Abstract:
Objective:To investigate the relationship between morphologic classification of hepatocellular carcinoma and clinicopathological features and prognosis in patients, as well as the factors affecting the prognosis of patients.
Methods:The clinical data of 119 patients with hepatocellular carcinoma who received surgical treatment at the Drum Tower Hospital from January 2008 to December 2013 were retrospectively analyzed. The tumors of all the patients were cut into sections with thickness of 1 cm in a coronal plane and were taken pictures for recording pathological features. The sections of tumors were divided into 4 types according to the references and clinical experiences: single nodular type(type 1), single nodular with extranodular growth type (type 2), confluent multinodular type (type 3)and infiltrating type (type 4). The clinicopathological features of patients with 4 types of tumors were compared. Patients were followed up via outpatient examination and telephone interview up to April 2014 or death. Data with normal distribution were presented as 〖AKx-D〗±s. Comparison among groups was evaluated with the repeated measures ANOVA and done by the KruskalWallis method. Pairwise comparison was analyzed using LSDt test and MannWhitney test. Data with skew distribution were presented as M(P25，P75). Count data and univariate analysis were done using chisquare test or Fisher exact probability. Survival curve was drawn by KaplanMeier method. Survival analysis were done using the Logrank test, and multivariate analysis was done using the COX regression model.
Results:Of the 119 patients with hepatocellular carcinoma, 20.17% patients (24/119) were in type 1, 25.21% patients (30/119) in type 2, 21.85% patients (26/119) in type 3 and 32.77% patients (39/119) in type 4. The age, positive HBsAg, preoperative alpha fetoprotein (AFP), operation time, volume of blood loss, duration of hospital stay, T stage and microvascular invasion in the patients with hepatocellular carcinoma of the 4 types were compared, showing significant differences (F=4.499, χ
2=2.944, 3.516, F=1.028, 2.837, 2.419, χ
2=6.606, 12.732, P<0.05). The preoperative AFP of the patients in type 4 was significantly higher than that in type 3, type 2 and type 1 (Z=2.183, 1.851, 2.083, P<0.05). The operation time of patients in type 4 was significantly longer than that in type 3 and type 1 (t=1.825, 1.758, P<0.05), and was no significantly different from that in type 2 (t=1.521, P>0.05). The volume of intraoperative blood loss of the patients in type 4 was obviously more than that in type 3, type 2 and type 1(t=1.769, 1.875, 2.205, P<0.05). The duration of hospital stay of patients in type 4 was significantly longer than that in type 2 and type 1 (t=2.159, 1.975, P<0.05), and was no significantly different from that in type 3 (t=0.248, P>0.05). The microvascular invasion of the patients in type 4 was significantly more than that in type 3, type 2 and type 1 (χ
2=5.905, 8.291, 4.729, P<0.05). Of the 119 patients, 116 patients were followed up with a followup rate of 97.48% (116/119), and the median time of followup was 26 months (range, 4-74 months). The median overall survival time of 119 patients was 25 months (range, 1-73 months). The 1, 3, 5year overall survival rates were 83.2%, 70.7% and 63.4%, respectively. The tumor free median survival time was 14 months (range, 1-70 months). The 1, 3, 5year tumor free survival rates were 73.3%, 42.7% and 11.4%, respectively. The median overall survival time of 24 patients in type 1 was 56 months (range, 51-61 months), the 1, 3, 5year overall survival rates were 94.1%, 82.5% and 65.3%, respectively, the tumor free median survival time was 48 months (range, 41-54 months), and the 1, 3, 5year tumor free survival rates were 81.3%, 66.7% and 58.6%, respectively. The median overall survival time of 30 patients in type 2 was 56 months (range, 5
2-60 months), the 1, 3, 5year overall survival rates were 91.6%, 82.6% and 82.6%, respectively, the tumor free median survival time was 46 months (range, 40-51 months), and the 1, 3, 5year tumor free survival rates were 81.4%, 64.1% and 64.1%, respectively. The median overall survival time of 26 patients in type 3 was 53 months (range, 48-58 months), the 1, 3, 5year overall survival rates were 91.6%，84.7% and 77.8%, respectively, the tumor free median survival time was 42 months (range, 36-48 months), and the 1, 3, 5year tumor free survival rates were 80.1%, 62.3% and 50.0%, respectively. The median overall survival time of 39 patients in type 4 was 46 months (range, 40-51 months), the 1, 3, 5year overall survival rates were 65.7%, 51.5% and 45.6%, respectively, the tumor free median survival time was 29 months (range, 23-34 months), and the 1, 3, 5year tumor free survival rates were 64.3%, 31.6% and 22.3%, respectively. There was a significant difference between the overall survival rates and the tumor free survival rates in the patients with morphologic classification of hepatocellular carcinoma (χ
2=7.971, 7.652, P<0.05). The overall survival rates and tumor free survival rates of the patients in type 4 were significantly different from those in type 3, type 2 and type 1 (overall survival rates: χ
2=4.823, 6.131, 5.785, P<0.05; tumor free survival rates: χ
2=5.184, 5.634, 9.262, P<0.05). The results of univariate analysis showed that preoperative AFP, T stage, microvascular invasion and morphologic classification of hepatocellular carcinoma were related factors affecting the prognosis of patients (χ
2=3.516, 6.687, 6.165, 7.974, P<0.05). The results of multivariate analysis showed that T3-T4 stage , microvascular invasion and hepatocellular carcinoma in type 4 were the independent risk factors affecting the prognosis of patients (RR=3.646, 2.397, 1.617, 95% confidence interval: 1.04
2-12.713, 1.063-5.403, 1.119-2.337, P<0.05).
Conclusions:The morphologic classification of hepatocellular carcinoma may be associated with the clinicopathological factors of patients. The patients with infiltrating hepatocellular carcinoma have the high level of preoperative AFP, much intraoperative blood loss, high incidence of microvascular invasion and poor prognosis. The T3-T4 Stage, microvascular invasion and infiltrating type of morphological classification are the independent risk factors affecting the prognoses of patients with hepatocellular carcinoma.
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