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.

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.

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.

Factors associated with thrombotic and hemorrhagic complications in pediatric liver transplant: A multi-center analysis from the Starzl Network for Excellence in Pediatric Transplantation.

BACKGROUND: Survival after pediatric liver transplantation (PLT) is negatively impacted by thrombotic and hemorrhagic complications. Limited data exists regarding factors associated with these complications and utilization of anticoagulation. METHODS: Retrospective review of donor, recipient variables and outcomes from four centers participating in the Starzl Network for Excellence in Pediatric Transplantation. RESULTS: 76 PLT included 39 (51%) technical variant transplants, with mean follow-up 628 ± 193.6 days. Median age/weight at transplant were 59.3 ± 53.8 months and 19.6 ± 17.2 kg. Seven (9.2%) transplants experienced intraoperative hepatic artery thrombosis (iHAT), all successfully corrected. Four HAT recurred postoperatively on POD 1,7,8 and 616. All three portal vein thromboses (PVT) occurred on POD1. Anticoagulation protocols were initiated intraoperatively in 50 and postoperatively in 66 and were active for all thrombotic and hemorrhagic events. Two patients were re-transplanted for HAT. Two patients died without having thrombotic or hemorrhagic complications. iHAT and post-operative HAT were associated with lower hepatic arterial flows. iHAT was associated with donor variant anatomy, reduced allografts and intraoperative blood loss. Intraoperative ultrasound could not predict post-operative HAT nor PVT. Surgeon pre-operative concern regarding the native portal vein correlated with postoperative PVT. Lower hepatic arterial and portal flows, higher estimated blood losses, higher prothrombin time and use of arterial interposition grafts were associated with postoperative hemorrhagic complications. CONCLUSIONS: Thrombotic and hemorrhagic complications after pediatric liver transplant remain rare but significant events. Their occurrence can be predicted with pre-operative assessment of donor and recipient vascular anatomy and direct flow measurement but may not be predicted with ultrasound evaluation nor prevented with anticoagulation.

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.

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.

Predictors of survival following liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma: Experience from the Society of Pediatric Liver Transplantation (SPLIT).

Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and postoperative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n = 157) and 62% for HCC (n = 18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p = NS). Salvage (n = 13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p = NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds) and those with larger tumors (48% for those beyond versus 83% within Milan criteria, p = NS). Risk of infection (HR 1.5, 95% CI 1.1-2.2, p = .02) and renal injury (HR 2.4, 95% CI 1.7-3.3, p < .001) were higher in malignant versus nonmalignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.

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.

Internal split liver transplants reduce the waiting list time for teenagers with a low calculated Model for End-stage Liver Disease score.

BACKGROUND: Split liver transplantation allows for the simultaneous transplantation of two patients, typically a child and an adult, with a single organ. We report our experience with "internal splits" in which 10 pediatric patients from our institution were transplanted with five organs. We hypothesized that this would reduce the WL time for teenagers with a low calculated MELD score. METHODS: A retrospective chart review of those 10 patients was done. Their WL time was compared with local, regional, and national data. P < .05 was considered significant. RESULTS: The median age of the five primary recipients to whom the liver was first allocated was 2.3 years (0.7-7.4) (median weight 10.4 kg (8.4-17.7)). They received a segment 2-3 graft. Five "secondary" recipients (median age 17.4 years (16.6-18.9); median weight 66.2 kg (53.7-70.0)) were identified on our WL to receive the trisector graft. At transplant, their median calculated MELD score was 11 (8-20). Their mean WL time (241.6 ± 218.9 days) was significantly shorter than local (480.6 ± 833.6 days), regional (370.4 ± 563.4 days), and national patients (245.6 ± 465.4 days) with MELD ≤ 20 (P = .047). There was no significant difference between their WL time and that of patients with a MELD 8 ≤ x≤31 (equivalent to their median exception score, P = .63). Patient and graft survival was 100% for all 10 patients. CONCLUSION: In our experience, simultaneous internal split liver transplantation allowed teenagers with a low calculated MELD score to be transplanted faster than patients with a similar score. Promoting the use of internal split liver transplantation could help reduce the pediatric waitlist mortality.

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.

Abernethy Malformations: Evaluation and Management of Congenital Portosystemic Shunts.

PURPOSE: To assess the utility of preoperative venography in evaluating and managing patients with congenital portosystemic shunts (CPSSs). MATERIALS AND METHODS: A retrospective study was performed of 42 patients (62% female; median age, 4.1 years) diagnosed with a CPSS from 2005 to 2018. Preoperative venography (n = 39) and balloon occlusive pressure measurements (n = 33) within the mesenteric venous system guided treatment. Primary outcome was serum ammonia levels at 1 month after shunt closure. Management strategies included single (n = 12) or staged (n = 18) operative ligation, endovascular occlusion (n = 8), combined surgical and endovascular closure (n = 2), and observation (n = 2). RESULTS: At 1 month, serum ammonia levels decreased from 82.5 ± 10.3 µmol/L to 38.4 ± 4.6 µmol/L (P < .001). No difference was observed in the decrease between patients treated surgically or endovascularly (P = .91). Mean occluded to non-occluded pressure gradients were significantly lower for endovascular closure (5.3 ± 1.8 mmHg) than for surgical closure (12.3 ± 3.3 mmHg, P = .02). Shunts were classified as extrahepatic in 29 patients and as intrahepatic in 13 patients; all shunts demonstrated filling of the portal system with occlusive venography. Broad and short shunts were closed surgically; narrow and long shunts were closed endovascularly. Shunts were closed in a single session (n = 20) if the pressure gradient was less than 10 mmHg and the occluded mesenteric pressure was less than 25 mmHg. CONCLUSIONS: Preoperative venography delineates shunt morphology, and balloon occlusion simulates closure hemodynamics. This information is necessary to determine whether definitive closure should be performed through endovascular or surgical methods and whether closure should be performed in a single or staged setting.

Esophageal dysmotility is present before surgery in isolated tracheoesophageal fistula.

After surgical correction of esophageal atresia with or without tracheoesophageal fistula, esophageal body motility dysfunction has been reported in nearly all patients. Using high-resolution esophageal manometry before surgical repair in 2 children with isolated tracheoesophageal fistula, we sought to determine whether dysmotility was present before any surgical insult to test the hypothesis that dysmotility associated with esophageal atresia with or without tracheoesophageal fistula is related to intrinsic primary factors linked to abnormal development of the esophagus. Both had an abnormal esophageal motility: one exhibited hypomotility with distal contraction, whereas the other showed a complete aperistalsis pattern. This suggests that esophageal dysmotility is congenital in nature rather than secondary to surgery.

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.

Peri-operative Anticoagulation Strategies, Bleeding and Thrombotic Complications in Pediatric Patients Undergoing Intervention for Congenital Portosystemic Shunts.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications. METHODS: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications. RESULTS: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported. CONCLUSIONS: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively. LEVELS OF EVIDENCE: Level II, retrospective study.

Choledochal Cyst and Right Congenital Diaphragmatic Hernia: When to Intervene?

Patients with congenital diaphragmatic hernia (CDH) can present with other congenital anomalies, but an associated choledochal cyst (CC) has rarely been described. The simultaneous diagnosis of both anomalies complicates patient management. There is no consensus on the ideal timing for CC excision. Unrepaired CC is associated with risks of developing biliary sludge, choledocholithiasis, and cholangitis. After a CDH repair with mesh, secondary bacterial translocation caused by a delayed CC repair could lead to mesh superinfection. Conversely, early CC surgical management could cause mesh displacement and lead to CDH recurrence, requiring reintervention. We present the rare case of a CC occurring in a neonate with a prenatally diagnosed right CDH. One month after an uncomplicated CDH repair with mesh, while the patient was still hospitalized for pulmonary hypertension, she developed progressive cholestasis and acholic stools. Investigations revealed a nonpreviously suspected CC. Conservative treatment was attempted, but CC perforation with secondary biliary peritonitis occurred. Open CC excision with a Roux-en-Y hepaticojejunostomy was therefore performed on day of life (DOL) 41. Having suffered no short-term surgical complications, the patient was discharged on DOL 83 because of prolonged ventilatory support due to pulmonary hypertension. Now 12 months after surgery, she is doing well with normal liver function tests and imaging studies. In summary, CC should be considered in the differential diagnosis of progressive cholestasis in patients with CDH. Surgical repair of a symptomatic CC should not be delayed even in the presence of mesh given the risks of CC complications.

Characterization of esophageal motility following esophageal atresia repair using high-resolution esophageal manometry.

BACKGROUND: Esophageal dysmotility, a considerable issue following esophageal atresia (EA) repair, has been reported but has not been precisely described and characterized. Using high-resolution esophageal manometry (HREM), we characterized the esophageal motility patterns in children with repaired EA and compared these patterns of dysmotility with symptomatology. METHODS: HREM was performed as an outpatient procedure in patients with repaired EA. The tracings were analyzed using the software provided by the company and were then reviewed visually. Charts were reviewed for medical/surgical histories and symptoms were assessed by a standardized questionnaire. RESULTS: Forty patients (25 boys, 15 girls) with a median age of 8 years (11 months-18 years) underwent an HREM. Thirty-five patients had type C EA and 5 had type A EA. Only 7 patients were asymptomatic at the time of the examination. HREM results were abnormal in all of the patients. Three different esophageal motility patterns were derived from HREM tracing analysis: aperistalsis (15 patients, 38%), pressurization (6 patients, 15%), and distal contractions (19 patients, 47%). Distal contractions pattern was found exclusively in type C EA. Dysphagia was encountered in the 3 groups. Gastroesophageal reflux disease-related symptoms predominated in the aperistalsis group. CONCLUSIONS: HREM improves our understanding and allows precise characterization of esophageal dysmotility in patients who have undergone EA repair.

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.