Regional oxygen saturation measured by two different oximetry monitors in infants and children undergoing living donor liver transplantation with bilirubin measurements: A prospective observational study.

BACKGROUND: Tissue oximetry devices use wavelengths in the 680-870 nm range to separate between oxygenated/deoxygenated hemoglobin. Conjugated bilirubin has an absorption peak at 730 nm. AIMS: We hypothesized that ForeSight Elite using 5 wavelengths reduces interference from bilirubin and shows higher regional tissue oxygen saturation (rSO2 ) than INVOS 5100C incorporating 2 wavelengths. METHODS: Infants and children undergoing living donor liver transplantation were included between March 2019 and September 2020. Cerebral and somatic rSO2 were measured, and real-time simultaneous data were collected. Additionally, measurements were collected at (1) baseline, (2) beginning of dissection phase, (3) beginning of anhepatic phase, (4) reperfusion phase, and (5) skin closure. Bilirubin level was available at baseline and at reperfusion. Hyperbilirubinemia was defined as bilirubin level ≥1.0 mg/dl. RESULTS: Thirty-three patients with median age of 27 months and median weight of 12 kg were included. Baseline bilirubin levels were higher compared to values at reperfusion (p = .021). A linear mixed effects model considering bilirubin as fixed and patient as random effect showed that there was a statistically significant difference in cerebral rSO2 readings in function of time (p = .031), device (p < .001), and bilirubin concentrations (p = .007) but not for hemoglobin (p = .347), SpO2 (p = .882), and arterial partial pressure of CO2 (Pa CO2 ) (p = .146). The model showed that there was a statistically significant difference in somatic rSO2 readings in function of device (p < .001) and bilirubin concentrations (p = .023) but not for time (p = .074), hemoglobin (p = .954), SpO2 (p = .108), and Pa CO2 (p = .775). Bland-Altman plot analyzing cerebral and somatic rSO2 between both devices showed respectively a mean absolute bias and 95% limits of agreement of 21.73% (-10.21 to 53.67) and 19.52% (-29.51 to 68.54). CONCLUSIONS: Oximetry devices emitting light at >2 wavelengths may overcome interference from hyperbilirubinemia providing higher rSO2 readings.

Management and outcome of hepatic artery thrombosis after pediatric liver transplantation.

BACKGROUND: Pediatric LT are at particular risk of HAT, and its management still constitutes a matter of debate. Our purpose was to study predisposing factors and outcome of HAT post-LT, including the impact of surgical revisions on survival and biliary complications. METHODS: Among 882 primary pediatric LT performed between 1993 and 2015, 36 HAT were encountered (4.1%, 35 fully documented). Each HAT case was retrospectively paired with a LT recipient without HAT, according to diagnosis, age at LT, type of graft, and era. RESULTS: Five-year patient survivals were 77.0% versus 83.9% in HAT and non-HAT paired groups, respectively (P = .321). Corresponding graft survivals were 20.0% versus 80.5% (P < .001), and retransplantation rates 77.7% versus 10.7%, respectively (P < .001). One-year biliary complication-free survivals were 16.6% versus 83.8% in the HAT and non-HAT groups, respectively (P < .001). Regarding chronology of surgical re-exploration, only HAT cases that occurred within 14 days post-LT were re-operated, fourteen of them being explored within 7 days post-LT (revascularization rate: 6/14), versus two beyond 7 days (no revascularization). When revascularization was achieved, graft and biliary complication-free survival rates at 1 year were 33.3% and 22.2%, respectively, both rates being 0.0% in case of failure. CONCLUSIONS: The pejorative prognosis associated with HAT in terms of graft survival is confirmed, whereas patient survival could be preserved through retransplantation. Results suggest that HAT should be re-operated if occurring within 7 days post-LT, but not beyond.

Living donor liver transplantation for hepatic malignancies in children.

BACKGROUND: Living donor liver transplantation is a treatment option for unresectable hepatic tumors in children. METHODS: We enrolled 45 living donor transplantations performed between 1993 and 2018 for liver malignacies, which included hepatoblastoma (n = 33), hepatocellular carcinoma (n = 10), hepatic angiosarcoma (n = 1), and rhabdomyosarcoma (n = 1). RESULTS: No mortality or major morbidities were encountered in any donor, and the complication rate was 9%. In the hepatoblastoma group, 5-year overall and event-free survival rate in recipients was 87.4% and 75.8%, respectively, and mortality was significantly higher in patients after rescue transplantation (p = .001). Inferior vena cava replacement in these recipients appeared to be associated with reduced mortality (p = .034), but this was not confirmed when rescue patients were excluded (p = .629). In hepatocellular carcinoma group, both 5-year overall and event-free survival rates were 75.4% each, and invasion of hepatic veins was significantly associated with increased risk of recurrence and death (p = .028). The patient with rhabdomyosarcoma died from EBV-induced lymphoma 2 months after transplantation. The patient with angiosarcoma was in complete remission at the last follow-up. Overall, 5-year graft survival rate was 81.3%, and one patient underwent re-transplantation due to chronic rejection. CONCLUSIONS: Pediatric oncological liver transplantation has become a key player in the management of malignancies with cancer cure in 84% of patients in this series. Living donor liver transplantation for pediatric recipients with unresectable tumors might be a beneficial surgical option, which is technically safe for donors and recipients, thus, allowing timely planning according to chemotherapy protocols.

Nasobiliary drainage prior to surgical biliary diversion in progressive familial intrahepatic cholestasis type II.

Progressive familial intrahepatic cholestasis (PFIC) can cause intense pruritus that is refractory to medical therapy. Surgical biliary diversion techniques, including partial internal biliary diversion (PIBD), have been developed over the years to relieve pruritus without requiring liver transplantation. No clinical or genetic features can currently predict postoperative pruritus response. We present three PFIC type 2 (PIFC 2) patients who underwent transient endoscopic nasobiliary drainage (NBD) prior to PIBD surgery. Two patients repeatedly responded to NBD and presented with complete pruritus resolution after subsequent PIBD. NBD failed technically in the third patient, and PIBD was partially successful. Mild post-endoscopic biological pancreatitis occurred in 2/6 NBD procedures and resolved spontaneously. The only adverse effect observed within 7 years post-PIBD was very mild transient osmotic diarrhea.Conclusion: Our limited data suggest that NBD is a safe and effective way to predict pruritus response before performing permanent biliary diversion surgery in PFIC patients. What is Known: • Surgical biliary diversion techniques have been developed to relieve intractable pruritus in progressive familial intrahepatic cholestasis (PFIC). • No clinical or genetic features can currently predict pruritus response to surgery. What is New: • Our data suggest that nasobiliary drainage could be a safe and effective tool to predict pruritus response to biliary diversion and avoid unnecessary surgery in PFIC patients.

Multiple Epstein-Barr Virus-associated Smooth Muscle Sarcomas of the Gut in a Child Treated for Acute Lymphoblastic Leukemia.

A 7-year-old boy with a history of low-risk acute lymphoblastic leukemia developed multiple intussusceptions shortly after the end of maintenance therapy. Explorative laparotomy showed >10 polyps in the small intestine. Histologic examination revealed intestinal smooth muscle sarcomas associated with Epstein-Barr virus. The patient recovered well after partial cuneiform resection of the largest polyps and treatment with sirolimus. This case report indicates that these tumors may arise even after moderate transient immunosuppression and that association with acute lymphoblastic leukemia is possible although rarely described. We discuss the potential benefit of the mTor/Akt signal inhibitors as treatment for these tumors.

Liver and systemic hemodynamics in children with cirrhosis: Impact on the surgical management in pediatric living donor liver transplantation.

Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation (LT) was evaluated. Liver and systemic hemodynamics were studied prospectively in 52 children (median age, 1 year; 33 with biliary atresia [BA]). The hemodynamics of native liver were studied preoperatively by Doppler ultrasound and intraoperatively using invasive flowmetry. Portosystemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography and intraoperatively by using transpulmonary thermodilution. Hemodynamic parameters were correlated with Pediatric End-Stage Liver Disease (PELD) score and the histological degree of fibrosis (collagen proportionate area [CPA]). Cirrhosis was associated with a 60% reduction of pretransplant total liver flow (n = 46; median, 36 mL/minute/100 g of liver) compared with noncirrhotic livers (n = 6; median, 86 mL/minute/100 g; P = 0.002). Total blood flow into the native liver was negatively correlated with PELD (P < 0.001) and liver CPA (P = 0.005). Median portosystemic gradient was 14.5 mm Hg in children with cirrhosis and positively correlated with PELD (P < 0.001). Portal vein (PV) hypoplasia was observed mainly in children with BA (P = 0.02). Systemic hemodynamics were not altered in our children with cirrhosis. Twenty-one children met the intraoperative criteria for PV reconstruction using a portoplasty technique during the LT procedure and had a smaller PV diameter at pretransplant Doppler ultrasound (median = 3.4 mm; P < 0.001). Cirrhosis in children appears also as a hemodynamic disease of the liver, correlated with cirrhosis severity. Surgical technique for PV reconstruction during LT was adapted accordingly. Liver Transplantation 23 1440-1450 2017 AASLD.

Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Université Catholique de Louvain.

OBJECTIVES: To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. BACKGROUND: LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. METHODS: Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. RESULTS: Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients. CONCLUSIONS: LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

Diagnostic and Therapeutic Roles of Endoscopic Ultrasound in Pediatric Pancreaticobiliary Disorders.

OBJECTIVES: The diagnostic role of endoscopic ultrasound (EUS) in children has only recently been demonstrated, and that also to a lesser extent than in adults. Data on the technique's therapeutic indications remain scarce. We therefore sought to evaluate diagnostic and interventional EUS indications, safety, and impact in children with pancreaticobiliary disorders. METHODS: We retrospectively reviewed our single pediatric center records, covering a 14-year period. RESULTS: From January 2000 to January 2014, 52 EUS procedures were performed in 48 children (mean age: 12 years; range: 2-17 years) with pancreaticobiliary disorders for the following indications: suspected biliary obstruction (n = 20/52), acute/chronic pancreatitis (n = 20), pancreatic mass (n = 3), pancreatic trauma (n = 7), and ampullary adenoma (n = 2). EUS was found to have a positive impact in 51 of 52 procedures, enabling us to avoid endoscopic retrograde cholangiopancreatography (ERCP) (n = 13 biliary; n = 6 pancreatic), focusing instead on endotherapy (n = 7 biliary; n = 14 pancreatic) or reorienting therapy toward surgery (n = 7). EUS-guided fine-needle aspiration was carried out on 12 patients for pancreatic tumor (n = 4), pancreatic cyst fluid analysis (n = 4), autoimmune pancreatitis (n = 2), and suspicion of biliary tumor (n = 2). A total of 13 therapeutic EUS procedures (11 children) were conducted, including 9 combined EUS-ERCP procedures (7 children, mean age: 8 years, range: 4-11 years), 3 EUS-guided pseudocyst drainage (2 children), and 1 EUS-guided transgastric biliary drainage. CONCLUSIONS: Our study reports on a large pediatric EUS series for diagnostic and therapeutic pancreaticobiliary disorders, demonstrating the impact of diagnostic EUS and affording insights into novel EUS and combined EUS-ERCP therapeutic applications. We suggest considering EUS as a diagnostic and therapeutic tool in the management of pediatric pancreaticobiliary diseases.

Risk factors and surgical management of anastomotic biliary complications after pediatric liver transplantation.

Biliary complications (BCs) still remain the Achilles heel of liver transplantation (LT) with an overall incidence of 10% to 35% in pediatric series. We hypothesized that (1) the use of alternative techniques (reduced size, split, and living donor grafts) in pediatric LT may contribute to an increased incidence of BCs, and (2) surgery as a first treatment option for anastomotic BCs could allow a definitive cure for the majority of these patients. Four hundred twenty-nine primary pediatric LT procedures, including 88, 91, 47, and 203 whole, reduced size, split, and living donor grafts, respectively, that were performed between July 1993 and November 2010 were retrospectively reviewed. Demographic and surgical variables were analyzed, and their respective impact on BCs was studied with univariate and multivariate analyses. The modalities of BC management were also reviewed. The 1- and 5-year patient survival rates were 94% and 90%, 89% and 85%, 94% and 89%, and 98% and 94% for whole, reduced size, split, and living donor liver grafts, respectively. The overall incidence of BCs was 23% (n = 98). Sixty were anastomotic complications [47 strictures (78%) and 13 fistulas (22%)]. The graft type was not found to be an independent risk factor for the development of BCs. According to a multivariate analysis, only hepatic artery thrombosis and acute rejection increased the risk of anastomotic BCs (P < 0.001 and P = 0.003, respectively). Anastomotic BCs were managed primarily with surgical repair in 59 of 60 cases with a primary patency rate of 80% (n = 47). These results suggest that (1) most of the BCs were anastomotic complications not influenced by the type of graft, and (2) the surgical management of anastomotic BCs may constitute the first and best therapeutic option.

Internalizing motivation to self-care: a multifaceted challenge for young liver transplant recipients.

The transition from parent-controlled care to self-managed care represents an important challenge for adolescents with chronic conditions. We sought to gain a deeper understanding of the factors influencing the internalization of motivation to self-care in adolescent liver transplant recipients. We conducted a qualitative study using in-depth interviews with 18 young patients. We triangulated the data collected from the patients with data from parents and health care providers, and used an inductive approach to analyze the data. Our results illustrate three interrelated challenges that impact on young patients' motivation to self-care: (a) the cognitive challenge of fully understanding one's condition and personal health risks; (b) the behavioral challenge of developing independence regarding self-management issues; and (c) the psychological challenge of building a sense of self-ownership and purpose. The latter involves overcoming the trauma of survival and coming to terms with feelings of obligation, two challenges inherent to transplantation that warrant further investigation.

Paediatric hepatocellular adenomas: Lessons from a systematic review of relevant literature.

Hepatocellular adenomas (HCAs) are rare benign liver tumours. Predisposing factors and complication rates appear to differ among children and adults. In the present study, we aimed to systematically characterise paediatric HCAs and determine their course, complications, and management. Medical history, clinical symptoms, imaging, histopathology, and genetics of children with HCAs were collected through a systematic and comprehensive review of the published literature. A total of 316 children with HCAs were included in the present study. HCAs were diagnosed primarily in girls (59.3%) and at a mean age of 11.5 (range 0-17.7) years. The majority (83.6%) of HCAs occurred in children with predisposing diseases, of which glycogen storage disease was the most common, followed by portosystemic shunts and MODY3 (maturity-onset diabetes of the young type 3). Each of these diseases leads to a well-defined HCA molecular pattern. A significant number of HCAs either bled (24.7%) or transformed (14.8%) over time. HCA transformation was significantly more frequent in children with portosystemic shunts and in ß-catenin-mutated HCAs, while haemorrhages were more frequent in children exposed to hormones and those with larger lesions. Management was primarily guided by any predisposing conditions and the number of lesions. Therefore, vascular shunts were closed when possible, while complicated lesions were resected. Liver transplantation has made it possible to treat adenomatosis, as well as any underlying diseases. Progress in understanding genetic and/or malformative contributions, which appear to be significant in paediatric HCAs, have provided insights into tumour pathogenesis and will further guide patient surveillance and management.

Sevoflurane preconditioning in living liver donation is associated with better initial graft function after pediatric transplantation: a retrospective study.

INTRODUCTION: Initial allograft function determines the patient's immediate prognosis in pediatric liver transplantation. Ischemia-reperfusion injuries play a role in initial poor graft function (IPGF). In animal studies, preconditioning with inhaled anesthetic agents has demonstrated a protective effect on the liver. In humans, the few available studies are conflicting. This study assesses the association between the hypnotic agent used to maintain anesthesia during hepatectomy in living donors and the occurrence of IPGF after pediatric transplantation. METHODS: We conducted a single-center retrospective analysis of children who received a living donor liver transplant (LDLT) between 2010 and 2019. We analyzed the incidence of EAD according to the hypnotic agent used to maintain general anesthesia during donor hepatectomy. RESULTS: We included 183 pairs of patients (living donors-recipients). The anesthetics used in the donor were propofol (n = 85), sevoflurane (n = 69), or propofol with sevoflurane started 30 min before clamping (n = 29). Forty-two children (23%) developed IPGF. After multivariate logistic regression analysis, factors significantly associated with the occurrence of IPGF were the anesthesia maintenance agent used in the donor (p = 0.004), age of the donor (p = 0.03), duration of transplant surgery (p = 0.009), preoperative receiver neutrophil to lymphocyte ratio (p = 0.02), and albumin (p = 0.05). CONCLUSION: Significantly fewer children who received a graft from a donor in whom only sevoflurane was used to maintain anesthesia developed IPGF. Although additional research is needed, this preconditioning strategy may provide an option to prevent IPGF after living liver donation.

Prope tolerance after pediatric liver transplantation.

pT, under mono- and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS-related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus-based regimens (median follow-up post-LT: 6.0 yr, range: 0.8-9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow-up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus-steroid regimen. Beyond April 2001, 105 patients received steroid-free tacrolimus-basiliximab or tacrolimus-daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS-free operational tolerance (n = 6), 27 of them belonging to the 43 steroid-free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid-free tacrolimus-based IS seems to promote long-term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT.

Premature senescence of the liver in Alagille patients.

INTRODUCTION: Alagille syndrome (ALGS) is an autosomal dominant disease characterized by a multisystem involvement including bile duct paucity and cholestasis, caused by JAG1 or NOTCH2 mutations in most of the cases. Jagged1-Notch2 interactions are known to be crucial for intrahepatic biliary tract development, but the Notch signaling pathway is also involved in the juxtacrine transmission of senescence and in the induction and modulation of the senescence-associated secretory phenotype (SASP). AIM: Our aim was to investigate premature senescence and SASP in ALGS livers. METHODS: Liver tissue from ALGS patients was prospectively obtained at the time of liver transplantation (n = 5) and compared to control livers (n = 5). RESULTS: We evidenced advanced premature senescence in the livers of five JAG1 mutated ALGS pediatric patients through increased senescence-associated beta-galactosidase activity (p<0.05), increased p16 and p21 gene expression (p<0.01), and increased p16 and γH2AX protein expression (p<0.01). Senescence was located in hepatocytes of the whole liver parenchyma as well as in remaining bile ducts. The classical SASP markers TGF-ß1, IL-6, and IL-8 were not overexpressed in the livers of our patients. CONCLUSIONS: We demonstrate for the first time that ALGS livers display important premature senescence despite Jagged1 mutation, underlying the complexity of senescence and SASP development pathways.

Long-term follow-up after retrosternal ileocolic esophagoplasty in two cases of long-gap esophageal atresia: why it is still a valid option as a rescue strategy.

Introduction: Esophageal replacement surgery in children is sometimes necessary for long-gap esophageal atresia. Ileocolic esophagoplasty in the retrosternal space can serve as a good alternative technique in case of hostile posterior mediastinum. We present two cases of successful ileocolic transposition performed at 6 months of age. Methods: Esophageal replacement was performed through a midline laparotomy incision associated with a left cervical approach. The ileocolic transplant was pediculized on the right superior colic artery after ligating the right colic and ileocolic vessels. A retrosternal tunnel was created, and the ileocolic transplant pulled through it to reach the cervical region. Proximally, esophageal-ileal anastomosis and, distally, colonic-gastric anastomosis were performed. Ileocolic continuity was repaired. Results: There were no early postoperative complications. In both cases, the patients presented oral feeding difficulties during the first 6 postoperative months. Thereafter, full oral feeding was achieved, and both patients were clinically asymptomatic during the following 18 and 20 years, respectively, with satisfactory oral radiological assessments, showing no redundancy or inappropriate growth of the graft and no anastomotic stricture. Currently, these patients do not complain of dysphagia, pathological reflux, or respiratory symptoms. Conclusion: When native esophagus preservation in long-gap esophageal atresia is estimated unfeasible, ileocolic transposition in the retrosternal space might be considered a good and safe option, particularly in those difficult cases after multiple previous surgical attempts and mediastinitis. This technique is putatively associated with a beneficial anti-reflux effect, thanks to the presence of the ileocecal valve, in preventing cervical peptic esophagitis. Long-term follow-up confirms that the transposed colon in the retrosternal space did not suffer any abnormal modification in size and growth.

Primary extrarenal rhabdoid tumour of the liver: a case report and literature review.

Background: Extrarenal rhabdoid tumours (ERT) are highly aggressive tumours that are poorly responsive to standard cytotoxic chemotherapy and are associated with a grim prognosis. Primary ERT of the liver are most commonly observed in early childhood and exceptionally rare later in life. Case presentation: We report the case of a 16-year-old male patient, presenting with flu-like symptoms after his second COVIDvaccination. During the work-up, a large solid liver lesion was incidentally discovered upon abdominal ultrasound examination. Pathological examination rendered the diagnosis of primary ERT of the liver, characterized by the loss of expression of INI-1 protein, encoded by the SMARCB1 gene. We summarized and discuss the existing literature by reviewing 53 pediatric and 6 adult cases, including the histological features treatment and outcomes of primary hepatic ERT. Conclusion: Primary ERT of the liver are usually not associated with specific signs or symptoms, making the diagnosis very challenging. As ERT are associated with a high metastatic rate, delayed diagnoses lead to increased mortality, as complete resection is not possible in advanced-stage cases. Therefore, early diagnoses, enabling complete resection of the tumour are crucial to improve patient outcomes. Of interest, primary ERT of the liver, is associated with biallelic loss of the SMARCB1 (SWI/ SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) gene, a potential target for cancer therapeutics. This is, to our knowledge, the first case of a hepatic rhabdoid tumour treated with liver transplantation.

Senescence and senotherapies in biliary atresia and biliary cirrhosis.

BACKGROUND: Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also arises in biliary atresia (BA), the first cause of pediatric liver transplantation. Since alternatives to transplantation are needed, our aim was to investigate premature senescence in BA and to assess senotherapies in a preclinical model of biliary cirrhosis. METHODS: BA liver tissues were prospectively obtained at hepatoportoenterostomy (n=5) and liver transplantation (n=30) and compared to controls (n=10). Senescence was investigated through spatial whole transcriptome analysis, SA-ß-gal activity, p16 and p21 expression, γ-H2AX and senescence-associated secretory phenotype (SASP). Human allogenic liver-derived progenitor cells (HALPC) or dasatinib and quercetin (D+Q) were administrated to two-month-old Wistar rats after bile duct ligation (BDL). RESULTS: Advanced premature senescence was evidenced in BA livers from early stage and continued to progress until liver transplantation. Senescence and SASP were predominant in cholangiocytes, but also present in surrounding hepatocytes. HALPC but not D+Q reduced the early marker of senescence p21 in BDL rats and improved biliary injury (serum γGT and Sox9 expression) and hepatocytes mass loss (Hnf4a). CONCLUSIONS: BA livers displayed advanced cellular senescence at diagnosis that continued to progress until liver transplantation. HALPC reduced early senescence and improved liver disease in a preclinical model of BA, providing encouraging preliminary results regarding the use of senotherapies in pediatric biliary cirrhosis.

Meso-Rex shunt for immediate portal revascularization in pediatric liver transplantation: first report.

We describe the case of a 13-month-old girl transplanted for biliary atresia with PV hypoplasia. She received the left liver lobe of her mother and presented intraoperative portal thrombosis. Because of technical reasons, the opportunity to have conventional PV reconstruction using the donor left PV stump was lost. Immediate conversion to a meso-Rex shunt, using the recipient jugular vein as a bridge between the superior mesenteric vein and the graft Rex recessus, allowed excellent portal revascularization of the transplant. We suggest that synchronous meso-Rex shunt may constitute a valid alternative to truncal PV anastomosis during pediatric LT.

Combination of tissue expansion and porcine mesh for secondary abdominal wall closure after pediatric liver transplantation.

We report the case of a two and a half yr boy hospitalized in our Pediatric Transplantation Unit for portal vein thrombosis following liver transplantation. After performing a meso-Rex shunt, abdominal wall closure was impossible without compressing the portal flow. A combination of two techniques was used to perform the reconstruction of the muscular fasciae and skin layers. The association of tissue expanders and porcine mesh (Surgisis(®)) allowed complete abdominal wall closure with good functional and esthetic results. Use of both techniques is a useful alternative for difficult abdominal closure after liver pediatric transplantation.