Li et al. BMC Cancer 2010, 10:535 http://www.biomedcentral.com/1471-2407/10/535 Fisher’s exact test was used to compare the difference of categorical variables. The primary endpoints were over- all survival (OS) and cumulative recurrence rates (CRR). OS was defined as the interval from curative surgery to the date of death or the date of last contact if the patient was still alive. Time to tumor recurrence was defined as the interval from surgery to the date when tumor recurrence or metastasis was diagnosed. The sur- vival curves were calculated by the Kaplan-Meier method and compared using the log-rank test. Signifi- cant prognostic factors on univariate analysis were entered into a multivariate analysis using the Cox pro- portional hazards model. A p-value < 0.05 was consid- ered as significant. Statistical procedures were performed using the SPSS software package (Version 15.0; SPSS Inc., Chicago, IL). Results Demographic and Clinicopathological Data The demographic and clinicopathological characteristics of the 298 patients with locally advanced HCC in this study are listed in Table 1. In 16 patients, TACE was given followed by hepatic resection after shrinkage of the tumor, and in 76 patients postoperative adjuvant TACE was given. At the time this study was censored, tumor recurrence was diagnosed in 271 patients (90.9%), and 253 patients (84.9%) had died. For the 271 patients with recurrence, 249 patients had intrahepatic recur- rence, 15 had both intrahepatic and extrahepatic recur- rences, and 7 had extrahepatic recurrence. The 3-year/ 5-year OS and CRR of the total cohort after hepatic resection were 28.2%/16.9% and 85.7%/90.8%, respectively. Prognostic Factors for Survival and Recurrence Among the 24 clinicopathological factors analyzed by univariate log-rank analysis, only albumin (ALB) level (P = 0.004), cirrhosis status (P = 0.028) and major vas- cular invasion (P < 0.001) were identified as poor prog- nostic factors for OS (Table 2). The significant prognostic factors found on univariate analysis were further tested in the multivariate Cox model. Major vas- cular invasion was found to be the most significant fac- tor (HR = 3.291, 95% CI 2.362-4.584, P < 0.001), followed by cirrhosis status (HR = 1.400, 95% CI 1.010- 1.941, P = 0.044). (Table 3) When the same factors in Tables 2 were analyzed for their prognostic influence on cumulative recurrence rate, only ALB level (P = 0.002) and major vascular invasion (P < 0.001) were significant factors in the uni- variate analysis. The 1-year/3-year CRRs of 61 patients with major vascular invasion were 85.2%/100.0%, whereas the corresponding CRRs of 237 patients with- out major vascular invasion were 54.7%/80.2%, Page 3 of 9 respectively. In multivariate analysis, major vascular invasion was the only significant predictive factor of CRR (HR = 2.242, 95% CI = 1.811-3.358, P < 0.001). (Table 3) The Impact of Major Vascular Invasion in Stage pT3/ 4N0M0 HCC To further verify the grave impact of major vascular invasion on overall survival and recurrence risk in stage pT3/4N0M0 HCC at presentation, we selected patients in whom the four pathologic features were present sin- gularly, and classified them into four subgroups: “Major vascular invasion (n = 21)” as Gp1, “Multiple tumors more than 5 cm (n = 108)” as Gp2, “Invasion of adja- cent organs (n = 32)” as Gp3, and “Perforation of visc- eral peritoneum (n = 57)” as Gp4. Comparisons of clinicopathological data of the four subgroups of patients with pT3/4N0M0 HCC are depicted in Table 1. The four groups were not significantly different in liver function parameters and tumor histological features, except that there was a significantly higher proportion of microvascular invasion in tumors with major vascular invasion than the other three groups. Serum AFP levels were also significantly higher in patients with major vas- cular invasion compared with the other three groups. Intraoperative blood loss, the proportion of patients requiring blood transfusion, and the proportion of patients receiving preoperative and postoperative TACE were all similar. As shown in Figure 1A, the OS of Gp1 (median 5.8 months) was significantly worse than Gp2 (median 21.7 months, P < 0.001), Gp3 (median 17.3 months, P < 0.001) and Gp4 (median 19.5 months, P = 0.001). Simi- larly, the 3-year CRR of Gp1 (100%) was significantly higher than Gp2 (79.9%, P < 0.001), Gp3 (85.5%, P = 0.006) and Gp4 (84.2%, P = 0.001) (Figure 1B). There were no significant differences in OS or in CRR between the latter three subgroups (P > 0.05). To evaluate whether concomitant major vascular inva- sion influenced survival of patients with other patholo- gic features, we identified the following three subgroups: “patients with multiple tumors more than 5 cm and major vascular invasion” as Gp5 (n = 17), “patients with invasion of adjacent organs and major vascular invasion” as Gp6 (n = 10), and “patients with perforation of visceral peritoneum and major vascular invasion” as Gp7 (n = 13). Median survivals of Gp5, Gp6 and Gp7 were 7.6 months, 5.7 months and 4.3 months, respectively, while the 3-year CRR of which was all 100%. The OS and CRR of Gp5, Gp6 and Gp7 were compared with Gp1 (major vascular invasion, n = 21). Results showed that there were no significant dif- ferences of OS (Figure 2A) or CRR (Figure 2B) among these four subgroups (P > 0.05).