Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC ≤ 5 cm or less than or equal to three HCCs ≤ 3 cm. We prospectively evaluated the possibility of slightly extending these criteria in a down-staging protocol, which included patients initially outside conventional criteria: single HCC 5–6 cm or two HCCs ≤ 5 cm or less than six HCCs ≤ 4 cm and sum diameter ≤ 12 cm, but within Milan criteria in the active tumors after the down-staging procedures. The outcome of patients down-staged was compared to that of Milan criteria after liver transplantation and since the first evaluation according to an intention-to-treat principle. From 2003 to 2006, 177 patients with HCC were considered for transplantation: the transplantation rate was comparable between the Milan and down-staging groups: 88/129 cases (68%) versus 32/48 cases (67%), respectively. At a median follow-up of 2.5 years after transplantation, the 1 and 3 years' disease-free survival rates were comparable: 80% and 71% in the Milan group versus 78% and 71% in the down-staging. The actuarial intention-to-treat survival was 27/48 patients (56.3%) in the down-staging and 81/129 cases (62.8%) in the Milan group, p = n.s. The proposed down-staging criteria provide a comparable outcome to the conventional criteria.

Objective: We assessed the effect of tacrolimus on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) and compared it with that of the other calcineurin inhibitor, cyclosporine. Introduction: HCC recurrence after LT can be favored by overexposure to cyclosporine. Tacrolimus is now the most widely used main immunosuppressant after LT; its possible effect on HCC recurrence has never been investigated. Materials and Methods: One hundred and thirty nine HCC patients who had LT were reviewed; 60 of them were administered tacrolimus, and 79, cyclosporine. The exposure to the drugs was calculated with the trapezoidal rule in each patient, using blood levels measured after transplantation and compared with HCC recurrence together with several clinical and pathologic risk factors. Results: HCC recurred in 12 of the 60 (20%) patients under tacrolimus in comparison with that in 9 of the 79 (11.4%) patients under cyclosporine; however, the proportion of poorly differentiated and more advanced tumors was significantly higher in the tacrolimus group than in the cyclosporine group. Exposure to tacrolimus was 11.6 ± 1.5 ng/mL in patients with recurrence and 8.6 ± 1.7 ng/mL in those without recurrence (P < 0.001). The optimal cut-off values of exposure identified with receiver operating characteristics analysis to categorize the risk of recurrence were 10 ng/mL for tacrolimus (area under the curve (AUC) = 0.913) and 220 ng/mL for cyclosporine (AUC = 0.752). In the tacrolimus group, high drug exposure independently predicted recurrence (P = 0.005). Multivariate analysis, including all patients (tacrolimus + cyclosporine) characterized higher exposure to immunosuppression (P = 0.01), alpha-fetoprotein levels (P = 0.001), tumor grading (P = 0.009), and microvascular invasion (P = 0.04) as independent predictors of HCC recurrence. Conclusions: Just as it is with cyclosporine, overexposure to tacrolimus increases the risk of HCC recurrence after LT. Careful management of calcineurin inhibitors is recommended in HCC patients.

Objective: To estimate risk factors affecting the early outcome after hepatic resection in a high volume center specialized in hepatobiliary surgery and to analyze the changing of results during 3 different periods of treatment. Design: Retrospective review. Patients: A series of 1500 consecutive patients who underwent hepatic resection. Methods: Postoperative morbidity and mortality were analyzed in relation to indications for surgery, period of operation, patient characteristics, and intraoperative variables. Patients were classified into 4 groups, according to the indication for surgery: primary liver tumors with cirrhosis (group 1, G1); other liver malignancies (group 2, G2); biliary malignancies (group 3, G3); and benign diseases (group 4, G4). Patients were also divided into 3 groups, according to the year of operation (period 1: June 1985 to October 1993; period 2: November 1993 to September 1999; period 3: October 1999 to September 2007). Results: Overall mortality and morbidity were 3% and 22.5%, respectively. Multivariate analysis revealed that blood transfusions, G1, and additional procedures were associated with an increased risk of postoperative complications, whereas blood transfusions, G1, G3, and extended hepatectomy were associated with an increased risk of postoperative mortality. G1 decreased, whereas G3, extended hepatectomies and additional procedures significantly increased between periods 2 and 3 (P < 0.05). The complication rate was significantly lower in period 2 (18.8%) compared with period 1 (23.8%) and period 3 (24.8%). Similarly, there was a significantly lower mortality rate in period 2 (1.6%) compared with period 1 (3.4%) and period 3 (4%). Conclusions: Slightly worse short-term outcomes in liver surgery were observed in recent years, with a concomitant increase of the aggressiveness of operative strategies. Nevertheless, the present results still justify an aggressive approach in liver resections.

The outcome of hepatic resection in cirrhotic patients has improved remarkably in recent years with improved surgical techniques and perioperative care; however, the role of portal hypertension is still uncertain. The aim of this study was to elucidate surgical outcomes of hepatectomy in patients with portal hypertension. Data from 241 cirrhotic patients who underwent resection for hepatocellular carcinoma were retrospectively collected and analyzed: patients were divided into 2 groups according to the presence (n = 89) or absence (n = 152) of portal hypertension at the time of surgery. To overcome biases owing to the different distribution of covariates throughout the 2 groups, a one-to-one match was created using propensity score analysis: after match, intraoperative, and postoperative course and survival rates were analyzed. Patients with portal hypertension experienced worse preoperative liver function (mean model for end-stage liver disease [MELD] score, 9.5 ± 7.8 vs. 8.4 ± 1.3; P = 0.001) and survival rates (P = 0.008) in comparison to those without portal hypertension: after one-to-one matching, patients with (n = 78) and without portal hypertension (n = 78) had the same preoperative characteristics and showed the same intraoperative course, postoperative occurrence of liver failure, morbidity, length of in-hospital stay and survival rates (P = ns in all cases). The only predictors of postoperative liver failure were MELD score (P = 0.001) and extent of hepatectomy (P = 0.005). Faced with the same MELD score and extent of hepatectomy planning, presence of portal hypertension should not be considered as a contraindication for hepatic resection in cirrhotic patients.