Metastasis of hepatocellular carcinoma to the right colon manifested by gastrointestinal bleeding.

An 82-year-old black woman with a history of hepatocellular carcinoma presented with gastrointestinal bleeding. Barium enema and fibrocolonoscopy revealed a 4-cm polypoid mass at the level of the ascending colon with evidence of active bleeding. Biopsies of the lesion proved it to be metastatic hepatocellular carcinoma. Exploratory laparotomy revealed no further dissemination of the tumor, and the patient underwent an ileocolectomy. The serosal side of the colonic lesion was free from tumor, and there was no peritoneal implantation, direct extension, or lymph node involvement. This case represents an extremely rare presentation of metastatic hepatocellular carcinoma.

Survey results of transplant patients' attitudes on xenografting.

For centuries, many cultures have described mythical creatures with bodies that combined human and animal features, often the result of violating taboos. This study attempted to investigate the beliefs of transplant patients about xenografting. A survey was given to 100 patients ranging in age from 17 to 74 years old, with 65 men and 35 women, including 72 whites, 18 Hispanics, 5 African Americans, and 4 Asian Americans. The subjects included liver, heart, kidney, lung, and multi-organ transplant patients. The patients were not aware of plans for xenografting at the center under study. Eighty patients agreed with xenografting in an emergency situation. Ten subjects replied, "under no circumstances." Ninety percent believed animal research has advanced medical science. In descending order, the patients preferred human (96%), monkey (44%), mechanical (43%), pig (42%), or dog (34%) organs. Twenty-four patients thought a xenograft would change their appearance, personality, or eating or sexual habits. Twenty patients believed animals have souls. The patients also documented any ethical concerns about xenografting.

Microbiological hazards related to xenotransplantation of porcine organs into man.

Pigs are emerging as the most likely providers of genetically engineered organs and cells for the purpose of clinical xenotransplantation. Introduction of clinical trials has been delayed primarily by uncertainties regarding the risk of swine pathogen transmission that could harm the recipient. The concern that xenotransplantation carries the potential for a new epidemic has been highlighted by recent experiences with both bovine spongiform encephalopathy and human immunodeficiency diseases. As clinical trials have been postponed and xenotransplantation teams are working actively to gather data for an estimation of the risk, this review provides the reader with a state-of-the-art estimation of the microbiological hazards related to xenotransplantation of porcine organs to man. Particular emphasis is put on viral and retroviral hazards. Both current diagnostic tools and those under development are described, along with breeding strategies to provide donor animals that would not put the recipient or the general population at risk.

Transarterial chemoembolization is a safe treatment for unresectable hepatic malignancies.

Acute liver failure has been reported as a frequent complication of transarterial chemoembolization (TACE). We prospectively evaluated the adverse effects and biochemical changes of TACE. From 10/95 to 9/96, 35 patients with hepatic malignancies were evaluated for TACE. Fifteen patients (9 male and 6 female) received 23 treatments. Ten of 15 patients had hepatocellular carcinoma, and 5 had metastatic tumors. Treatment exclusion criteria included advanced liver disease, hepatic vascular thrombosis, and severe comorbidity. TACE consisted of intra-arterial infusion of a mixture of doxorubicin, cisplatin, and mitomycin followed by embolization. Clinical symptoms and laboratory studies were monitored following treatment. Technical success was achieved in all patients. Adverse symptoms were transient, and most resolved within 1 week. Changes in hepatic, renal, and hematologic function were temporary and returned to pre-TACE levels by 1 month. None developed acute liver failure. The mean hospital stay was 3 days. Ten of 13 patients had a significant decrease in baseline tumor markers. The actual survival was 93 per cent with a median follow-up of 10 months. TACE can be performed safely in patients with hepatic tumors. The adverse effects can be anticipated and easily managed.

Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation.

Recurrent hepatitis C infection after orthotopic liver transplantation (OLT) is frequent and may occur as early as a few weeks postoperatively. Early histopathological features of recurrent hepatitis C virus (HCV) infection may be modified by immunosuppressive therapy and can be difficult to differentiate from acute allograft rejection (AAR). Thus, we retrospectively compared histopathological features of liver biopsy specimens from two carefully selected patient groups: one with unequivocal recurrent hepatitis C, the other with unequivocal AAR. Index biopsy specimens obtained at the time of the appearance of liver test abnormalities after OLT and all serial liver biopsy specimens (2 to 13 per patient) were assessed under code and scored semiquantitatively for 44 histopathological variables. The index biopsy specimens from patients with recurrent HCV infection and AAR index biopsies (AAR-Ib) differed significantly (P < .05) for 11 features (10 features were statistically associated with AAR and 1 with early recurrence of HCV infection). Statistically significant features associated with AAR included bile duct injury with overlapping nuclei, lymphocytic infiltrates and necrosis, endothelialitis, portal inflammatory infiltrates containing eosinophils and polymorphonuclear leukocytes, hepatocyte mitoses, and zone 3 canalicular cholestasis. In contrast, the only statistically significant feature associated with early recurrent HCV was sinusoidal dilatation. Stepwise discriminant analysis showed that the presence of eosinophils in the portal inflammatory infiltrate, bile duct necrosis, and bile duct lymphocytic infiltrates were independently associated with AAR. However, serial biopsy specimens from patients with recurrent HCV infection showed statistically significant progression in scores for portal inflammation, portal lymphoid aggregates, and lobular inflammation. We conclude that (1) multiple histopathological features are associated with AAR; (2) early recurrent HCV infection is characterized by elevated alanine aminotransferase levels, positive HCV RNA by polymerase chain reaction (PCR), and absence of diagnostic histopathological features; and (3) serial biopsies are needed to demonstrate progression of histopathological features of recurrent hepatitis C.

Preoperative serum levels of wild-type and hepatitis B e antigen-negative hepatitis B virus (HBV) and graft infection after liver transplantation for HBV-related hepatocellular carcinoma.

Allograft infection in hepatitis B surface antigen (HBsAg)-positive patients undergoing liver transplant (OLT) is still significant, despite post-transplant prophylaxis with high doses of immunoglobulin to HBsAg. Baseline status and post-OLT levels of viraemia and wild-type and hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) were correlated with the clinical course of 16 consecutive HBsAg carriers. positive for hepatitis B e antibody, with hepatocellular carcinoma who underwent OLT and received permanent post-OLT prophylaxis with antibody to HBsAg (HBsAb). Fourteen patients had less than 10(3) HBV genome equivalents ml(-1) (eq ml[-1]) at baseline and remained HBV free after a median of 36 months following OLT. Two patients with mean pre-OLT viraemia higher than 10(5) genome eq ml(-1) and prevalent HBeAg-negative HBV viraemia before OLT suffered a severe graft hepatitis. Interferon-alpha2b (3 MU m(-2) per day) was able to reduce viraemia in both patients and to revert the clinical course of the infection in one, who remained infection-free 22 months after IFN treatment. Fourteen patients had less than 10(3) HBV genome eq ml(-1) at baseline and remained HBV free, after a median of 36 months following OLT, with permanent HBsAb immunoprophylaxis. These observations suggest that the quantitative analysis of HBV pre-OLT viraemia levels may provide a very useful tool for predicting the ideal time of liver replacement. Clinical trials on the use of antiviral drugs capable of inhibiting HBV serum levels before liver transplantation should be pursued on this premise.

Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: a report of the U.S. Multicenter Liver Study Group.

BACKGROUND: A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. METHODS: Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. RESULTS: Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. CONCLUSIONS: Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

Human serum reactivity to porcine endothelial cells after antisense-mediated down-regulation of GpIIIa expression.

The hyperacute rejection of vascularized grafts exchanged between discordant species is a result of the binding of preformed natural antibodies to the endothelium of the donor organ, and the subsequent activation of the complement system. Human natural antibodies to pig endothelial cell antigens appear to be predominantly directed at carbohydrate epitopes expressed by a variety of porcine integrins, including GpIIIa. The identification of porcine xenoantigens whose recognition by human natural antibodies results in hyperacute rejection would allow for the development of strategies to genetically modify the xenograft reaction. We have used antisense technology to down-regulate the expression of one of seven recently identified xenoantigens from the surface of pig aortic endothelial cells. Down-regulation of GpIIIa on endothelial cells resulted in a 20.8% decrease in the mean channel shift (MCS) of IgM natural antibody binding from pooled human sera, and a 28-35% decrease in the MCS of IgM binding from two high-titer individuals. The MCS for human IgG natural antibody binding to the surface of pig cells decreased by 27%. Natural antibody-mediated cytotoxicity to pig endothelial cells was not significantly altered, as indicated by a 2.5-6% decline in complement-mediated cytotoxicity. These results indicate that down-regulation of GpIIIa alone may not be sufficient to significantly alter xenograft rejection. Our results also suggest, however, that antisense-mediated regulation of a functionally important target antigen is technically feasible and may represent a strategy to prevent the xenograft reaction.