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.     

Organ Transplantation in Taiwan

Abstract: We performed the first successful kidney transplantation in Taiwan on May 27, 1968. Since then, kidney, heart, lung, pancreas, liver, and heart-kidney transplantations have been increasingly successful in restoring lives of otherwise dying patients with organ failure. The first successful kidney, liver, and heart transplantations in Asia were achieved in Taiwan in 1968, 1984, and 1987, respectively. Individual organ transplantation, organ transplant recipient survival, graft survival, and problems and pitfalls encountered in the care of organ transplantation recipients are analyzed. Using polymerase chain reaction amplification with sequence-specific primers, donor-specific DNA was detected in the peripheral blood of the patient who survived the longest (26 years) in this series. Interestingly enough, recently, we had a patient undergoing cadaveric renal transplantation in whom chi-merism was detected in her lymph nodes and skin only 3 years after transplantation. Organ procurement in Taiwan is the greatest problem, and we have been exerting our maximal effort to establish a transplantation coordination team to create a central network and to educate, procure, preserve, distribute, and increase the availability of organs and tissues for transplantation.     

Cadaveric kidney transplantation: five years experience at a single center

BACKGROUND: In the past, the majority of renal transplantations in Iran were from living donors, but recently cadaveric donation of organs is increasing. We reviewed our experience on kidney transplantation from cadaveric donors for the past 5 years in our center. METHODS: Between July 1998 and September 2004, 122 kidneys were removed from 61 cases of brain-dead patients and transplanted in 114 patients with end-stage renal disease in our center. Two kidneys had tumoral involvement and were discarded. Three kidneys were transplanted in other centers and three patients received en bloc kidney transplantations. In addition, we performed nine cases of heart, one case of liver, and one case of lung transplantations. All the recipients were followed for at least 1 year and posttreatment renal function and graft survival were determined. RESULTS: All cadaveric donors were brain dead due to car (30%) and motocycle (70%) accidents, with ages ranging from 5 to 56 years (mean, 24/4 years). The mean warm and total cold ischemia times were 7 minutes and 8.1 hours, respectively. The mean distance between harvesting center and our hospital was 65 km. The 1-year graft survival was 92.3%, with mean serum creatinine of 1.76 +/- 0.79 at 1 year. Of other transplanted organs, the liver and lung recipients died 24 hours and 45 days after operation. Among heart recipients, four are still alive. CONCLUSION: Cadaveric donors in developing countries including Iran can be excellent sources of organ donation.     

Pediatric transplantation, 1994–2003

This article uses OPTN/SRTR data to review trends in pediatric transplantation over the last decade. In 2003, children younger than 18 made up 3% of the 82,885 candidates for organ transplantation and 7% of the 25,469 organ transplant recipients. Children accounted for 14% of the 6,455 deceased organ donors. Pediatric organ transplant recipients differ from their adult counterparts in several important aspects, including the underlying etiology of organ failure, the complexity of the surgical procedures, the pharmacokinetic properties of common immunosuppressants, the immune response following transplantation, the number and degree of comorbid conditions, and the susceptibility to post-transplant complications, especially infectious diseases. Specialized pediatric organ transplant programs have been developed to address these special problems, The transplant community has responded to the particular needs of children and has provided them special consideration in the allocation of deceased donor organs. As a result of these programs and protocols, children are now frequently the most successful recipients of organ transplantation; their outcomes following kidney, liver, and heart transplantation rank among the best. This article demonstrates that substantial improvement is needed in several areas: adolescent outcomes, outcomes following intestine transplants, and waiting list mortality among pediatric heart and lung candidates,     

Organ Transplantation in the Madrid Autonomous Region

The Madrid Autonomous Region, a Spanish area with 6,200,000 inhabitants, has 7 hospitals authorized for organ transplantation, with 25 active programs for carrying out various transplantations: 18 for adults and 7 for children. Most of these hospitals are reference transplant centers for other Spanish regions. Between 715 and 760 transplantations are performed annually, which represents between 19% and 22% of Spanish activity. During 2007, 395 kidney, 220 liver, 55 heart, and 35 lung transplantations were performed, as well as 23 isolated or combination transplantations of other abdominal organs (pancreatic, intestinal, or multivisceral). Kidney, liver, heart, and children's intestinal transplant activity in 2007 represented 37%, 63%, 80%, and 100%, respectively, of all pediatric national activity. The Madrid Autonomous Region has a donation rate of 34.2 donors per million inhabitants. Of these, 30% are from non–heart-beating donors (NHBD), Maastrich criteria category 1 or 2. Various hospitals perform kidney, liver, and lung transplantations with these organs, representing 11% of the lung transplantations carried out in recent years, with this being a pioneer procedure worldwide. Despite the important transplant activity, we are working to increase donations, to improve organ donor detection and management protocols, as well as to reach a consensus on criteria to decrease the nonviability rates of potential transplant organs.     

Insulin resistance, LDL particle size, and LDL susceptibility to oxidation in pediatric kidney and liver recipients

BACKGROUND: Dyslipidemia is common after solid organ transplantation. We have described hypertriglyceridemia in about 50% of our pediatric kidney, and in about 30% of our liver recipients. The aim of the present study was to find out whether this post-transplantation hypertriglyceridemia after pediatric solid organ transplantation is associated with insulin resistance and the occurrence of small, dense low-density lipoprotein (LDL). METHODS: Fifty kidney and 25 liver recipients (aged 4 to 18 years) on triple immunosuppression, and 181 control children participated in the study for an average of 5.3 and 6.4 years after kidney and liver transplantation (range 1 to 11 years), respectively. Homeostasis model assessments for insulin resistance (HOMA) were calculated and fasting lipoprotein lipid profile, apolipoprotein A-I and B concentrations, LDL particle diameter, and indices of LDL susceptibility to copper-induced oxidation determined. RESULTS: Kidney patients had significantly higher serum total, high-density, and low-density lipoprotein cholesterol, triglyceride, apolipoprotein A-I and B concentrations than liver patients or control subjects (P < 0.003 for all). HOMA indices higher than the 95th percentile of Canadian normal children were seen in 50.0% of kidney (of liver 41.2%) recipients younger than 11 years, and in 27.3% of older recipients (of liver 37.5%). Smaller sized LDL or LDL of increased oxidizability was not more frequent in patients than in control children. CONCLUSION: Pediatric kidney recipients had significantly higher lipid and insulin concentrations than healthy control children. Combined hyperlipidemia and features of the dysmetabolic syndrome were common in children after kidney and liver transplantation. However, no small, dense LDL, or LDL prone to oxidation was seen in either group.     

Pediatric transplantation: the Hamburg experience

BACKGROUND: Since starting our program in 1989, 455 pediatric orthotopic liver transplantations have been performed using all techniques. In April 2001, we experienced our last in-hospital death of a pediatric liver-transplant recipient. Since then, all our liver-transplant children (n=170) were able to be discharged from the hospital. The aim of this study is to analyze the actual status of pediatric liver transplantation at the University of Hamburg and to find future perspectives to improve the results after pediatric liver transplantation. METHODS: From May 4, 2001 until September 8, 2004, 22 (13%) whole organs, 18 (11%) reduced-size organs, 79 (47%) split organs, and 51 (30%) organs from living donors were transplanted into 142 patients. One hundred forty-one were primary liver transplants, 25 retransplants, 3 third, and 1 fourth liver transplants. Of the 170 orthotopic liver transplantations (OLT), 31 (18%) were highly urgent (United Network of Organ Sharing [UNOS] I). RESULTS: After 170 consecutive pediatric liver transplants, no patients died during the hospital course (100% patient survival<3 months), but overall, 5 (2.9%) recipients died during further follow-up. The 3-month and actual graft survival rates are 93% and 85%, respectively. Twenty (11.8%) children had to undergo retransplantation. However, patient survival was not sustained by longer graft survival. Analyzing our series, we see that graft survival after reduced-size liver transplantation showed a significantly lower rate versus living-donor liver transplantation. CONCLUSION: The learning curve in pediatric liver transplantation has reached a turning point where immediate patient survival is considered the rule. The challenge is to increase graft survival to the same level. The long-term management of the transplant patients, with the aim of avoiding late graft loss and achieving excellent quality of life, will become the center of the debate.     

Cholesterol absorption and synthesis in pediatric kidney, liver, and heart transplant recipients

BACKGROUND: Hypercholesterolemia after organ transplantation is common. Previously, we observed higher serum total cholesterol (TC) concentrations in our pediatric kidney than liver or heart transplant recipients. To find an explanation to the observed difference, our kidney recipients' cholesterol synthesis and absorption efficiency was compared to those of liver and heart recipients. METHODS: Serum noncholesterol sterol ratios (10 x mmol to the mol of TC, surrogate estimates of hepatic cholesterol synthesis and intestinal absorption) were studied in 50 pediatric kidney, 25 liver and 12 heart transplant recipients without diabetes or cholestasis, and in 29 controls. RESULTS: The kidney recipients had lower Delta-cholesterol (P=0.031), similar lathosterol and higher desmosterol ratios (markers of cholesterol synthesis) (P=0.020), and similar campesterol and sitosterol ratios (markers of cholesterol absorption) when compared to the controls. The liver recipients had lower campesterol ratios than the kidney recipients and controls (P=0.002). Glomerular filtration rates were not associated with the ratios of noncholesterol sterols. Multivariate analysis showed markers of cholesterol synthesis to be lower and absorption to be higher in the kidney than the liver or the heart transplant recipients. Weight-adjusted dosages of immunosuppressive agents were associated with some ratios of noncholesterol sterols and cholestanol though these varied between the transplant recipient groups. CONCLUSIONS: Serum TC concentration in kidney recipients was not significantly associated with absorption efficiency or synthesis of cholesterol, though kidney transplantation was associated with low synthesis and high absorption efficiency of cholesterol. Immunosuppressive therapy with cyclosporine and methylprednisolone may modulate absorption efficiency and synthesis of cholesterol.     

The history and activities of transplantation in Turkey

The cornerstone events of transplantation history in Turkey are summarized herein. In 1975, we performed the first living-related renal transplant in Turkey. This was followed in 1978, by the first deceased donor kidney transplantation, using an organ supplied by Eurotransplant. In 1979 the law on harvesting, storage, grafting, and transplantation of organs and tissues was enacted; later that year, the first local deceased donor kidney transplantation was performed by our team. In 1988, another groundbreaking event in Turkey was successfully achieved; the first cadaveric liver transplantation; and in 1990, the first pediatric living-related segmental liver transplantation in Turkey and in the region by our team. One month later, an adult-to-adult living-related liver transplantation was successfully performed. Until now, we have performed 1506 kidney and since 1988, 121 liver transplantations. During 29 years of solid organ transplantation history in Turkey, 6686 kidney transplants have been performed nationwide in 28 different centers; 696 livers; 13278 corneas; 2883 bone marrow; 132 hearts; and 15 pancreas transplants. In 2001, the health ministry established the National Coordination Center as an umbrella organization to promote transplantation activities, especially for deceased donor organ procurement. Transplantation activities are accelerating day by day all around the country, but deceased donors are still far below the desired rates. Improvements in the fields of education and coordination should increase the quality and the quantity of transplantation activities.     

The use of pediatric cadaver kidneys in renal transplantation (Experience with 97 cases and comparison with adult kidneys)

Pediatric cadaver donors are an important pool of kidneys for human allotransplantation. Experiences with 97 transplantations of pediatric cadaveric kidneys (age: 4 months to 15 years) and comparison with 230 transplantations of adult kidneys (age: 16–25 and 40–68 years) are presented. The cumulative patient survival was similar in both groups, however, the graft survival was significantly lower in the pediatric donor group (p<0.05). This difference was established almost exclusively within the first 3 months after transplantation. In this group the percentage of technical complications in the first month was higher (13.4%) than in the adult kidney group (6.5%). The analysis of the whole pool of harvested kidneys shows a significantly higher rate of transplanted kidneys in the pediatric group (61%) as compared with the adult group (44.7%). In both groups the mode of arterial vascular anastomosis (end-to-end or end-to-side) does not influence the graft survival.Further investigations on pediatric donor kidneys are necessary. The utilization of pediatric cadaveric kidneys for transplantation should be increased because 20–25% of all potential kidney donors are younger than 15 years.     

Transplantation registry in Iran

National registries provide valuable bases for comparisons and aid innovative policies. Iran, with 70 million inhabitants, has a governmentally supported system of organ and tissue procurement and transplantation. By two acts of legislation, first in 1997 regarding governmental rewarding living kidney donation and second in 2000 regarding cadaveric transplantation, this field has had remarkable growth in the last decade, under the supervision of the Ministry of Health. Since the beginning of each organ or tissue transplantation activity up to 2006, 21,359 kidneys, 338 livers, 122 hearts, 20 lungs, 7 pancreas, 1898 bone marrows, 28,838 corneas, 1380 heart valves, and 1366 bones were transplanted in our country. Increases in the number of live kidney transplantations are taking place, but cannot keep pace with the increasing number of patients. It is highly recommended that we try to increase cadaveric transplantation in coming years.     

Combined liver and kidney transplantation: analysis of Padova experience

BACKGROUND/AIM: The main indications for combined liver and kidney transplantation (CLKT) are as follows: (1) cirrhosis with renal damage dependent or not upon liver disease, (2) renal failure with dialysis and concomitant liver end-stage disease, (3) congenital diseases, and (4) enzymatic liver deficiency with concomitant renal failure. The aim of this study was to evaluate our results with CLKT both in adult and pediatric patients. METHODS: From September 1995 to September 2006, 15 CLKT (2.8%) among 541 liver transplantations included 4 pediatric patients (27%). The main indications for CLKT were hepatitis C virus (HCV) and polycystic diseases in adult patients, and primary hyperoxaluria in pediatric patients. RESULTS: The double transplantation was performed from the same donor in all cases. All adult patients received whole liver grafts, whereas 3 split transplants and 1 whole liver graft were transplanted in the pediatric patients. Median liver and kidney cold ischemia times were 468 and 675 minutes, respectively. After a median follow-up of 36 months (range, 1-125), the overall survival rate was 80%. Five-year patient and graft survival rates were 100% for adult CLKT, whereas they were 50% for pediatric patients. We observed only 2 cases (18%) of delayed renal function, requiring temporary hemodialysis with progressive graft improvement. There was only 1 case of kidney retransplantation due to early graft nonfunction in a pediatric patient. CONCLUSION: Although CLKT is related to major surgical risks, results after transplantation are satisfactory with an evident immunological advantage.     

Live donor liver transplantation for acute liver failure

BACKGROUND: Acute liver failure (ALF) carries a high mortality unless urgent orthotopic liver transplantation (OLT) is performed on time. Live donors are utilized to treat this irreversible condition first in pediatric cases and then in adults. Herein, we aimed to report our experience with live donors for ALF in a country of a deceased donor organ donation rate is only 1.5 per million people. METHODS: Among the 245 live donor liver transplantations (LDLT) performed from June 1999 to December 2005, 14 of them (6%) were performed for ALF in 8 pediatric and 6 adult cases. Right lobes were harvested for the adult cases whereas left lateral segments were harvested for pediatric cases, except one child transplanted with a right lobe graft. The etiology of the disease was; acute hepatitis B in four cases, hepatitis A in three cases, Wilson disease two cases, autoimmune hepatitis in two cases, and was unknown in three cases. RESULTS: Three-year graft and patient survival is 79% for these series. Five of the six adult patients and six of the eight pediatric cases survived after transplantation. There was not any donor mortality or major morbidity. CONCLUSIONS: LDLT offers a safe and effective modality of treatment for ALF for both pediatric and adult patients to overcome the problem of organ shortage especially in countries where the chance of receiving an organ from a deceased donor is low.     

Technique of multiple organ procurement. Does the participation of the urology make sense?

Summary Today the organ donor operation in brain dead donors is mostly projected as multiple organ procurement (MOP). Not only the kidneys, but heart and liver or additionally lungs and pancreas are removed in MOP. A good synchronization between the collaborating transplantation groups (thoracic and abdominal surgeon, urologist) is essential to prevent loss of an organ because of technical problems. In Germany urologists perform more than 40 % of kidney transplantations. These urologic institutions perform the cadaver kidney retrievals and participate on MOP. If possible, an urologist experienced in renal transplantation should contribute to the care for quality of the kidneys. Since 1987 the transplant center of Bremen obtained 390 donor registrations. 202 organ donor operations have been performed (106 MOP and 96 exclusive kidney retrievals). 398 donor kidneys have been collected and 382 could be transplanted.      

Increasing organ donation rates from Muslim donors: lessons from a successful model

As the great majority of the population in Saudi Arabia is Muslim, the Islamic views about organ donation and transplantation have been the focus of interest to the transplant community in this and other Muslim countries. The first resolution of the Islamic council in Saudi Arabia (Senior Ulama Commission) about organ donation and transplantation was issued in 1982. It permitted tissue and organ transplantation from both living and cadaveric donors. This resolution marked a new era in organ transplantation in Saudi Arabia, leading to the formation of the Saudi Center of organ transplantation (SCOT), which organizes the process of organ donation and transplantation in Saudi Arabia. There were major strategies to reach the goals of the organ procurement centers adopted by SCOT: improving the awareness of the medical community to the importance of organ donation and transplantation, improving the awareness of the public at large to the importance of organ donation and transplantation, and developing an efficient coordinated system with both the donating hospitals and the transplant centers. Various organs had been transplanted in Saudi Arabia through the end of 2002: 3759 kidney transplants (1267 cadaver, 2492 living); 279 liver transplants(225 cadaver, 54 living); 92 heart transplants; 421 cornea transplants; 8 lungs; and 5 combined kidneys and pancreas. In addition, there have been many tissue donations of bone marrow, heart valves (264 hearts), skin, and bone. Despite the success of the Saudi program, there have been public and medical obstacles that have obviated the full benefit of cadaver donors. We suggest increasing the awareness of the medical community and the public at large to the importance of organ donation and transplantation.     

Skin disorders in patients transplanted in childhood

Only few data are available on skin disorders in pediatric organ transplant recipients. In order to describe the whole range of dermatological diseases in a population of pediatric organ transplant recipients, we studied a group of 217 consecutive organ transplant recipients (168 kidney, 29 heart, 19 liver, one lung) aged <18 years at transplantation followed at a single center. A total of 193 patients showed at least one skin disorder; 149 had more than one skin disease. The most common skin infections were warts (24.4%), pityriasis versicolor (20.7%), folliculitis (12.9%), intertrigo (6.5%); the most common drug side effects were hypertrichosis (69.6%), steroid acne (39.6%), gingival hyperplasia (29%) and severe xerosis (20.7%). Two patients (0.9%) developed nonmelanoma skin cancer. Our study summarizes the main skin complications in patients transplanted in childhood and underlines the necessity of regular dermatologic surveillance of these patients.     

Ecstasy-induced brain death and acute hepatocellular failure: multiorgan donor and liver transplantation

BACKGROUND: Ecstasy is a neurotoxic and hepatotoxic drug. Brain edema and fulminant hepatic failure are two of the most serious complications associated with the consumption of ecstasy. Acute ecstasy intoxication can transform a patient into an organ donor or a hepatic graft recipient. MATERIALS AND METHODS: In the last 5 years in our centers, we have had two multiorgan donors who died from ecstasy-induced brain edema and three patients who required urgent orthotopic liver transplantation for treatment of severe acute hepatocellular failure induced by this drug. We performed eight transplantations using the organs of these two brain-dead donors: one heart, one bipulmonary, three kidneys, one kidney-pancreas, and two livers. RESULTS: Toxicity caused by ecstasy was not observed in any of the eight patients who underwent transplantation. The clinical state and the graft function of the heart, two liver, renopancreatic, and three kidney recipients were normal for a follow-up period that ranged between 7 months and 4.5 years. The lung recipient died from multiorgan failure secondary to bilateral pneumonia 5 days after the transplantation, and one of the kidney transplant patients died as a result of intestinal lymphoma 6 months after transplantation. The three liver transplantations in the three patients with ecstasy-induced fulminant hepatic failure were performed successfully using orthotopic transplantation. These three recipients are asymptomatic and have normal-functioning hepatic grafts after follow-up of 3.5 years, 15 months, and 11 months, respectively. CONCLUSIONS: The thoracic and abdominal organs of people dying from ecstasy intoxication can be viable for transplantation. The short- and medium-term survival of the graft and of the recipient have been similar to that of other organ donors. Urgent liver transplantation is an effective therapeutic option in patients with ecstasy-induced acute hepatocellular failure.     

Living-related liver transplantation in pediatric patients

INTRODUCTION: Many developments in surgical technique, immunosuppression, and patient selection criteria have led to improved long-term patient and graft survival in pediatric patients receiving liver transplants. In this study, we examined the early results of 26 pediatric recipients who underwent 26 liver transplantations between January 2003 and December 2004 at our institution. MATERIALS AND METHODS: The most common indications for liver transplantation were cholestasis in 10 patients (38.5%) and Wilson's disease in 8 (30.8%). Other indications were fulminant hepatic failure (4 patients, 15.4%), tyrosinemia (2 patients, 7.7%), Caroli disease (1 patient, 3.8%), and cryptogenic cirrhosis (1 patient, 3.8%). One recipient with Byler disease and two with tyrosinemia also had incidental hepatocellular carcinoma. RESULTS: Of 26 patients, 24 (92.3%) underwent living-related liver transplantation and 2 (7.7%) underwent cadaveric transplantation. The medical records of all patients were retrospectively reviewed. Twenty-two of 26 survived with excellent graft function, showing 91.2%, 86.4%, and 81.6% at 3, 12, and 24 months graft and patient survival rates, respectively. Sixteen patients (61.5%) developed various morbidities with biliary and vascular complications being the most common. Four patients (15.3%) developed bile leaks. Four patients (15.3%) developed hepatic artery thromboses. Five patients (19.2%) developed life-threatening infections. Four patients (15.4%) died during the study period, three owing to infectious complications. The other patient died due to acute respiratory distress syndrome. CONCLUSION: Despite technical difficulties and a donor organ shortage, the results of liver transplantation in pediatric patients with end-stage liver disease have demonstrated promising results at our institution.     

Aspects of Present and Future Data Presentation in Scandiatransplant

Scandiatransplant is the Nordic organ exchange organization having existed for almost 40 years. With close collaboration between transplant centers in the Nordic countries, it has been valuable to ensure the optimal usage of available organs. The heart is the most often exchanged organ within the collaboration. It has been decided to create a priority for hyperimmunized kidney patients for compulsory exchange of organs from deceased donors.The age of the deceased organ donors has changed from younger to older donors. The evaluation of deceased kidney transplantations and deceased liver transplantations from 1995 to 2007 is shown for 4 countries. Iceland by itself is performing living donor kidney transplantations with great intensity. Scandiatransplant will make efforts to present more data than just transplantation to yield a more complete picture of organ transplantation.     

Selected activities in Scandiatransplant

Scandiatransplant is the Nordic organ exchange organization. It has existed for 35 years and it is owned by all organ transplantation hospital departments in the five Nordic countries--Denmark, Finland, Iceland, Norway, and Sweden. The use of living organ donors for kidney transplantation has become a more common procedure not only in Norway but also in Sweden and Denmark. For the first time, in 2003, one transplant center performed relatively more living donor kidney transplantations than with deceased donors. The overall organ transplant activity reveals a remarkably stable situation in the area covered by Scandiatransplant. Scandiatransplant as an organ exchange organization has changed from a solely kidney exchange organization to an organization in which the more immediate vital organs as liver and heart are exchanged more commonly than kidneys.