养阴抗毒法对兔肝癌射频治疗的影响

目的：观察养阴抗毒法对兔肝VX2移植瘤RFA术后反应的影响。方法：采用移植法建立兔肝移植瘤模型。分为4组：A组,预防组;B组,治疗组;C组,抗生素组;D组,空白组。在B超引导下行RFA治疗,术后1周处死动物并做肝组织病理切片在光镜下观察,检测治疗前后血常规及肝肾功变化。结果：A、B、C组肝组织病理切片可见细胞大量凝固性坏死,血常规、肝肾功变化有统计学意义（P〈0.05）;B、C组可见少量炎性细胞,以C组为甚。D组病理及实验检验指标无变化。结论：养阴抗毒法可以提高兔肝移植瘤RFA疗效并减轻或缓解对正常组织的损伤。     

养阴抗毒胶囊对兔肝VX2移植瘤射频治疗前后cAMP、cGMP及CORT影响的实验研究

目的:探讨中药养阴抗毒胶囊对兔肝VX2移植瘤射频消融(RFA)术前后CORT、cAMP、cGMP的动态变化的影响.方法:将40只新西兰大白兔采用移植法建立兔肝移植瘤模型,分为:A组中药干预组、B组RFA组、C组模型组、D组空白组,在B超引导下行RFA治疗,术前1天、术后1、3、5、7天检测血清中CORT、cAMP、cGMP动态变化.结果:RFA后普遍存在cAMP和CORT升高、cGMP降低现象,中药养阴抗毒胶囊可显著升高cAMP、降低cGMP并使CORT在适当范围内波动.结论:中药养阴抗毒胶囊可能通过升高cAMP,降低cGMP而启动人体内第二信使并激活HPA使CORT在适当范围内波动而提高RFA治疗效果.     

养阴抗毒胶囊对兔肝VX2移植瘤射频治疗前后cAMP、cGMP及CORT影响的实验研究

目的：探讨中药养阴抗毒胶囊对兔肝VX2移植瘤射频消融（RFA）术前后CORT、cAMP、cGMP的动态变化的影响。方法：将40只新西兰大白兔采用移植法建立兔肝移植瘤模型,分为：A组中药干预组、B组RFA组、C组模型组、D组空白组,在B超引导下行RFA治疗,术前1天、术后1、3、5、7天检测血清中CORT、cAMP、cGMP动态变化。结果：RFA后普遍存在cAMP和CORT升高、cGMP降低现象,中药养阴抗毒胶囊可显著升高cAMP、降低cGMP并使CORT在适当范围内波动。结论：中药养阴抗毒胶囊可能通过升高cAMP,降低cGMP而启动人体内第二信使并激活HPA使CORT在适当范围内波动而提高RFA治疗效果。     

养阴抗毒胶囊对放射损伤大鼠肾组织热休克蛋白70与糖皮质激素受体表达的影响

目的:研究养阴抗毒胶囊对放射性损伤大鼠肾热休克蛋白70(HSP70)与糖皮质激素受体的表达的影响及作用机制.方法:40只雄性SD大鼠随机分成4组,即正常对照组(A)、放射对照组(B)、放射+养阴抗毒组(C)和放射+桂附地黄组(D),以6GyX射线照射大鼠造成重度造血型放射损伤模型,用蛋白印迹法(Western Blot)检测肾组织热休克蛋白70与糖皮质激素受体(GR)的表达情况.结果:HSPT0在放射对照组(B)、放射+养阴抗毒组(C)和放射+桂附地黄组(D)均有高表达,以B组最为明显,D组其次,C组最弱.而GR在C组表达最明显,其次在D组.结论:养阴抗毒胶囊能显著降低放射损伤大鼠肾组织中HSP70的表达,而桂附地黄丸的此作用相对较弱,养阴抗毒胶囊能明显提高糖皮质激素受体的表达.     

放射性125I粒子组织间植入治疗肝移植癌的实验研究

目的:研究瘤体内植入125I粒子治疗兔VX2肝移植癌的疗效及其病理变化,探讨125I粒子组织间植入治疗肝癌的可行性.方法:建立荷瘤兔肝移植癌动物模型.对照组(A组)植入空白剂量(OmCi)125I粒子,B组植入1.0mCi125I粒子,C组植入0.7mCi125I粒子,D组植入0.4mCi125I粒子.观察植入前后各组肿瘤体积并计算抑瘤率,切除肿瘤组织进行常规病理检查.结果:各治疗组肿瘤大小在治疗前后比较具有显著差异(P<0.01),均小于同期对照组(P<0.01).在不同观察时期抑瘤率差别均有统计学意义(P<0.05),治疗1周后抑瘤率变化显著;各个组间抑瘤率差异在治疗后2周最为明显(P<0.01),以后减小,但均高于D组(P<0.01).病理切片显示靠近125I粒子处肿瘤细胞坏死,但远离粒子处仍可见存活肿瘤细胞.1.0mCi粒子对正常肝组织损伤较大.结论:125I粒子组织间植入治疗肝癌有效,单个粒子活度以0.7mCi左右较为适宜.     

养阴抗毒胶囊对放射损伤大鼠肾组织热休克蛋白70与糖皮质激素受体表达的影响

目的：研究养阴抗毒胶囊对放射性损伤大鼠肾热休克蛋白70（HSP70）与糖皮质激素受体的表达的影响及作用机制.方法：40只雄性SD大鼠随机分成4组,即正常对照组（A）、放射对照组（B）、放射＋养阴抗毒组（C）和放射＋桂附地黄组（D）,以6GyX射线照射大鼠造成重度造血型放射损伤模型,用蛋白印迹法（Western Blot）检测肾组织热休克蛋白70与糖皮质激素受体（GR）的表达情况.结果：HSPT0在放射对照组（B）、放射＋养阴抗毒组（C）和放射＋桂附地黄组（D）均有高表达,以B组最为明显,D组其次,C组最弱.而GR在C组表达最明显,其次在D组.结论：养阴抗毒胶囊能显著降低放射损伤大鼠肾组织中HSP70的表达,而桂附地黄丸的此作用相对较弱,养阴抗毒胶囊能明显提高糖皮质激素受体的表达.     

放射性125I粒子组织间植入治疗肝移植癌的实验研究

目的：研究瘤体内植入125I粒子治疗兔VX2肝移植癌的疗效及其病理变化,探讨125I粒子组织间植入治疗肝癌的可行性.方法：建立荷瘤兔肝移植癌动物模型.对照组（A组）植入空白剂量（OmCi）125I粒子,B组植入1.0mCi125I粒子,C组植入0.7mCi125I粒子,D组植入0.4mCi125I粒子.观察植入前后各组肿瘤体积并计算抑瘤率,切除肿瘤组织进行常规病理检查.结果：各治疗组肿瘤大小在治疗前后比较具有显著差异（P〈0.01）,均小于同期对照组（P〈0.01）.在不同观察时期抑瘤率差别均有统计学意义（P〈0.05）,治疗1周后抑瘤率变化显著;各个组间抑瘤率差异在治疗后2周最为明显（P〈0.01）,以后减小,但均高于D组（P〈0.01）.病理切片显示靠近125I粒子处肿瘤细胞坏死,但远离粒子处仍可见存活肿瘤细胞.1.0mCi粒子对正常肝组织损伤较大.结论：125I粒子组织间植入治疗肝癌有效,单个粒子活度以0.7mCi左右较为适宜.     

125I放射性粒子对人食管癌裸鼠皮下移植瘤的抑制作用研究

目的:观察125I粒子植入对人食管癌裸鼠皮下移植瘤的抑制作用.方法:采用雄性BALB/C裸小鼠建立人食管癌Eca-109细胞株的裸鼠皮下移植瘤模型,将荷瘤鼠随机分为5组(每组5只):对照组(A组)、假手术组(B组) 、低剂量组(C组,植入7.4 ×106 Bq粒子1枚)、中剂量组(D组,植入14.8 ×106 Bq粒子1枚)和高剂量组(E组,植入29.6 ×106 Bq粒子1枚).第30天检测各组移植瘤体积,并观察各组移植瘤组织病理学变化.结果: C、D、E组瘤体积与A组比较显著缩小,差异均有统计学意义(P<0.05), D、E组瘤体积与C组瘤体积相比均有统计学意义(均P<0.05),但D、E组之间瘤体积相比差异无统计学意义(P>0.05).B组和A组瘤体积相比差异无统计学意义(P>0.05),C、D、E植入后30d肿瘤体积抑瘤率分别为71.5 %、90.8%、92.1%. 结论:125I粒子对人食管癌裸鼠移植瘤具有一定的抑制和杀伤作用.     

解毒消癥饮和扶正抑瘤方对肝癌移植瘤小鼠外周血中VEGF的影响

目的: 探讨解毒消癥饮和扶正抑瘤方对小鼠肝癌移植瘤血管生成的抑制作用.方法: 40只ICR小鼠随机分为A组、B组、c组及D组,造模给药后20d采瘤、取血,计算抑瘤率及测定外周血中VEGF表达.结果: B组瘤重明显小于A组(P<0.05),抑瘤率为19%;A组和B组VEGF表达量均高于C、D两组,四组比较差异具有显著性(P<0.01):进一步两两比较表明,B组与A、C、D组之间差异显著(P<0.01);A与C、D组之间差异显著(P<0.01).结论: 解毒消癥饮和扶正抑瘤方影响小鼠肝癌移植瘤的VEGF表达.     

Ad-KDR-CDglyTK双自杀基因系统对荷瘤鼠胃癌体内抑制实验

目的:探讨KDR启动子驱动双自杀基因体系对荷瘤鼠胃癌的体内抑瘤作用.方法:建立胃癌移植瘤动物模型,当肿瘤直径达0.5 cm时,随机分为A组:空白对照,不施加任何处理;B组:注射重组腺病毒AdKDR-CDglyTK与前药5-FC和GCV;C组:仅注射重组腺病毒AdKDR-CDglyTK;D组:仅注射前药5-FC和GCV.治疗过程中绘制肿瘤生长曲线,观察该治疗体系的体内抑瘤效应;通过RT-PCR检测肿瘤组织内融合基因的表达;采用免疫组化行微血管密度检查.结果:接种肿瘤细胞后13d,裸鼠出现右臀区皮下瘤结节.治疗结束后A、B、C、D组间瘤质量差异有统计学意义(F=12 727.42,P=0.000),B组明显缩小.重组腺病毒转基因荷瘤鼠胃癌组织内可检测到CDglyTK融合基因产物的表达.肿瘤组织的MVD值在A、B、C、D组之间差异有统计学意义,F=27.04,P=0.000.结论:KDR启动子驱动双自杀基因体系对裸鼠皮下移植瘤有明显的抑瘤作用,表现为肿瘤的生长抑制和瘤体微血管密度减少等.     

超声介导二次射频消融术联合化疗治疗复发性肝转移瘤的疗效评估

目的:探索对于首次行超声引导下肝转移瘤射频消融术（RFA）后复发的患者分别进行二次RFA联合化疗、单纯化疗的疗效。 方法:RFA治疗肝转移瘤的患者复发后,分为A、B两个治疗组。A组进行二次RFA联合化疗治疗,B组进行单纯化疗治疗。观察两组患者治疗后的缓解率、生存质量和半年、1年、2年的生存率。 结果:A组短期缓解率明显高于B组。A、B两组半年、1年、2年生活自理能力比较P<0.05,有统计学意义。 A、B两组1年、2年生存率差异P<0.01,有显著统计学意义。 结论:治疗RFA后复发性肝转移瘤患者,二次RFA联合化疗与单纯化疗都可以治疗单发及多发的肝内病灶,RFA组的局部疗效更让人满意,短期内缓解率高,生存期内患者生活质量高,自理能力强,能够延长生存期,优势明显。     

In Vivo Experimental Study on the Effects of Fluid in Increasing the Efficiency of Radiofrequency Ablation

Background: Radiofrequency ablation (RFA) is the most widely used and studied method internationallyfor the local treatment of liver tumors. However, the extension of coagulation necrosis in one RFA procedureis limited and incomplete coverage of the damaged area can lead to a high local recurrence rate. Objective: Inthis study, we compared the effects of different solutions in enhancing hepatic radiofrequency by establishinga rabbit VX2 liver cancer model. We also determined the optimal solution to maximise effects on the extent ofRFA-induced coagulation necrosis. Methods: Thirty VX2 tumor rabbits were randomly assigned to five groups:group A, RFA alone; group B, RFA with anhydrous ethanol injection; group C, RFA with 5% hypertonic salineinjection; group D, RFA with lidocaine injection; and group E, RFA with a mixed solution. Routine ultrasoundexaminations and contrast-enhanced ultrasound (CEUS) of the ablation areas were performed after RFA. Then,we measured the major axis and transverse diameter and compared the areas of coagulation necrosis inducedby RFA. Results: The mean ablation area range increased in groups B, C and especially E, and the scopes weregreater compared with group A. Preoperative application of anhydrous ethanol, hypertonic saline, lidocaineand the mixed solution (groups B, C, D and E, respectively) resulted in larger coagulation necrosis areas than ingroup A (p<0.05). Among the groups, the coagulation necrosis areas in group E was largest, and the differencewas statistically significant compared with other groups (p<0.05). Pathological findings were consistent withimaging results. Conclusions: A mixture of dehydrated alcohol, hypertonic saline and lidocaine injected withRFA increases the extent of coagulation necrosis in the liver with a single application, and the mixed solution ismore effective than any other injection alone.     

肝门阻断增强兔肝的射频消融作用

目的探讨肝门阻断(Pringle法)可否提高肝脏射频消融术(radiofrequency ablation,RFA)的效果。方法将24只正常家兔随机分为3组:假手术组(A组)、射频消融组(B组)和肝门阻断射频消融组(C组),每组8只。将消融电极垂直刺入肝左外叶的肝实质内1.5 cm,展开子针1.0 cm。治疗温度90℃,消融时间4分钟。各组距射频消融中心1.0 cm,1.5 cm及2.0 cm范围内放射状取材,行HE染色和NADH细胞活力染色。术后第1、3、5天采集静脉血检测肝功能。结果 A组肝组织结构无明显改变。B组和C组距射频消融中心1.0 cm、1.5 cm和2.0 cm范围内,肝细胞完全凝固坏死的例数分别为8、2、0和8、7、0(均P<0.05)。术后各组肝功能有轻度且可逆的损害。结论肝门阻断可有效扩大肝脏消融范围,且对肝功能的影响较小。     

Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression‐free survival for patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) recurs frequently after minimally invasive therapy. The aim of our study was to observe the efficiency and safety of the combined treatment of radiofrequency ablation (RFA) with cellular immunotherapy (CIT) for HCC patients. In our study, 62 patients with HCC who were treated with radical RFA were divided into two groups: RFA alone (32 patients) and RFA/CIT (30 patients). Autologous mononuclear cells were collected from the peripheral blood and separated by apheresis, and then induced into natural killer (NK) cells, γδT cells and cytokine‐induced killer (CIK) cells. These cells were identified by flow cytometry with their specific antibodies and then were infused intravenously to RFA/CIT patients for three or six courses. The tumor recurrent status of these patients was evaluated with computed tomography or magnetic resonance imaging every 3 months after RFA. Progression‐free survival (PFS), liver function, viral load and adverse effects were examined. The results implied that PFS was higher in RFA/CIT group than that in RFA group. In RFA/CIT group, six courses had better survival prognosis than three courses. Viral load of hepatitis C was decreased in two of three patients without antiviral therapy in RFA/CIT group, but was increased in RFA group. No significant adverse reaction was found in the patients with CIT. In summary, these preliminary results suggest that combination of sequential CIT with RFA for HCC patients was efficient and safe, and may be helpful in the prevention of the recurrence for the patients with HCC after RFA.     

Combination of percutaneous radiofrequency ablation with transarterial chemoembolization for hepatocellular carcinoma： observation of clinical effects

Objective： To observe the clinical effect of radiofrequency ablation （RFA） combined with transcatheter arterial chemoembolization （TACE） for advanced hepatocellnlar carcinoma （HCC）. Methods： A total of 92 eases of advanced primary liver cancer underwent TACE and RFA treatment from June 2005 to 2011 at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College. A total of 88 cases with complete clinical treatment and follow-up data were divided into two groups： 43 patients treated with TACE （TACE group） and 45 patients that received TACE combined with RFA treatment （TACE ＋ RFA group）. After clinical data assessment, tumor size and survival status were not significantly different between the groups as determined by stratified analysis. Results： Before and after surgery, spiral CT radiography and color comparison observed ablation conditions. The tumor necrosis rates after treatment （CR ＋ PR） were 67.4% （29/43） and 91.1% （41/45） for the TACE and combined treatment groups, respectively, and the difference was statistically significant （P〈0.05）. The quality of life was significantly improved for patients undergoing TACE ~ RFA compared with the control group. Survival duration was not significantly different in patients undergoing TACE ~ RFA compared with the control group. Conclusions： In this study, the effect of RFA combined with TACE treatment was better than TACE alone in treating advanced HCC.     

射频消融治疗原发性肝癌的生命质量对比评价

背景与目的以往对原发性肝癌(hepatocellularcarcinoma,HCC)各种治疗疗效的评价主要从治愈率、生存率和生存时间方面进行,近年来生命质量(qualityoflife,QOL)研究倍受关注,能较全面地反映肝癌患者体能恢复状况和切身感受而被广泛应用于癌症、慢性病的疗效评价。目前对于经皮射频消融(radiofrequencyablation,RFA)、经动脉插管栓塞化疗(transcatheterhepaticarterialchemo-embolization,TACE)治疗意义的评价大多关注局部肿瘤灭活率及患者生存率,而对治疗后患者生命质量的研究尚不多见。本研究从患者整体角度对比评估原发性肝癌经皮射频消融治疗后患者的生命质量。方法采用国内肝癌特异性生命质量量表(QOL-LCV2.0),对80例HCC经RFA治疗后QOL进行评定;并与同期40例经动脉插管栓塞化疗(TACE组)以及TACE RFA(联合组)40例分别进行比较。3组患者在年龄、性别、临床分期等方面分布均衡,无明显差异。结果RFA组的QOL总分中位数(168.6)高于TACE组(146.8),差异有显著性(P=0.025);RFA组和联合组在症状/副作用领域的得分中位数45.5、46.0,分别优于单纯TACE组38.1(P<0.01);RFA组躯体功能领域得分呈略高于TACE组的趋势。患者的年龄、收入、治疗后Child-Pugh分级、治疗后新生/复发率、并发症等方面与患者生命质量相关。TACE组和联合组于治疗后Child-Pugh分级提高的比例分别高于RFA组;TACE组新生/复发的比例明显高于RFA组。RFA组的1年、2年和3年生存率(92.8%、89.3%和76.5%)与联合治疗组(94.1%、87.4%、60.0%)比较无统计学差异,但高于TACE组(74.3%、48.2%、48.2%)。结论RFA治疗肝癌,多数患者可获得较好的疗效,严重的副作用少。TACE与RFA联合治疗与单纯TACE相比,可减少患者肝功能损伤,有利于提高原发性肝癌患者的生命质量。     

原发性肝癌肝移植术围手术期辅助治疗的研究

目的:探讨围手术期辅助治疗在原发性肝癌肝移植中的意义。方法:回顾性分析36例原发性肝癌肝移植手术病例的临床资料,比较单纯行经肝动脉栓塞化疗(TACE)、TACE 经皮瘤内无水酒精注射(PEI),多电极射频治疗(RFA) TACE以及全身化疗等围手术辅助治疗措施对患者复发率及生存率的影响。结果:12例患者经辅助治疗后肿瘤直径缩小(66.7%),平均(4.8±1.2)cm,13例肿瘤临床分期降级。术后1、2、3年复发率分别为33.3%、47.2%、55.6%。TACE PEI、RFA及TACE RFA组病例总体治疗效果较好。结论:原发性肝癌肝移植围手术期辅助治疗可明显改善肝移植的效果,降低术后的复发率或延长复发时间。     

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients

Radiofrequency tumor ablation (RFA) is a therapeutic modality for liver cancer patients inducing localized tumor necrosis with maximal preservation of normal liver parenchyma. We investigated the immunomodulatory effects exerted by RFA treatment in liver cancer patients with metastatic liver lesions (13 patients) or hepatocellular carcinoma (HCC) (4 patients). Analysis of lymphocyte subsets by flow cytometry revealed that after RFA, CD3+ T cells, in particular CD4+, were decreased in metastatic cancer patients, while no change was observed in HCC patients. Moreover, RFA induced trafficking of na?ve and memory CD62L+ T cells from circulation to tissues. When characterizing the function of T cells, proliferative response to PHA was strongly increased after 48 h from RFA in metastatic cancer patients. Furthermore, T cells produced IFN-gamma in response to the tumor associated MUC1 antigen. In contrast, humoral immune responses against tumor antigens such as MUC1 and HCV proteins were unaffected by RFA treatment, although increase of circulating B cells was observed only in metastatic cancer patients. These results indicate that RFA application can exert an activating effect on the immune system in metastatic cancer patients, favouring trafficking of lymphocyte subsets and enhancing tumor antigen specific cellular immune responses.