Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoperative prediction of prognosis remains a challenge. This study aimed to identify clinical prognostic indicators by investigating the molecular profiles of ICC and evaluating the preoperative imaging data of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET). A retrospective analysis was performed on 50 consecutive patients with ICC who underwent curative hepatectomy after ¹⁸F-FDG-PET examination. To evaluate the molecular profiles of ICC, KRAS mutation status was assessed in resected specimens. For the assessment of glucose uptake, we observed the expression of glucose transporter-1 (GLUT-1) by immunohistochemistry. The data of ¹⁸F-FDG-PET were re-evaluated as follows: maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cut-off values were determined using receiver operating characteristic (ROC) curve analysis. Cumulative overall survival (OS) was analyzed using the Kaplan–Meier analysis. Overall, 16 (32.0%) patients had mutations in KRAS. Patients with mutated KRAS exhibited shorter OS than those with wild-type KRAS (5-year OS, 0% vs. 35.1%, P < 0.001). GLUT-1 expression was significantly higher in tumors with mutated KRAS than in tumors with wild-type KRAS (median, 4.0 vs. 1.0, P < 0.001). Survival was significantly different when stratified by expression of GLUT-1 (5-year OS, 0% vs. 46.5%, P <0.001). Among the ¹⁸F-FDG-PET parameters, the MTV and TLG were significantly higher in the mutated KRAS group than in the wild-type KRAS group (P = 0.013 and P = 0.026, respectively). ROC curve analysis revealed a cut-off value of 38 for the MTV, with the highest accuracy (area under the curve = 0.789; 95% confidence interval, 0.581–0.902) for predicting KRAS mutation. This cut-off value permitted stratification of OS (high vs. low: 5-year OS, 13.1% vs. 36.7%, P = 0.008). High MTV is associated with KRAS mutation and poor postoperative outcomes in patients with ICC, suggesting that the MTV of ICC measured by ¹⁸F-FDG-PET may provide useful information for tumor molecular profiles and prognosis.

Malignant hepatic tumors (MHTs) in children are rare and account for approximately 5% of candidates for pediatric liver transplantation (LT) in Japan. We conducted a national survey of pediatric patients undergoing living donor LT for MHTs between October 1990 and April 2018. In total, 116 children underwent LT for MHTs during this study period: 100 hepatoblastomas (HBLs), 10 hepatocellular carcinomas (HCCs), and 6 other MHTs. The overall patient survival rate at 5 years was 81.3% for HBL, 60.0% for HCC, and 80.0% for other MHTs (P = 0.047). In HBL patients, there was no significant difference in the 1- and 5-year patient survival rates between patients undergoing primary LT and those who received salvage LT for tumor recurrence (89.7%, 81.6% vs. 88.0%, 76%) (P = 0.526). The 5-year overall survival rate after LT for HBL significantly improved from 63.2% in 1996–2008 to 89.8% in 2009–2018 (P = 0.018). The presence of lung metastasis before LT had no significant influence on the long-term survival (P = 0.742). Five patients with HCC died, including two who fell outside the Milan criteria. In conclusion, LT for pediatric MHTs, especially HBL, is a valuable treatment option for select patients.

Donor–recipient human leukocyte antigen (HLA) compatibility has not been considered to significantly affect liver transplantation (LT) outcomes; however, its significance in living‐donor LT (LDLT), which is mostly performed between blood relatives, remains unclear. This retrospective cohort study included 1954 LDLTs at our institution (1990–2020). The primary and secondary endpoints were recipient survival and the incidence of T cell–mediated rejection (TCMR) after LDLT, respectively, according to the number of HLA mismatches at all five loci: HLA‐A, HLA‐B, HLA‐C, HLA‐DR, and HLA‐DQ. Subgroup analyses were also performed in between‐siblings that characteristically have widely distributed 0–10 HLA mismatches. A total of 1304 cases of primary LDLTs were finally enrolled, including 631 adults (recipient age at LT ≥18 years) and 673 children (<18 years). In adult‐to‐adult LDLT, the more HLA mismatches at each locus, the significantly worse the recipient survival was (p = 0.03, 0.01, 0.03, 0.001, and <0.001 for HLA‐A, HLA‐B, HLA‐C, HLA‐DR, and HLA‐DQ, respectively). This trend was more pronounced when multiple loci were combined (all p < 0.001 for A + B + DR, A + B + C, DR + DQ, and A + B + C + DR + DQ). Notably, a total of three or more HLA‐B + DR mismatches was an independent risk factor for both TCMR (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.21–5.87; p = 0.02) and recipient survival (HR 2.44, 95% CI 1.11–5.35; p = 0.03) in between‐siblings. By contrast, HLA mismatch did not affect pediatric LDLT outcomes at any locus or in any combinations; however, it should be noted that all donor–recipient relationships are parent‐to‐child that characteristically possesses one or less HLA mismatch at each locus and maximally five or less mismatches in total. In conclusion, HLA mismatch significantly affects not only TCMR development but also recipient survival in adult LDLT, but not in children.

Antibody-mediated rejection (AMR) of liver allograft transplantation was considered as anecdotal for many decades. However recently, AMR has gained clinical awareness as a potential cause of chronic liver injury, leading to liver allograft fibrosis and eventual graft failure. (1) Methods: Literature on chronic AMR (cAMR) in pediatric post-liver transplant patients was reviewed for epidemiologic data, physiopathology, diagnosis, and treatment approaches. (2) Results: Accurate incidence of cAMR in pediatric liver transplantation remains unknown. Diagnostic criteria of cAMR were suggested by the Banff Working Group in 2016 and are based on standardized histopathological findings, C4d staining pattern, associated with the presence of donor-specific antibodies (DSA). Physio-pathological mechanisms are not clear for the technically difficult-to-obtain animal models reproducing cAMR. Treatment protocols are not established, being limited to case reports and case series, based on experience in ABO incompatible transplantation and kidney transplantation. Immunosuppression compliance with adequate dose adjustment may prevent cAMR. Conversion of Cyclosporine to Tacrolimus may improve pathological findings if treated in early phase. The association of steroids, Mycophenolate Mofetil (MMF) and mTOR inhibitors have shown some synergistic effects. Second-line treatments such as intravenous immunoglobulin (IVIG) and plasma exchange may decrease antibody titers based on ABO incompatible transplant protocols. The use of anti-CD20 (Rituximab) and proteasome inhibitors (Bortezomib) is controversial due to the lack of qualified studies. Therefore, multicenter randomized trials are needed to establish the best therapeutic strategy. In refractory cases, re-transplantation is the only treatment for allograft failure. (3) Conclusions: This literature review collects recent clinical, histopathological, and therapeutical advances of cAMR in liver allograft transplantation of pediatric patients. There are many physio-pathological aspects of cAMR to be clarified. Further efforts with multicenter prospective protocols to manage patients with cAMR are needed to improve its outcome.