肝硬化背景下肝细胞癌超声造影参数与病理预后因素的相关性分析

发布时间：2018-06-08 13:40

本文选题：超声造影 + 肝细胞癌　；参考：《第三军医大学》2014年硕士论文

【摘要】：研究背景肝细胞癌(hepatocellular carcinoma, HCC)是世界上最常见的恶性肿瘤之一，影像学是其重要的诊断方法。在临床研究中，由于肝脏的双重血供特点，微泡造影剂提供了肝脏特殊时相变化图像，使超声造影在肝脏的局灶性病变(Focal liver lesion FLL)鉴别诊断中得到广泛应用。近年来，肝细胞癌的诊断和治疗上已取得很大的进步，尤其在手术及靶向治疗方面，但是肝细胞癌的高复发率仍是有待攻克的难关。目前对于手术切除后易转移及复发的肝细胞癌，肝移植可以获得更好的疗效。因此，寻求能提示肝细胞癌预后信息的影像学参数，有助于临床上预测早期转移及复发，进而为术前治疗方案的选择提供更多的依据。近年有学者研究乳腺癌超声造影的增强模式及增强参数与病理预后因素的相关性，提示某些超声造影参数与乳腺癌预后有明显的相关性[1]；也有研究报道，观察术中超声造影肝细胞癌的血管供应模式，发现其与肝癌细胞的增殖活性及不良预后密切相关[2]。关于肝细胞癌超声造影模式与预后因素的关系目前鲜见报道，我们拟通过分析肝细胞癌超声造影参数与病理预后因素及临床治疗结局的关系，探讨其在肝细胞癌预后判断中的价值及临床意义。研究目的研究肝细胞癌术前超声造影(contrast-enchancement ultrasound，CEUS)的参数以及影响肝细胞癌预后的病理因素，分析二者之间的相关性，进一步探讨超声造影参数与肝细胞癌预后因素之间的关系。方法 1、收集第三军医大学西南医院术前已行超声造影检查，经手术或穿刺病理证实为HCC的病例。筛选具有肝硬化背景且肿瘤标本切片已行Ki-67、CD34、甲胎蛋白(α-fetoprotein AFP)或者细胞角蛋白-19(Cytokeratin19CK19)免疫组化染色的病例作为研究对象，并收集上述病例的临床资料、超声造影及病理资料。 2、选取肿瘤标本已行CK19免疫组化染色的HCC病例，分为CK19阳性组和CK19阴性组。观察两组病例超声造影的动脉相增强模式、门脉相增强强度；采用DFY-Ⅱ型超声图像定量分析仪测量两组病例肿瘤的动脉相增强强度、不均匀度，门脉相肿瘤增强强度、肿瘤旁肝实质组织增强强度；计算门脉相肿瘤与肿瘤旁肝实质组织增强强度比值。分析比较两组之间上述参数的差异。 3、选取肿瘤标本已行Ki-67、CD34、AFP免疫组化染色的HCC病例。观察上述病例的肿瘤标本病理组织HE染色切片，记录有无微血管癌栓浸润(microvesselinvasion，MVI)；免疫组化CD34染色的肿瘤标本病理组织切片用于计数微血管密度(Microvessel density，MVD)；随访肝癌手术切除后复发情况。观察上述病例常规超声与超声造影动脉相肿瘤的大小变化；超声造影动脉相增强模式、增强形态及内部有无杂乱扭曲血管；门脉相增强强度、消退时间、消退程度。分析超声造影参数与肿瘤标本组织分化程度、Ki-67、MVD、MVI、AFP及复发之间的关系。结果 1、(1)CK19阳性组与CK19阴性组的性别比例、年龄、病灶大小、乙肝血清标志物阳性患者所占比例均无统计学差异(P0.05)；CK19阴性组高分化肝癌比例(17.65%)高于CK19阳性组(2.53%)，CK19阳性组低分化肝癌比例(15.19%)高于CK19阴性组(3.53%)(χ2=15.172,p=0.001)。 (2)动脉相呈不均匀增强的病例，其CK19阳性检出率(60.58%)高于动脉相呈均匀增强的病例(26.67%)(χ2=17.524,p=0.000)；门脉相呈低增强CK19阳性检出率(52.20%)高于门脉相高或等增强的病例(28.57%)(χ2=5.195,p=0.023)。 (3)DFY-Ⅱ型超声图像定量分析仪测量结果，CK19阳性组肿瘤动脉相不均匀度(2.64±0.64)高于CK19阴性组(2.29±0.31)(W=4.4,p=0.000)；CK19阳性组动脉相峰值强度(102.83±29.78dB)低于CK19阴性组(120.65±25.49dB)(t=3.887,p=0.000)；CK19阳性组门脉相增强强度(66.83±20.13dB)低于CK19阴性组(79.99±27.15dB)(t=3.115,p=0.002)； CK19阳性组肿瘤与肿瘤旁肝实质组织门脉相增强强度比值(0.74±0.03)低于与CK19阴性组(0.92±0.22)(t=5.221,p=0.000)。 2、(1)肿瘤标本组织分化程度高低、Ki-67阳性率、MVI检出率、MVD高低、AFP阳性率、是否复发及复发早晚与性别比例、年龄、病灶大小、乙肝血清标志物阳性患者所占比例无明显关系(p0.05)。 (2)造影后肿瘤测值增大明显的病例，其Ki-67阳性检出率越高(χ2=7.126,p=0.008)、MVI检出率越高(χ2=4.087,p=0.043)。超声造影动脉相呈不均匀增强的病例，其组织分化程度越低(χ2=7.654,p=0.006)、Ki-67阳性检出率越高(χ2=9.659,p=0.002)、早期复发率高(χ2=7.485,p=0.024)。动脉相增强形态不规则的病例，其组织分化程度越低(χ2=4.414,p=0.036)、Ki-67阳性检出率越高(χ2=6.443,p=0.011)、MVI检出率越高(χ2=6.985,p=0.008)。动脉相增强内部具有杂乱扭曲血管的病例，其组织分化程度越低(χ2=6.210,p=0.013)、MVI检出率越高(χ2=6.985,p=0.008)。 (3)超声造影门脉相呈低增强的病例，其组织分化程度越低(χ2=7.450,p=0.006)、Ki-67阳性检出率越高(χ2=5.349,p=0.021)。门脉相开始消退时间越快的病例，其组织分化程度越低(χ2=3.963,p=0.047)、Ki-67阳性检出率越高(χ2=6.018,p=0.014)、MVI检出率越高(χ2=5.379,p=0.020)。门脉相消退程度明显的病例，其组织分化程度越低(χ2=8.268,p=0.004)、Ki-67阳性检出率越高(χ2=5.782,p=0.016)。 (4)Logistic回归结果显示超声造影动脉相内部呈不均匀增强与Ki-67阳性及早期复发密切相关；动脉相增强形态不规则易发生肿瘤MVI；门脉相增强呈低增强，可能提示组织分化程度较低。结论 1、肝硬化背景下CK19表达不同的HCC超声造影增强模式、量化参数存在明显差异；动脉相呈不均匀增强及门脉相造影剂明显阔清CK19阳性发生率高，可能提示不良预后。 2、肝细胞癌超声造影的增强模式及参数可能有助于预测HCC手术切除的预后。动脉相呈不均匀增强可能预测肿瘤细胞增殖活性及复发时间；动脉相增强形态不规则可能提示肿瘤微血管浸润；门脉相肿瘤呈低增强可能预测其组织分化程度更低，肿瘤恶性程度大，，预后较差。
[Abstract]:Research background
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Imaging is an important diagnostic method. In clinical study, the microbubble contrast agent provides a special phase change image of the liver because of the dual blood supply of the liver, and makes ultrasound contrast in the focal lesion of the liver (Focal liver lesion FLL). It has been widely used in differential diagnosis. In recent years, great progress has been made in the diagnosis and treatment of hepatocellular carcinoma, especially in operation and targeting therapy, but the high recurrence rate of hepatocellular carcinoma is still a difficult problem to be overcome. Therefore, the imaging parameters that can prompt the prognostic information of hepatocellular carcinoma can be used to predict early metastasis and recurrence in the clinic, and thus provide more basis for the selection of preoperative treatment options. In recent years, some scholars have studied the enhancement pattern of ultrasound contrast in breast cancer and the correlation between the enhancement parameters and the prognosis factors of the disease. There is a significant correlation between the parameters and the prognosis of breast cancer [1]. There is also a study to observe the vascular supply pattern of hepatocellular carcinoma in intraoperative ultrasound, and it is found that it is closely related to the proliferation activity and poor prognosis of hepatoma cells. The relationship between the mode of ultrasound contrast and the prognostic factors of hepatocellular carcinoma is rarely reported. We should analyze the relationship between [2]. and the prognostic factors of HCC. The value of contrast-enhanced ultrasound (CEUS) in hepatocellular carcinoma (NPC) is associated with pathological prognosis and clinical outcome.
research objective
To study the parameters of Contrast-enchancement ultrasound (CEUS) before operation of hepatocellular carcinoma (CEUS) and the pathological factors that affect the prognosis of hepatocellular carcinoma, analyze the correlation between them, and further explore the relationship between the parameters of ultrasound contrast and the prognostic factors of hepatocellular carcinoma.
Method
1, a case of HCC, which was confirmed by ultrasound contrast examination before surgery in Southwest Hospital of Third Military Medical University, was confirmed by surgery or puncture pathology. Screening cases with Ki-67, CD34, alpha fetoprotein (alpha -fetoprotein AFP) or cytokeratin -19 (Cytokeratin19CK19) immunohistochemical staining with liver cirrhosis and tumor specimens were selected as the study. The clinical data, sonography and pathological data of the above cases were collected.
2, HCC cases with CK19 immunohistochemical staining were selected and divided into CK19 positive group and CK19 negative group. The arterial phase enhancement mode and portal phase enhancement intensity were observed in the two groups of cases with contrast enhanced ultrasound imaging, and the enhanced intensity, inhomogeneity and portal phase tumor enhancement were measured by DFY- II ultrasonic image quantitative analyzer. Strong strength, enhanced intensity of parenchyma tissue adjacent to the tumor; calculated the ratio of portal vein tumor to the parenchyma tissue in the parenchyma. Analysis and comparison of the differences between the two groups.
3, the tumor specimens were selected for Ki-67, CD34, and AFP immunohistochemical staining of HCC cases. The HE staining section of the pathological tissue of the tumor specimens of the above cases was observed, and the microvascular tumor thrombus infiltration (microvesselinvasion, MVI) was recorded. The pathological tissue section of the tumor specimen with immunohistochemical CD34 staining was used to count the microvascular density (Microvessel density, MVD). Follow up the recurrence of liver cancer after resection. Observe the changes in the size of the tumor in the arterial phase of the conventional ultrasound and ultrasound contrast, contrast the contrast with the contrast-enhanced mode of the arteriography, the enhancement of the shape and the internal disorderly twisted blood vessels, the enhancement of the portal phase, the fading time and the regression degree. The relationship between degree of Ki-67, MVD, MVI, AFP and recurrence.
Result
1, (1) the sex ratio of CK19 positive group and CK19 negative group had no statistical difference (P0.05), the proportion of high differentiated liver cancer (17.65%) in CK19 negative group was higher than that in CK19 positive group (2.53%), and the proportion of low differentiated hepatocellular carcinoma (15.19%) in CK19 positive group was higher than that in CK19 negative group (3.53%) (x 2=15.172, p=0.). 001).
(2) the positive rate of CK19 (60.58%) was higher than that of the arterial phase (26.67%) (x 2=17.524, p=0.000), and the positive rate of CK19 in the portal vein was lower than that of the portal vein (28.57%) (28.57%) (28.57%) (x 2=5.195, p=0.023).
(3) the measurement of DFY- II ultrasonic image quantitative analyzer showed that the inhomogeneity of the arterial phase in the CK19 positive group (2.64 + 0.64) was higher than that of the CK19 negative group (2.29 + 0.31) (W=4.4, p=0.000), and the peak intensity of the arterial phase (102.83 + 29.78dB) in the CK19 positive group was lower than that of the CK19 negative group (120.65 + 25.49dB) (t=3.887, p=0.000), and the portal phase enhancement intensity of the CK19 positive group (66. 83 + 20.13dB) was lower than that of the CK19 negative group (79.99 + 27.15dB) (t=3.115, p=0.002), and the ratio of the tumor to the parenchyma parenchyma phase enhanced intensity ratio (0.74 + 0.03) in the CK19 positive group was lower than that in the CK19 negative group (0.92 + 0.22) (t=5.221, p=0.000).
2, (1) the degree of tissue differentiation of tumor specimens, Ki-67 positive rate, MVI detection rate, MVD high and low, AFP positive rate, whether the recurrence and relapse early and night with sex ratio, age, size of the focus, the proportion of hepatitis B serum markers positive patients have no significant relationship (P0.05).
(2) the positive rate of Ki-67 was higher (x 2=7.126, p=0.008), the higher the detection rate of MVI (x 2=4.087, p=0.043). The lower the degree of tissue differentiation (chi 2=7.654, p=0.006), the higher the positive rate of Ki-67 (chi 2=9.659, p=0.002), and the higher rate of the recurrence (x 2=7) in the early stage (x 2=7). .485, p=0.024). The degree of tissue differentiation was lower (x 2=4.414, p=0.036), the higher the positive rate of Ki-67 (x 2=6.443, p=0.011), the higher the detection rate of MVI (chi 2=6.985, p=0.008). The lower the degree of tissue differentiation in the arterial phase, the lower the degree of tissue differentiation (chi 2=6.210, p=0.013), and the detection rate. The higher (x 2=6.985, p=0.008).
(3) the higher the degree of tissue differentiation (x 2=7.450, p=0.006), the higher the positive rate of Ki-67 (x 2=5.349, p=0.021), the higher the degree of differentiation (chi 2=3.963, p=0.047), the higher the positive rate of Ki-67 (chi 2=6.018, p=0.014), the higher the positive rate of Ki-67 (x 2=6.018, p=0.014), and the higher the positive rate of MVI (x 2=5) (x 2=5). .379 (p=0.020). The degree of tissue differentiation was lower in patients with significant degree of portal regression (2=8.268, p=0.004), and the positive rate of Ki-67 positive was higher (chi 2=5.782, p=0.016).
(4) the results of Logistic regression showed that the inhomogeneous enhancement in the arterial phase was closely related to the Ki-67 positive and the early recurrence; the irregular arterial phase was irregular and the tumor MVI was easy to occur, and the portal phase enhancement showed low enhancement, which may suggest the low degree of tissue differentiation.
conclusion
1, under the background of liver cirrhosis, the expression of CK19 with different HCC contrast-enhanced ultrasound enhanced patterns, and there were significant differences in quantitative parameters. The incidence of arterial phase inhomogeneous enhancement and portal phase contrast agent obviously broad-leaved CK19 positive was high, which may suggest bad prognosis.
2, enhanced mode and parameters of contrast-enhanced ultrasound in hepatocellular carcinoma may help predict the prognosis of HCC resection. Inhomogeneous enhancement in arterial phase may predict tumor cell proliferation activity and recurrence time; irregular arterial phase enhanced morphological changes may suggest tumor microvascular infiltration, and a low enhancement in portal phase tumor may predict its tissue differentiation The degree is lower, the malignant degree of the tumor is large and the prognosis is poor.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R735.7;R445.1

【参考文献】