本文選題：肝細(xì)胞癌(HCC) + 總生存率(OS)　； 參考：《山東大學(xué)》2017年碩士論文

【摘要】：目的:肝細(xì)胞癌(HCC)在全球范圍內(nèi)是嚴(yán)重危害人類(lèi)健康的疾病,肝癌在我國(guó)尤為高發(fā),目前手術(shù)切除仍然是肝癌最重要的治療手段。然而,即便是接受根治性切除術(shù)后的患者其高復(fù)發(fā)率及死亡率仍然是制約肝癌手術(shù)治療效果的主要因素,70%接受肝癌根治切除術(shù)的患者最終會(huì)在5年內(nèi)復(fù)發(fā),因此研究者便希望通過(guò)根治性手術(shù)后的輔助治療來(lái)改善預(yù)后。本研究通過(guò)對(duì)肝細(xì)胞癌根治性切除術(shù)后不同次數(shù)肝動(dòng)脈化療栓塞治療(TACEE)產(chǎn)生的生存和預(yù)后差異分析,評(píng)估其在伴有不同危險(xiǎn)因素的肝細(xì)胞癌患者根治性切除術(shù)后的作用,并確定合適的介入次數(shù),篩選出從這項(xiàng)輔助治療中獲益的人群。資料和方法:回顧性分析了山東大學(xué)齊魯醫(yī)院在2010年1月至2014年1月間320例行根治性切除術(shù)的肝細(xì)胞癌患者的臨床病例資料,包括性別,年齡,血清總膽紅素、谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶、谷氨酰轉(zhuǎn)肽酶、堿性磷酸酶、血清白蛋白水平,乙肝表面抗原,肝硬化,Chi ld-pugh分級(jí),血清甲胎蛋白水平,腫瘤大小,腫瘤數(shù)目,腫瘤細(xì)胞分化程度,是否合并微血管侵犯,以及術(shù)后輔助性TACE的次數(shù),并根據(jù)肝癌根治術(shù)后所行輔助性TACE次數(shù)(0-3次)將其分為4組,為了進(jìn)一步明確輔助性TACE在具有不同復(fù)發(fā)及死亡風(fēng)險(xiǎn)人群中的作用并篩選出最終的獲益人群,又采用了多因素分析,篩選出包括肝細(xì)胞癌根治性切除術(shù)后輔助性TACE次數(shù),腫瘤大小,Edmondson分級(jí)在內(nèi)的復(fù)發(fā)及生存的影響因素,并將患者進(jìn)一步分層為具有低或高危因素復(fù)發(fā)或死亡的亞組(腫瘤直徑≤5厘米或5厘米)。復(fù)發(fā)或死亡的低危因素被定義為無(wú)微血管侵犯(MiVI)的EdmondsonⅠ/Ⅱ級(jí),而高危因素被定義為EdmondsonⅢ/Ⅳ級(jí)或微血管侵犯。使用Kaplan-Meier方法比較生存和復(fù)發(fā)率,Cox回歸進(jìn)行單因素和多因素分析。結(jié)果:四個(gè)組的患者在性別,年齡,血清總膽紅素、谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶、谷氨酰轉(zhuǎn)肽酶、堿性磷酸酶、血清白蛋白水平,乙肝表面抗原,肝硬化,Child-pugh分級(jí),血清甲胎蛋白水平,腫瘤大小,腫瘤數(shù)目,腫瘤細(xì)胞分化程度,是否合并微血管侵犯等方面具有可比性(P0.05),在沒(méi)有接受根治術(shù)后輔助性TACE的患者相比,接受了2次(log-rank,χ 2= 9.054,P=0.003)或3次(log-rank,χ2=4.228,P=0.04)TACE的患者顯示復(fù)發(fā)延遲,且接受2次或3次TACE患者與其他患者相比,總生存率(OS)增加。隨后的亞組分析中,采用多因素分析顯示,肝細(xì)胞癌根治性切除術(shù)后輔助性TACE次數(shù)(HR = 0.797,95%CI:0.707-0.897,P0.001),腫瘤大小(HR = 0.649,95%,CI:0.484-0.871,P = 0.004),Edmondson分級(jí)(Edmondson分級(jí):HR = 0.563,95%,CI:0.423-0.750,P0.001)和MiVI(HR = 0.240,95%,CI:0.155-0.373,P0.001)是復(fù)發(fā)的影響因素。同時(shí),這些因素也是生存的影響因素(輔助性TACE次數(shù):HR = 0.523,95%CI:0.411-0.666,P0.001;腫瘤大小:HR = 0.434,95%,CI:0.261-0.719,P =0.001;Edmondson等級(jí):HR = 0.317,95%,CI:0.193-0.521,P0.001;MiVI:HR = 0.137,95%,CI:0.072-0.259,P0.001)。然后我們根據(jù)腫瘤直徑進(jìn)行分層分析,以確定對(duì)復(fù)發(fā)或死亡的影響。復(fù)發(fā)或死亡的低危因素被定義為沒(méi)有微血管侵犯(MiVI)的Edmondson Ⅰ/Ⅱ級(jí),而高危因素被定義為Edmondson Ⅲ/Ⅳ級(jí)或微血管侵犯。低危亞組腫瘤直徑≤5cm的患者人數(shù)分別為66,24,24,29例。而高危亞組腫瘤直徑≤5cm的患者,分別為32,12,11,10。在腫瘤直徑5cm的低危亞組中,人數(shù)分別為26,14,7,11,腫瘤直徑5cm高危亞組,人數(shù)分別為22,10,9,13。在低危亞組,所有組無(wú)病生存率(DFS)和總生存率(OS)之間無(wú)統(tǒng)計(jì)學(xué)差異。在腫瘤直徑≤5的高危亞組患者中,與不接受根治性術(shù)后輔助TACE的患者相比,TACE組顯示復(fù)發(fā)延遲,且2次或3次TACE可改善OS。對(duì)于腫瘤直徑5的高危亞組,2次或3次TACE可延緩復(fù)發(fā)并改善OS。結(jié)論:根治性切除術(shù)后2-3次輔助性TACE對(duì)腫瘤分化差和伴有微血管侵犯的肝細(xì)胞癌患者有利,特別是對(duì)于腫瘤直徑5 cm的患者。
[Abstract]:Objective: hepatocellular carcinoma (HCC) is a worldwide disease which seriously endangers human health. Liver cancer is especially high in our country. Surgical resection is still the most important treatment for liver cancer. However, even after radical resection, the high recurrence rate and death rate are still the main factors restricting the effect of liver cancer. 70% patients who undergo radical resection of liver cancer will eventually have a recurrence within 5 years, so the researchers hope to improve the prognosis by adjuvant therapy after radical resection. This study evaluated the differences in survival and prognosis by different times of hepatic arterial chemoembolization (TACEE) after radical resection of hepatocellular carcinoma. The effect of radical excision of hepatocarcinoma patients with risk factors, and the appropriate number of interventions, and screening out people who benefit from this adjuvant therapy. Data and methods: a retrospective analysis of the clinical cases of 320 cases of hepatocarcinoma in the Qilu Hospital from January 2010 to January 2014 in Shandong University. Data, including sex, age, serum total bilirubin, alanine aminotransferase, cereal aminotransferase, glutamyl transpeptidase, alkaline phosphatase, serum albumin level, hepatitis B surface antigen, liver cirrhosis, Chi ld-pugh grading, serum alpha fetoprotein level, tumor size, tumor number, tumor cell differentiation, microvascular invasion, and postoperative The number of auxiliary TACE was divided into 4 groups according to the number of auxiliary TACE times (0-3 times) after radical resection of liver cancer. In order to further clarify the role of auxiliary TACE in people with different recurrence and death risk and to screen out the final benefiting crowd, the multifactor analysis was used to screen out the radical resection of hepatocellular carcinoma after radical resection. Adjuvant TACE times, tumor size, Edmondson classification, recurrence and survival factors, and further stratifying patients into subgroups with low or high risk factors for relapse or death (tumor diameter less than 5 cm or 5 cm). Low risk factors for recurrence or death are defined as Edmondson I / II of MiVI without microvascular invasion, and high risk The factors were defined as Edmondson III / IV or microvascular invasion. Kaplan-Meier method was used to compare survival and recurrence rates and Cox regression for single factor and multifactor analysis. Results: four groups of patients were in sex, age, serum total bilirubin, alanine transaminase, glutamine transaminase, glutamyl transpeptidase, alkaline phosphatase, serum albumin level, Hepatitis B surface antigen, liver cirrhosis, Child-pugh grading, serum alpha fetoprotein level, tumor size, tumor number, tumor cell differentiation, and microvascular invasion were comparable (P0.05), and received 2 times (log-rank, X 2= 9.054, P=0.003) or 3 times (log-rank, chi square) in patients who had not received radical resection (log-rank, 2=, P=0.003). 2=4.228, P=0.04) TACE patients showed delayed recurrence, and the total survival rate (OS) increased in 2 or 3 TACE patients compared with other patients. In subsequent subgroup analysis, multivariate analysis showed that the number of auxiliary TACE times after radical resection of hepatocellular carcinoma (HR = 0.797,95%CI:0.707-0.897, P0.001), tumor size (HR = 0.649,95%, CI:0.4) 84-0.871, P = 0.004), Edmondson classification (Edmondson grading: HR = 0.563,95%, CI:0.423-0.750, P0.001) and MiVI (HR = 0.240,95%, CI:0.155-0.373,) are the factors affecting the recurrence. 0.719, P =0.001; Edmondson grade: HR = 0.317,95%, CI:0.193-0.521, P0.001; MiVI:HR = 0.137,95%, CI:0.072-0.259, P0.001). Then we make a stratified analysis based on the diameter of the tumor to determine the effect on recurrence or death. The low risk factors for recurrence or death are defined as grade I / II without microvascular invasion (MiVI), and high risk The factors were defined as Edmondson III / IV or microvascular invasion. The number of patients with a diameter of less than 5cm in the low risk subgroup was 66,24,24,29, respectively. The patients in the high risk subgroup, with a diameter of less than 5cm, were 32,12,11,10. in the low risk subgroup of the tumor diameter 5cm, respectively, the number was 26,14,7,11, and the tumor diameter 5cm high risk subgroup, the number was 22, respectively. 10,9,13. in the low risk subgroup, there was no statistical difference between all groups of disease free survival (DFS) and total survival (OS). In the high risk subgroups with a tumor diameter less than 5, the TACE group showed a delayed recurrence compared with those who did not receive radical postoperative adjuvant TACE, and the 2 or 3 times TACE could improve the high risk subgroup of the tumor diameter 5, 2 or 3 times TAC. E can delay recurrence and improve the OS. conclusion: 2-3 adjuvant TACE after radical resection are favorable for poor differentiation of tumors and patients with hepatocellular carcinoma with microvascular invasion, especially for patients with a diameter of 5 cm.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735.7

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