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  本文關(guān)鍵詞： 氬氦刀冷凍消融 肝動脈化療栓塞 原發(fā)性肝癌 甲胎蛋白 T細胞亞群 1年生存率　出處：《河北醫(yī)科大學》2016年碩士論文　論文類型：學位論文

【摘要】：目的:原發(fā)性肝細胞癌是惡性程度高,預后不良的惡性腫瘤之一。目前原發(fā)性肝癌治療的首選治療手段仍然是手術(shù)治療,然而患者在初診時大多數(shù)已經(jīng)發(fā)展為中晚期病人,已失去手術(shù)切除機會。微創(chuàng)介入治療目前是失去手術(shù)切除機會的的原發(fā)性肝癌患者重要治療手段。微創(chuàng)介入治療不僅可以改善原發(fā)性肝癌患者的生存質(zhì)量和生存期,甚至對早期肝癌可達到臨床治愈的效果。微創(chuàng)介入治療分為非血管性介入治療和血管性介入治療。血管性介入治療主要是經(jīng)導管通過動脈進行化療藥物灌注和應用栓塞劑堵塞腫瘤血管,也稱TACE(transcatheter arterial chemoembolization)。非血管性介入治療包括射頻消融、微波消融、無水酒精瘤體注射、高強度聚焦超聲、氬氦刀等。氬氦刀技術(shù)以局部腫瘤靶細胞滅活為主的治療技術(shù),是近年來從傳統(tǒng)冷凍治療發(fā)展起來新的冷凍消融技術(shù),因安全有效,損傷小、痛苦小、恢復快,對不能手術(shù)切除或不能忍受手術(shù)的患者提供了一種新的治療方法。氬氦刀技術(shù)可單獨及聯(lián)合應用治療腫瘤,對肝癌的治療是安全有效的。因此,我們分析了中晚期肝癌患者接受肝動脈化療栓塞治療、氬氦刀冷凍消融治療及經(jīng)肝動脈化療及栓塞聯(lián)合應用氬氦刀冷凍消融治療的療效,為失去手術(shù)機會的中晚期肝癌患者選擇合適的治療方法提供臨床依據(jù)。方法:我們回顧性分析2012-05~2015-06我科共156例不能手術(shù)的中晚期原發(fā)性肝癌患者,所有患者均經(jīng)B超、CT、核磁等影像學檢查,并行超聲引導下活檢,病理證實,依照肝癌診斷標準確診的原發(fā)性肝癌患者,且腫瘤直徑≥2cm,≤15cm。原發(fā)性肝癌癌灶≤3個,肝內(nèi)轉(zhuǎn)移病灶≤5個;ECOG生活狀況評分≤2分;肝功能Child分級A~B;心、肺、腎功能正常,凝血功能無明顯障礙,無并發(fā)嚴重感染;生存期預計≥3個月。把肝癌患者分入TACE聯(lián)合應用氬氦刀冷凍消融組(47例)、TACE(肝動脈化療栓塞)組(51例)、氬氦刀冷凍消融組(49例)。所有病例治療周期3~6月以內(nèi),以治療后6個月評效,各組治療根據(jù)患者治療過程中病情,兩種治療手段可反復多次或交替使用。以肝臟CT增強掃描監(jiān)測病灶變化,采用m RECIST標準判定療效;采用電化學發(fā)光法進行AFP測定觀察治療前后血清AFP水平變化;采用流式細胞儀測定T細胞亞群觀察機體免疫功能變化。采用SPSS15.0統(tǒng)計學軟件進行數(shù)據(jù)統(tǒng)計分析,采用卡方檢驗進行差異顯著性檢驗和率的比較,P0.05時差異有統(tǒng)計學意義;采用Log-Rank法進行生存分析;均數(shù)采用單因素方差分析。結(jié)果:1聯(lián)合治療組總有效率(72.3%)明顯高于氬氦刀冷凍消融組(53.1%)和TACE組(47.1%),差異均有統(tǒng)計學意義(P0.05)氬氦刀冷凍消融組總有效率高于TACE組,但無統(tǒng)計學意義(P0.05)。2甲胎蛋白(AFP)變化情況147例患者中有104例明顯升高,其中AFP400ng/m L者104例,1000ng/m L者28例,高于正常值但小于400ng/m L者40例。三組治療后AFP水平均有明顯下降,差異具有統(tǒng)計學意義(P0.05)。TACE組AFP異常者共50例,下降50%者35例(70.0%);氬氦刀冷凍消融組中AFP異常者47例,38例肝癌患者AFP下降50%(78.7%);聯(lián)合組中AFP異常者49例,41例肝癌患者AFP下降50%(83.7%)。聯(lián)合組AFP下降明顯優(yōu)于單純TACE組及氬氦刀冷凍消融組,具有統(tǒng)計學差異(P0.05)。3治療后T細胞亞群檢測:氬氦刀冷凍消融組、TACE組、聯(lián)合治療組CD3+、CD4+細胞明顯上升,以聯(lián)合治療組最為顯著,差異具有統(tǒng)計學意義(P0.05);治療后各組CD8+、CD16+/CD56+細胞檢測無明顯差異,無統(tǒng)計學意義(P0.05)。4對生存率的影響三組6個月生存率無明顯差異(P0.05)。1年生存率TACE聯(lián)合氬氦刀冷凍消融組較TACE組、氬氦刀冷凍消融組明顯提高(P0.01)。而氬氦刀冷凍消融組6個月生存率和1年生存率均高TACE組,但均無統(tǒng)計學差異(P0.05)。5不良反應其中入組的147例患者順利完成TACE治療和氬氦刀冷凍消融治療,術(shù)中死亡病例無;肝區(qū)脹痛不適、發(fā)熱、轉(zhuǎn)氨酶及膽紅素輕度升高等為常見不良反應,偶有胸腔積液。結(jié)論:本研究結(jié)果顯示,TACE聯(lián)合氬氦刀冷凍消融治療原發(fā)性肝癌較任何單一方案有效率高,能顯著降低甲胎蛋白水平,增強機體免疫機能,且能明顯提高患者1年生存率,不良反應輕微。
[Abstract]:Objective: primary hepatocellular carcinoma is one of the high degree of malignancy and poor prognosis of malignant tumors. The treatment of choice for the treatment of primary liver cancer is still surgery, but patients at diagnosis has been developed for the most advanced patients have lost the opportunity of surgery. Minimally invasive interventional therapy is currently lost operation opportunity the patients with primary liver cancer treatment. Not only can improve the interventional treatment of primary liver cancer with minimally invasive quality of life and survival, even for early cancer can achieve clinical cure effect. Minimally invasive interventional treatment for vascular interventional therapy and vascular interventional treatment. Vascular interventional treatment is mainly by catheter through the artery perfusion chemotherapy and Application of embolic agents blocking tumor blood vessels, also known as TACE (transcatheter arterial chemoembolization). Non vascular interventional therapy including injection Frequency ablation, microwave ablation, percutaneous ethanol injection, high intensity focused ultrasound, cryoablation. Argon helium knife technology to local tumor target cell inactivation treatment technology in recent years, from the traditional cryotherapy developed new cryoablation technology for safe and effective, little injury, little pain. Fast recovery, provides a new method for the treatment of unresectable or cannot tolerate surgery. Argon helium knife can be used alone and combined treatment of tumors is safe and effective for the treatment of liver cancer. Therefore, we analyzed the advanced liver cancer patients received chemotherapy of hepatic artery embolization, cryoablation treatment and transcatheter arterial chemotherapy and embolization with cryoablation therapy, for unresectable advanced hepatocellular carcinoma patients to choose the appropriate treatment to provide clinical basis. Methods: We retrospectively analyzed 2012-05 Advanced ~2015-06 a total of 156 patients with primary liver cancer patients, all patients were treated by ultrasound, CT examination, magnetic imaging, parallel ultrasound guided biopsy, pathology, in accordance with the standard confirmed diagnosis of hepatocellular carcinoma in patients with primary liver cancer, and the tumor diameter is larger than 2cm, less than 15cm. in primary hepatocellular carcinoma the cancer is less than 3, intrahepatic metastasis lesions less than 5 ECOG; the living conditions were below 2 points; Child classification of liver function A~B; heart, lung, kidney function, blood coagulation function has no obvious obstacles, no severe infection; survival period is expected to exceed 3 months. The patients were divided into TACE hepatocellular carcinoma combined with argon cryoablation group (47 cases), TACE (TACE) group (51 cases), cryoablation group (49 cases). All patients within 3~6 months period, in 6 months after the treatment group were treated according to the assessment results, the treatment process of patients, two treatment methods repeated or alternate to To use. Hepatic CT enhancement scanning and monitoring changes to determine the efficacy of using the m RECIST standard; luminescence method to observe the changes of serum AFP levels before and after treatment were measured by using electrochemical AFP; Determination of T cell subsets on immune function was measured by flow cytometry. Using SPSS15.0 statistical data analysis software, using chi square test comparison a significant difference test and rate, the difference was statistically significant P0.05; survival analysis was performed using Log-Rank method; mean by single factor variance analysis. Results: 1 the total effective rate of combined treatment group (72.3%) was significantly higher than that of cryoablation group (53.1%) and TACE group (47.1%), the differences were statistically meaning (P0.05) cryoablation group total efficiency is higher than that of TACE group, but no statistical significance (P0.05.2) and alpha fetoprotein (AFP) changes in 147 cases, 104 cases markedly increased, AFP400ng/m L In 104 cases, 28 cases of 1000ng/m L were higher than normal in 40 cases, but less than 400ng/m L. The three groups after treatment AFP levels were significantly decreased, the difference was statistically significant (P0.05) group.TACE AFP abnormalities were 50 cases, 35 cases decreased 50% (70%); 47 cases of cryoablation group AFP abnormal, 38 cases of AFP patients with liver cancer decreased by 50% (78.7%); 49 cases with abnormal AFP group, 41 cases of AFP patients with liver cancer decreased by 50% (83.7%). Group AFP were lower than that of the pure TACE group and cryoablation group, with statistical difference (P0.05) after the treatment of.3 T cell subsets: Cryoablation group, TACE group, CD3+ treatment group, CD4+ cells increased significantly, with the combined treatment group was the most significant, the difference was statistically significant (P0.05); CD8+ after treatment, no significant difference was detected in CD16+/CD56+ cell (P0.05), there was no significant effect of.4 on survival rate the three group of 6 month survival No significant differences in the rates of (P0.05).1 year survival rate of TACE combined with argon helium cryoablation group than TACE group, cryoablation group was significantly increased (P0.01). While cryoablation group, the survival rate of 6 months and 1 year survival rates were higher in TACE group, but there were no significant differences (P0.05.5) adverse reactions including 147 cases of patients were treated with TACE successfully and cryoablation treatment, intraoperative death cases; liver area pain and discomfort, fever, transaminase and bilirubin increased slightly as the common adverse reactions, with pleural effusion. Conclusion: the results of this study show that TACE combined with argon helium cryoablation for the treatment of primary hepatocellular carcinoma is more effective than any single solution rate, can significantly reduce the level of alpha fetoprotein, enhance immune function, and can significantly improve the 1 year survival rate of patients, mild adverse reactions.

【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R735.7

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