Standardized quick en bloc technique for procurement of cadaveric liver grafts for pediatric liver transplantation

This paper describes a quick procedure for cadaveric liver graft retrieval during multiple organ harvesting. The technique is based on minimal preliminary dissection, absence of in situ direct portal perfusion, and en bloc removal of the liver and pancreas, with an aortic patch encompassing the coeliac trunk and superior mesenteric artery. The results of 110 pediatric liver transplantations with 109 organs harvested using this technique are reported. There were no graft harvesting injuries. The liver graft primary nonfunction rate was 4.5% (5/110). The 3-month retransplantation rate was 10%. The actual patient survival rates were 93% at 3 months and 90% at 1 year; actual graft survival rates were 85.5% and 78%, respectively. The technique described was at least as safe as conventional procedures. A major advantage of the procedure is its flexibility, which allows for the easily combined procurement of other organs (whole pancreas and intestine).     

Clinical pharmacokinetics of Neoral in pediatric recipients of primary liver transplants

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i. v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22 % and 21 % for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability. Received: 29 November 1996 Received after revision: 10 April 1997 Accepted: 15 May 1997     

Living-Related Versus Deceased Donor Pediatric Liver Transplantation: A Multivariate Analysis of Technical and Immunological Complications in 235 Recipients

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.     

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.     

CD4+ T cell response to factor VIII in hemophilia A, acquired hemophilia, and healthy subjects

These studies have begun to clarify the complex cellular mechanisms involved in the immune response to factor VIII. Although vigorous sensitization of CD4+ cells occurs in healthy subjects, the absence of clinically significant levels of inhibitor antibodies is likely related to the prompt down-regulation of the immune response. It may also be possible that the specific epitope repertoire recognized by CD4+ cells plays a role in the outcome of the immune response to factor VIII. Further characterization and comparison of the CD4+ repertoire in healthy subjects with that of hemophilia patients with and without inhibitors will help clarify which mechanism explains the absence of productive inhibitor synthesis in certain individuals. Also, it might identify CD4+ epitopes recognized by T helper cells that are essential for inhibitor synthesis. Additional studies to further characterize the role of Th1 and Th2 cells in the immune response to factor VIII may also be needed for the design of novel therapeutic strategies aimed at preventing inhibitor development.     

Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation

Between 1984 and 1996, the authors performed 499 liver transplants in 416 children less than 15 years old. The overall patient survival at 10 years was 76.5%. It was 71.3% for the 209 children grafted in 1984–1990; 78.5% for biliary atresia (n =?286), 87.3% for metabolic diseases (n?=?59), and 72.7% for acute liver failure (n?=?22). The 5-year survival was 73.6% for the 209 children grafted in 1984–1990 and 85% for the 206 grafted in 1991–1996. Scarcity of size-matched donors led to the development of innovative techniques: 174 children who electively received a reduced liver as a first graft in our center had a 5-year survival of 76% while 168 who received a full-size graft had a survival of 85% (NS). Results of the European Split Liver Registry showed 6-month graft survival similar to results obtained with full-size grafts collected by the European Liver Transplant Registry. Extensive use of these techniques allowed the mortality while waiting to be reduced from 16.5% in 1984–1990 to 10% in 1991–1992. It rose again to 17% in 1993, leading the authors to develop a program of living related liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In elective cases, a detailed analysis was made of the 45 children listed for LRLT between July 1993 and March 1997 and the 79 registered on the cadaveric waiting list during the same period. Mortality while waiting was 2% and 14.5% for the LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and 16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant survival was 88% and 82% for children who received a LRLT or a cadaveric graft, respectively. Overall survival from the date of registration was 86% and 70% (P?<?0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival in children less than 1?year of age at transplantation was 88.8% and 80.3% with a LRLT or cadaveric graft, respectively; patient survival after 3 months post-transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and 93.7% in children hospitalized for complications of their disease, and 89.5% and 77.7% for children hospitalized in an intensive care unit at the time of transplantation for children who received a LRLT or cadaveric graft, respectively. It is concluded that LRLT seems to be justified for multidisciplinary teams having a large experience with reduced and split liver grafting.     

Catheter problems in the use of ventricular cardiovascular assist systems

The prerequisite for efficient assist-ventricles and impulses in the pulsatile pumping function are sufficiently dimensioned afflux and flowing off connections. In systematic investigations on the hydraulic circulation model the cannulas from an internal parameter of 12 mm with a total length of the connection distance to the inflow and outflow valve, respectively, at the bypass ventricle of 30 cm proved sufficient for performing a volume of output of 5-6 l/min in clinic-relevant filling pressures in a hypodynamic circulatory situation. Connection cannulas for the heart-lung machine used in routine work are not sufficient in periodic filling and ejection processes in the pulsatile pumping function for an effective decompression and effective increase of the cardiac output. In case of an ECG-triggered mode of action of the ventricular assist-system an increase of frequency up to 130/min in after that incomplete filling of the assist-ventricle does not remarkably restrict the effectiveness of the assist-system.     

Characteristics of Epstein-Barr virus primary infection in pediatric liver transplant recipients

BACKGROUND/AIM: Pediatric liver transplant recipients are at high risk of Epstein-Barr virus infection. However the incidence of clinical symptoms and the graft function at the time of acute infection remains poorly documented. The aim of this study was to monitor the clinical and biochemical events associated with primary Epstein-Barr virus infection. METHODS: Clinical and biological patterns associated with Epstein-Barr virus infection were prospectively searched in 38 liver transplanted children. Polymerase chain reaction and anti-Epstein-Barr virus IgM antibodies were used at regular intervals to detect the timing of primary infection. RESULTS: Five children (13%) had pretransplant immunity, 26 (68.5%) developed primary Epstein-Barr virus infection 15 to 90 days after transplantation and seven (18.5%) remained Epstein-Barr virus negative. The four patients with clinical symptoms at the time of infection subsequently developed post-transplant lymphoproliferative disease. A single post-transplant lymphoproliferative disease occurred in non-symptomatic patients (overall incidence 13%). No mortality was associated with post-transplant lymphoproliferative disease. Two asymptomatic patients had abnormal liver function tests possibly related to primary Epstein-Barr virus infection. CONCLUSION: Epstein-Barr virus primary infection occurs in 80% of seronegative patients within 3 months after OLT. Clinical symptoms are rare and closely associated with post-transplant lymphoproliferative disease. Outside post-transplant lymphoproliferative disease, the consequences of infection are marginal.     

Current status and actual need for pediatric liver transplantation in Southern Vietnam

Liver transplantation (LT) has considerably improved the outcome of patients with end‐stage liver disease, especially in children. The first pediatric LT in Vietnam was performed in 2004. To assess the current need for pediatric LT in Southern Vietnam, a total of 280 patients with chronic liver disease followed at Children's Hospital 2 (Ho Chi Minh City), the only pediatric LT center in this region, were evaluated from January 2009 to June 2014. Sixty‐seven patients satisfied criteria for LT but only one transplant surgery occurred since 2009. Parental consent for LT was obtained only in 28.4% of patients. The main reasons for the small number of LTs were financial costs, far distance from home, lifelong follow‐up and treatment, and shortage of organ donors. We conclude that the current need for pediatric LT in Southern Vietnam is high. Efforts should be made to develop the liver transplant program in this developing country.