First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion

One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion. The full‐size liver graft was derived from a 13‐year‐old, female DCD donor and was end‐ischemic pretreated with dual hypothermic oxygenated machine perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers . During 2 hours of machine perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16‐year‐old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion and illustrates the potential role of ex situ machine perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation.     

Transmission of clear cell tumor in a graft liver from cadaveric donor: Case report

Backes AN, Tannuri ACA, de Mello ES, Gibelli NEM, de Castro Andrade W, Tannuri U. Transmission of clear cell tumor in a graft liver from cadaveric donor: Case report. Abstract: Neoplasms in children after organ transplantation are related to the type and intensity of immunosuppression and the donor–recipient serostatus, especially in relation to the Epstein–Barr virus. The patient was a two‐yr‐old female child with biliary atresia who underwent a liver transplantation from a female cadaver donor. Two adults received kidney transplants from the same donor. Nine months after transplantation, one of the adult recipients developed an urothelial tumor in the kidney graft. Imaging tests were repeated monthly in the liver‐transplanted child and revealed no abnormalities. However, one yr and two months after the transplantation, the patient developed episodes of fever. At that time, imaging and liver biopsy showed a clear cell tumor of urothelial origin in the graft and the disease was limited to the liver. The patient underwent liver retransplantation, and she is currently free of tumor recurrence. Although rare, the occurrence of tumors in the post‐transplant period from cadaver donors, without previously diagnosed tumors, is one of the many problems encountered in the complex world of organ transplantation.     

The treatment of end-stage liver disease in childhood

With the availability of orthotopic liver transplantation as a definitive treatment option for most cases of end-stage liver disease in children, there is renewed interest in this hitherto universally fatal condition. The potential for long-term survival after liver transplantation without disability is a realistic prospect for the majority, although the surgery is one of the most difficult surgical procedures available and represents a daunting prospect. The success of liver transplantation (80% one year and approximately 70% five year survival) has required virtually a re-definition of the diagnosis of end-stage liver disease with a view to predicted outcome and timely intervention. This includes a more aggressive approach to supportive treatment in order to maintain (if not improve) the patient's clinical status, if the treatment option of transplantation is decided upon. Preferably this treatment option should be considered and offered immediately the condition of end-stage liver disease is realised, in order to allow time for full and frank discussion of treatment options, to optimize supportive therapy, to evaluate suitability for liver transplantation and to maximize prospects of obtaining a donor organ. In Australia, particularly in children, liver transplantation is limited by the scarcity of suitable donor organs, although the development of reduction hepatectomy of an adult organ has allowed access to a much larger donor pool. This development has particular advantages in Australia, allowing organs from 80 kg adults to be transplanted successfully into 5 kg or 6 kg infants and has, at the time of writing, virtually eliminated potential paediatric recipient deaths while awaiting a suitable donor.     

Early complications after liver transplantation in children and adults: Are split grafts equal to each other and equal to whole livers?

Split‐liver transplantation (LT) allows transplantation of two recipients from one deceased donor, thereby increasing pool of grafts. However, split LT may be hampered by technical problems, and split grafts are still considered suboptimal organs in some centres. We analysed the outcomes in split‐ and whole‐liver recipients in a combined adult‐to‐paediatric transplantation programme. Records of paediatric and adult patients having undergone LT from 1999 to 2013 were analysed retrospectively. All splits were performed in situ. Adult split‐graft recipients were matched 1:2 with whole‐graft recipients (matching criteria: BMI, MELD, year of transplantation, age), and matched to the paediatric recipient transplanted from the same donor. Post‐LT complications were classified according to the Clavien scale. Among children, 32 split‐ and 31 whole‐graft recipients were analysed. Among adults, 20 split‐ and 40 matched whole‐graft recipients were analysed. In both populations, the post‐operative complications did not differ between split‐ and whole‐graft recipients. There was no difference in 1‐year graft and patient survival between split‐ and whole‐graft recipients in paediatric (90% vs. 97%, 94% vs. 97%, respectively) and in adult recipients (89% in both, 89% vs. 92%, respectively). In the analysis of both recipients issued from the same donor, there was no association in the prevalence and severity of complications. A case‐by‐case analysis showed that split mortality was unrelated to LT in all but one patient (small‐for‐size left split graft). In the setting of careful donor selection, recipient matching and surgical skill, in situ split LT is an effective and safe technique to increase the number of available organs, and split livers should no longer considered marginal grafts.     

Pediatric liver transplantation

Considerable strides have been made over the last several decades toward improving outcomes in pediatric liver transplantation. Refinements in surgical technique has allowed for the use of living donor and deceased donor split-liver grafts, thus expanding the pool of available organs and reducing waitlist mortality. The use of a multidisciplinary team continues to be paramount in the care of the transplant recipient. With improvements in overall graft and survival, indications for liver transplantation have also broadened. Currently, pediatric transplant patients have a 5-year survival of over 85%. Long-term morbidity is mainly associated with complications from immunosuppression and chronic rejection. Here we review indications for liver transplantation in children, surgical considerations, post-operative complications, and long-term outcomes.     

Liver transplantation from a deceased donor with β‐thalassemia intermedia is not contraindicated: A case report

The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with β‐thalassemia intermedia. A patient, 6‐year‐old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver. Hepatocellular injury due to acute graft rejection might have contributed to elevated ferritin levels by causing release of stored iron from the hemosiderotic liver graft. Iron chelation and phlebotomy therapies were started simultaneously in the early postoperative period to avoid iron‐related organ toxicity and transplant failure. Follow‐up with monthly phlebotomies after discharge yielded a favorable outcome with normal transplant functions. Thalassemia intermedia patients can be candidates of liver donors to decrease pretransplant waitlist mortality. After transplantation of a hemosiderotic liver, it is important to monitor the recipient in terms of iron overload and toxicity. Early attempts to lower iron burden including chelation therapy and/or phlebotomy should be considered to avoid organ toxicity and transplant failure.     

Donor‐to‐recipient weight ratio is a risk factor for hepatic artery thrombosis after whole‐liver transplantation in children under 25 kg

Hepatic artery thrombosis (HAT) following pediatric liver transplantation increases morbidity and risk of graft failure. We performed a retrospective chart review of all patients who underwent deceased‐donor liver transplantation from August 2002 to July 2016. Multi‐organ transplant recipients were excluded. We examined the incidence of HAT at our institution and sought to identify associated donor or recipient risk factors. A total of 127 deceased‐donor liver transplant patients with a median age of 1.7 years (IQR 0.67‐6.7) were identified. Of those, 14 developed HAT, all weighing under 25 kg. Among 100 patients under 25 kg, whole‐liver graft recipients had an odds ratio of 3.98 (95% confidence interval [CI]: 1.03, 15.34; P = .045) for developing HAT compared with split‐liver graft recipients. Within the whole‐liver recipient group under 25 kg, 11 patients developed HAT with a median donor‐to‐recipient ratio (DRWR) of 0.9 (IQR: 0.7‐1.2) compared with a median DRWR of 1.4 (IQR: 1.1‐1.9) for those who did not develop HAT. Multivariate analysis showed DRWR to be an independent risk factor for HAT in patients weighing under 25 kg who received whole organ grafts, with an odds ratio of 3.89 (95% CI: 1.43, 10.54; P = .008) for each 0.5 unit decrease in DRWR. Our results suggest that in recipients under 25 kg 1) split‐liver grafts may have a lower rate of HAT and 2) selecting whole organ donors with a higher DRWR may decrease the incidence of HAT.     

Using pediatric liver grafts (≤6 yr) for adult recipients: A considerable option?

In LT, the common policy is to allocate pediatric liver grafts to pediatric recipients. Pediatric organs are also offered to adults if there is no pediatric recipient. However, they are rarely accepted for adult recipients. So far, there is no information available reporting outcome of LT in adult recipients using pediatric livers from donors ≤6 yr. In this study, we included nine adult recipients (seven females and two males) who received grafts from children ≤6 yr from January 2008 to December 2013. We evaluated the graft quality, the GBWR and analyzed the recipients’ perioperative course. Laboratory samples and graft perfusion were analyzed. Nine adults with a median age of 49 yr (range: 25–65) and a median weight of 60 kg (range: 48–64) underwent LT with a pediatric donor graft. Median donor age was five yr (range: 3–6). Median GBWR was 1.02 (range: 0.86–1.45). After a median follow‐up of 3.9 yr (range: 11 months–6.6 yr), patient survival was 100%; graft survival was 89%. One patient needed re‐transplantation on the second postoperative day due to PNF. Eight recipients were discharged from the ICU after 2–9 days with a regular graft function. Doppler scans revealed regular flow patterns at any time. Only if denied for pediatric recipients, the use of pediatric livers from donors ≤6 yr for adult recipients is a considerable option.     

Potential of neonatal organ donation and outcome after transplantation

Organ transplantation is limited by access to suitable organs. Infant recipient waitlist mortality is increased due to the scarcity of size-matched organs. Neonatal organ donors have been proposed as an underutilized source of donor organs. However, the literature on the actual prevalence and outcome of neonatal organ donation and transplantation is fragmented and not well analyzed. This literature review aims to summarize the available literature on the potential of neonatal organ donation and to analyze published cases of neonatal organ transplantation. A systematic search of the Medline and Cochrane databases yielded 2964 articles, which were screened for eligibility. In total, 86 articles were considered eligible, of which 34 were included in the literature review: 8 articles describing the potential of neonatal organ donation programs, and 26 articles describing clinical transplantation. Current evidence suggests there is a large pool of potential neonatal organ donors. In contrast, the literature on neonatal organ donor utilization is sparse. However, case series of successful kidney, heart, liver, hepatocyte, and multivisceral transplantation using organs from neonatal donors are summarized. Although good posttransplant organ function was achieved, the use of neonatal organs is associated with increased risk of thrombosis in both kidney and liver transplantation. Neonatal organ donation is a promising alternative for expanding the current donor pool. Experience is limited, but reported patient and graft survival are acceptable and more research on the subject is warranted.     

小儿临床活体肝部分移植术

目的探讨小儿临床活体部分移植术的技术。方法 １９７年６月３０日我科成功地进行了１例小儿活体肝部分移植术。供体男性,４０岁,系患儿父亲,行肝左外侧切除术。术中用Ｂ超确认肝血管走向,确定切肝界线,以超声刀和双极电凝器断肝,切肝过程不断阻肝脏血流,肝脏热缺血时间为零。受体为１０岁女童。体重２４ｋｇ,身高１２１ｃｍ,为先天性弥漫性肝内胆管囊性扩张症、复发性胆管炎、肝硬变。结果 供体无任何术后并发症,受体早     

An alternative method of arterial reconstruction in pediatric living donor liver transplantation with the recipient right gastroepiploic artery

The classical method for arterial reconstruction in pediatric living donor liver transplantation using left lateral segment consists of end-to-end anastomosis between the donor left hepatic artery and the recipient right hepatic artery. In the present case, an intra-operative hepatic artery thrombosis occurred because of extensive intima wall dissection of the recipient hepatic artery. The patient was a 6-yr-old boy with fulminant hepatic failure, who underwent living donor partial liver transplantation with left lateral segment from his father. The graft was irrigated by a left hepatic artery and an accessory left hepatic artery from gastric artery, both arteries with diameter of <2 mm. These arteries were anastomosed to the recipient right and left hepatic arteries, respectively. Before performing the bile duct reconstruction it was noted that these anastomoses were occluded by clots of blood. An extensive subintimal dissection of the recipient hepatic artery was the cause of this problem. The creation of a new anastomosis by using a more proximal part of this artery without subintimal dissection was judged impossible. Then, the right gastroepiploic artery was mobilized and an anastomosis was performed with the donor left hepatic artery in an end-to-end fashion. Arterial blood flow to the graft was established successfully and the patient's postoperative recovery was excellent. Fifteen days after the transplantation, an angiotomography demonstrated a good hepatic arterial blood flow. The patient is now alive and well, 4 months after the transplantation. In conclusion, the method of hepatic graft arterialization described here is an important option for patients who undergo living donor or split liver transplantation.     

Graft reduction in pediatric hepatic transplantation: value, technique and results]

The benefit of liver transplantation in children with end-stage liver disease is now well established. A few years ago, the scarcity of suitable pediatric donors was responsible for death in 30 to 50% of children on the waiting list and most of them died before the age of 3 years. Since 1981, the use of reduced-size graft in pediatric liver transplantation allowed a dramatic decrease of the pretransplant mortality rate which is now 2 to 14%. The choice of the reduction technique is based on two parameters; the first one is the donor recipient body weight ratio, the second one is the intra-operative measurement of the recipient's internal transverse basithoracic distance. Nowadays, 30 to 50% of the children undergoing a liver transplant, receive a reduced-size graft. The results of reduced-size orthotopic liver transplantation are comparable with full-size orthotopic liver transplantation; the one-year survival rate is 70 to 85%. These results justify the continued use of reduced-size liver transplantation in children with end-stage liver disease. Transplantation of two patients with one liver (bipartition) and liver transplantation from living related donor, which represents an improvement of the reduction technique, was recently performed successfully and may become a useful concept in pediatric liver transplantation.     

Factors affecting graft function in pediatric and adult recipients of adult live donor kidney transplants

The aims of this investigation were to compare changes of function of adult living kidney grafts transplanted into adult and child recipients and to analyze factors associated with graft function during the first post-transplant year. The study involved 53 adult and 23 pediatric recipients with immediate graft function and without complications that could influence graft function. In comparison to children, adult recipients and their donors were older, and having been longer on hemodialysis they had received more transfusions. Although similar baseline graft function--GFR(0) was transplanted in both groups, absolute and relative GFR in adults rose and maintained stable, while in children absolute GFR decreased and remained similar to the GFR(0) until the end of the study. Significant predictors of kidney function in both adult and child recipients were donor age, ratio between GFR(0) and recipient BSA, induction immunosuppression, and systolic hypertension. In conclusion, the function of adult live kidney grafts changed differently in children and adults because of different functional requirements of recipients but donor age, induction immunosuppression and hypertension are significant predictor of graft function in both adults and children.     

Pediatric liver transplantation using left hepatic segments from living related donors: surgical experience in 100 recipients at Saint-Luc University Clinics

Living-related liver transplantation was developed in the context of deceased donor organ shortage, which is particularly acute for pediatric recipients. This retrospective study analyzes the surgical technique and complications in the first 100 pediatric liver transplantation using left segmental liver grafts from living donors, performed at Saint-Luc University Clinics between July 1993 and April 2002. Pre-operative evaluation in donors and recipients, analysis of the surgical technique, and postoperative complications were reviewed. After a median follow-up period of 2526 days, no donor mortality was encountered, with a minimal morbidity and no long-term sequelae. At one and five yr post-transplantation, the actuarial patient survival rates were 94% and 92%, the corresponding figures being 92% and 89% for graft survival. The incidences of portal vein and hepatic artery thromboses, and of biliary complications were 14%, 1%, and 27%, respectively. Living-related liver transplantation in children constitutes an efficient therapy for liver failure to face the increased demand for liver grafts. Donor morbidity was kept to acceptable incidence, and surgical technique in the recipient needs to be tailored to minimize postoperative complications.     

Transient severe tricuspid regurgitation after transplantation of an extremely oversized donor heart in a child—Does size matter? A case report

In pediatric heart transplantation, the size of the donor organ is an important criterion for organ allocation. Oversized donor hearts are often accepted with good results, but some complications in relation to a high donor‐recipient ratio have been described. Our patient was transplanted for progressive heart failure in dilated cardiomyopathy. The donor‐to‐recipient weight ratio was 3 (donor weight 65 kg, recipient weight 22 kg). The intra‐operative echocardiography before chest closure showed excellent cardiac function, no tricuspid valve regurgitation, and a normal central venous pressure. After chest closure, central venous pressure increased substantially and echocardiography revealed a severe tricuspid insufficiency. As other reasons for right ventricular dysfunction, that is, myocardial ischemia, pulmonary hypertension, and rejection, were excluded, we assumed that the insufficiency was caused by an alteration of the right ventricular geometry. After 1 week, the valve insufficiency regressed to a minimal degree. In pediatric heart transplant patients with a high donor‐to‐recipient weight ratio, the outlined complication may occur. If other reasons for right ventricular heart failure can be ruled out, this entity is most likely caused by an acute and transient alteration of the right ventricular geometry that may disappear over time.     

Technique advance to avoid hepatic venous outflow obstruction in pediatric living‐donor liver transplantation

HVOO represents a serious critical complication of pediatric living‐donor liver transplantation because open surgical repair is virtually impossible. Currently, despite several technical innovations and the introduction of triangulated anastomosis for hepatic vein reconstruction, the reported incidence of HVOO is still considerable. The aim of this study was to propose a new technique for hepatic venous reconstruction that avoids the original orifice of the recipient hepatic veins. Instead, anastomosis is performed in a newly created wide longitudinal orifice in the anterior wall of the recipient inferior vena cava. A total of 210 living related‐donor liver transplantations were performed using two methods for reconstruction of the hepatic vein. Group 1 included 69 patients subjected to direct anastomosis of the orifice of the graft hepatic vein and a wide orifice created in the recipient inferior vena cava by the confluence of the orifices of the right, left, and middle hepatic veins. Group 2 included 141 patients in whom the original orifices of the recipient hepatic veins were closed, the inferior vena cava was widely opened, and a long longitudinal anastomosis was performed using two lines of continuous sutures. Diagnosis of HVOO was suspected based on clinical findings and ultrasound studies and then confirmed by liver biopsy and interventional radiology examinations. Among the 69 recipients in group 1, 16 patients died due to graft problems during the postoperative period and eight of the survivors (15.1%) presented with HVOO. In group 2 (141 patients), 21 patients died, and there were no cases of HVOO. A comparison of the incidence of HVOO between groups revealed a significant difference (p = 0.01). Hepatic venous reconstruction during pediatric living‐donor liver transplantation should be performed using a wide longitudinal incision in the anterior wall of the recipient inferior vena cava because this technique eliminated anastomosis complications.     

Solid organ donation in a child after extracorporeal membrane oxygenation,orthotopic heart transplantation,and ventricular assist device support

Gupta P, Blanco C, Madigan M, Dodgen A, Hanson M, Frazier EA, Bhutta AT, Fiser WP. Solid organ donation in a child after extracorporeal membrane oxygenation, orthotopic heart transplantation, and ventricular assist device support. Abstract: Use of high‐risk or marginal donors is the most viable short‐term means to boost the organ supply and bridge the widening gap between the number of patients on the waiting list for organ transplantation and the insufficient numbers of organ donors. Expansion of the donor pool requires an understanding of the impact on survival likely to result from extending one or more high risk factors. Use of extended donor pool results in shorter waiting list times and limits the morbidity and mortality associated with long‐term mechanical support needed to support diseased organs. In this report, we present one such example of expanding donor pool in which a pediatric patient donated a solid organ after two heart transplants and successful use of ECMO and VAD.     

Very small pediatric donor kidney transplantation in pediatric recipients

Kidneys from very small pediatric donors (age <5 years, weight <21 kg) may be a means to increase the donor pool for pediatric recipients. Transplantation of small pediatric kidneys is more commonly performed in adult recipients due to the increased risks of technical complications, thrombosis, and early graft failure. While these risks are abrogated in adult recipients by limiting the donor weight to ≥10 kg and using the EB technique, it is unknown whether pediatric recipients achieve comparable results. US national data were assessed for all first‐time, deceased‐donor, kidney‐only pediatric recipients, 1/1996‐10/2013, who received very small pediatric donor grafts or grafts from ideal adult donors. We identified 57 pediatric EB, 110 pediatric SK, and 2350 adult transplants. The primary outcome was 3‐year all‐cause graft survival. Kaplan‐Meier curves showed worse outcomes for pediatric grafts compared to adult ideal grafts (P=.042). On multivariate analysis, pediatric recipients of SK grafts had significantly higher HRs (aHR 2.01, 95% CI 1.34‐3.00) and pediatric recipients of EB grafts had somewhat higher non‐significant HRs (1.57; 95% CI 0.88‐2.79) for graft survival. These results suggest cautionary use of very small pediatric donors as a source to expand the donor pool for pediatric candidates.     

The first case of domino‐split‐liver transplantation in maple syrup urine disease

The enzymatic defect in MSUD results in accumulation of neurotoxic metabolites of BCAAs. LTX has shown to be a feasible strategy in patients non‐responsive to diet. Because of sufficient enzyme activity in extrahepatic tissues in healthy people, the MSUD liver graft is a suitable domino organ. We present the first case of a technical challenging ex situ split of a MSUD domino organ transplanted into two pediatric recipients. The domino graft donor was a 21‐year‐old female (58 kg) suffering from MSUD with recurrent metabolic decompensation despite strict diet. The organ was allocated to a 14‐year‐old girl (55 kg) with primary sclerosing cholangitis. Due to excellent organ quality and suitable anatomy, a backward split for a girl of 3 months (5 kg) with decompensated liver cirrhosis due to biliary atresia was performed. The postoperative course was without relevant complications, and the three recipients were discharged on postoperative days 28, 29, and 45, respectively, with good organ function. BCAAs in plasma were normal in the two domino graft recipients, and the MSUD patient showed mildly elevated but stable BCAA concentrations despite an unrestricted diet. Split‐domino LTX enabled successful transplantation of three patients of the waiting list with only one deceased donor graft.     

Liver transplantation with monosegment from a living donor

The shortage of organ donors for low-weight liver transplant recipients, especially for small children, has led to the development of new surgical techniques to increase the donor pool. Almost all of these techniques use the left lateral segment (Couinaud's segments II and III), but even this graft could be too large for children under 10 kg. We report here the case of an 8-month-old boy, weighing 6.1 kg, who received a monosegmental graft (segment III) from his grandmother weighing 68 kg. The graft was reduced at the donor surgery, before clamping of the vessels. The donor was discharged on the fourth post-operative day; the recipient had an uneventful post-operative period and was discharged after 22 days.