Long-term outcomes and prognostic factors of surgical resection of hepatitis B virus-related solitary large hepatocellular carcinoma

Objective:To investigate the prognosis of patients with solitary large hepatocellular carcinoma (SLHCC) and with small hepatocellular carcinoma (SHCC), and analyze the risk factors affecting the prognosis of patients with SLHCC.
Methods:The retrospective casecontrol study was conducted. The clinicopathological data of 856 patients with hepatitis B virus (HBV)related HCC who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 2008 to December 2008 were collected. Of 856 patients, 693 HCC patients with tumor diameter ≤5 cm were allocated into the SHCC group and 163 HCC patients with tumor diameter >5 cm and with solitary, expansive growth and complete capsule tumors were allocated into the SLHCC group. Patients underwent preoperative antiviral therapy, laboratory and imaging examinations, and then surgical planning was determined based on the preoperative results. Observation indicators: (1) comparisons of clinicopathological features between the 2 groups: sex, age, ChildPugh grade, HBeAg, serum level of HBVDNA, platelet (PLT), albumin (Alb), total bilirubin (TBil), alphafetoprotein (AFP), tumor diameter, microvascular invasion, EdmondsonSteiner grade and liver cirrhosis; (2) treatment situations between the 2 groups: surgical procedures, operation time, volume of intraoperative blood loss, number of patients with blood transfusion and time of hepatic inflow occlusion; (3) survival analysis between the 2 groups; (4) prognostic analysis of patients with SLHCC. Followup using telephone interview and outpatient examination was performed once every 3 months within 2 years postoperatively and once every 6 months after 2 years postoperatively up to June 23, 2014. Followup included tumor marker, liver function, serum level of HBVDNA and abdominal Bultrasound examination. The patients received reexamination of computed tomography (CT) or magnetic resonance imaging (MRI) once every 6 months or when there was suspicion of tumor recurrence or metastasis. Tumor recurrence or metastasis was confirmed through typical HCC imaging findings of CT and MRI, and PET/CT examination was conducted if necessary. Tumorfree survival time was from operation time to time of tumor recurrence, and overall survival time was from operation time to death or the last followup. Measurement data with normal distribution were represented as ±s, and continuous variables were analyzed by the t test or MannWhitney U test. Measurement data with skewed distribution were described as M (range). Categorical variables were represented as count (percentage) and analyzed by the chisquare test or calibration chisquare test. The survival curve and survival rate were respectively drawn and calculated by the KaplanMeier method and Logrank test. COX regression model was used for prognostic analysis.
Results:(1) Comparisons of clinicopathological features between the 2 groups: number of patients with PLT<100×109/L, with positive microvascular invasion and with liver cirrhosis and tumor diameter were 197, 133, 447, (3.1±1.1)cm in the SHCC group and 28, 53, 79, (8.9±3.3)cm in the SLHCC group, respectively, with significant differences between the 2 groups x²=28.618, t=37.286, χ2=213.773, 214.325, P<0.05). (2) Treatment situations between the 2 groups: all the 856 patients underwent hepatectomy, including 326 with hepatic segments of resection ≥3 and 530 with hepatic segments of resection <3. Operation time, volume of intraoperative blood loss, number of patients with intraoperative blood transfusion and with time of hepatic inflow occlusion >20 minutes were 90 minutes (range, 60-200 minutes), 200 mL (range, 20-5 200 mL), 47, 125 in the SHCC group and 110 minutes (range, 60-230 min), 300 mL (range, 50-3 200 mL), 31, 58 in the SLHCC group, respectively. (3) Survival analysis between the 2 groups: all the 856 patients were followed up for 32.5 months (range, 1.0-72.3 months). The median survival time, median tumorfree survival time, 1, 3, 5year overall survival rates and 1, 3, 5year tumorfree survival rates were 56.2 months (range,1.6-75.8 months), 39.5 months(range,1.0-75.0 months), 90%, 71%, 58%, 70%, 48%, 38% in the SHCC and 50.3 months (range, 1.1- 76.0 months), 30.7 months (range, 1.0-72.0 months), 87%, 59%, 47%, 65%, 46%, 33% in the SLHCC group, respectively, with no significant difference in tumorfree survival between the 2 groups x²=0.514, P>0.05) and with a significant difference in overall survival between the 2 groups x²=10.067, P<0.05). Stratified analysis: there were 117 SLHCC patients with 5 cm < tumor diameter <10 cm and 46 SLHCC patients with tumor diameter >10 cm. The 1, 3, 5year overall survival rates and 1, 3, 5year tumorfree survival rates were 91%, 65%, 53%, 70%, 48%, 35% in 117 SLHCC patients with 5 cm < tumor diameter <10 cm, respectively, with no significant difference compared with SHCC group x²=1.832, 0.042, P>0.05). The 1, 3, 5year overall survival rates and 1, 3, 5year tumorfree survival rates were 78%, 46%, 31%, 49%, 39%, 30% in 46 SLHCC patients with tumor diameter >10 cm, respectively, with significant differences compared with SHCC group x²=21.136, 4.097, P<0.05). (4) Prognostic analysis of patients with SLHCC: results of univariate analysis showed that serum level of HBVDNA, tumor diameter and microvascular invasion were risk factors affecting postoperative 5year tumorfree survival rate of SLHCC patients x²=5.193, 3.377, 5.509, P<0.05); sex, serum level of HBVDNA, tumor diameter and microvascular invasion were risk factors affecting postoperative 5year overall survival rate of SLHCC patients x²=4.546, 18.053, 7.780, 10.569, P<0.05). Results of multivariate analysis showed that serum level of HBVDNA≥104 U/mL, tumor diameter >10 cm and positive microvascular invasion were independent risk factors affecting postoperative 5year tumorfree survival rate of SLHCC patients ［HR=2.77, 1.85, 1.86, 95% confidence interval (CI): 1.74-4.40, 1.16-2.94, 1.17-2.96, P<0.05］ and affecting postoperative 5year overall survival rate of SLHCC patients (HR=2.73, 1.98, 1.69, 95%CI: 1.72-4.33, 1.23-3.17, 1.04-2.72, P<0.05).
Conclusions:There are similar prognosis between SLHCC patients with 5 cm < tumor diameter <10 cm and SHCC patients, however, prognosis of SLHCC patients with tumor diameter >10 cm is worse than that of SHCC patients. Serum level of HBVDNA≥104 U/mL, tumor diameter >10 cm and positive microvascular invasion are independent risk factors affecting prognosis of SLHCC patients.