Relationship Of Characteristics Of Contrast Enhanced Ultrasonography On Hepatocellular Carcinoma With Expression Of VEGF And Recurrence After Microwave Ablation

Objective: To investigate the relationship of contrast enhanced ultrasonography on hepatocellular carcinoma with expression of vascular endothelial growth factor (VEGF), and the relationship of contrast enhanced ultrasonography with recurrence after microwave ablation. And to gain the parameters of contrast enhanced ultrasonography which could noninvasively and effectively predict recurrence after treatment. Materials and methods: 30 patients with HCC histopathologically proven without metastasis and vascular invasion were enrolled in the study, whose maximal diameter of tumor was no more than 5cm, numbers of tumor no more than 2. All patients, with liver function of Child A or B, without other diseases, had not accepted any therapy before enrolled in the study. Microwave ablations were performed on HCC. Contrast enhanced ultrasound examinations were performed before treatment and on every follow-up: 1 week, 1 month, 3～4 months after treatment, and the following every 3 months. The parameters of CEUS were quantitatively acquired by intensity-time curve of enhancement. CT or MRI was performed before treatment, on 3 months, half a year after treatment, and when suspicious recurrence was found by US. Biopsy guided by US was performed to get tumor specimens before MW ablation. HE and immunohistochemical stains for VEGF and CD34 were performed in 23 cases. Serum VEGF was detected by ELISA before treatment and on every follow-up: 1 week, 1 month, 3～4 month after treatment, and the following every 3 months. All cases were divided into 2 groups: recurrence group and non-recurrence group. The parameters of CEUS, tumor MVD, tumor VEGF expression, and Serum VEGF were compared in two groups. Relationship was statistically analyzed between the parameters of CEUS and tumor MVD, tumor VEGF expression, recurrence, etc.In addition, serum VEGF of 20 cirrhosis patients and 20 healthy persons was detected, as comparison with HCC patients. Results: (1) p-t TTP showed a significantly inverse correlation with rumor VEGF expression (r= - 0.600, P=0.002), as well as tumor MVD (r= -0.672, P=0.000). No correlation was detected between t TTP and VEGF expression (r= - 0.318, P=0.140), MVD(r= -0.248, P=0.254). (2) Significant correlation was found between MVD and VEGF expression (r=0.549, P=0.007). (3) VEGF expression of recurrence group was significantly higher than that of non-recurrence group(P=0.010). MVD expression of recurrence group was significantly higher than that of non-recurrence group(P=0.000). (4) In the parameters of CEUS before treatment, p TTP of recurrence group was significantly earlier than that of non-recurrence group(P< 0.01); p-t TTP of recurrence group was significantly less than that of non-recurrence group(P<0.01); p PI of recurrence group was less than that of non-recurrence group(P<0.05); t-p PI of recurrence group was more than that of non-recurrence group(P<0.05). However, between recurrence group and non-recurrence group, wash-in time, t BTLE, p wash- in time, t TTP and t PI were not found statistical difference(P>0.05). (5) p-t TTP and serum VEGF on 1 month after treatment were related to recurrence after MW ablation. (6) There was a significantly statistical difference in serum VEGF on 1 month after treatment between recurrence group and non-recurrence group(P<0.01), And a statistical difference in serum VEGF on 3～4 month after treatment between 2 groups(P< 0.05). However, there was no statistical difference in serum VEGF before treatment, on 1 week after treatment, the variance between 1 week and pretreatment, and the variance between 1 month and pretreatment between recurrence group and non-recurrence group (P>0.05). (7) p-t TTP was correlated with serum VEGF on 1 month after treatment(r=0.568, P<0.01), variance between 1 month and pretreatment(r=0.569, P<0.01). (8) There was no difference in histopathological grading between recurrence group and non-recurrence group. No significant correlation was detected betweenhistopathological grading and MVD, VEGF expression(P>0.05). (9) Serum VEGF of HCC patients was higher than cirrhosis patients and healthy persons, and no difference between cirrhosis patients and healthy persons. Conclusions: (1) In the parameters of CEUS on HCC, p-t TTP (the difference between time to peak of tumor and that of parenchyma) could evaluate MVD and VEGF expression of tumor, and could effectively predict recurrence after microwave ablation. (2) In the parameters of CEUS before treatment, p TTP of recurrence group was significantly earlier than that of non-recurrence group; p-t TTP of recurrence group was significantly less than that of non-recurrence group; p PI of recurrence group was less than that of non-recurrence group; t-p PI of recurrence group was more than that of non-recurrence group. (3) In the parameters of CEUS before treatment, p-t TTP, Serum VEGF level on 1 month after treatment is related to recurrence after MW ablation on HCC. (4) In HCC, MVD of tumor is significantly correlated with VEGF expression. VEGF is a positive regulatory factor in angiogenesis of HCC. Histopathological grading is not correlated with MVD and VEGF expression. (5) MVD, VEGF expression in tumor before treatment on HCC of the patients with recurrence are higher than those of patients without recurrence. Serum VEGF level on 1 month after treatment on HCC of the patients with recurrence is lower than that of patients without recurrence. (6) CEUS is a noninvasive, effective method which could evaluate angiogenesis of HCC and predict the recurrence and prognosis.