本文選題：超聲造影 + 肝細胞癌�。� 參考：《第三軍醫(yī)大學》2014年碩士論文

【摘要】：研究背景 肝細胞癌(hepatocellular carcinoma, HCC)是世界上最常見的惡性腫瘤之一，影像學是其重要的診斷方法。在臨床研究中，由于肝臟的雙重血供特點，微泡造影劑提供了肝臟特殊時相變化圖像，使超聲造影在肝臟的局灶性病變(Focal liver lesion FLL)鑒別診斷中得到廣泛應用。近年來，肝細胞癌的診斷和治療上已取得很大的進步，尤其在手術及靶向治療方面，但是肝細胞癌的高復發(fā)率仍是有待攻克的難關。目前對于手術切除后易轉移及復發(fā)的肝細胞癌，肝移植可以獲得更好的療效。因此，尋求能提示肝細胞癌預后信息的影像學參數(shù)，有助于臨床上預測早期轉移及復發(fā)，進而為術前治療方案的選擇提供更多的依據(jù)。近年有學者研究乳腺癌超聲造影的增強模式及增強參數(shù)與病理預后因素的相關性，提示某些超聲造影參數(shù)與乳腺癌預后有明顯的相關性[1]；也有研究報道，觀察術中超聲造影肝細胞癌的血管供應模式，發(fā)現(xiàn)其與肝癌細胞的增殖活性及不良預后密切相關[2]。關于肝細胞癌超聲造影模式與預后因素的關系目前鮮見報道，我們擬通過分析肝細胞癌超聲造影參數(shù)與病理預后因素及臨床治療結局的關系，探討其在肝細胞癌預后判斷中的價值及臨床意義。 研究目的 研究肝細胞癌術前超聲造影(contrast-enchancement ultrasound，CEUS)的參數(shù)以及影響肝細胞癌預后的病理因素，分析二者之間的相關性，進一步探討超聲造影參數(shù)與肝細胞癌預后因素之間的關系。 方法 1、收集第三軍醫(yī)大學西南醫(yī)院術前已行超聲造影檢查，經(jīng)手術或穿刺病理證實為HCC的病例。篩選具有肝硬化背景且腫瘤標本切片已行Ki-67、CD34、甲胎蛋白(α-fetoprotein AFP)或者細胞角蛋白-19(Cytokeratin19CK19)免疫組化染色的病例作為研究對象，并收集上述病例的臨床資料、超聲造影及病理資料。 2、選取腫瘤標本已行CK19免疫組化染色的HCC病例，分為CK19陽性組和CK19陰性組。觀察兩組病例超聲造影的動脈相增強模式、門脈相增強強度；采用DFY-Ⅱ型超聲圖像定量分析儀測量兩組病例腫瘤的動脈相增強強度、不均勻度，門脈相腫瘤增強強度、腫瘤旁肝實質(zhì)組織增強強度；計算門脈相腫瘤與腫瘤旁肝實質(zhì)組織增強強度比值。分析比較兩組之間上述參數(shù)的差異。 3、選取腫瘤標本已行Ki-67、CD34、AFP免疫組化染色的HCC病例。觀察上述病例的腫瘤標本病理組織HE染色切片，記錄有無微血管癌栓浸潤(microvesselinvasion，MVI)；免疫組化CD34染色的腫瘤標本病理組織切片用于計數(shù)微血管密度(Microvessel density，MVD)；隨訪肝癌手術切除后復發(fā)情況。觀察上述病例常規(guī)超聲與超聲造影動脈相腫瘤的大小變化；超聲造影動脈相增強模式、增強形態(tài)及內(nèi)部有無雜亂扭曲血管；門脈相增強強度、消退時間、消退程度。分析超聲造影參數(shù)與腫瘤標本組織分化程度、Ki-67、MVD、MVI、AFP及復發(fā)之間的關系。 結果 1、(1)CK19陽性組與CK19陰性組的性別比例、年齡、病灶大小、乙肝血清標志物陽性患者所占比例均無統(tǒng)計學差異(P0.05)；CK19陰性組高分化肝癌比例(17.65%)高于CK19陽性組(2.53%)，CK19陽性組低分化肝癌比例(15.19%)高于CK19陰性組(3.53%)(χ2=15.172,p=0.001)。 (2)動脈相呈不均勻增強的病例，其CK19陽性檢出率(60.58%)高于動脈相呈均勻增強的病例(26.67%)(χ2=17.524,p=0.000)；門脈相呈低增強CK19陽性檢出率(52.20%)高于門脈相高或等增強的病例(28.57%)(χ2=5.195,p=0.023)。 (3)DFY-Ⅱ型超聲圖像定量分析儀測量結果，CK19陽性組腫瘤動脈相不均勻度(2.64±0.64)高于CK19陰性組(2.29±0.31)(W=4.4,p=0.000)；CK19陽性組動脈相峰值強度(102.83±29.78dB)低于CK19陰性組(120.65±25.49dB)(t=3.887,p=0.000)；CK19陽性組門脈相增強強度(66.83±20.13dB)低于CK19陰性組(79.99±27.15dB)(t=3.115,p=0.002)； CK19陽性組腫瘤與腫瘤旁肝實質(zhì)組織門脈相增強強度比值(0.74±0.03)低于與CK19陰性組(0.92±0.22)(t=5.221,p=0.000)。 2、(1)腫瘤標本組織分化程度高低、Ki-67陽性率、MVI檢出率、MVD高低、AFP陽性率、是否復發(fā)及復發(fā)早晚與性別比例、年齡、病灶大小、乙肝血清標志物陽性患者所占比例無明顯關系(p0.05)。 (2)造影后腫瘤測值增大明顯的病例，其Ki-67陽性檢出率越高(χ2=7.126,p=0.008)、MVI檢出率越高(χ2=4.087,p=0.043)。超聲造影動脈相呈不均勻增強的病例，其組織分化程度越低(χ2=7.654,p=0.006)、Ki-67陽性檢出率越高(χ2=9.659,p=0.002)、早期復發(fā)率高(χ2=7.485,p=0.024)。動脈相增強形態(tài)不規(guī)則的病例，其組織分化程度越低(χ2=4.414,p=0.036)、Ki-67陽性檢出率越高(χ2=6.443,p=0.011)、MVI檢出率越高(χ2=6.985,p=0.008)。動脈相增強內(nèi)部具有雜亂扭曲血管的病例，其組織分化程度越低(χ2=6.210,p=0.013)、MVI檢出率越高(χ2=6.985,p=0.008)。 (3)超聲造影門脈相呈低增強的病例，其組織分化程度越低(χ2=7.450,p=0.006)、Ki-67陽性檢出率越高(χ2=5.349,p=0.021)。門脈相開始消退時間越快的病例，其組織分化程度越低(χ2=3.963,p=0.047)、Ki-67陽性檢出率越高(χ2=6.018,p=0.014)、MVI檢出率越高(χ2=5.379,p=0.020)。門脈相消退程度明顯的病例，其組織分化程度越低(χ2=8.268,p=0.004)、Ki-67陽性檢出率越高(χ2=5.782,p=0.016)。 (4)Logistic回歸結果顯示超聲造影動脈相內(nèi)部呈不均勻增強與Ki-67陽性及早期復發(fā)密切相關；動脈相增強形態(tài)不規(guī)則易發(fā)生腫瘤MVI；門脈相增強呈低增強，可能提示組織分化程度較低。 結論 1、肝硬化背景下CK19表達不同的HCC超聲造影增強模式、量化參數(shù)存在明顯差異；動脈相呈不均勻增強及門脈相造影劑明顯闊清CK19陽性發(fā)生率高，可能提示不良預后。 2、肝細胞癌超聲造影的增強模式及參數(shù)可能有助于預測HCC手術切除的預后。動脈相呈不均勻增強可能預測腫瘤細胞增殖活性及復發(fā)時間；動脈相增強形態(tài)不規(guī)則可能提示腫瘤微血管浸潤；門脈相腫瘤呈低增強可能預測其組織分化程度更低，腫瘤惡性程度大，，預后較差。
[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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R735.7;R445.1

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本文編號：1995978