Caroli disease, bilateral diffuse cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas: a ciliopathy caused by a homozygous NPHP3 mutation

We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. Conclusion: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnanc

Stratégies d'anticoagulation et antiagrégation plaquettaire en transplantation hépatique pédiatrique

Les stratégies d’anticoagulation et antiagrégation plaquettaire sont utilisées après transplantation hépatique pédiatrique pour réduire le risque de thrombose vasculaire. Si le principe est généralement approuvé, les stratégies sont nombreuses. Afin de connaître les différentes approches au niveau mondial, nous avons développé un questionnaire sémi standardisé qui a visé une documentation internationale de ces stratégies. Vingt-quatre centres ont répondu au questionnaire. Les 20 centres utilisant une stratégie d’anticoagulation et antiagrégation ont 20 stratégies différentes, avec une utilisation majoritaire d’acide acétylsalicylique (19/24 centres, 79%). Selon les réponses, le choix d’une stratégie spécifique est influencée par : les problèmes vasculaires peropératoires, la taille de l’artère hépatique et le poids du patient. Le taux de thrombose de l’artère hépatique rapportée a été de moins de 5% dans 79% (19/24) des centres ayant participé au questionnaire. En résumé, nous avons objectivé, après transplantation hépatique pédiatrique, des variations internationales importantes dans les stratégies d’anticoagulation et antiagrégation. Les taux rapportés de thrombose de l’artère hépatique ne semblent pas correlés avec la stratégie employée

Perioperative Complications in Neonatal Surgery: Biliary Atresia and Choledochal Malformations

Biliary atresia (BA) and congenital choledochal malformations (CCM) are rare. Both pathologies must (BA) or may (CCM) be operated during the neonatal period or early infancy. We briefly describe the classical operative techniques for both pathologies, followed by the most common and severe perioperative complications encountered during and up to 30 days after surgery in children operated for BA and CCM early in life. For patients with BA, intestinal complications represent the most common and hazardous perioperative surgical complications. Cholangitis is the most frequently encountered medical complication post hepato-porto-enterostomy. For CCM, it seems that neonates encounter little perioperative complications; however, reports are scarce; bile leak and/or cholangitis are the most reported. Overall, for patients with CCM, the literature is ambivalent whether more perioperative complications occur in the younger or in the older patient, and whether these occur more frequently in those symptomatic or asymptomatic at operation. It is difficult to give clear advice for when children with asymptomatic CCM should be operated, and benefits and risks must be carefully counterbalanced. Perioperative mortality for both BA and CCM is low and is reported to be around 1 to 2%

Impact of length of donor ICU stay on outcome of patients after pediatric liver transplantation with whole and in situ split liver grafts

Background: Patients who have a prolonged stay in the intensive care unit (ICU) are often excluded for organ donation because of supposed deleterious effects of a lengthy ICU stay. We aimed to determine the effects of a prolonged donor stay in the ICU on the outcome of liver transplantation (LT) in children. Methods: Retrospective review of 89 pediatric LT patients, age 0-18 years, period 2003-2018, including patients having undergone whole organ or in situ split LT. The patients were divided into two groups according to the donor length of stay in the ICU. A prolonged stay was defined as &gt;5 days. Recipient, graft, and donor characteristics were compared; outcome parameters included recipient and graft survival rates and postoperative complications. Results: Group short (donor ICU stay &lt;5 days) included 75 patients, group long (donor ICU stay &gt;5 days) 14 patients. Baseline characteristics between recipients did not differ. Donors in group long had significantly more infectious complications and a higher gamma glutamyl transferase (gGT) the day of organ recovery. Incidence of biliary complications post-LT was significantly higher in group long (p = .029). Patient and graft survival rates did not differ significantly between groups. Conclusions: Donors with a prolonged stay in the ICU should still be considered for liver donation if they fulfill most other selection criteria. Recipients from donors having stayed in ICU &gt;5 days may be at increased risk of biliary complications.</p

Outcomes of combined liver-kidney transplantation in children: analysis of the scientific registry of transplant recipients

Combined liver-kidney transplantation (CLKT) in children is uncommon and outcomes have not been well defined. Using the Scientific Registry of Transplant Recipients, data were analyzed on 152 primary pediatric CLKTs performed from October 1987 to February 2011, to determine their outcome in the largest series reported to date. Patient survival was 86.8%, 82.1% and 78.9% at 1, 5 and 10 years, liver graft survival was 81.9%, 76.5% and 72.6%, and kidney graft survival was 83.4%, 76.5% and 66.8%. By way of comparison, the Registry was queried for pediatric patient survival following isolated liver transplantation (LT) during the same time frame: 86.7%, 81.2% and 77.4% and following isolated kidney transplant (KT): 98.2%, 95.4% and 90% at 1, 5 and 10 years. In patients having undergone CLKT, primary hyperoxaluria was associated with reduced patient (p = 0.01), liver graft (p = 0.01) and kidney graft survival (p = 0.01). Furthermore, graft outcome following CLKT improved over the past decade (p = 0.04 for liver, p = 0.02 for kidney), but this did not translate into improved patient outcome (p = 0.2). All in all, our results confirmed that survival following LT was less than following KT, and that CLKT offered similar patient survival to isolated LT

Features of Nodules in Explants of Children Undergoing Liver Transplantation for Biliary Atresia

Background: In patients with biliary atresia (BA) liver nodules can be identified either by pre-transplant imaging or on the explant. This study aimed to (i) analyze the histopathology of liver nodules, and (ii) to correlate histopathology with pretransplant radiological features.Methods: Retrospective analysis of liver nodules in explants of BA patients transplanted in our center (2000–2021). Correlations with pretransplant radiological characteristics, patient age at liver transplantation (LT), time from Kasai hepatoportoenterostomy (KPE) to LT, age at KPE and draining KPE. Results: Of the 63 BA-patients included in the analysis, 27/63 (43%) had nodules on explants. A majority were benign macroregenerative nodules. Premalignant (low-grade and high-grade dysplastic) and malignant (hepatocellular carcinoma) nodules were identified in 6/63 and 2/63 patients, respectively. On pretransplant imaging, only 13/63 (21%) patients had liver nodules, none meeting radiological criteria for malignancy. The occurrence of liver nodules correlated with patient age at LT (p Conclusion: In BA patients, pretransplant imaging did not correlate with the presence of liver nodules in explants. Liver nodules were frequent in explanted livers, whereby 25% of explants harboured malignant/pre-malignant nodules, emphasizing the need for careful surveillance in BA children whose clinical course may require LT. </p

Effect of centralization on surgical outcome of children operated for liver tumors in switzerland: a retrospective comparative study

Background: Pediatric liver surgery is complex, and complications are not uncommon. Centralization of highly specialized surgery has been shown to improve quality of care. In 2012, pediatric liver surgery was centralized in Switzerland in one national center. This study analyses results before and after centralization. Methods: Retrospective monocentric comparative study. Analysis of medical records of children (0-16 years) operated for any liver tumor between 1 January 2001 and 31 December 2020. Forty-one patients were included: 14 before centralization (before 1 January 2012) and 27 after centralization (after 1 January 2012). Epidemiological, pre-, intra-, and post-operative data were collected. Fischer's exact and t-test were used to compare groups. Results: The two cohorts were homogeneous. Operating time was reduced, although not significantly, from 366 to 277 min. Length of postoperative stay and mortality were not statistically different between groups. Yet, after centralization, overall postoperative complication rate decreased significantly from 57% to 15% (p = 0.01), Clavien > III complications decreased from 50% to 7% (p < 0.01), and hepatic recurrences were also significantly reduced (40% to 5%, p = 0.03). Conclusion: Centralization of the surgical management of liver tumors in Switzerland has improved quality of care in our center by significantly reducing postoperative complications and hepatic recurrence

International survey on anticoagulation and antiplatelet strategies after pediatric liver transplantation

In pediatric LT, anticoagulants and antiplatelet agents are regularly used to reduce the risk of vascular thrombosis. As evidence for optimal strategy is lacking, local practices vary greatly. The present survey aimed to compile an international overview of anticoagulation and antiplatelet strategies in pediatric LT. An online survey was sent to 98 pediatric LT centers in North and South America, Europe, Asia, and Australia. Twenty-four centers answered the survey. 20/24 (83%) use some sort of anticoagulation and antiplatelet therapy, yielding 20 different strategies. Perioperative vascular problems, size of the hepatic artery, and patient weight were the most frequent determinants of changes in anticoagulant and antiplatelet strategy. Early HAT rates were reported to be 5% or less in 79% of responding centers. Anticoagulation and antiplatelet strategies were not significantly associated with early HAT rates (P = 0.63), or with the number of pediatric LTs performed per year and center (P = 0.92). Internationally, there is a wide variety in anticoagulation and antiplatelet strategies after pediatric LT. Efforts must be made to design a prospective multicentric trial to identify the optimal antithrombotic strategy

Caroli disease, bilateral diffuse cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas: a ciliopathy caused by a homozygous NPHP3 mutation

We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. Conclusion: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy