Tissue Expression of Programmed Cell Death 1 Ligand1 (PD-L1) in Biopsies of Transplant Livers of Pediatric Patients as a Possible Marker of Acute Cellular Rejection.

INTRODUCTION: Preclinical models have demonstrated that PD-1 and its ligand programmed death ligand1 (PD-L1) play significant roles in both graft induction and the maintenance of immune tolerance. It has also been suggested that PD-L1 tissue expression may predict graft rejection; however, the available data are sparse and inconclusive. Some studies were conducted on patients with cancer; most of them do not concern the liver, especially within the context of the use of immunohistochemical tests. Therefore, the aim of our study was to assess the relationship between tissue expression of PD-L1 in a unique material, i.e., in the liver biopsies of pediatric patients after transplantation with the presence of acute cellular rejection (ACR). MATERIAL AND METHODS: This retrospective study enrolled 55 biopsies from 55 patients who underwent protocol liver biopsies. The control group consisted of 19 biopsies from 13 patients diagnosed with acute cellular rejection (rejection activity index/RAI/ from 2 to 8). An immunohistochemical (IHC) staining for PD-L1 was performed in all of the liver specimens; its expression was analyzed in different regions of liver tissue (in inflammatory infiltrates and within the endothelium and hepatocytes). The following changes were re-evaluated in each specimen: features of any kind of rejection (acute cellular, antibody-mediated, chronic); the presence and severity of fibrosis (Ishak scale); and the presence of cholestasis and steatosis. Clinical parameters were also evaluated, including tests of liver function (AST, ALT, GGT, bilirubin). RESULTS: The age of patients in the study group ranged from 2.37 to 18.9 years (median 13.87 years), with the time after transplantation being 1-17 years (median 8.36 years). The age of patients in the control group ranged from 1.48 to 17.51 years (median 7.93 years), with their biopsies being taken 0.62-14.39 years (median 1.33 years) after transplantation. We found a statistically significant relationship between PD-L1 expression on inflammatory infiltrates and ACR; however, there was no statistically significant relationship between PD-L1 endothelial expression and ACR. PD-L1 was not positive in the hepatocytes regardless of if it was the study or control group that was under observation. CONCLUSION: PD-L1 appears to be a promising marker to predict graft rejection.

The Impact of Hepatic Artery Thrombosis on the Outcome of Pediatric Living Donor Liver Transplantations.

The aim of our study was to assess risk factors for hepatic artery thrombosis (HAT) and to evaluate the impact of HAT management on long-term outcomes after pediatric living donor liver transplantation (LDLT). We retrospectively analyzed 400 patients who underwent primary LDLT between 1999 and 2020. We compared preoperative data, surgical factors, complications, and patient and graft survivals in patients with HAT (HAT Group) and without HAT (non-HAT Group). A total of 27 patients (6.75%) developed HAT. Acute liver failure, a hepatic artery (HA) anastomosis diameter below 2 mm, and intraoperative HA flow dysfunction were significantly more common in the HAT Group (p < 0.05, p = 0.02026, and p = 0.0019, respectively). In the HAT Group, 21 patients (77.8%) underwent urgent surgical revision. The incidence of biliary stenosis and retransplantation was significantly higher in the HAT Group (p = 0.00002 and p < 0.0001, respectively). Patient and graft survivals were significantly worse in the HAT Group (p < 0.05). The close monitoring of HA flow with Doppler ultrasound during the critical period of 2 to 3 weeks after LDLT and the immediate attempt of surgical revascularization may attenuate the elevated risk of biliary stenosis, graft loss, and the need for retransplantation due to HAT.

Inferior Vena Cava and Venous Outflow Reconstruction in Living Donor Liver Transplantation in Children: A Single-Center Retrospective Study and Literature Review.

BACKGROUND In this report, we present technical problems and solutions used in the reconstruction of the inferior vena cava and graft venous outflow during living donor liver transplantation (LDLT) in children. MATERIAL AND METHODS In 65 grafts out of 379 liver transplantations from living donors, reconstruction of multiple hepatic venous branches and/or IVC was necessary. In 4 cases, cryopreserved deceased donor venous grafts were used for the reconstruction of the IVC and/or HV. RESULTS Follow-up ranged from 2 months to 17.8 years (median 7.2 years). In 4 children, liver re-transplantation was required for a reason not related to venous outflow (biliary complications in 3 patients, graft insufficiency caused by small-for-size syndrome). Two patients died: 1 due to tumor recurrence and 1 due to multi-organ failure. Fifty-nine patients are alive with good liver function. One patient (1.5%) after deceased donor venous graft reconstruction showed symptoms of venous outflow obstruction, which was successfully treated with endovascular balloon angioplasty and stent placement. The remaining 59 transplanted patients do not show any signs of venous outflow obstruction. CONCLUSIONS In most cases, the reconstruction of multiple hepatic veins of living donor allografts can successfully be done with local venoplasty, while using cold-stored vein grafts may be helpful in selected cases of LDLT.

Kidney Transplantation in Children with Thrombosed Inferior Caval Vein - Atypical Vascular Anastomoses.

BACKGROUND Diffuse thrombosis of iliac veins and IVC has been considered a significant technical obstacle in pediatric kidney transplantation (KT). MATERIAL AND METHODS Between 1984 and 2018, 951 KTs were performed in our institution. In 4 children qualified for KT, diffuse thrombosis of iliac veins or IVC was found. The surgical techniques, complications, patient and graft survival, and long-term renal function were studied retrospectively. The patients' age at transplantation was 2.5-13 years and body mass was 11-39 kg. RESULTS All children were transplanted with venous anastomoses made to infrahepatic IVC (3 patients) or collateral circulation (1 patient). Early complications developed in 2 patients: significant bleeding from the graft area requiring revision on the second day after transplantation and chyle leak that resolved spontaneously. The follow-up period was 1-12.5 years. Three patients are alive with a follow-up at 7 months, 4.5, and 12 years with serum creatinine 0.7 mg%, 0.6 mg% and 1.4 mg%, respectively. One patient died 1 year after KT, with normal graft function. No late complications related to KT were observed in any patient. CONCLUSIONS Renal transplantation in pediatric patients with thrombotic vascular complications is associated with a number of technical difficulties and problems.

Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature.

Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed.