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.

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.

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.

The regulation of circadian period by phototransduction pathways in Arabidopsis.

Transgenic Arabidopsis plants expressing a luciferase gene fused to a circadian-regulated promoter exhibited robust rhythms in bioluminescence. The cyclic luminescence has a 24.7-hour period in white light but 30- to 36-hour periods under constant darkness. Either red or blue light shortened the period of the wild type to 25 hours. A phytochrome-deficient mutation lengthened the period in continuous red light but had little effect in continuous blue light, whereas seedlings carrying mutations that activate light-dependent pathways in darkness maintained shorter periods in constant darkness. These results suggest that both phytochrome- and blue light-responsive photoreceptor pathways control the period of the circadian clock.

Circadian clock mutants in Arabidopsis identified by luciferase imaging.

The cycling bioluminescence of Arabidopsis plants carrying a firefly luciferase fusion construct was used to identify mutant individuals with aberrant cycling patterns. Both long- and short-period mutants were recovered. A semidominant short-period mutation, timing of CAB expression (toc1), was mapped to chromosome 5. The toc1 mutation shortens the period of two distinct circadian rhythms, the expression of chlorophyll a/b-binding protein (CAB) genes and the movements of primary leaves, although toc1 mutants do not show extensive pleiotropy for other phenotypes.

Conditional circadian dysfunction of the Arabidopsis early-flowering 3 mutant.

Photoperiodic responses, such as the daylength-dependent control of reproductive development, are associated with a circadian biological clock. The photoperiod-insensitive early-flowering 3 (elf3) mutant of Arabidopsis thaliana lacks rhythmicity in two distinct circadian-regulated processes. This defect was apparent only when plants were assayed under constant light conditions. elf3 mutants retain rhythmicity in constant dark and anticipate light/dark transitions under most light/dark regimes. The conditional arrhythmic phenotype suggests that the circadian pacemaker is intact in darkness in elf3 mutant plants, but the transduction of light signals to the circadian clock is impaired.

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.

Clock proteins: turned over after hours?

Light sensitivity and the involvement of unstable proteins are key features of circadian clocks. Both photoreception and ubiquitin conjugation may be associated with nuclear regulators encoded by genes recently identified in Arabidopsis.

Circadian rhythms: PASsing time.

Links are being discovered between the circadian clock mechanisms in different species. The Neurospora Frequency protein has a rhythm of abundance and phosphorylation similar to that of the Drosophila Period protein, and Neurospora and mouse clock components, like Period, have 'PAS' domains.

Functional independence of circadian clocks that regulate plant gene expression.

BACKGROUND: Circadian clocks regulate the gene expression, metabolism and behaviour of most eukaryotes, controlling an orderly succession of physiological processes that are synchronised with the environmental day/night cycle. Central circadian pacemakers that control animal behaviour are located in the brains of insects and rodents, but the location of such a pacemaker has not been determined in plants. Peripheral plant and animal tissues also maintain circadian rhythms when isolated in culture, indicating that these tissues contain circadian clocks. The degree of autonomy that the multiple, peripheral circadian clocks have in the intact organism is unclear. RESULTS: We used the bioluminescent luciferase reporter gene to monitor rhythmic expression from three promoters in transgenic Arabidopsis and tobacco plants. The rhythmic expression of a single gene could be set at up to three phases in different anatomical locations of a single plant, by applying light/dark treatments to restricted tissue areas. The initial phases were stably maintained after the entraining treatments ended, indicating that the circadian oscillators in intact plants are autonomous. This result held for all the vegetative plant organs and for promoters expressed in all major cell types. The rhythms of one organ were unaffected by entrainment of the rest of the plant, indicating that phase-resetting signals are also autonomous. CONCLUSIONS: Higher plants contain a spatial array of autonomous circadian clocks that regulate gene expression without a localised pacemaker. Circadian timing in plants might be less accurate but more flexible than the vertebrate circadian system.

Circadian biology: clocks for the real world.

The circadian system of Neurospora crassa includes a molecular feedback loop that is entrainable by light. A recent study has shown that a second, elusive oscillator interacts with the feedback loop to drive output rhythms.

Circadian Control of cab Gene Transcription and mRNA Accumulation in Arabidopsis.

An intriguing property of many organisms is their ability to exhibit rhythmic cellular events that continue independently of environmental stimuli. These rhythmic processes are generated by an endogenous mechanism known as the biological clock. We wished to determine whether Arabidopsis thaliana will serve as a model plant system for a molecular genetic dissection of the circadian clock. To this end, we investigated the expression of Arabidopsis chlorophyll a/b-binding protein (cab) genes throughout the circadian cycle. Steady-state mRNA levels of the cab2 and cab3 genes showed a dramatic circadian cycling in plants shifted from light/dark cycles to constant darkness, whereas the cab1 mRNA level exhibited little or no cycling under the same conditions. Analysis of cab promoter fusions in transgenic tobacco revealed that both the cab1 and cab2 5[prime] upstream regions confer circadian-regulated expression on a chloramphenicol acetyltransferase (cat) reporter gene. In vitro nuclear run-on transcription assays also indicated that the transcription of the cab1 and cab2 genes is circadian regulated in Arabidopsis. Taken together, these data suggest that a post-transcriptional mechanism influences cab1 mRNA levels in Arabidopsis. The identification of circadian-regulated cis-acting elements in the cab1 and cab2 upstream regions will provide powerful tools for both molecular and genetic analysis of the higher plant circadian clock.

Ischaemic preconditioning of the liver before transplantation.

PURPOSE: Assessment of the effect of a short ischaemic time prior to liver transplantation on the liver graft. METHODS: White X Landrace pigs (N=10) were subjected to liver transplantation. Before being removed from the donor animal, the livers were randomised into two groups: group 1--pre-procurement ischaemia (15 minutes' temporary arrest of portal venous and hepatic arterial inflow to the liver, followed by reperfusion of these vessels for a period of 15 minutes); group 2--no prior inflow occlusion (control group). In group 1 a spleno-jugular bypass was established to prevent venous congestion, portal venous hypertension, intestinal oedema and bacterial translocation. The livers were perfused with Eurocollins solution (4 degrees C), after which they were stored on ice for a period of 3 hours' cold ischaemic time. Hepatocellular injury was assessed according to liver cell function tests (aspartate aminotransferase, AST), biochemical indicators of reperfusion injury (malondialdehyde) and histopathology. RESULTS: There was a significant rise of AST in both groups 1 hour after transplantation (from 51 +/- 27 IU/l to 357 +/- 152 IU/l in group 1 and from 29 +/- 10 IU/l to 359 +/- 198 IU/l in group 2). AST levels were marginally lower in group 1 at 2 and 4 hours after transplantation. There was also a rise in malondialdehyde levels in both groups at 5, 20, 40 and 60 minutes after transplantation. Levels of malondialdehyde were lower in the primed group at 5, 20 and 40 minutes, while the levels at 60 minutes after transplantation were comparable. Histological changes, as measured by vacuolisation, neutrophil infiltration and hepatic cell necrosis, were less in livers transplanted after ischaemic preconditioning, although the difference was not significant. CONCLUSIONS: Ischaemic preconditioning of the donor liver seems to decrease hepatocellular damage, reperfusion injury and histological changes in the liver after transplantation. Further studies with larger numbers are indicated.

How plants tell the time.

The components of the circadian system that have recently been discovered in plants share some characteristics with those from cyanobacterial, fungal and animal circadian clocks. Light input signals to the clock are contributed by multiple photoreceptors: some of these have now been shown to function specifically in response to light of defined wavelength and fluence rate. New reports of clock-controlled processes and genes are highlighting the importance of time management for plant development.

Is serum gentamicin level a good predictor of graft injury in intestinal transplantation?

INTRODUCTION: Following intestinal transplant (SBT), the early diagnosis and treatment of rejection is a major management aim. The diagnosis of rejection is based on histology of stomal biopsies. Oral gentamycin (2.5 mg/kg) was used for selective decontamination of the digestive system. Our hypothesis was that gentamycin might be absorbed in the presence of graft dysfunction. AIM: Our goal was to assess the correlation between serum gentamycin level and the health of the intestinal graft. SUBJECTS AND METHODS: Among 33 SBT performed from 1993 to 2005, serum gentamycin levels were performed once weekly or more often when there was a suspicion of rejection. All data were analyzed retrospectively. RESULTS: Adequate trough levels were achieved for only 23 patients, six of whom had histologically proven rejection and only one did not have a raised gentamycin content. Five patients with raised levels but no rejection included two with severe intestinal ischemia and three with bowel obstruction/ileus. Four of the five patients required laparotomies. CONCLUSION: We concluded that in our study raised serum gentamycin levels were a good predictor of rejection or significant injury to the graft.

Liver transplantation for children: Red Cross Children's Hospital experience.

BACKGROUND: The liver transplant program for infants and children at the Red Cross Children's Memorial Hospital is the only established pediatric service in sub-Saharan Africa. Since 1985, 250 infants and children have been assessed and 155 accepted for transplantation. METHODS: Since 1987, 76 children (range 6 months to 14 years) have had 79 liver transplants, with biliary atresia being the most frequent diagnosis. The indications for transplantation include biliary atresia (n = 44), metabolic (n = 7), fulminant hepatic failure (n = 10), redo transplants (n = 3), and other (n = 15). Three combined liver/kidney transplants have been performed. Forty-nine were reduced-size transplants with donor: recipient weight ratios ranging from 2:1 to 11:1, and 29 children weighed < 10 kg. RESULTS: Fifty-six (74%) patients survived 3 months to 12 years posttransplant. Cumulative 1- and 5-year patient survival data are 79% and 70%, respectively. However, with the introduction of prophylactic intravenous gancyclovir and the exclusion of hepatitis B virus (HBV) IgG core Ab-positive donors, the projected 5-year pediatric survival has been >80%. Early (<1 month) post-liver-transplant mortality was low, but included: primary malfunction (n = 1); inferior vena cava thrombosis (n = 1); bleeding esophageal ulcer (n = 1); and sepsis (n = 1). Late morbidity and mortality was mainly due to infections: de novo hepatitis B (5 patients, 2 deaths); Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disease (12 patients, 7 deaths); and cytomegalovirus disease (10 patients, 5 deaths). Tuberculosis (TB) treatment in three patients was complicated by chronic rejection (n = 1) and TB drug-induced subfulminant liver failure (n = 1). CONCLUSIONS: Despite limited resources, a successful pediatric program has been established with good patient and graft survival figures and excellent quality of life. Shortage of donors due to HBV and human immunodeficiency virus (HIV) leads to significant waiting list mortality and infrequent transplantation.