Liver transplantation as a new treatment option for perihilar cholangiocarcinoma and colorectal liver metastases: a review.

Liver transplantation (LT) has become widespread in recent years owing to advances in the elucidation of its pathogenesis, surgical procedures, and perioperative management. Historically, LT was only performed in patients with end-stage liver disease and certain malignancies, such as hepatocellular carcinoma, but its indications have recently been expanded to include unresectable perihilar cholangiocarcinoma (pCCA) and colorectal liver metastases (CRLM). In this review, we discuss the current status and future prospects of LT for these expanded indications.

Sclerosing Angiomatoid Nodular Transformation of the Laparoscopically Resected Spleen: Case Reports and Review of the Literature.

Introduction: Most splenic tumors are benign; however, it is essential to differentiate them from malignant tumors, such as malignant lymphoma and metastatic tumors. Sclerosing angiomatoid nodular transformation (SANT) is a relatively rare benign tumor that has been reported recently. Splenectomy is performed in most cases of SANT because of the challenges associated with a definitive diagnosis.

Recipient toll-like receptor 4 determines the outcome of ischemia-reperfusion injury in steatotic liver transplantation in mice.

Toll-like receptor 4 (TLR4) plays a crucial role in ischemia-reperfusion injury (IRI) after liver transplantation (LT). However, the role of TLR4 in the context of steatotic grafts remains unclear. In this study, we developed a mouse model to explore IRI mechanisms in steatotic LT using TLR4 knockout mice as recipients.

Novel Technique for Liver Segmentation by Fluorescence Intensity Gradient Using Two Different Doses of Indocyanine Green.

Background: Techniques involving dye injection or regional ischemia are commonly used for the precise identification of liver regions during hepatectomy. The visualization of regions with indocyanine green (ICG) has been widely used for liver segmentation. ICG is typically administered only once during each hepatectomy.

Living-donor liver transplantation for non-resectable colorectal liver metastases: protocol for a multicentric, single-arm study.

Introduction: The only treatment for non-resectable colorectal liver metastasis (CRLM) is medical therapy, and the overall survival (OS) rate at 3 and 5 years is approximately 30%-40% and less than 10%, respectively. In 2020, a group in Norway reported that liver transplantation for non-resectable CRLM improved the 5-year OS rate to up to 83%. Clinical trials have been launched since that report was published, but most have involved deceased-donor liver transplantation rather than living-donor liver transplantation.

Liver Retransplantation Using Living Donor Grafts: A Feasible Approach for Chronic Allograft Failure.

Background: The indication of living donor liver retransplantation (re-LDLT) for retransplant candidates with chronic allograft failure (CAF) is increasing because of the high mortality rate of patients on the waiting list. However, evidence supporting re-LDLT for CAF remains scarce because of technical difficulties. We aimed to examine the feasibility based on our significant case experience.

Chronological alterations in de novo malignancies after living-donor liver transplantation: A cohort study of 1781 recipients using annual comparisons of standardized incidence ratios.

Background: De novo malignancies (DNMs) are a major adverse event after solid organ transplantation; however, their characteristics and recent trends after living-donor liver transplantation (LDLT) remain unclear.

Methods: We retrospectively reviewed 1781 primary LDLT recipients (1990-2020) and annually calculated standardized incidence ratios (SIRs) of DNMs compared to the age-adjusted Japanese general population.

Results: After 21 845 person-years follow-up, 153 DNM lesions (8.

Impact of thoracic shape on the surgical outcomes of laparoscopic-assisted living donor hepatectomy.

Background: Although laparoscopic-assisted donor hepatectomy (LADH) has become the definitive procedure for harvesting living donor livers, its surgical outcomes in association with donor body shape have not been elucidated.

Methods: The impact of donor factors, including thoracic shape, on LADH outcomes was retrospectively investigated. Thoracic anthropometric data were examined in all LADHs with a left/right graft between 2013 and 2022.

Venous outflow reconstruction in living-donor liver transplantation for Budd-Chiari syndrome involving vena cava.

Ironically, the hepatic vena cava is mostly involved in Budd-Chiari syndrome in the Asia-Pacific region, whereas living-donor liver transplantation is predominant, which cannot replace the hepatic cava. Hata and colleagues introduced a new surgical technique for venous reconstruction in living-donor liver transplantation, providing a novel solution to this longstanding dilemma.

SIRT1 regulates hepatocyte programmed cell death via GSDME - IL18 axis in human and mouse liver transplantation.

Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates the inflamed liver's canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain.

Properdin inhibition ameliorates hepatic ischemia/reperfusion injury without interfering with liver regeneration in mice.

Hepatic ischemia/reperfusion injury (IRI) often causes serious complications in liver surgeries, including transplantation. Complement activation seems to be involved in hepatic IRI; however, no complement-targeted intervention has been clinically applied. We investigated the therapeutic potential of Properdin-targeted complement regulation in hepatic IRI.

Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans.

Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We have shown that carcinoembryonic antigen-related cell adhesion molecule (Ceacam1; ), a transmembrane biliary glycoprotein expressed in epithelial, endothelial, and immune cells, determines donor liver transplant quality. Here, we studied how AS of affects ischemia-reperfusion injury (IRI) in mouse and human livers.

SIRT1 Regulates Hepatocyte Programmed Cell Death via GSDME - IL18 Axis in Human and Mouse Liver Transplantation.

Sirtuin 1 (SIRT1) is a histone/protein deacetylase involved in cellular senescence, inflammation, and stress resistance. We previously reported that myeloid SIRT1 signaling regulates the inflamed liver's canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain.

Anti-complement 5 antibody ameliorates antibody-mediated rejection after liver transplantation in rats.

Antibody-mediated rejection (AMR) remains a refractory rejection after donor-specific antibody (DSA)-positive or blood-type incompatible liver transplantation (LT), even in the era of pre-transplant rituximab desensitization. This is due to the lack of not only effective post-transplant treatments but also robust animal models to develop/validate new interventions. Orthotopic LT from male Dark Agouti (DA) to male Lewis (LEW) rats was used to develop a rat LT-AMR model.

Recipient signaling regulates ischemia reperfusion-induced ER stress and metabolic responses in liver transplantation: from mouse-to-human.

T-cell immunoglobulin and mucin ()4 is expressed on APCs, including macrophages, as one of the main amplifiers in the mechanism of liver ischemia-reperfusion injury (IRI) following orthotopic liver transplantation (OLT). Though donor selectively expressed on Kupffer cells serves as a checkpoint regulator of innate immune-driven IRI cascades, its role on cells outside the OLT remains unclear. To dissect the role of donor vs.

Risk factors for antibody-mediated rejection in ABO blood-type incompatible and donor-specific antibody-positive liver transplantation.

Antibody-mediated rejection (AMR) is a refractory rejection after ABO blood-type incompatible (ABOi) or donor-specific antibody (DSA)-positive liver transplantation (LT). Pretransplant rituximab desensitization dramatically reduced posttransplant AMR development; however, risk factors for AMR in the rituximab era remain unclear in both ABOi living-donor LT (ABOi-LDLT) and preformed DSA-positive LT (pDSA-LT). Of our 596 adult LDLTs (≥18 y) after rituximab introduction (2004-2019), 136 were ABOi-LDLT (22.

The impact of human leukocyte antigen mismatch on recipient outcomes in living-donor liver transplantation.

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.

En bloc excision of giant polycystic liver with hepatic cava and its auto-transplant caval reconstruction as a safe surgical procedure for liver transplantation.

Safely excising a giant liver while leaving the hepatic inferior vena cava intact is difficult. Hata et al. present images and videos describing their novel technique consisting of total hepatectomy including the hepatic cava; extracorporeal retrieval; and auto-transplant inferior vena cava reconstruction, for an extremely enlarged polycystic liver weighing 24 kg.

Myeloid Ikaros-SIRT1 signaling axis regulates hepatic inflammation and pyroptosis in ischemia-stressed mouse and human liver.

Background & Aims: Although Ikaros (IKZF1) is a well-established transcriptional regulator in leukocyte lymphopoiesis and differentiation, its role in myeloid innate immune responses remains unclear. Sirtuin 1 (SIRT1) is a histone/protein deacetylase involved in cellular senescence, inflammation, and stress resistance. Whether SIRT1 signaling is essential in myeloid cell activation remains uncertain, while the molecular communication between Ikaros and SIRT1, two major transcriptional regulators, has not been studied.

Donor Hepatic Occult Collagen Deposition Predisposes to Peritransplant Stress and Impacts Human Liver Transplantation.

Background And Aims: Environmentally triggered chronic liver inflammation can cause collagen deposits, whereas early stages of fibrosis without any specific symptoms could hardly be detectable. We hypothesized that some of the human donor grafts in clinical liver transplantation (LT) might possess unrecognizable fibrosis, affecting their susceptibility to LT-induced stress and hepatocellular damage. This retrospective study aimed to assess the impact of occult hepatic fibrosis on clinical LT outcomes.

Ischemia-reperfusion Injury in Allogeneic Liver Transplantation: A Role of CD4 T Cells in Early Allograft Injury.

Background: A major discrepancy between clinical and most experimental settings of liver ischemia-reperfusion injury (IRI) is the allogenicity.

Methods: In the current study, we first established a murine model of allogeneic orthotopic liver transplantation with extended cold ischemia time (18 h). Roles of CD4 T cells in the pathogenesis of IRI in liver allografts were determined using a depleting anti-CD4 antibody.