82, 95% CI = 1.87-12.41, P = 0.001). The fact that the Milan criteria did not appear to be prognostic may not be surprising because 89% of the patients fulfilled the up-to-7 criteria at the time of orthotopic LT. In a series of 51 patients undergoing GDC941
LT for HCC, Choi et al.37 retrospectively analyzed 5 cases of incidental HCC with a mean size of 1.16 cm, no MVI, and good to moderate tumor differentiation. They found no recurrence of HCC in a mean follow-up period of 14 months. Lai et al.47 reported that only MVI and exceeding the University of California San Francisco criteria were independent risk factors for recurrence in a multivariate analysis. However, many have reported that a combination of a larger tumor size, a higher histological grade (less differentiation), and MVI is the strongest factor related to recurrence and a poor prognosis after LT. Jonas et al.5 found the presence of vascular invasion and the histological grade to be the only statistically significant independent predictors of poor survival after LT. In a study of 69 patients with HCC who underwent LT, Plessier et al.54 reported PD0325901
that MVI was significantly correlated with the presence of satellite nodules (P < 0.02) and a poor prognosis. On the other hand, a few studies have not been able to correlate poor results with MVI, although macrovascular invasion has been related to bad outcomes. Lee et al.49 followed 38 patients after LT for HCC for a mean period of 17.7 months (range = 4-30 months), and they found that the number of tumor nodules and the presence of MVI did not affect tumor recurrence. Fan et al.55 studied 1078 patients who underwent orthotopic LT and found no correlation between MVI and overall or disease-free survival. Kornberg et al.46 EPZ-6438 clinical trial
documented MVI as a risk factor for tumor recurrence after LT. A poor tumor grade (HR = 21.8, 95% CI = 4.9-95.3, P < 0.001) and MVI (HR = 14.1, 95% CI = 1.4-147.1, P = 0.027) were identified as independent risk factors for reduced recurrence-free survival after LT. Although the risk of recurrence is higher in patients with MVI, not all patients with MVI will experience recurrence. This has to be balanced with macrovascular invasion and satellite nodules (all detected by imaging techniques), which are contraindications for LT because of the high incidence of recurrence. Table 2 summarizes the publications documenting several types of tumor features, biomarkers, and imaging modalities. Table 3 summarizes the publications specifically documenting MVI and several of these issues, and available correlations are included. Other issues that should be taken into consideration are as follows: 1 The indication for LT in patients with HCC beyond the Milan criteria.