Influence of tumor characteristics on the outcome of liver transplantation among patients with liver cirrhosis and hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) may recur after liver transplantation (LT), mainly in patients with multinodular and large tumors. However, factors predictive of outcome after LT in patients with small tumors remain ill defined. We investigated which factors were related to mortality or tumor recurrence among 47 liver transplant recipients with liver cirrhosis and HCC and compared them with 107 patients with liver cirrhosis without tumor who underwent LT in the same period. Patients with HCC were older (P < .001), more frequently had cirrhosis of a viral origin (P < .001), and had lower Child-Pugh scores (P < T he role of liver transplantation (LT) in the treatment of hepatocellular carcinoma (HCC) has evolved. In the early ages, LT was indicated in all cases of unresectable HCC without known extrahepatic spread. 1,2 Long-term survival was poor among patients with advanced disease because of a high incidence of tumor recurrence. 3 In the 1990s, several series showed that early HCC seldom recurred after LT and survival was similar in patients with cirrhosis with or without HCC. 2,4-6 Some prefer LT over resection in these patients. 2,[6][7][8] Several studies investigated which factors predispose to HCC recurrence after LT. Several investigators studied which factors are related to post-LT outcome. 2,5,[8][9][10][11] Llovet et al 5 did not find any factor predictive of post-LT outcome. In other series, poor differentiation, vascular invasion, greater number of tumor nodules, and greater tumor size were related to lower survival or disease-free survival rates, 2,8,9,11 but most series were based on unselected groups of patients and included a considerable proportion of patients with large nodules..The present study investigates factors associated with mortality and tumor recurrence among 47 patients with HCC who underwent LT according to well-defined selection criteria in a single center. Patients and MethodsBetween 1991 and June 2000 in our center, 160 adult patients with liver cirrhosis underwent a first LT. Forty-seven of these patients also had HCC diagnosed before LT, 6 patients had incidental HCC, and 107 patients had liver cirrhosis without HCC. Patients with incidental HCC were excluded from this retrospective study.Patients with HCC were selected for LT if they had a single nodule not exceeding 60 mm in diameter or 2 or 3 tumors, none exceeding 50 mm in diameter, assessed by computed tomographic (CT) scan. Patients in whom vascular invasion or extrahepatic spread was evident preoperatively were excluded. LT was considered the treatment of choice for all patients with HCC if they fulfilled these criteria and did not have a contraindication for LT. Patients with HCC did not have a priority for LT compared to other patients with cirrhosis. During this period, only 2 patients were excluded from the LT waiting list 6 and 7 months after their listing because of progressing HCC.As well as ultrasonography and CT scan, hepatic angiography was generally performed before LT. When HCC had been detected or suspected an...

Liver transplantation for hepatocellular carcinoma: Comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria

“…The 1-and 5-year recurrence-free survival rates were 87% and 70%, respectively, with these selection criteria, and the overall 1-to 5-year survival rates were not significantly different compared with that for patients transplanted without HCC. 7 In the present study, slightly over one third of our cohort of 70 patients were found to have histopathologic tumor characteristics exceeding the Milan criteria, and 10 patients exceeded the proposed UCSF criteria. The two key points that emerge from our study are as follows: (1) The difference in survival among those .…”

“…[1][2][3][4][5] Attempts to define the optimal upper limits of tumor size and number as predictors for outcome after OLT, however, have yielded conflicting results. 3,[6][7][8] The United Network of Organ Sharing (UNOS) 9 has adopted the criteria proposed by the group from Milan, Italy 3 -solitary tumor Յ5 cm, or three or fewer lesions none Ͼ3 cm (the Milan criteria)-as selection guidelines for OLT.…”

Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: Clinical patterns and outcome variables

“…Several transplant groups have demonstrated that, apart from number and size of tumor nodules, parameters of tumor biology, such as differentiation and microvascular tumor invasion (MVI) play an important role for predicting patient prognosis, and should be, therefore, incorporated in the pretransplant selection process (4,8,9,10,11). However, since expanding the selection criteria may increase the risk of tumor relapse, its justification will very much depend on outcome of posttransplant HCC recurrence (13)(14)(15)(16)(17)(18)(19) …”

“…As of recent, there is increasing concern that organ allocation based on these stringent selection variables might exclude a significant number of patients who, although not meeting the Milan criteria, would nonetheless benefit from LT (8)(9)(10)(11)(12). Several transplant groups have demonstrated that, apart from number and size of tumor nodules, parameters of tumor biology, such as differentiation and microvascular tumor invasion (MVI) play an important role for predicting patient prognosis, and should be, therefore, incorporated in the pretransplant selection process (4,8,9,10,11).…”

Toward optimizing the indications for orthotopic liver transplantation in hepatocellular carcinoma

“…34,35 Several groups have proposed extensions of the Milan criteria for liver transplantation, but most studies that are cited in support of these proposals have been retrospective and have been based on analyses of explanted livers (ie, information not available before surgery). 24,[35][36][37][38][39] Recently, Mazzaferro et al 25 made an interesting contribution to this controversy in their retrospective review of pathology after liver transplantation for HCC in 1556 patients; 1112 of these patients had tumors that did not fulfill the Milan criteria. In a subgroup of 283 patients not meeting the Milan criteria whose tumors were within the up-to-7 criteria (ie, HCCs with a maximum score of 7, with the score being the sum of the size of the largest tumor and the total number of tumors) and were not characterized by microvascular invasion, the overall 5-year survival rate was 71.2%.…”