Successful surgical treatment for huge retroperitoneal liposarcoma involving the pancreas, right kidney, abdominal aorta and inferior vena cava.

Retroperitoneal liposarcoma is a rare neoplasm that often involves other organs and major blood vessels. Complete surgical resection with negative margins is the only potential curative treatment. Here, we report the case of a patient with a large retroperitoneum liposarcoma that was removed by resection of the descending abdominal aorta and infrahepatic inferior vena cava, right nephrectomy and pancreatoduodenectomy following creation of an extra anatomical femoro-femoral crossover bypass after left axillo-left femoral bypass.

Cerebral Infarction by Paradoxical Gas Embolism During Laparoscopic Liver Resection with Injury of the Hepatic Vessels in a Patient without a Right-to-Left Systemic Shunt.

BACKGROUND Carbon dioxide (CO2) is believed to be the safest gas for laparoscopic surgery, which is a standard procedure. We experienced severe cerebral infarction caused by paradoxical CO2 embolism during laparoscopic liver resection with injury of the hepatic vessels despite the absence of a right-to-left systemic shunt. CASE REPORT A 60-year-old man was diagnosed with hepatocellular carcinoma in the right hepatic lobe secondary to alcoholic liver disease.

Three-dimensional tumor volume and serum alpha-fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria.

Total tumor volume (TTV), as a better predictor of hepatocellular carcinoma (HCC) recurrence after liver transplant, has been explored by our center. Some tumors are not typically spherical but rather ellipsoid or spheroid, and calculating their TTV based on one dimension only may overestimate their volume and exclude them from candidacy for transplantation. Our aim was to study the actual tumor volume (ATV) calculated using the ellipsoid formula and assess its impact on recurrence.

Additive effect of sirolimus and anti-death receptor 5 agonistic antibody against hepatocellular carcinoma.

Background & Aims: Despite careful patient selection, hepatocellular carcinoma (HCC) recurs in 10-20% of cases after liver transplantation, and the use of potent adjuvant anticancer drugs would be welcome. The aim of this study was to evaluate the efficiency of a combined therapy of rapamycin (sirolimus) and anti-death receptor (DR)5 monoclonal antibody (mAb) on HCC.

Methods: We first assessed the side effects of anti-DR5 mAb administration in vivo by giving various doses of anti-DR5 mAb.

Arylacetamide deacetylase: a novel host factor with important roles in the lipolysis of cellular triacylglycerol stores, VLDL assembly and HCV production.

Background & Aims: Very low density lipoproteins (VLDLs) are triacylglycerol (TG)-rich lipoproteins produced by the human liver. VLDLs derive the majority of their TG cargo from the lipolysis of TG stored in hepatocellular lipid droplets (LDs). Important roles for LDs and the VLDL secretory pathway in the cell culture production of infectious hepatitis C virus (HCV) have been established.

Human cytomegalovirus infection in humanized liver chimeric mice.

Aim: Cytomegalovirus is a common viral pathogen that influences the outcome of organ transplantation. To date, there is no established method to evaluate the effects of human CMV (HCMV) treatments in vivo except for human clinical trials. In the current study, we describe the development of a mouse model that supports the in vivo propagation of HCMV.

A comparison of islet autotransplantation with allotransplantation and factors elevating acute portal pressure in clinical islet transplantation.

Background: Acute portal pressure rise is occasionally observed during intraportal islet infusion, especially in islet autotransplantation (IAT) where tissue purification is rarely applied. In this paper we investigate factors associated with acute portal pressure rise, a known risk factor for portal vein thrombosis.

Methods: Retrospective data was collected on 15 islet autotransplant and 122 allogeneic islet transplant subjects.

m-TOR inhibitors: what role in liver transplantation?

The development of calcineurin inhibitors (CNIs) led to marked improvements in patient and graft survival after liver transplantation (LTx). We have been left, however, with a dependence on immunosuppressive agents with nephrotoxicity, neurotoxicity, adverse impacts on cardiac risk profile, and risk for malignancy. These challenges need to be met against a dominance of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) as indications for liver transplant.

Factors affecting hepatocyte isolation, engraftment, and replication in an in vivo model.

Human hepatocyte transplantation is an alternative treatment for acute liver failure and liver diseases involving enzyme deficiencies. Although it has been successfully applied in selected recipients, both isolation and transplantation outcomes have the potential to be improved by better donor selection. This study assessed the impact of various donor variables on isolation outcomes (yield and viability) and posttransplant engraftment, using the SCID/Alb-uPA (severe combined immunodeficient/urokinase type plasminogen activator under the control of an albumin promoter) human liver chimeric mouse model.

Critical role of natural killer cells in the rejection of human hepatocytes after xenotransplantation into immunodeficient mice.

The severe combined immunodeficiency/albumin linked-urokinase type plasminogen activator (SCID/Alb-uPA) human liver chimeric mouse model has added a new dimension to studies of liver based human diseases and has important potential for study of human hepatic drug metabolism. However, it remains unclear if natural killer (NK) cell in SCID/Alb-uPA mice has an important negative impact on engraftment and expansion of human hepatocytes after transplantation. Here, we explore the role of mouse NK cells in the rejection of transplanted human hepatocytes in SCID/Alb-uPA mice.

Therapeutic efficacy of human hepatocyte transplantation in a SCID/uPA mouse model with inducible liver disease.

Background: Severe Combined Immune Deficient (SCID)/Urokinase-type Plasminogen Activator (uPA) mice undergo liver failure and are useful hosts for the propagation of transplanted human hepatocytes (HH) which must compete with recipient-derived hepatocytes for replacement of the diseased liver parenchyma. While partial replacement by HH has proven useful for studies with Hepatitis C virus, complete replacement of SCID/uPA mouse liver by HH has never been achieved and limits the broader application of these mice for other areas of biomedical research. The herpes simplex virus type-1 thymidine kinase (HSVtk)/ganciclovir (GCV) system is a powerful tool for cell-specific ablation in transgenic animals.

The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation.

Background: There is a lack of data on the use of sirolimus after partial liver transplantation, especially regarding its impact on post-transplant regeneration.

Methods: We reviewed adult living donor transplantations, with de novo sirolimus (n = 7) and without sirolimus (n = 21). Liver biopsies were stained for KI-67, a proliferation marker.

Effect of olprinone, a phosphodiesterase III inhibitor, on hepatic ischemia-reperfusion injury in rats.

I/R injury is the main cause for hepatic dysfunction and failure after liver transplantation and liver resection. Therefore, reduction of I/R injury is the most important goal to improve the outcome of these procedures. Olprinone is a newly developed selective phosphodiesterase III inhibitor, which has been reported to ameliorate renal I/R injury in rats.

B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance induction of anti-alphaGAL-producing B-1 cells.

B-1b cells produce IgM natural antibodies against alpha1-3Galbeta1-4GlcNAc (alphaGal). These can be tolerized by nonmyeloablative induction of mixed chimerism using alphaGal-positive (alphaGal+) donor marrow. We assessed the role of CR1/2 in this model for induction of tolerance of B-1b cells.

Mixed hematopoietic chimerism for the simultaneous induction of T and B cell tolerance.

Nonmyeloablative induction of mixed hematopoietic chimerism provides a strategy for inducing T cell tolerance across allogeneic and xenogeneic barriers. We have utilized alpha1-3Gal transferase (GalT) knockout mice, which, like humans, produce anti-Gal natural antibodies, to investigate the ability of mixed chimerism to tolerize B cells producing antibodies of this important specificity, which limits xenotransplantation by causing hyperacute and delayed xenograft rejection. Mixed allogeneic or xenogeneic chimerism indeed tolerizes both preexisting anti-Gal-producing B cells and those developing de novo after establishment of mixed chimerism, even in presensitized mice.

Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells.

Peritoneal cavity B-1 cells are believed to produce IgM natural Abs. We have used alpha1,3-galactosyltransferase-deficient (GalT(-/-)) mice, which, like humans, produce IgM natural Abs against the carbohydrate epitope Galalpha1,3Gal (Gal), to demonstrate that peritoneal cavity B-1b cells with anti-Gal receptors produce anti-Gal IgM Abs only after LPS stimulation. Likewise, peritoneal cavity cells of GalT(-/-) and wild-type mice do not produce IgM Abs of other specificities without LPS stimulation.

Induction of donor-specific tolerance to allogeneic hepatocytes by allogeneic bone marrow transplantation.

Allogenic hepatocytes are rejected within a few days after transplantation without immunosuppression. We previously showed that the peripheral tolerance did not effectively prolong the survival of allogeneic hepatocytes transplanted in the spleen, because anergic T cells lysed allogeneic hepatocytes through Fas/Fas ligand system. The aim of this study was to address whether or not the central tolerance induced by allogeneic bone marrow transplantation (BMT) allows transplanted hepatocytes to survive in the spleen of the recipient.

Allogeneic hepatocyte transplantation: Contribution of Fas-Fas ligand interaction to allogeneic hepatocyte rejection.

Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation.