论文标题:肝细胞癌超声造影表现与VEGF表达及微波治疗后复发关系的研究
Relationship of Characteristics of Contrast Enhanced Ultrasonography on Hepatocellular Carcinoma with Expression of VEGF and Recurrence after Microwave Ablation
论文作者
论文导师 于晓玲,论文学位 硕士,论文专业 影像医学与核医学
论文单位 中国人民解放军军医进修学院,点击次数 677,论文页数 81页File Size4835K
论文网 http://www.lw23.com/lunwen_127032/
contrast enhanced ultrasonography (CEUS); hepatocellular carcinoma (HCC); vascular endothelial growth factor (VEGF); recurrence; microvessel density (MVD)
目的探讨肝细胞癌超声造影表现与VEGF表达水平的关系，以及治疗前超声造影表现与微波治疗后近期复发的关系，寻求可无创、有效预测治疗后复发的超声造影特征参数。 资料与方法(1)入组条件：经穿刺活检病理证实的HCC患者，病灶数目≤2个，病灶最大直径≤5cm，无血管侵犯及肝外转移，肝功能Child-Pugh分级A-B级，无严重心、脑、肾、血管等疾病，所有患者入选本研究前未接受其他任何治疗。(2)符合入组条件的30例患者治疗前行超声造影检查，记录超声造影过程并绘制时间-强度曲线，分析各参数。行超声引导下微波消融治疗。在治疗后的1周、1个月、3-4个月及其后每3个月时行超声造影复查。并于治疗前、治疗后3个月、半年及超声发现可疑复发灶时行增强CT/MRI检查。(3)在治疗前及治疗后的1周、1个月、3-4个月及其后每3个月时采集静脉血标本，检测血清VEGF水平。(4)微波消融前超声引导下穿刺活检取得HCC组织标本行HE染色进行病理分化程度分级。其中23例HCC组织标本行CD34、VEGF免疫组化染色，将MVD及VEGF表达分级。(5)将上述患者按照是否复发分为2组，比较超声造影参数、血清VEGF、癌组织病理分化程度、MVD及VEGF表达水平，分析它们之间的相关性，并分析超声造影参数与复发的相关性。(6)抽取20例肝硬化患者及20例健康志愿者的静脉血测其血清VEGF水平与HCC组对照。 结果(1)HCC治疗前超声造影参数中，p-t TTP与VEGF表达之间在统计学上呈显著的负相关(r=-0.600，P=0.002)，p-t TTP与MVD表达之间在统计学上呈显著的负相关(r=-0.672，P=0.000)；t TTP与VEGF表达之间在统计学上无相关性(r=-0.318，P=0.140)，tTTP与MVD表达之间在统计学上无相关性(r=-0.248，P=0.254)。(2)肿瘤MVD与VEGF表达水平之间在统计学上呈显著的正相关(r=0.549，P=0.007)。(3)复发组的肿瘤VEGF表达在统计学上显著高于未复发组(P=0.010)，复发组的肿瘤MVD水平在统计学上显著高于未复发组(P=0.000)。(4)HCC未复发组与复发组治疗前超声造影参数中，复发组的pTTP显著早于未复发组(P＜0.01)，复发组的p-tTTP显著小于未复发组(P＜0.01)，差异有显著统计学意义；复发组的p PI小于未复发组(P＜0.05)，复发组的t-p PI大于未复发组(P＜0.05)，差异有统计学意义；而两组之间t wash-in time、t BTLE、p wash-in time、t TTP、t PI无统计学差异(P＞0.05)。(5)Logistic回归结果显示，p-t TTP、治疗后1个月时血清VEGF与HCC微波治疗后近期复发有关。(6)复发组的治疗后1个月时血清VEGF值在统计学上显著低于未复发组(P＜0.01)，复发组治疗后3-4个月时血清VEGF值在统计学上低于未复发组(P＜0.05)；而未复发组与复发组之间，治疗前血清VEGF值、治疗后1周血清VEGF值、治疗后1周血清VEGF与治疗前差值、治疗后1个月时血清VEGF与治疗前差值无统计学差异(P＞0.05)。(7)p-t TTP与治疗后1个月时血清VEGF值(r=0.568，P＜0.01)之间、p-t TTP与治疗后1个月时血清VEGF与治疗前差值(r=0.569，P＜0.01)之间具有相关性。(8)HCC复发组与未复发组病理分化程度无统计学差异(P＞0.05)。病理分化程度与MVD之间、病理分化程度与VEGF之间在统计学上未发现明确相关性(P＞0.05)。(9)HCC病例组血清VEGF水平高于肝硬化组与健康组(P＜0.05)，肝硬化组与健康组之间血清VEGF无统计学差异(P＞0.05)。 结论(1)HCC超声造影参数肿瘤达峰早于肝实质的时间与肿瘤组织MVD、VEGF表达水平呈负相关，有望成为微波消融后近期复发的预测指标。(2)HCC微波消融后复发与未复发组的治疗前超声造影参数中，复发组的肝实质达峰时间显著早于未复发组，复发组的肿瘤达峰早于肝实质的时间显著小于未复发组，复发组的肝实质峰值强度小于未复发组，复发组的肿瘤峰值强度高于肝实质的值大于未复发组。(3)HCC治疗前超声造影参数中，肿瘤达峰早于肝实质的时间与HCC患者微波消融后近期复发有关。治疗后1个月血清VEGF值与复发有关。(4)HCC组织VEGF表达水平与MVD显著正相关，VEGF是新生肿瘤血管形成的正向调控因子。HCC病理分化程度与MVD、VEGF表达水平未发现明确相关性。(5)HCC微波消融后复发者的疗前肝癌组织MVD与VEGF表达水平高于未复发者，治疗后1个月时血清VEGF水平复发者低于未复发者。(6)超声造影检查有望成为评估肝癌血管生成及判断预后的一种无创、有效的方法。
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.
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