Advocating for a "shift-to-left" in transplant oncology: left grafts, RAPID and dual graft.

The extension of liver transplantation to new oncologic indications might exacerbate the shortage of grafts. Living donor liver transplantation (LDLT) may emerge as a viable resource, although its diffusion in the Western world is still very limited. Several groups have advocated for minimizing the impact on donors by reducing the extent of donor hepatectomy, i.

The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation.

Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors.

Partial orthotopic liver transplantation in combination with two-stage hepatectomy: A proof-of-concept explained by mathematical modeling.

Background: Resection And Partial Liver Segment 2/3 Transplantation with Delayed total hepatectomy (RAPID) includes total hepatectomy in 2 steps with small graft transplantation at first stage. To avoid graft portal hyperperfusion, portal vein pressure monitoring is required after revascularization and right portal vein clamping. To date, portal flow modulation has not been reported but simulating hemodynamics in RAPID patients would be useful to anticipate these procedures.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei in a liver-transplanted patient: a case report.

Background: Diagnostic work-ups in transplanted immunosuppressed patients are a challenge as non-specific findings may be interpreted as transplant-related complications. If the disease in question is rare and slowly developing like pseudomyxoma peritonei (PMP), it is even more difficult. Cytoreductive surgery (CRS) and subsequent hyperthermic intraperitoneal chemotherapy (HIPEC) is the recommended treatment for PMP even with extensive peritoneal spread.

A Young, Immunocompetent Woman with Small Bowel and Hepatic Mucormycosis Successfully Treated with Aggressive Surgical Debridements and Antifungal Therapy.

A 24-year-old woman with coeliac disease and transient neutropenia developed mucormycosis with extensive involvement of the liver and small intestine. She was successfully treated with aggressive surgical debridements and long-term antifungal therapy with liposomal amphotericin B and posaconazole.

Survival of children after liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively.

The prognostic value of F-FDG PET/CT prior to liver transplantation for nonresectable colorectal liver metastases.

Purpose: The main objective of this study was to evaluate the prognostic value of volumetric and metabolic information derivied from F-18 fluorodeoxyglucose positron emission tomography (F-FDG PET) in combination with computed tomography (CT) prior to liver transplantation (LT) in patients with nonresectable colorectal liver metastases (CLM). Due to scarcity of liver grafts, prognostic information enabling selection of candidates who will gain the highest survival after LT is of vital importance. F-FDG PET/CT was a part of the preoperative study protocol.

CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer.

CD8 T cells that express retinoic acid-related orphan receptor (ROR)γt (T17 cells) have been shown to promote procarcinogenic inflammation and contribute to a tolerogenic microenvironment in tumors. We investigated their phenotype and functional properties in relationship to the pathogenesis of human distal bile duct cancer (DBDC). DBDC patients had an elevated level of type 17 immune responses and the frequency of CD8RORγt T cells (T17 cells) was increased in peripheral blood.

Indications and Outcomes in Liver Transplantation in Patients With Primary Sclerosing Cholangitis in Norway.

Background: Primary sclerosing cholangitis (PSC) is 1 of the leading causes of liver transplantation (LTX) in Scandinavia, and an increasing number of PSC patients have been transplanted in Norway during the last 2 decades. This trend is partly attributable to the recently established practice in Norway of offering LTX to PSC patients with cholangiocellular dysplasia. Based on the controversy associated with this practice, we herein aimed to report the main features and outcomes of our LTX program in PSC.

Regulatory T cells that co-express RORγt and FOXP3 are pro-inflammatory and immunosuppressive and expand in human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is highly infiltrated by CD4T cells that express RORγt and IL-17 (T17). Compelling evidence from the tumor microenvironment suggest that regulatory T cells (T) contribute to T17 mediated inflammation. Concurrently, PDAC patients have elevated levels of pro-inflammatory cytokines that may lead to T17 associated functional plasticity in T.

Human regulatory T cells control TCR signaling and susceptibility to suppression in CD4+ T cells.

Human CD4(+)CD25(hi)FOXP3(+) regulatory T cells maintain immunologic tolerance and prevent autoimmune and inflammatory immune responses. Regulatory T cells undergo a similar activation cycle as conventional CD4(+) T cells upon antigen stimulation. Here, we demonstrate that T cell receptors and costimulation are required to activate the regulatory T cell suppressive function.

Low use of surveillance and early diagnosis of hepatocellular carcinoma in Norway--a population-based cohort study.

Background And Aims: Curative treatment of hepatocellular carcinoma (HCC) is dependent on early diagnosis. Surveillance of patients at high risk for HCC is a key determinant to achieve this goal, but may be an underutilized tool. The aim of this study was to determine the rate of pre-diagnosis surveillance in patients with HCC in a large population-based cohort and to assess to what extent cirrhosis was known prior to the diagnosis of HCC.

Mycophenolate pharmacokinetics and inosine monophosphate dehydrogenase activity in liver transplant recipients with an emphasis on therapeutic drug monitoring.

Background: The pharmacokinetics of the immunosuppressant mycophenolic acid (MPA) demonstrates high inter- and intra-patient variability. Variation in the binding of MPA to albumin has been postulated to be an important factor in this variability, and monitoring of free MPA has been suggested to improve therapeutic drug monitoring (TDM) of MPA. Inosine monophosphate dehydrogenase (IMPDH) is the target enzyme for MPA, therefore the IMPDH activity in lymphocytes can serve as a marker of the MPA-specific response.

Clinical experience with microdialysis catheters in pediatric liver transplants.

Ischemic vascular complications and rejection occur more frequently with pediatric liver transplants versus adult liver transplants. Using intrahepatic microdialysis catheters, we measured lactate, pyruvate, glucose, and glycerol values at the bedside for a median of 10 days in 20 pediatric liver grafts. Ischemia (n = 6), which was defined as a lactate level > 3.

Hepatic and abdominal carbon dioxide measurements detect and distinguish hepatic artery occlusion and portal vein occlusion in pigs.

Hepatic artery (HA) occlusion and portal vein (PV) occlusion are the most common vascular complications after liver transplantation with an impact on mortality and retransplantation rates. The detection of severe hypoperfusion may be delayed with currently available diagnostic tools. Hypoperfusion and anaerobically produced lactic acid lead to increases in tissue carbon dioxide.

Inflammatory markers sampled by microdialysis catheters distinguish rejection from ischemia in liver grafts.

Rejection and ischemia are serious complications after liver transplantation. Early detection is mandatory, but specific markers are largely missing, particularly for rejection. The objective of this study was to explore the ability of microdialysis catheters inserted in liver grafts to detect and discriminate rejection and ischemia through postoperative measurements of inflammatory mediators.

Early bedside detection of ischemia and rejection in liver transplants by microdialysis.

This study was performed to explore whether lactate, pyruvate, glucose, and glycerol levels sampled via microdialysis catheters in the transplanted liver could be used to detect ischemia and/or rejection. The metabolites were measured at the bedside every 1 to 2 hours after the operation for a median of 10 days. Twelve grafts with biopsy-proven rejection and 9 grafts with ischemia were compared to a reference group of 39 grafts with uneventful courses.

[Liver transplantation in Norway through 25 years].

Background: In Norway, liver transplantation has been the treatment of choice for irreversible acute and chronic liver failure for 25 years. The aim of this article is to present a summary of the results obtained.

Material And Methods: All liver transplants performed in Norway in the period 25.

Experience from an active preemptive kidney transplantation program--809 cases revisited.

Background: Preemptive kidney transplantation (PKT) is increasingly acknowledged. We wanted to investigate the results of an active PKT policy in an unselected end-stage renal disease population with high prevalence of PKT.

Methods: From 1989 to 2007, 3400 first kidney transplantations were performed in which 809 were PKTs (24%).

Expression of IMPDH1 and IMPDH2 after transplantation and initiation of immunosuppression.

Background: Mycophenolic acid (MPA) mediates immunosuppressive effects by inhibiting inosine monophosphate dehydrogenase (IMPDH). Induction of IMPDH activity has been observed in whole blood and erythrocyte samples during immunosuppressive therapy. Information concerning the mechanisms for increased IMPDH activity is limited and the potential implications of induction have been debated.

Living donor kidney transplantation: the effects of donor age and gender on short- and long-term outcomes.

Background: The influence of donor age and sex on acute rejection episodes and short- and long-term graft survival in living donor (LD) kidney transplantation has not been well characterized.

Methods: This prospective cohort study includes 739 first time LD transplantations with median follow-up time of 55.1 months.

Calcineurin inhibitor avoidance with daclizumab, mycophenolate mofetil, and prednisolone in DR-matched de novo kidney transplant recipients.

Background: Calcineurin inhibitor (CNI)-free regimens posttransplantation have been claimed to conserve graft function in addition to reduce the risk factors for cardiovascular and malignant disease in renal transplant recipients.

Methods: The primary aim of this prospective, open-label, randomized, parallel-group, single-center study was to compare the effect of complete CNI-avoidance posttransplant (daclizumab + mycophenolate mofetil + prednisolone: Dac-group, n=27) with the standard CNI-based immunosuppressive protocol at our transplant unit (cyclosporine A + mycophenolate mofetil + prednisolone: CsA-group, n=27) on renal function (glomerular filtration rate [GFR] determined as plasma clearance of 51Cr-EDTA) in a selected low immunogenic risk population (DR-matched, PRA-negative de novo cadaveric transplant recipients).

Results: There were no significant difference in GFR at week 10 (P=0.