肝癌动脉内化疗栓塞联合免疫治疗兔移植性肝肿瘤实验研究

目的观察经导管肝动脉化疗栓塞术联合超液化碘油+细胞因子对兔移植性肝肿瘤的治疗作用。方法采用新西兰大白兔VX2肿瘤株移植到肝脏的方法制作肝肿瘤模型30只,根据治疗方案的不同随机平均分为生理盐水对照组(G1),常规TACE组(G2),TACE+肝动脉灌注细胞因子组(G3),TACE+脾动脉灌注细胞因子组(G4)及TACE联合超液化碘油+细胞因子组(G5)共5组,每组6只,进行肝动脉插管治疗。观察各组肿瘤生长、坏死情况以及肿瘤组织内增殖细胞核抗原的表达。结果①治疗后第7天,G5肿瘤增长率显著低于G1、G2、G3、G4(P<0.05);G3、G4与G2比较(P<0.05);G5生长抑制率则显著高于G2、G3、G4(P<0.05),G3、G4与G2比较(P<0.05)。②G5肿瘤坏死范围与G1、G2、G3、G4相比较有显著性差异;G3、G4与G2相比较无显著性差异(P(0.05)。③G3组、G4组、G5组的肿瘤组织内增殖细胞核抗原标记指数显著小于对照组G1和G2组(P<0.01);而G2组与G1组相比较,无显著意义(P>0.05);G5组与G3组、G4组比较(P<0.05)。结论TACE联合超液化碘油+细胞因子免疫疗法...     

TNP-470联合碘化油介入治疗兔VX2肝癌的实验研究

目的 研究血管生成抑制剂TNP-470与碘化油混合栓塞对兔VX2肝癌的治疗作用及不同给药途径之间的疗效差异.方法 39只兔VX2肝癌动物模型随机分为3组,A组14只,生理盐水1 ml经肝动脉注入作为对照组;B组13只,经肝动脉灌注超液态碘化油0.6 ml栓塞加TNP-470静脉注射(10 mg/kg,每日1次,连续3 d);C组12只,TNP-470(30 mg/kg)与超液态碘化油0.6 ml混合乳化行肝动脉栓塞.术后1周称体重后处死制备标本,观察以下指标:测量肿瘤的体积并计算抑瘤率,计数肺内转移灶数量(肺表面及5个冠状切面上结节计数),用免疫组化检测各组血管内皮生长因子(VEGF)的表达以及检测肿瘤组织微血管密度(MVD).结果 2个实验组的肿瘤平均体积明显低于对照组(P＜0.05),抑瘤率分别为41.31%和34.01%.A组转移率64.28%(9/14),B组转移率38.46%(5/13),C组转移率8.33%(2/12),经X2检验,3组肺转移率不完全相同,两两间均有显著差异(P＜0.05).VEGF的表达阳性率A组78.57%,B组84.61%,C组83.33%,X2=0.96,P＞0.05,三者间无统计学差异.A组MVD值为56.1±9.5,B组MVD值为40.1 ±11.2,C组MVD值为29.7±10.1,两两比较均有显著性差异(P＜0.05).结论 TNP-470与碘化油混合经肝动脉栓塞对兔VX2肝癌的治疗效果明显优于经静脉注射给药.     

槐耳清膏联合化疗栓塞对兔VX2肝癌凋亡及其相关蛋白表达的影响

目的 观察槐耳清膏联合经导管肝动脉化疗栓塞(TACE)对兔VX2肝癌凋亡及其相关蛋白P53、Bax和Bcl-2表达的影响.材料与方法将36只MRI证实已成功接种VX2肝癌的荷瘤兔随机分为3组,开腹经肝动脉穿刺分别给予不同处理:A组为生理盐水对照组.经肝动脉注入0.2 ml/kg体重生理盐水;B组为TACE组.经肝动脉注入超液态碘油0.2 ml/kg+丝裂霉素0.5 ms/kg体重乳剂;C组为TACE+槐耳清膏灌服组,TACE方法同B组,同时术后每天灌服槐耳清膏500 mg/kg体重.术后二周用原位缺口末端标记(TUNEL)法检测各组肿瘤细胞的凋亡指数,用免疫组织化学方法检测各组肿瘤细胞的P53、Bax和Bcl-2蛋白的表达情况.结果 A组的肿瘤细胞凋亡指数最小,C组的肿瘤细胞凋亡指数最高;3组动物肿瘤细胞的凋亡指数相比差异有统计学意义(P<0.05),C组与B组相比差异有统计学意义(P<0.05).3组动物肿瘤细胞的Bax蛋白表达阳性率A组最低,C组最高;P53和Bcl-2蛋白表达阳性率c组最低,A组最高;3组动物肿瘤细胞的P53、Bax和Bcl-2蛋白表达阳性率相比差异有统计学意义(P<0.05),C组与B组相比相比差异均有统计学意义(P<0.05).结论 槐耳清膏可能通过促进肝癌细胞Bax蛋白表达增高,使P53和Bcl-2蛋白表达下降,导致肝癌细胞的凋亡增加达到治疗肝癌的目的 .     

槐耳清膏联合化疗栓塞治疗兔VX2肝癌的实验研究

目的 观察槐耳清膏联合经肝动脉化疗栓塞(TACE)对兔VX2肝癌生长及转移的影响.材料与方法将VX2瘤粒直接种植于新西兰大白兔左肝内2周,MRI证实已成功接种VX2的荷瘤兔随机分为3组,每组12只,开腹经肝动脉穿刺分别给予不同处理:A组为生理盐水对照组,经肝动脉注入0.2 ml/kg体重生理盐水;B组为TACE组,经肝动脉注入超液态碘化油0.2 ml/kg+丝裂霉素0.5 mg/ks乳剂;C组为TACE+槐耳清膏灌服组,TA-CE方法同B组,同时术后每天灌服槐耳清膏500 mg/kg.每天观察动物生长情况,术后2周处死动物,测量动物体重、肿瘤体积、坏死区面积,计算肿瘤生长率、坏死率;观察肝、肺及腹腔淋巴结转移情况.结果 术前1天3组动物体重、肿瘤体积差异无统计学意义(P>0.05).术后2周,B组动物体重下降明显,与A组、C组相比差异均有统计学意义(P<0.05);A组与C组相比差异无统计学意义(P>0.05).治疗后2周肿瘤体积、肿瘤生长率和肿瘤坏死率B组、C组与A组相比差异均具有统计学意义(P<0.01),B组与C组相比差异亦具有统计学意义(P<0.05).肝和肺的转移:B组与A组相比差异无统计学意义(P>0.05),C组与B组、A组相比差异均具有统计学意义(P<0.05);腹腔淋巴结转移3组相比差异无统计学意义(P>0.05).结论 槐耳清膏可以改善动物TACE术后的生存质量;抑制肿瘤生长,促进肿瘤坏死;抑制肿瘤转移.     

介入性灌注化疗与热灌注化疗对兔VX2肝癌模型的作用比较研究

目的观察热灌注化疗对兔VX2肝癌模型疗效及安全性。方法新西兰大白兔20只,制备兔肝VX2模型,随机分为对照组(A)和实验组(B),分别A组给于常温(22～25℃)5%葡萄糖100ml+5-Fu(20mg/kg),B组给于60℃5%葡萄糖100ml+5-Fu(20mg/kg),用B超观察处理前后肿瘤大小,抽血查ALT变化。结果A组肿瘤体积由(1627±473)mm3缩小为(1334±641)mm3,B组肿瘤体积由(1682±397)mm3缩小为(1130±559)mm3,两组差别有统计学意义(P<0.05);ALTA组由(755±203)u/L增加为(834±262)u/L,B组由(781±197)u/L增加为(865±237)u/L,组间差异无统计学意义。结论介入性热灌注化疗比常温灌注化疗对兔VX2肝癌模型有更高的抑制作用。     

Lp-THAE诱导兔VX2肝癌细胞凋亡

目的 研究Lp-THAE诱导兔肝VX2肿瘤细胞凋亡.方法 27只新西兰大白兔种植性VX2肝癌,均分成Lp-THAE组、THAI组和对照组,处理后2～5 d处死动物,在肿瘤中央部位、外周部位和非瘤肝区正常组织取材.采用HE染色光镜观察典型凋亡细胞、计算凋亡指数,FTTC-Annexin V/PI双染色双变量流式细胞术分析凋亡细胞百分率.结果 THAE组肿瘤中央与外周部位的凋亡指数分别为(17.769±2.417)%.(4.129±1.172)%,P＜0.01,凋亡细胞百分率分别为(16.483±1.404)%,(9.478±0.964)%,P＜0.01,坏死细胞百分率分别为(43.559±5.053)%,(33.460±1.840)%,P=0.093.凋亡细胞与坏死细胞百分率总和分别为(60.042±13.979)%,(42.938±8.979)%,P＜0.01.THAE组的肿瘤细胞凋亡指数、凋亡细胞百分率和坏死细胞百分率都显著大于THAI组和对照组(P＜0.01),肿瘤中央部位的细胞凋亡指数、凋亡细胞百分率都显著大于肿瘤外周部位(P＜0.01).结论 Lp-THAE诱导肿瘤细胞凋亡和引起肿瘤细胞坏死是其作用机制的两种形式.     

肝动脉导管栓塞化疗治疗肝癌的护理

目的:探讨肝动脉栓塞化疗治疗肝癌的术前、术后的护理措施。方法:对36例行TACE的患者在术前充分准备、术后精心护理。结果:肝动脉栓塞化疗治疗有效率82 % ,术后出现不良反应的患者,经对症治疗、护理均痊愈。结论:肝动脉栓塞化疗治疗肝癌是手术不能切除或术后复发HCC的首选方法,细致、周到的护理是治疗成功的重要保证     

经动脉灌注5-FU缓释微球治疗兔VX2肝肿瘤

目的 研究5-FU缓释微球经胃十二指肠动脉灌注对兔VX2肝肿瘤的治疗作用.方法 将成功接种肝VX2肿瘤的模型兔随机分成4组,每组10只,用显微外科手术临时阻断肝总动脉血流,经胃十二指肠动脉插管至肝固有动脉起始部给药行介入治疗,术毕结扎胃十二指肠动脉.A组(生理盐水对照组),注射生理盐水0.5～1 ml;B组(碘佛醇对照组)注射碘佛醇0.5～1 ml;C组为碘油组(疗效对比组),注射超液化碘油0.5～1.0ml;D组为5-FU缓释微球组,注射5-FU缓释微球10mg和碘佛醇1 ml混合溶液.4组实验动物于治疗1周后观察肿瘤生长情况、坏死程度.并采用原位末端标记法(TUNEL)检测肿瘤细胞凋亡指数(AI).结果 治疗1周后5-FU缓释微球组肿瘤生长受到抑制,肿瘤生长率低于生理盐水对照组和碘佛醇对照组(P<0.05),与碘油组差异无统计学意义(P>0.05).4组肿瘤均有不同程度坏死,5-FU缓释微球组和碘油组肿瘤坏死率明显高于另两组(P<0.05).生理盐水对照组、碘佛醇对照组和5-FU缓释微球组肿瘤细胞凋亡指数分别为1.69±0.18、1.75±0.27和8.03±0.63,5-FU缓释微球组与各对照组相比差异有统计学意义(P<0.05).结论 5-FU缓释微球经动脉灌注可抑制肝肿瘤生长,诱导肿瘤细胞凋亡,促进肿瘤坏死,是有效的化疗栓塞剂.     

经膈下动脉介入化疗栓塞术治疗原发性肝癌

目的观察膈下动脉形成肝癌侧枝血供的因素和几率。方法在对137例患者介入治疗中,造影寻找膈下动脉,并超选形成肿瘤血供的膈下动脉,进行化疗栓塞。结果137例患者中有21例经膈下动脉介入治疗(占15.3%),其中原发性肝癌手术切除后复发2例(9.5%),首次介入治疗出现膈下动脉供血3例(14.3%),2次或多次介入治疗后出现膈下动脉供血16例(76.2%)。结论膈下动脉是原发性肝癌的最重要侧枝供血动脉,经膈下动脉介入化疗栓塞原发性肝癌成功率高而且并发症少。     

Supplemental Transcatheter Arterial Chemoembolization Through a Collateral Omental Artery: Treatment for Hepatocellular Carcinoma

Purpose: To evaluate the therapeutic efficacy and safety of supplemental transcatheter arterial chemoembolization (TACE) through the extrahepatic collateral omental artery (OA) for the treatment of hepatocellular carcinoma (HCC). Methods: We studied 21 patients with extrahepatic collaterals of the OA, among 1,512 patients with HCC who had undergone angiography. HCCs supplied by collateral OAs were located at: segment IV in seven, segment V in five, segment III in three, segment VI in three and segment VIII in three patients (Couinaud classification of segments). On preoperative CT scans, every HCC was abutting the liver surface. Adjacent omental infiltration or engorgement was noted in 11 patients. Celiac and hepatic arteriograms showed hypertrophy of the feeding OA in all patients. TACE of the OA was performed in 19 patients with an emulsion of iodized oil and doxorubicin hydrochloride. Embolization with gelatin sponge particles was added in five patients. Results: Collaterals of the OA to the HCC were found on the first to seventeenth sessions of TACE. On follow-up CT scans, five patients showed complete uptake of iodized oil in the tumor. Partial uptake of iodized oil was noted in 13 patients and no uptake in one patient. There was no serious complication that related to the omental embolization, such as omental or bowel ischemia. The cumulative survival rates from the time of the TACE of the OA were 81% at 6 months and 68% at 12 months. Conclusion: TACE of the OA is safe and has a potential therapeutic effect in the treatment of HCC.     

肝动脉化疗栓塞对肝癌肿瘤新生血管生成的影响

目的　研究肝细胞癌 (hepatocellularcarcinoma ,HCC)经导管动脉化疗栓塞 (transcatheterarterialchemoembolization ,TACE)后残癌组织微血管密度 (microvesseldensity ,MVD)、微血管直径的情况及其意义。方法　经病理证实的HCC 63例 ,包括单纯手术切除42例 (对照组 ) ,TACE术后行Ⅱ期手术切除 2 1例 (TACE组 ) ,TACE组患者手术前接受 1～ 2次不等的TACE术治疗 ,均按统一规范标准给予化疗药物灌注 栓塞治疗。对手术切除标本进行免疫组化染色 ,其中TACE组取病灶边缘残存肿瘤部分 ,检测肿瘤组织的MVD、微血管直径。结果　对照组MVD值为 5 1.69± 18.17,TACE组MVD值为 5 8.5 7± 15 .75 ,二者之间比较无显著性差异 (t=1.48,P >0 .0 5 ) ;对照组微血管直径为 ( 17.62± 10 .5 4) μm ,TACE组微血管直径为 ( 15 .79± 7.65 ) μm ,二者之间比较无显著性差异 (t =0 .71,P >0 .0 5 )。结论　TACE术很难彻底消除肿瘤血供 ,术后残癌组织可通过各种途径重新生成丰富血供     

Rhabdomyolysis Developing After Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma

A 25-year-old man with hepatocellular carcinoma developed severe muscular weakness and pain 15 days after transcatheter arterial chemoembolization (TACE). The diagnosis of rhabdomyolysis was made based on myalgia localized in the bilateral upper extremities (bilateral trapezius, deltoid, biceps brachii, and teres major muscles) on magnetic resonance imaging and increased levels of muscle-derived serum enzymes. In this case, some drugs administered during the clinical course of TACE (diclofenac, famotidine, and cefotiam dihydrochloride) were suspected to be involved in the rhabdomyolysis, but the exact cause of rhabdomyolysis was not identified. The symptoms were completely improved by right trisegmentectomy of the liver following conservative treatment.     

经导管动脉化疗栓塞对肝癌患者肝功能的影响

原发性肝癌(简称肝癌)是指发生于肝细胞或肝内胆管细胞的恶性肿瘤,因起病隐匿,在临床发现时大多数已失去外科切除机会,因此经导管动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)已成为治疗中晚期肝癌的首选方法[1].     

术前经动脉化疗栓塞对肝细胞癌细胞凋亡的影响

目的 评价术前经导管动脉化疗栓塞(17ACE)对肝细胞癌(HCC)细胞凋亡的影响。资料与方法经手术病理证实的HCC136例，其中行1～5次TACE后Ⅱ期手术切除79例(TACE组)，按治疗方式不同分4组，A组：仅灌注化疗药物ll例，治疗1～4次；B组：化疗药 碘化油栓塞33例，治疗1～5次；C组：化疗药 碘化油 明胶海绵颗粒栓塞23例，治疗1—3次；D组：化疗药 碘化油、无水乙醇、明胶海绵颗粒栓塞12例，治疗1～3次。单纯手术57例(非TACE组)，用TUNEL(terminal deoxynucleotidyl transferase(TdT)-mediated dUTP-digoxigenin nick—end labeling)法检测凋亡细胞，用免疫组织化学检测各标本Bcl-2和Bax蛋白表达。结果 TACE组的A、B、C、D各组HCC细胞凋亡指数及Bax蛋白表达均显著高于非TACE组；而Bcl-2蛋白表达及Bcl-2和Bax蛋白表达比值TACE组的A、B、C、D各组均显著低于非TACE组。结论 术前TACE通过上调Bax蛋白表达，下调Bcl-2蛋白表达及Bcl-2和Bax蛋白表达比值使HCC细胞发生凋亡。     

经皮穿刺左肱动脉入路介入治疗原发性肝癌:兼与股动脉入路比较

目的　总结经皮穿刺左肱动脉入路介入治疗肝癌的初步经验 ,与股动脉入路比较该技术的优缺点。方法　 45 2例患者分为肱动脉组 5 2例和股动脉组 40 0例 ,2组患者均行超选择性肿瘤化疗栓塞。通过比较 2组操作的技术成功率、穿刺口血肿发生率、微导管可控性、患者的舒适程度 ,评价 2种方法的优缺点。结果　股动脉组失败 4例 ,技术成功率 99.0 % ,改用肱动脉入路和锁股下入路成功 ;肱动脉组全部成功 ,技术成功率 10 0 % ,Ρ >0 .0 5 ,无差别。股动脉组 4例 (1% )术后穿刺口形成血肿 ,肱动脉组有 9例 (17.3 % ) ,Ρ <0 .0 5 ,有差别。血肿未予特殊处理均自行吸收。股动脉组 75例使用微导管 ,5例操作困难 ,占 6.7% ;肱动脉组 3 6例使用微导管 ,2例不顺利 ,占 5 .6% ,Ρ >0 .0 5 ,无差别。股动脉组术后卧床 6h以上 ,均诉腰背酸痛 ,2 3例需插导尿管 ;肱动脉组术后不需卧床 ,无腰背痛。结论　经左肱动脉入路介入治疗肝癌 ,提高了患者的舒适和便利 ,是股动脉入路的补充。     

Transcatheter Arterial Chemoembolization with Doxorubicin-Eluting Superabsorbent Polymer Microspheres in the Treatment of Hepatocellular Carcinoma: Midterm Follow-up

PurposeTo investigate prospectively the safety, tolerability, and efficacy of transarterial chemoembolization using superabsorbent polymer (SAP) microspheres loaded with doxorubicin for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsDuring the years 2006–2011, 64 patients underwent 144 transarterial chemoembolization with SAP microspheres procedures. Most of the patients were staged as Barcelona Clinic Liver Cancer class B (65%). The most frequent underlying liver diseases were hepatitis C (35%) and alcoholic liver disease (28%) resulting in Child-Pugh A (73.4%) or Child-Pugh B (17%) liver cirrhosis. Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors with magnetic resonance (MR) imaging performed 4–6 weeks after each procedure.ResultsSerious adverse events (n = 9) were ischemic or infectious in nature. Transarterial chemoembolization with SAP microspheres resulted in objective response rates of 67.5%, 44.5%, and 25% after first, second, and third sessions. There were 16 patients (25%) who underwent orthotopic liver transplantation after transarterial chemoembolization with SAP microspheres, of whom 2 experienced recurrent disease. During a median follow-up time of 14 months (range, 2–55 mo), 26 patients (40.5%) died. Median overall and transplant-free survivals were 20.5 months (95% confidence interval, 13.2–27.7) and 18 months (95% confidence interval, 14.2–21.8), respectively.ConclusionsTransarterial chemoembolization with SAP microspheres has an excellent safety profile in cirrhotic patients, even in the presence of advanced liver disease (Child-Pugh B) or advanced stages of HCC. This treatment produced meaningful tumor response rates as assessed by MR imaging.