention of these injuries are outlined.

Assaults with a sharp object in small children: a 16-year review.

Injuries as a result of assaults with sharp object in small children are rare and data on them are scarce. The Red Cross War Memorial Children's Hospital is presently the only Children's Hospital in South Africa with a dedicated Level 1 trauma unit for children under the age of 13 years, and we have an annual trauma load of over 10,000 patients. A retrospective review was performed using the Data Base of the Child Accident Prevention Foundation of Southern Africa at the Red Cross War Memorial Children's Hospital in Cape Town. All children who were coded as an 'assault with sharp object' were included in this study. Five-hundred-and-fifty-one (551) patients were retrospectively reviewed, of which 373 (68%) were boys and 177 (32%) girls. The mean age of the children was 7 years. The majority of children (51%) sustained injuries at the head or neck region, 26% sustained an injury at the trunk and 26% at the extremities. The majority of children sustained minor injuries (62%), thirty-three (33%) moderate and 5% severe injuries. Three children died. The most commonly recorded object used in the assault was glass or (broken) bottles (33%) and knives (18%). Other objects recorded included sticks, stones, pens, pencils, scissors, machetes and nails. The majority of perpetrators were known to the child. Assaults with a sharp object in small children are relatively rare and represent only 0.328% of all paediatric trauma patients. Although rare, these injuries carry a significant morbidity and even mortality. The majority of injuries occurred at home. Prevention programmes, specifically targeting the caretakers, should be implemented to prevent these tragic injuries.