Evaluation and post-transplant management of children after multi-organ-with-kidney transplantation.

Multi-organ transplantation involves the transplant of two or more organs from a single donor into a single recipient; in most cases, one of these organs is a kidney. Multi-organ transplantation is uncommon in pediatric transplantation but can be life-saving or significantly life-improving for children with rare diseases, including primary heart, liver, pancreas, or intestinal failure with secondary kidney failure, metabolic disorders, and genetic conditions causing multi-organ dysfunction. This manuscript reviews the current state of pediatric multi-organ transplantation that includes a kidney, with a focus on indications, evaluation, and key differences in management compared to kidney-alone transplantation. Guidelines and consensus statements for pediatric multi-organ transplantation are nonexistent; this review condenses reported statistics and peer-reviewed expert opinion while highlighting areas in need of further research.

A History of Umbilical Vein Catheterization Does Not Preclude Children from a Successful Meso-Rex Bypass.

INTRODUCTION: Umbilical vein catheterization (UVC) can cause portal venous thrombosis, leading to the development of extrahepatic portal venous obstruction (EHPVO) and portal hypertension (PHT). The feasibility of the Meso-Rex bypass (MRB) for the treatment of EHPVO in patients with a history of UVC has been questioned. We compared the feasibility of performing an MRB in patients with or without a history of previous UVC. METHODS: A retrospective review of patients with EHPVO and known UVC status explored for a possible MRB at our institution was performed (1997-2022). Patients were categorized in two groups: with (UVC(+)) or without (UVC(-)) a history of UVC for comparison. A p-value less than 0.05 was considered significant. RESULTS: One hundred and eighty-seven patients were included (n = 57 in UVC(+); n = 130 in UVC(-)). Patients in the UVC group were significantly younger at surgery and the incidence of prematurity was higher. Other risk factors for the development of EHPVO were similar between the groups, but only history of UVC could predict the ability to receive MRB (odds ratio [OR]: 7.4 [3.5-15.4]; p < 0.001). The success rate of MRB was significantly higher in patients with no history of UVC (28/57 [49.1%] in UVC(+) vs. 114/130 [87.7%] in UVC(-); p < 0.001). However, MRB patency at discharge (25/28 [89.3%] in UVC(+) vs. 106/114 [94.7%] in UVC(-); p = 0.3) was equally high in both groups. CONCLUSION: Our results indicate that a history of UVC is not a contraindication to MRB. Half of the patients were able to successfully receive an MRB. Patients with symptomatic PHT from EHPVO should not be excluded from consideration for MRB based on UVC history.

Critical elements of pediatric liver cancer surgery.

The appropriate management of pediatric liver malignancies, primarily hepatoblastoma and hepatocellular carcinoma, requires an in depth understanding of contemporary preoperative risk stratification, experience with advanced hepatobiliary surgery, and a good relationship with one's local or regional liver transplant center. While chemotherapy regimens have become more effective, operative indications more well-defined, and overall survival improved, the complexity of liver surgery in small children provides ample opportunity for protocol violation, inadequate resection, and iatrogenic morbidity. These guidelines represent the distillation of contemporary literature and expert opinion as a means to provide a framework for preoperative planning and intraoperative decision-making for the pediatric surgeon.

Outcomes after ABO incompatible pediatric liver transplantation are comparable to ABO identical/compatible transplant.

Background: ABO incompatible (ABOi) liver transplantation (LT) was initially associated with a higher incidence of vascular, biliary, and rejection complications and a lower survival than ABO compatible (ABOc) LT. Various protocols have been proposed to manage anti-isohemagglutinin antibodies and hyperacute rejection. We present our experience with a simplified protocol using only plasmapheresis. Methods: A retrospective review of all patients who received an ABOi LT at our institution was performed. Comparisons were made based on era (early: 1997-2008, modern: 2009-2020) and severity of disease (status 1 vs. exception PELD at transplant). A pair-matched comparison was done to patients who received an ABOc LT. p < 0.05 was considered significant. Results: 17 patients received 18 ABOi LT (3 retransplants). Median age at transplant was 7.4 months (1.1-28.9). 66.7% patients were listed as status 1. Hepatic artery thrombosis (HAT) occurred in one patient (5.6%), there were 2 cases of portal vein thrombosis (PVT) (11.1%), and 2 biliary strictures (11.1%). Patient and graft survival improved in the ABOi modern era, although not significantly. In the pair-matched comparison, complications (HAT p = 0.29; PVT p = 0.37; biliary complications p = 0.15) and survival rates were similar. Patient and graft survivals were 100% in the non-status 1 ABOi patients compared to 67% (p = 0.11) and 58% (p = 0.081) respectively for patients who were transplanted as status 1. Conclusion: ABO incompatible liver transplants in infants with a high PELD score have excellent outcomes. Indications for ABO incompatible transplants should be liberalized to prevent deaths on the waiting list or deterioration of children with high PELD scores.

Pediatric Liver and Transplant Surgery: Results of an International Survey and Expert Consensus Recommendations.

BACKGROUND: Pediatric liver surgery is a complex and challenging procedure and can be associated with major complications, including mortality. Best practices are not established. The aims of this study were to evaluate surgeons' individual and institutional practices in pediatric liver surgery and make recommendations applicable to the management of children who require liver surgery. METHODS: A web-based survey was developed, focusing on the surgical management of children with liver conditions. It was distributed to 34 pediatric surgery faculty members of the Biliary Atresia and Related Disorders (BARD) consortium and 28 centers of the European Reference Network-Rare Liver. Using the Delphi method, a series of questions was then created to develop ideas about potential future developments in pediatric liver surgery. RESULTS: The overall survey response rate was 70.6% (24/34), while the response rate for the Delphi questionnaire was 26.5% (9/34). In centers performing pediatric liver surgery, most pediatric subspecialties were present, although pediatric oncology was the least present (79.2%). Nearly all participants surveyed agreed that basic and advanced imaging modalities (including ERCP) should be available in those centers. Most pediatric liver surgeries were performed by pediatric surgeons (69.6%). A majority of participants agreed that centers treating pediatric liver tumors should include a pediatric transplant program (86%) able to perform technical variant grafts and living donor liver transplantation. Fifty-six percent of responders believe pediatric liver transplantation should be performed by specialized pediatric surgeons. CONCLUSION: Pediatric liver surgery should be performed by specialized pediatric surgeons and should be centralized in regional centers of excellence where all pediatric subspecialists are present. Pediatric hepatobiliary and transplant training needs to be better promoted amongst pediatric surgery fellows to increase this subspecialized workforce.

Fluid balance in pediatric postoperative liver transplant recipients.

BACKGROUND: Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients. METHODS: We performed a retrospective cohort study of first-time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72 h postoperatively: <10%, 10-20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator-free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)-III score. RESULTS: We included 129 patients with median PRISM-III score of 9 (interquartile range, IQR 7-15) and calculated Pediatric End-stage Liver Disease score of 15 (IQR 2-23). A total of 37 patients (28.7%) had 10-20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18-2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10-1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74-0.97). There were no differences between groups in the likelihood of postoperative complications. CONCLUSIONS: In pediatric LT recipients, >20% FB at 72 h postoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes.

State of pediatric liver transplantation in the United States and achieving zero wait list mortality with ideal outcomes: A statement from the Starzl Network for Excellence in Pediatric Transplant Surgeon's Working Group.

BACKGROUND: Liver transplant is a life-saving therapy that can restore quality life for several pediatric liver diseases. However, it is not available to all children who need one. Expertise in medical and surgical management is heterogeneous, and allocation policies are not optimally serving children. Technical variant grafts from both living and deceased donors are underutilized. METHODS: Several national efforts in pediatric liver transplant to improve access to and outcomes from liver transplant for children have been instituted and include adjustments to allocation policies, UNOS-sponsored collaborative improvement projects, and the emergence of national learning networks to study ongoing challenges in the field the Surgical Working group of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) discusses key issues and proposes potential solutions to eliminate the persistent wait list mortality that pediatric patients face. RESULTS: A discussion of the factors impacting pediatric patients' access to liver transplant is undertaken, along with a proposal of several measures to ensure equitable access to life-saving liver transplant. CONCLUSIONS: Pediatric liver transplant wait list mortality can and should be eliminated. Several measures, including collaborative efforts among centers, could be leveraged to acheive this goal.

Indocyanine green fluorescence imaging as an adjunct for the localization of a bile leak after split liver transplantation.

BACKGROUND: The intraoperative identification of a bile leak after liver transplantation can be challenging, especially when using technical variant grafts. Possible sources of leakage include the sometimes multiple biliary anastomoses or orphan ducts leading to cut surface leak. Preoperative imaging is often unable to precisely identify the location of the leak. Indocyanine green (ICG) fluorescence imaging has been utilized in adult hepatobiliary and transplant surgery, but not for the management of postoperative biliary complications. METHODS: We present a case where ICG fluorescence imaging was used to identify a cut surface bile leak after pediatric split liver transplantation. RESULTS: A 5-year-old girl with methylmalonic acidemia underwent a left lobe split liver transplantation. A single Roux-en-Y choledochojejunostomy was performed. Nine days after transplant, bile was noted in the surgical drain. Imaging confirmed the patency of the hepatic artery and the absence of intraabdominal collection. A hepatobiliary iminodiacetic acid scan showed the majority of radiotracer was excreted through the surgical drain. The patient was explored surgically: 4.5× loupe magnification did not allow for the localization of the leak. ICG was administered intravenously, after which a cut surface bile leak could be identified and repaired. There was no recurrence of bile leak after repair. Eighteen months after transplant, the patient is alive and well and has not suffered from any additional biliary complications. CONCLUSION: Indocyanine green constitutes an additional tool in the arsenal of measures available to facilitate the intraoperative detection and management of bile leaks occurring after pediatric technical variant graft transplant.

Identification of Early Clinical and Histological Factors Predictive of Kasai Portoenterostomy Failure.

Background: It is impossible to predict which patients with biliary atresia (BA) will fail after Kasai portoenterostomy (KPE). We evaluated the predictive nature of pre-KPE clinical and histological factors on transplant-free survival (TFS) and jaundice clearance. Methods: A retrospective review of patients who received a KPE at our institution (1997−2018) was performed. Primary outcomes were two-year TFS, five-year TFS, and jaundice clearance 3 months after KPE. p < 0.05 was considered significant. Results: Fifty-four patients were included in this study. The two-year TFS was 35.1%, five-year TFS was 24.5%, and 37% patients reached a direct bilirubin (DB) ≤ 2.0 mg/dL 3 months post KPE. The median age at biopsy was younger in the five-year TFS (39.0 (24.5−55.5) vs. 56.0 days (51.0−67.0), p = 0.011). Patients with DB ≤ 1.0 mg/dL 3 months after KPE were statistically younger at biopsy (DB ≤ 1.0 44.0 (26.0−56.0) vs. DB > 1.0 56.0 days (51.0−69.0), p = 0.016). Ductal plate malformation was less frequent in the five-year TFS (16/17, 94.1%, vs. 1/17, 5.9%, p = 0.037). Portal fibrosis (19/23, 82.6%, vs. 4/23, 17.4%, p = 0.028) and acute cholangitis (6/7, 85.7%, vs. 1/7, 14.3%, p = 0.047) occurred less frequently in two-year TFS. Conclusion: Older age at biopsy, acute cholangitis, portal fibrosis, and ductal plate malformation were associated with lower native liver survival. Evaluation in a larger study population is needed to validate these results.

Early thrombotic and hemorrhagic complications associated with a risk-adjusted postoperative anticoagulation protocol after pediatric liver transplantation.

BACKGROUND: Systemic anticoagulation after pediatric liver transplantation (pLT) is believed to reduce the incidence of vascular thrombosis, but it may also cause an increase in hemorrhagic complications. PROCEDURE: A 5-year retrospective review of pLT done at our institution was performed (2014-2018). The occurrence of early hemorrhagic and thrombotic complications was compared when using low-dose or high-dose anticoagulation after transplant (p < .05 considered significant). RESULTS: Sixty-nine patients received 73 transplants during the study period. Median age at transplant was 2.3 years (40 days to 18.5 years). Low-dose anticoagulation was utilized in 71% cases. Additionally, six patients were converted from low-dose to high-dose anticoagulation because of a thrombotic event or concerns for suboptimal vascular inflow. Postoperative anticoagulation was discontinued in 18 occurrences due to bleeding (low dose 19%, high dose 47% vs. low dose to high dose 17%, p = .085). Surgical take back for bleeding occurred in 17 occasions (low dose 13.5%, high dose 53% vs. low dose to high dose 33%, p = .005). The overall incidence of hepatic artery thrombosis (HAT) and portal vein thrombosis were each 5.5%, respectively. While patient survival was not statistically different between groups, graft survival was significantly lower in the high-dose group (low dose 93%, high dose 73% vs. low dose to high dose 100%, p = .046). However, graft losses from HAT were similar between groups (low dose 2%, high dose 7% vs. low dose to high dose 0%, p = .56). CONCLUSION: The use of a standardized risk-adjusted anticoagulation protocol after pLT is associated with a low occurrence of thrombotic and hemorrhagic complications. High-dose anticoagulation leads to more bleeding, but those risks outweigh the risks of possible graft loss.

Primary Liver Transplantation vs. Transplant after Kasai Portoenterostomy for Infants with Biliary Atresia.

Introduction: Primary liver transplants (pLT) in patients with biliary atresia (BA) are infrequent, since most babies with BA undergo a prior Kasai portoenterostomy (KPE). This study compared transplant outcomes in children with BA with or without a prior KPE. We hypothesized that pLT have less morbidity and better outcomes compared to those done after a failed KPE. Methods: A retrospective review of patients with BA transplanted at our institution was performed. Patients were included if they received a pLT or if they were transplanted less than 2 years from KPE. Outcomes were compared between those groups. Comparisons were also made based on era (early: 1997−2008 vs. modern: 2009−2020). p < 0.05 was considered significant. Results: Patients who received a pLT were older at diagnosis (141.5 ± 46.0 vs. KPE 67.1 ± 25.5 days, p < 0.001). The time between diagnosis and listing for transplant was shorter in the pLT group (44.5 ± 44.7 vs. KPE 140.8 ± 102.8 days, p < 0.001). In the modern era, the calculated PELD score for the pLT was significantly higher (23 ± 8 vs. KPE 16 ± 8, p = 0.022). Two waitlist deaths occurred in the KPE group (none in pLT, p = 0.14). Both the duration of transplant surgery and transfusion requirements were similar in both groups. There was a significant improvement in graft survival in transplants after KPE between eras (early era 84.3% vs. modern era 97.8%, p = 0.025). The 1-year patient and graft survival after pLT was 100%. Conclusions: Patient and graft survival after pLT are comparable to transplants after a failed KPE but pLT avoids a prior intervention. There was no significant difference in pre- or peri-transplant morbidity between groups other than wait list mortality. A multicenter collaboration with more patients may help demonstrate the potential benefits of pLT in patients predicted to have early failure of KPE.

Overview of pediatric kidney transplantation.

Kidney transplantation is the treatment of choice for pediatric patients with end-stage kidney disease. Unlike adult recipients undergoing transplantation, special considerations must be taken when transplanting children based on the underlying etiology of kidney disease, previous surgical procedures, anatomical limitations and necessary technical adjustments. Additionally, the choice of donor must be measured to ensure optimal graft survival given a longer post-transplant life expectancy. Those topics as well as frequently encountered postoperative complications are also discussed in this publication.

Normal long-term neurologic and graft outcome after liver transplantation in an infant with Neimann-Pick type C disease.

Niemann-Pick type C disease is a rare autosomal recessive lysosomal disorder that leads to the accumulation of lipids in cellular organelles. Affected infants are often cholestatic with hepatosplenomegaly, developmental delay and may present in acute liver failure. Medical therapy has shown some promise in long-term studies, in patients with milder phenotypes of the disease. Liver transplantation has generally not been considered a therapeutic option due to the systemic nature of the condition, and frequent unremitting neurological decline leading to death. We report an infant with multisystem organ failure, and known Niemann-Pick C disease who was successfully transplanted and has maintained normal neurological outcomes now five years after transplantation. We highlight the need for multidisciplinary care in order to recognize different phenotypes that may exist, even in rare diseases, and to be aware of evolving therapeutic options.

Ethical considerations in pediatric solid organ transplantation.

Solid organ transplantation is now an accepted therapeutic modality for children and teenagers suffering from a wide variety of complex medical conditions. Unfortunately, patients continue to die while on the organ waiting list as there remains an imbalance between the number of recipients listed for transplantation and the number of donors available. The organ allocation process continues to generate ethical questions and debates. In this publication, we discuss some of the most frequently reported ethical matters in the field of pediatric solid organ transplantation.

Bivalirudin for the prevention of hepatic artery thrombosis in pediatric liver transplantation.

BACKGROUND: Early hepatic artery thrombosis (HAT) after liver transplantation is a serious complication that frequently results in graft loss and the need for retransplantation. Although studies have reported on various operative and endovascular treatment approaches, pharmacologic strategies for the prevention or management of HAT are not well defined. Patients with blood clotting disorders, those with a contraindication to heparin, and those who have previously developed HAT represent unique challenges in management. METHODS: We present the case of a 9-month-old male with a hypercoagulable state who developed early HAT after two liver transplants, despite the use of postoperative therapeutic heparin infusion. RESULTS AND CONCLUSION: The patient successfully underwent a third liver transplant using intraoperative and postoperative bivalirudin infusion, a direct thrombin inhibitor. Rotational thromboelastometry (ROTEM) was used to guide anticoagulation and blood product administration in the perioperative period. At 1.5 years post-transplant, the patient has good graft function with patent hepatic vasculature. This case demonstrates the innovative use of bivalirudin anticoagulant therapy and viscoelastic methodologies to improve outcomes in hypercoagulable liver transplant recipients.