Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis for liver transplantation follows limits of number and diameter of tumor nodules. It has not been investigated whether there is a correlation of these parameters with vascular invasion. From 1989 to 2000, 1,188 liver transplantations were performed in 1,087 patients, including 120 patients (11%) with an HCC in cirrhosis. Selection criteria were a maximal diameter of up to 5 cm if the tumor appeared to be uninodular or of up to 3 cm in the case of 2 or 3 nodules. The postoperative mortality rate was 1.7%. One-, 5-, and 10-year survival was 90%, 71%, and 60%, respectively. In 940 transplantation patients without an HCC, these rates were 93%, 87%, and 83% (P < .0001). Vascular invasion and histopathologic grading were identified as prognostic parameters by multivariate analysis. In a logistic regression analysis, histopathologic grading and maximal diameter showed a significant correlation with a vascular invasion. Analyzing tumors larger than 5 cm, i.e., tumors not fulfilling the selection criteria as a result of diagnostic inaccuracy or progression thereafter, the rates of vascular invasion were significantly (P < .01) lower in patients suffering from well-differentiated tumors ( De novo hepatocellular carcinoma (HCC) within cirrhotic livers or missed small satellites in patients undergoing formally curative liver resection have been reported to occur at a rate of 60%. 1 Most of these recurrent intrahepatic tumors were detected in a distance from the resection margin of at least 2 cm. However, only half of the patients with HCC in cirrhosis die from recurrence after resection, while the remaining half dies as a result of the underlying chronic liver disease. 2,3 Today, liver transplantation is the only simultaneous treatment of cirrhosis as well as of HCC. A crucial factor for outcome after liver transplantation is the appropriate selection of patients. TNM and UICC classification of HCC must be considered with caution for therapeutic decision making, because they comprise biologically different tumors in common categories, e.g., carcinomas with and without vascular invasion in T stages 2 to 4. 4 Bismuth et al. 5 were the first to show that in the early era of liver transplantation, the surgical strategy for the treatment of HCC in cirrhosis had followed a misconception in selecting patients suffering from advanced, and therefore unresectable, cancers, as transplant candidates. Conversely, small HCC in cirrhosis with diameters of less than 3 cm comprising only 1 or 2 nodules-tumors frequently suitable for resection-showed the most favorable outcome. Patients in whom the cancer has exceeded the hepatic confines should be ruled out for liver transplantation. Gross metastases or lymph node infiltration as indicators of an extrahepatic spread may easily be detectable pretransplantation by imaging procedures, laparoscopic staging, or intraoperatively. 6,7 However, the current state of pretransplantation and even intraoperative diagnostic ...

The incidence, clinical presentation, therapeutic options, and outcome of hepatic artery thrombosis (HAT) were analyzed in a series of 1,192 consecutive adult orthotopic liver transplantations (OLTs). HAT after OLT was observed in 30 cases, resulting in an incidence of 2.5%. The incidence of HAT increased 5.76-fold when the donor hepatic artery was reconstructed with an interposition graft to the supraceliac aorta (P <.05). Early HAT (within the first 30 days after OLT) occurred in 14 of these patients (46.7%), whereas in 16 patients (53.3%), HAT occurred beyond 30 days post-OLT. Clinical presentation of HAT ranged from an increase in serum transaminase levels with or without cholestasis to liver abscess and biliary complications, including cholangitis, bile duct stenosis or necrosis, to liver dysfunction and failure. Impairment of graft function was observed in patients with early HAT, whereas biliary tract destruction was seen more often in patients with late HAT. In only 1 patient was HAT clinically asymptomatic. Therapy consisted of recombinant plasminogen lysis with hepaticojejunostomy, liver abscess drainage, endoscopy or surveillance, and surgical thrombectomy. In 14 of 30 patients (46.7%), the occurrence of HAT required re-OLT. Nine patients with HAT died during follow-up; however, only 4 of these deaths were related to HAT, resulting in a mortality rate of 13.3%. Our results indicate that HAT is a rare but serious complication after OLT, requiring re-OLT in almost 50% of patients. In particular, conservative treatment modalities may significantly prolong graft survival, thus postponing re-OLT.

BackgroundWe investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC).MethodsIn a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint.ResultsRecurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874).ConclusionsSirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.