Living-donor liver transplantation in adults

End-stage liver disease is being treated by liver transplantation. Despite legislative and social efforts, the number of cadaveric organs suitable for liver transplantation has not grown to match the increasing demand. The insufficient number of grafts results in high mortality for patients on the waiting list and prolonged waiting times with increasing morbidity. Following the success of living related-donor segmental liver transplantation in children, an amended concept has been applied to the adult patients. The early experience with this technique, the process concerning the selection of the donor for the recipient, the risks of the donor, and the future evolution of living related-donor liver transplantation are the topics of this article. Received: 15 October 1999 Accepted: 20 October 1999     

Successful ABO-incompatible heart transplantation in two infants

In the pediatric age group shortage of donor hearts leads to mortality rates of 30-50% on the waiting list. Because of the immaturity of the immune system of infants, ABO-incompatible heart transplantation may be an option to increase donor availability. We transplanted two infants with blood type O at the age of 7 and 5 months, respectively, with complex congenital heart disease. Intraoperative plasma exchange was performed during cardiopulmonary bypass followed by standard immunosuppression. Both recipients received a blood type A donor organ. Plasma was exchanged up to six times until anti-A antibodies were eliminated. No hyperacute rejection occurred, ventricular function is excellent and there have been no acute rejection episodes up to 4 months after transplantation. Anti-A antibody titers remained low and eventually disappeared. ABO-incompatible cardiac transplantation shows good short-term results in young infants and appears to be a safe procedure to reduce mortality on the waiting list.     

Laparoscopic Living Donor Hepatectomy for Pediatric Liver Transplantation

Living donor liver transplantation is a well established modality, especially for pediatric transplantation with excellent early graft function and long-term results. Left lateral sectionectomy through open approach is a well-standardized procedure. Considering our acquired experience in both laparoscopic liver resection and standard open surgery for live donation in pediatric and adult patients, we decided to offer, for the first time in Belgium, a laparoscopic approach for the left lateral sectionectomy to a young mother. The patient was a child 6-months old, affected by biliary atresia and rapidly deteriorating while waiting on a deceased donor liver graft. Surgical technique and key-points of this procedure in the living donor are hereby discussed.     

Split-liver Transplantation: Future Use of Scarce Donor Organs

The main obstacle to a expansion of human liver transplantation is the lack of donor organs. At present mortality reported for pediatric and adult patients on the waiting list is 10%to 20%. This article focuses on several techniques to alleviate this problem. Several years ago, application of reduced-size liver transplantation overcame the donor shortage among small infants through the use of grafts shaped to almost any size needed. Today reduced-size grafts are only rarely used, most commonly with traumatized donor livers or particularly small pediatric donor livers. Split liver transplantation also yields a net gain of organs, in that it uses one organ to save either an adult and a child or, recently, two adults. The technique of ex situ splitting is progressively being replaced by the in situ splitting technique, which yields better preserved grafts,optimization of graft/donor matching by pretransplant manipulation(preconditioning), avoidance of early rejection in the recipient,portal decompression, temporary liver support, if necessary, and induction of fast regeneration. In acute hepatic failure, auxiliary heterotopic liver transplantation might be sufficient to support liver function until regeneration of the native liver has begun. Domino transplantation in some patients with inborn errors of metabolism or storage disease should be considered. This article focuses on increasing the organ supply by using split liver transplantation techniques and living-donor liver transplantation.     

Living-donor liver transplantation in children

Introduction: Living- related liver transplantation (LRLT) for paediatric recipients was developed 10 years ago to overcome the high mortality on the waiting list. Since then, liver transplantation programs around the world have begun to employ this method with encouraging results. This review describes the actual status of LRLT in children, aspects of donor selection, donor risks, and surgical technique, as well as an update of the results of the leading LRLT programs in the world. The donor operation has matured to the stage of being a standardised, teachable procedure with a low risk of morbidity or mortality. However, there is a percentage of potential donations that have to be declined for medical or socio- psychological reasons. LRLT provides grafts of excellent quality and short cold ischemic times. A major advantage is the fact that the optimal moment for the transplantation procedure can be chosen. Together with split-liver techniques, LRLT has a positive effect on the general situation of the paediatric waiting list for liver transplantation, with a reduction of pre-transplant mortality to nearly 0%. Received: 14 October 1999//Accepted: 20 October 1999     

Chronic myelogenous leukemia following kidney transplantation in a pediatric patient

The incidence of cancer is increased follow- ing kidney transplantation. Chronic myelogenous leukemia (CML) has been previously reported in ten adult patients and only one pediatric patient post kidney transplantation. We report one male patient aged 18.8 years, on chronic dialysis from the age of 2 years, who was transplanted from a cadaver donor at the age of 8 years. He was treated with recombinant human growth hormone (rhGH) before transplantation and with azathioprine after kidney transplantation. Eight years after transplantation, CML was diagnosed and he was successfully treated with hydroxyurea and α-interferon. The follow-up is 28 months. The possible role of the combined action of rhGH and azathioprine in CML genesis is discussed. Received: 2 February 2001 / Revised: 29 May 2001 / Accepted: 30 May 2001     

Combined Pancreatic Islet and Kidney Transplantation in a Child With Unstable Type 1 Diabetes and End‐Stage Renal Disease

Islet transplantation after successful kidney transplantation is a recognized treatment for adults with diabetes and end‐stage renal disease (ESRD), but has not been considered an option in the pediatric population. To our knowledge, we report the first combined islet and kidney transplant in a child. The patient was born with bilateral renal hypoplasia and was diagnosed with type 1 diabetes mellitus at age 13 months. He had erratic glycemic control and hypoglycemia unawareness. At 6 years of age, the child safely underwent simultaneous islet and live donor kidney transplantation. Although function of the islet graft was transient, the combined transplant provided significant benefits in terms of glucose control and overall growth and development. Such an approach represents a viable treatment option for pediatric patients with ESRD and unstable diabetes.     

Use of Vascularized Posterior Rectus Sheath Allograft in Pediatric Multivisceral Transplantation—Report of Two Cases

Restoring abdominal wall cover and contour in children undergoing bowel and multivisceral transplantation is often challenging due to discrepancy in size between donor and recipient, poor musculature related to birth defects and loss of abdominal wall integrity from multiple surgeries. A recent innovation is the use of vascularized posterior rectus sheath to enable closure of abdomen. We describe the application of this technique in two pediatric multivisceral transplant recipients—one to buttress a lax abdominal wall in a 22‐month‐old child with megacystis microcolon intestinal hypoperistalsis syndrome and another to accommodate transplanted viscera in a 10‐month child with short bowel secondary to gastoschisis and loss of domain. This is the first successful report of this procedure with long‐term survival. The procedure has potential application to facilitate difficult abdominal closure in both adults and pediatric liver and multivisceral transplantation.     

Liberal policy of split liver for pediatric liver transplantation. A single centre experience

Abstract We adopted a liberal policy of extensive use of split liver in a pediatric liver transplantation (LT) program. Over a 19‐month period, we have performed 64 LT in 54 patients with pediatric indications. One patient received two liver grafts as a part of a liver‐small bowel transplantation and was not considered. Of the 60 LT considered, performed in 53 patients, 34 were with split grafts. The 1‐year actuarial survival for the patients transplanted with a split graft was 81 % and 89% when only elective cases were considered. The median time on the waiting list was 22 days with no mortality. The extensive use of split liver allowed transplantation in a large number of pediatric patients, with good results without the need for living donor liver transplantation. We envisage a trend towards systematic splitting of liver grafts.     

Advantages of inferior vena caval flow preservation in combined transplantation of the liver and heart

Only a few cases of combined liver and heart transplantation have been reported in the literature, and no standard surgical procedure has yet been established. We report the successful transplantation of both liver and heart in a 28-year-old patient suffering from homozygous beta-thalassemia. We used Belghiti's technique of inferior vena caval flow preservation for liver transplantation, which avoids inferior vena cava occlusion by a side-to-side caval anastomosis. Applied to combined liver and heart transplantation, preservation of caval flow during liver transplantation may allow early discontinuation of cardiopulmonary bypass and, thus, minimize the general consequences of prolonged bypass. Received: 21 May 1996 Received after revision: 11 September 1996 Accepted: 23 September 1996     

Advances in pediatric liver and intestinal transplantation

BACKGROUND: Significant progress has been made with liver and intestinal transplantation in pediatric patients. Shortage of whole-organ cadaveric grafts has resulted in a high mortality rate for children awaiting transplantation. New surgical procedures such as split-liver transplantation and living-related liver transplantation have evolved over the last decade to maximize donor utilization in pediatric patients. METHODS: In this article we review the current indications and contraindications for liver and intestinal transplantation in children, the surgical innovations to expand an exceedingly small cadaveric liver pool, postoperative management, and the impact on patient and graft survival. RESULTS: Reduced-size liver transplantation provides children with much needed small grafts; however, split-liver transplantation may eliminate the need for reduced-size and living-related liver transplantation except in urgent situations. CONCLUSION: Liver transplantation is a durable procedure that provides excellent long-term survival. The use of living-related and split-liver transplantation has dramatically reduced the waiting periods for children and improved survival. In the past decade significant progress has been made with intestinal transplantation owing to improvements in surgical technique, immunosuppressive agents, and early identification and treatment of postoperative complications.     

Living related small bowel transplantation: donor surgical technique

OBJECTIVE: To describe a standardized technique for ileal graft procurement in the setting of living related bowel transplantation. SUMMARY BACKGROUND DATA: Living donor transplantation has been successfully developed for kidney, liver, pancreas, and lung transplantation. More recently, living related small bowel transplantation (LR-SBTx) has been developed with the aim of expanding the pool of intestinal graft donors and reducing the mortality in patients on the waiting list. To date, a total of 25 LR-SBTx worldwide have been reported to the international registry. We herein report the largest single center experience. METHODS: A segment of ileum, 150 to 200 cm, is resected 20 cm proximal to the ileocecal valve (ICV), which is always preserved. The arterial inflow is given by the terminal branch of the superior mesenteric artery and venous outflow by a proximal segment of the superior mesenteric vein. The entire bowel is measured intraoperatively and at least 60% of intestine length is left in the donor. RESULTS: Since 1998, we have performed 9 terminal ileum resections for small bowel donation. None of the donors has experienced persistent alteration of bowel habits or malabsorption; only 1 minor wound complication has occurred. CONCLUSIONS: Terminal ileal resection with preservation of the ICV seems to assure fast functional recovery of the donor and has minimal postoperative complications.     

Intestinal Transplantation in Children: The First Successful Italian Series

The preliminary experience of the first Italian program of pediatric intestinal transplantation is presented herein. A multidisciplinary group with broad experience in pediatric solid organ transplantation started the program. Nine children with complications of chronic intestinal failure were listed for transplantation. One child died on the waiting list; one received an isolated liver transplantation; three isolated intestinal; three multivisceral; and one, a combined liver/intestine transplantation. There was no in-hospital mortality, and all children were weaned from parenteral nutrition. The recipient of the multivisceral graft died after 14 months for unknown causes. All other recipients are alive after a median follow-up of 13 months. Patient and graft actuarial survivals for recipients of intestinal grafts were 100% at 1 year and 75% at 2 years.     

Delayed primary closure of the abdominal wall after cadaveric and living related donor liver graft transplantation in children: a safe and useful technique

Due to the shortage of size-matched liver donors, relatively oversized liver grafts (even after ex situ volume reduction) are frequently used for liver transplantation in children. This was recently observed when livers from large, living related donors were procured for transplantation in very small recipients. Given that abdominal hyperpressure can compromise vascular flow in the new graft, primary closure of the abdomen was delayed by temporary Silastic prosthetic closure in selected cases. The new technique was original in that the skin was closed, avoiding fluid loss and reducing the risk of infections reported with other techniques, and in that reoperation allowed for a delayed, but primary-type, closure (fascia and skin) that resulted in an esthetically correct aspect. Over a period of 7 years, 330 pediatric liver transplantations were performed, and delayed prosthetic closure was achieved successfully and safely in 47 cases. The present report outlines this clinical experience. Received: 26 May 1997 Received after revision: 14 October 1997 Accepted: 19 November 1997     

Impact of Adult Living Donor Liver Transplantation on Waiting Time Survival in Candidates Listed for Liver Transplantation

Studies comparing adult living donor liver transplantation to deceased donor liver transplantation have focused on post-transplant survival. Our aim was to focus on the impact of living donor liver transplant on waiting time mortality and overall mortality. We analyzed the affect of living donor liver transplantation on waiting time mortality and overall mortality (from listing until last follow up) in a cohort of 116 transplant candidates. Fifty-eight candidates who had individuals present as potential living donors (volunteer group) were matched by MELD score to 58 liver transplant candidates who did not have individuals present as a potential living donor (no volunteer group). Twenty-seven percent of candidates in the no volunteer group and 62% of candidates in the volunteer group underwent liver transplantation, p = 0.0003. One-year waiting list mortality for the volunteer group and no volunteer group was 10% and 20%, respectively, p = 0.03. Patient survival from the time of listing to last follow up was similar between the two groups. In our study group, living donor liver transplantation is associated with a higher rate of liver transplantation and lower waiting time mortality. In the era of living donor liver transplantation, estimates of patient survival should incorporate waiting time mortality.     

Splenic artery aneurysm and orthotopic liver transplantation

Splenic artery aneurysms are a rare but potentially fatal complication after liver transplantation. We report three cases presenting in a 12-month period in adult patients who underwent transplantation for chronic liver disease. Doppler ultrasound of the splenic artery should be performed in all patients with cirrhosis and portal hypertension who are being assessed for liver transplantation. The aneurysm can be ligated at the time of transplantation. Received: 28 April 1998 Received after revision: 31 July 1998 Accepted: 23 September 1998     

Situs inversus of donor or recipient in liver transplantation

Situs inversus is a rare anatomical abnormality that is often associated with multiple, complex malformations. In the past, patients with situs inversus were considered unsuitable candidates for transplantation or organ donation because associated visceral, and especially vascular, anomalies pose special technical difficulties. Recently, several cases of successful liver transplantation in recipients with situs inversus have been published using modified surgical techniques. This report reviews the literature and describes our own experience, including two liver graft recipients with complete and incomplete situs inversus, and one patient who underwent successful transplantation using a liver from a donor with situs inversus. Received: 10 October 1997 Received after revision: 22 December 1997 Accepted: 9 January 1998     

Pediatric liver transplantation. Introduction of a program for southern Germany in Heidelberg

Abstract:  Pediatric liver transplantation in Germany is exclusively performed in four centers in the north of Germany. We report our experience with the implementation of a new pediatric liver transplantation program in Heidelberg for children living in the south of Germany. In a pilot phase, we have transplanted eight children with various transplantation techniques including reduced size, left lateral split (segments 2 and 3), and full left split (segments 1–4). All transplantations were successful. No vascular complications occurred. The immunosuppressive regimen we used was cyclosporine A and methylprednisolone. The rate of acute rejection was three of eight patients. No patient required a retransplantation. One patient died due to a severe fungal sepsis he had acquired prior to transplantation. We conclude that in a multidisciplinary approach with careful patient selection a new program for pediatric liver transplantation can be successfully established.     

Survival Advantage of Pediatric Recipients of a First Kidney Transplant Among Children Awaiting Kidney Transplantation

The mortality rate in children with ESRD is substantially lower than the rate experienced by adults. However, the risk of death while awaiting kidney transplantation and the impact of transplantation on long‐term survival has not been well characterized in the pediatric population. We performed a longitudinal study of 5961 patients under age 19 who were placed on the kidney transplant waiting list in the United States. Of these, 5270 received their first kidney transplant between 1990 and 2003. Survival was assessed via a time‐varying nonproportional hazards model adjusted for potential confounders. Transplanted children had a lower mortality rate (13.1 deaths/1000 patient‐years) compared to patients on the waiting list (17.6 deaths/1000 patient‐years). Within the first 6 months of transplant, there was no significant excess in mortality compared to patients remaining on the waiting list (adjusted Relative Risk (aRR) = 1.01; p = 0.93). After 6 months, the risk of death was significantly lower: at 6–12 months (aRR = 0.37; p < 0.001) and at 30 months (aRR 0.26; p < 0.001). Compared to children who remain on the kidney transplant waiting list, those who receive a transplant have a long‐term survival advantage. With the potential for unmeasured bias in this observational data, the results of the analysis should be interpreted conservatively.     

Improved graft survival of pediatric liver recipients transplanted with pediatric-aged liver donors

BACKGROUND: Improving graft survival after liver transplantation is an important goal for the transplant community, particularly given the increasing donor shortage. We have examined graft survivals of livers procured from pediatric donors compared to adult donors. METHODS: The effect of donor age (<18 years or > or =18 years) on graft survivals for both pediatric and adult liver recipients was analyzed using data reported to the UNOS Scientific Registry from January 1, 1992 through December 31, 1997. Graft survival, stratified by age, status at listing, and type of transplant was computed using the Kaplan-Meier method. In addition, odds ratios of graft failure at 3 months, 1 year, and 3 years posttransplant were calculated using a multivariate logistic regression analysis controlling for several donor and recipient factors. Modeling, using the UNOS Liver Allocation Model investigated the impact of a proposed policy giving pediatric patients preference to pediatric donors. RESULTS: Between 1992 and 1997 pediatric recipients received 35.6% of pediatric aged donor livers. In 1998 the percent of children dying on the list was 7.4%, compared with 7.3% of adults. Kaplan-Meier graft survivals showed that pediatric patients receiving livers from pediatric aged donors had an 81% 3-year graft survival compared with 63% if children received livers from donors > or =18 years (P<0.001). In contrast, adult recipients had similar 3-year graft survivals irrespective of donor age. In the multivariate analysis, the odds of graft failure were reduced to 0.66 if pediatric recipients received livers from pediatric aged donors (P<0.01). The odds of graft failure were not affected at any time point for adults whether they received an adult or pediatric- aged donor. The modeling results showed that the number of pediatric patients trans planted increased by at most 59 transplants per year. This had no significant effect on the probability of pretransplant death for adults on the waiting list. Waiting time for children at status 2B was reduced by as much as 160 days whereas adult waiting time at status 2B was increased by at most 20 days. CONCLUSION: A policy that would direct some livers procured from pediatric- aged donors to children improves the graft survival of children after liver transplantation. The effect of this policy does not increase mortality of adults waiting. Such a policy should increase the practice of split liver transplantation, which remains an important method to increase the cadaveric donor supply.