Kosuke Endo

Splenectomy does not offer immunological benefits in ABO-incompatible liver transplantation with a preoperative rituximab.

Background. Preformed anti-ABO antibodies are primarily responsible for antibody-mediated rejection (AMR) after ABO-incompatible (ABO-I) liver transplantation (LT) resulting in lethal hepatic necrosis and biliary complications. Splenectomy, an integral part of protocol for ABO-I LT, decreases anti-ABO antibodies. With the preoperative rituximab prophylaxis, role of the splenectomy for ABO-I LT is now under debate. We investigated the necessity of splenectomy by retrospective analyses of the short-term anti-ABO antibody response and long-term outcomes of ABO-I LT. Methods. Thirty-seven ABO-I LTs performed from May 2006 through July 2009, at Kyoto University Hospital, Kyoto, Japan, were retrospectively analyzed. Twenty-seven patients who underwent splenectomy (splenectomy group) received 329.6±35.8 mg rituximab 17.7±11.9 days before living donor LT. Ten patients without splenectomy (nonsplenectomy group) received 320.0±10.3 mg rituximab 26.6±21.3 days before transplantation. All patients received a posttransplant hepatic artery infusion with prostaglandin E1 and methylprednisolone. Perioperative anti-ABO immunoglobulin M and immunoglobulin G antibody titers, rejections, biliary complications, infections, and survival results were compared. Results. Preoperative rituximab with plasma exchange effectively reduced anti-ABO antibodies in both patient groups at the time of LT. There was no statistically significant difference observed in anti-ABO immunoglobulin M and immunoglobulin G antibody titers between the “splenectomy” and “nonsplenectomy” groups during the initial 8 weeks. The clinical outcomes, including AMR, biliary complications, infections, and survival, were similar in both the groups. Conclusions. Preoperative rituximab effectively decreased the anti-ABO antibodies sufficiently to prevent the AMR irrespective of splenectomy. Splenectomy does not offer any immunological benefit in ABO-I LT with preoperative rituximab.

Immunohistochemical studies on the localization of cancer associated antigens DU‐PAN‐2 and CA19‐9 in carcinomas of the digestive tract

The immunohistochemical localization of DU‐PAN‐2 antigen and CA19‐9 antigen in carcinomas of the digestive tract was studied using an immunoperoxidase technique. Staining for DU‐PAN‐2 antigen and CA19‐9 antigen was observed in 104 (79%) and 96 (73%) of 131 carcinomas of the digestive tract, respectively. Diffuse staining (more than 20% of carcinoma cell stained) for DU‐PAN‐2 was detected in 14 of 21 (67%) pancreatic carcinomas and 11 of 19 (58%) carcinomas of the biliary tract (including cholangiocarcinoma). Diffuse staining for CA19‐9 was detected in 15 (71%) of pancreatic carcinomas and nine (47%) of the carcinomas of the biliary tract. In colon carcinomas, no diffuse staining for DU‐PAN‐2 was observed, whereas diffuse staining for CA19‐9 was found in 41%. There was a positive correlation between the differentiation degree (or grade) of the adenocarcinomas of the colon and the expression of CA19‐9, but not that of DU‐PAN‐2.

Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats.

OBJECTIVE Liver fibrosis and subsequent cirrhosis is a major cause of death worldwide, but few effective antifibrotic therapies are reported. Whey-hydrolyzed peptide (WHP), a major peptide component of bovine milk, exerts anti-inflammatory effects in experimental models. A WHP-enriched diet is widely used for immunomodulating diets (IMD) in clinical fields. However, the effects of WHP on liver fibrosis remain unknown. The aim of this study was to investigate the antifibrotic effects of WHP in a rat cirrhosis model. METHODS Progressive liver fibrosis was induced by repeated intraperitoneal administration of dimethylnitrosamine (DMN) for 3 wk. Rats were fed either a WHP-enriched IMD (WHP group) or a control enteral diet (control group). The degree of liver fibrosis was compared between groups. Hepatocyte-protective effects were examined using hepatocytes isolated from rats fed a WHP diet. Reactive oxygen species and glutathione in liver tissue were investigated in the DMN cirrhosis model. RESULTS Macroscopic and microscopic progression of liver fibrosis was remarkably suppressed in the WHP group. Elevated serum levels of liver enzymes and hyaluronic acid, and liver tissue hydroxyproline content were significantly attenuated in the WHP group. Necrotic hepatocyte rates with DMN challenge, isolated from rats fed a WHP-enriched IMD, were significantly lower. In the DMN cirrhosis model, reactive oxygen species were significantly lower, and glutathione was significantly higher in the WHP groups whole liver tissue. CONCLUSION A WHP-enriched IMD effectively prevented progression of DMN-induced liver fibrosis in rats via a direct hepatocyte-protective effect and an antioxidant effect through glutathione synthesis.

Pretransplant replacement of donor liver grafts with recipient Kupffer cells attenuates liver graft rejection in rats

Rejection of liver grafts is a difficult issue that has not been resolved. Preoperative replacement of liver cells in the graft with cells from the intended recipient may attenuate rejection. We investigated whether preoperative transplant of recipient bone marrow cells (BMCs) to the donor replaced liver allograft cells and attenuated rejection.

AUXILIARY TRANSPLANTATION OF THE CHIMERIC LIVER GRAFT IN MOUSE AND RAT COMBINATION AND EVALUATION OF THE LONG-TERM SURVIVAL AND PROLIFERATIVE CAPACITY OF THE TRANSPLANTED GRAFT IN THE RECIPIENT RAT: 1356

T. Hata1, K. Endo1, K. Jobara1, J. Iwasaki1, E. Kobayashi2, S. Uemoto3 1Division Of Hepato-pancreato-biliary Surgery And Transplantation, Department Of Surgery, Kyoto University, Kyoto/JAPAN, 2Division Of Development Of Advanced Treatment, Center For Development Of Advanced Medical Technology, Jichi Medical University, Shimotsuke/ JAPAN, 3Hepatopancreatobillary Surgery And Liver Transplantation, Kyoto University Hospital, Kyoto/JAPAN