大鼠肝细胞凋亡和坏死动物模型的建立及评价

目的:通过大鼠肝右叶血供干预分别建立肝细胞凋亡和坏死动物模型,为进一步的磁共振成像实验奠定基础。方法:选取体重为250-300克的SD大鼠90只,随机分为A、B、C三组,每组30只,分别行肝右叶门静脉和肝动脉结扎术、门静脉结扎术及假手术,各组在术后3 h及1、3、7和14 d分别处死6只大鼠,取肝脏标本送病理及电镜检查。结果: A组30只大鼠肝右叶发生凝固性坏死,光镜及电镜下均呈典型的坏死改变,TUNEL染色呈阴性;B组30只大鼠肝右叶发生小灶性凋亡,光镜下可见肝细胞核固缩改变,电镜下见肝组织核边集和凋亡小体,TUNEL染色呈阳性改变。术后3 h 即可见凋亡细胞,24 h时凋亡细胞数最多,7 d后肝组织开始发生小灶性坏死;C组30只大鼠肝右叶未发生凋亡和坏死的病理改变。结论:大鼠肝右叶门静脉和肝动脉双结扎可建立胆脏凝固性坏死模型,单纯肝右叶门静脉结扎能构建肝细胞小灶性凋亡模型。     

家兔急性周围型肺栓塞影像模型的制备

目的探讨用可吸收性明胶海绵制作家兔急性肺栓塞(PE)影像模型的可行性。方法20只实验组家兔随机分成5组,采用明胶海绵栓子经股静脉插管制成急性PE的动物模型。栓塞后行肺动脉造影检查,栓塞后2h、24h、3d、7d、14d(A、B、C、D、E组)分批处死家兔,解剖肺动脉并观察栓塞区肺组织病理变化。对照组2只注入生理盐水,分别于第7天,14天处死。结果20只实验组家兔1只麻醉意外死亡,19只制备模型后成活,模型制备成功率95%。肺动脉造影显示46支叶及段肺动脉栓塞。肺动脉解剖共发现栓子65个,栓塞动脉50支。A组肺体积肿胀,色深红,镜下观察见肺组织充血。B组、C组、D组、E组中15只家兔肺表面呈苍白色、暗红色、黑色或苍白色区内见黑色坏死区,另外1只仅见肺体积肿大,肺颜色无变化,E组1只第3天左侧发生气胸,肺萎缩;光镜下观察肺组织水肿、淤血、出血、坏死,炎性细胞浸润,肺泡含气减少,肺泡支架结构破坏,E组2例栓塞区见肺组织机化,栓子周围有血小板血栓和/或混合血栓形成。对照组2只家兔肺部仅见少量炎性细胞浸润。结论用明胶海绵作为栓塞物制备家兔急性肺栓塞模型,其方法简便、成功率高,为肺栓塞影像学研究提供了一种较好的实验模型。     

肝癌术前门静脉栓塞的临床应用

肝癌术前门静脉栓塞(PVE)是通过栓塞患侧门静脉使同侧肝叶萎缩,对侧肝细胞增生,诱导预留肝体积增大。目前临床主要应用于剩余肝脏体积太小而无法耐受肝叶切除术的肝癌患者。从而扩大肝癌肝切除手术的适应证,提高了手术的安全性。现就PVE的应用现状及进展等做一概述。     

血管生成抑制剂烟曲霉素衍生物在介入治疗肝细胞癌实验中的应用

目的研究经肝动脉化疗栓塞术结合肝动脉灌注血管生成抑制剂合成的烟曲霉素衍生物（TNP-470）治疗ACI大鼠肝细胞癌的疗效。方法在20只雄性ACI大鼠肝包膜下移植Morris Hepatoma3924A肝癌小瘤块（2mm^3），移植术后第13天时进行MR检查，测量肿瘤体积V1，第14天时，在荷瘤大鼠经胃十二指肠动脉逆行插管至肝动脉而采取以下介入治疗方案：治疗组：碘化油（0．1ml）＋丝裂霉素（0．1mg）＋TNP-470（5．0mg）（10只）；对照组：碘化油（0．1ml）＋丝裂霉素（0．1mg）（10只）。治疗后再次进行MR检查测量肿瘤体积V2，比较肝肿瘤体积变化（V2／V1）。结果治疗组和对照组大鼠经介入治疗前后的肝肿瘤平均体积分别为0．04cm^3和0．15cm^3以及0．04cm^3和0．34cm^3。治疗组和对照组肿瘤体积平均增长倍数（V2／V1）分别为4．11和9．14。与对照组相比，治疗组能明显抑制肝肿瘤体积的增长（P〈0．01）。结论在ACI大鼠肝细胞癌模型，采用肝动脉化疗栓塞术结合肝动脉灌注血管生成抑制剂TNP-470的治疗方法可明显抑制肝肿瘤体积的生长。     

碘油磁液经肝动脉栓塞热疗兔VX2肝癌的实验研究

目的 探讨碘油磁液经肝动脉栓塞热疗术对荷瘤兔肝、肾功能的影响及其疗效.方法 VX2兔肝癌模型32只,数字表法随机等分成4组:碘油磁液栓塞热疗组(A组)、碘油磁液栓塞组(B组)、单纯碘油栓塞组(C组)、对照组(D组).A、B两组实验兔经肝动脉注入碘油磁液0.5～0.8 ml栓塞病灶,C组实验兔仅用碘油栓塞.栓塞后仅A组实验兔在交变磁场下诱导热疗.实验兔分别于栓塞或栓塞热疗术前1 d和术后1、7、14 d经耳缘静脉取血,行肝、肾功能检查.肝功能指标选取丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST),肾功能指标选取血清尿素氮(BUN)和血清肌酐(Cr).栓塞术前、术后即刻、术后7、14 d行CT扫描并随访,观察碘油磁液或碘油在瘤内沉积分布情况并分别测量肿瘤大小.术后14 d处死实验兔,完整切取肝脏、脾、肾和肺,作病理检查.各组测量数据以重复测量方差分析进行统计学分析.结果 A组实验兔术前1 d和术后1、7、14 d ALT分别为(43.9±19.0)、(795.1±327.1)、(67.0±9.3)、(41.9±10.8)U/L,AST分别为(50.2±13.6)、(1011.2±655.9)、(62.4±24.1)、(51.6±7.9)U/L;B组ALT分别为(45.0±19.1)、(580.8±160.4)、(67.2±31.0)、(47.6±7.8)U/L,AST分另U为(52.9±20.3)、(735.2±186.1)、(57.9±24.8)、(50.9±9.8)U/L;C组ALT分别为(47.4±14.6)、(558.5±167.8)、(63.5±21.9)、(48.0.±9.3)U/L,AST分别为(51.8±9.5)、(752.5±112.0)、(56.5 ±20.6)、(51.4±8.6)U/L;术后1 dALT和AST较术前和D组明显升高(P值均<0.01),术后7、14 d所测值与术前比较差异无统计学意义.栓塞术前后4组实验兔BUN和Cr值组间和组内比较,差异均无统计学意义.术后7 d CT示A、B、C 3组瘤区碘油磁液和碘油沉积分布与栓塞或栓塞热疗前相比无明显变化.术后14 d CT示A组瘤区碘油磁液沉积更集中、密实,B、C两组共5例肿瘤瘤周碘油磁液或碘油移位、部分消失.术后14 d,A组肿瘤体积[(6.1±0.6)cm~3]较术前[(7.8±1.4)cm~3]平均缩小约21.7%(F=17.56,P<0.01),而术前B、C两组肿瘤体积分别为(7.9±1.1)、(7.8±0.9)cm~3,治疗后14 d分别为(9.1±0.8)、(9.3±1.0)cm~3,较术前平均增大16.2%、18.9%(F值分别为25.23、55.50,P值均<0.01).病理检查,栓塞14 d后,A组肿瘤坏死均达80%以上,B、C两组肿瘤坏死约30%~50%.结论 碘油磁液对兔VX2肝癌行选择性肝动脉栓塞热疗是安全有效的,具有可行性.     

肝组织坏死和凋亡MRI鉴别诊断的实验研究

目的:通过对大鼠肝右叶坏死和凋亡的动物模型进行磁共振T1WI、T2WI、DWI和ADC等检查,观察形态和信号变化特点,探索MRI新技术对肝脏组织坏死或凋亡的鉴别诊断能力。材料和方法:78只大白鼠随机分成13组,每组6只,A1、B1、C1、D1、E1、F1六组动物同时结扎肝动脉右支和门静脉右支。A2、B2、C2、D2、E2、F2六组动物单独结扎门静脉右支,另6只大鼠为假手术对照组。各组实验大鼠于手术后3h、12h、24h、3d、7d、14d进行MRI检查,然后处死动物并取得肝脏标本,进行HE染色、TUNEL染色、透视电镜等病理检查。每例均进行常规MRI和DWI、ADC图成像。结果:动物麻醉和结扎手术成功率93.8%。右侧肝动脉与门静脉分支均结扎后,病理显示肝右叶发生凝固性坏死。单独右侧门静脉分支结扎后,3h即出现凋亡细胞,24h达高峰。坏死肝组织在DWI上早期即呈高信号,中晚期呈长T1和中等T2表现。单纯门静脉右支结扎的A2、B2、C2组大鼠肝右叶在T1WI上呈特征性较高信号,T2WI呈等信号,72h后出现斑点状高信号,DWI上早期呈信号减低改变,后期呈等信号或小片状高信号。结论:肝组织细胞坏死和凋亡在T1WI和T2WI上有明显的信号差异表现。结合DWI和ADC检查表现,可以区分肝脏细胞发生坏死或凋亡的不同病理改变。     

门静脉分支栓塞联合肝细胞生长因子应用对肝硬化肝脏再生的实验研究

目的:探讨兔门静脉栓塞(portal vein embolization,PVE)联合肝细胞生长因子(hepatocyte growth factor,HGF)应用对肝纤维化模型肝脏再生的作用。方法:20只肝纤维化新西兰大白兔模型,随机分为两组(HGF组,对照组),每组各10只。两组动物均以碘化油无水乙醇乳剂施行保留右下叶门静脉的门静脉栓塞。HGF组在PVE后经门静脉及术后3天经腹腔注射HGF,对照组在PVE后经门静脉及术后3天经腹腔注射生理盐水。PVE后连续随访4-5周,定期复查腹部CT检查,计算肝右下叶增生率。动物处死后行肝组织病理检查,所获数据行统计学分析处理。结果:两组动物PVE均获成功,处死前血管造影显示门静脉主干及部分分支再通。腹部CT检查显示,HGF组肝右下叶占全肝比率增长15.97±2.54%,对照组肝右下叶占全肝比率增长7.65±2.48%,两组间的增生率具有统计学上的显著性差异。结论:PVE联合门静脉及腹腔内注射HGF能明显促进未栓塞肝叶再生。     

大鼠门静脉右支介入栓塞的实验研究

目的 研究各种栓塞剂对门静脉分支栓塞后肝脏在形态学上的变化和对肝功能的影响。方法 对45只大鼠为实验对象,除5只留作对照组外,40只分成4组,用4种不同的栓塞材料进行门静脉右支栓塞,术后第14天和第21天分别处死每组5只动物,剖腹观察肝脏各叶的形态变化,然后分离法对各组结果进行统计学分析。结果 栓塞后见肝右叶明显变苍白,表面呈斑纹状,各组之间差异不大,在术后14d及21d,第1、2、3组的大鼠肝右叶均见明显变小,表面见大小不等淡黄色小瘢痕,第4组小鼠的肝脏形态变化不明显。统计学分析显示,碘油酒精2：1的高浓度混合液的栓塞作用明显好于碘酒酒精4：1混合物（P＜0．05）,明胶海绵粉的栓塞作用也十分明显,效果与碘油酒精4：1混合物相仿（P＞0．05）,但明显好于明胶海绵小块（P＜0．05）。结论 本实验结果提示,门静脉分支的栓塞既可引起该肝叶的萎缩,又可促使其他肝叶的代偿性增生,门静脉分支塞是安全有效的,但不同的栓塞剂或栓塞材料有不同的栓塞效果,其中碘油酒精2：1混合物效果最好。     

肝右叶前、后段原发性肝癌TACE后VEGF及CD34的表达水平

目的探讨肝右叶后段原发性肝癌病灶较前段易发生侧支循环的可能机制。方法取经导管肝动脉化疗栓塞术(TACE)后手术切除的肝细胞癌组织标本57份和未经任何治疗直接手术切除的肝细胞癌组织标本40份(单纯手术组),按影像学检查符合筛选标准3l例分两组。A组:13例,病灶位于肝右叶前段(V、Ⅷ段);B组:18例,病灶位于肝右后段(Ⅵ、Ⅶ段)。采用免疫组化联酶卵白素染色(SP)法,检测残癌组织血管内皮生长因子(VEGF)表达水平和微血管密度[MVD(CD34标记)]。结果 TACE组VEGF蛋白阳性表达率显著高于单纯手术组,分别为86.0%和65.0%,差异有统计学意义(p=0.015);TACE组MVD值较单纯手术组显著增高,分别为79.37±15.36和43.23±14.98,差异有统计学意义(p=0.000)。TACE组VEGF蛋白阳性表达与MVD值变化呈正相关(r_s=0.493,P<0.01)。B组病灶周围MVD略高于A组,分别为80.44±13.74和78.08±15.33,但差异无统计学意义(P>0.05)。结论 TACE诱导的新生血管生成理论可能并非肝右叶前后段病灶侧支循环建立差异的机制。     

纳米超顺磁性碘油肝动脉栓塞热疗VX2兔肝肿瘤的实验研究

目的 观察纳米超顺磁性碘油经肝动脉栓塞热疗对实验性肝肿瘤的疗效。方法 VX2兔肝癌模型24只，分成纳米超顺磁性碘油栓塞热疗组（A组）、碘油栓塞组（B组）、纳米超顺磁性碘油栓塞组（C组）、对照组（D组），每组6只。VX2肝肿瘤模型接种后14d进行治疗，3个治疗组VX2兔均采用3F SP微导管经右股动脉插管，选择性进入肝固有动脉，注射10％的纳米超顺磁性碘油0．5ml（A组和C组）或超液化碘油0．5ml（B组）。注射后3d，A组和B组动物置于裂隙式交变磁场中热疗30min。而C组和D组动物不进行磁诱导热疗。各组兔于治疗前CT检查，测量肿瘤大小，栓塞后14d再次作CT检查，检查结束后处死，取肝脏、脾脏、肾脏、心肌、肺组织作病理组织学检查，并直接测量兔肝脏肿瘤大小。结果 所有兔均存活至处死，生化检查显示各组栓塞前和栓塞后14d的肝肾功能无明显变化。治疗后14d，纳米超顺磁性碘油栓塞热疗组兔肝肿瘤平均缩小了8．09％，碘化油栓塞组和纳米超顺磁性碘油栓塞组肿瘤分别增长了9．72％和13．00％，A组分别与B、c组对比，差异有统计学意义（P〈0．05）。而对照组肿瘤增长了57．50％，与其他组对比，差异有统计学意义（P〈0．01）。病理组织学检查，各治疗组肿瘤均有明显的坏死，肿瘤实质内几乎无肿瘤细胞残留，其中栓塞热疗组最明显。结论 动物实验表明，纳米超顺磁性碘油栓塞热疗具有明显的抑制肿瘤生长的效果，有必要对其进一步研究开发，使得这一技术早日应用于临床。     

Hepatocellular necrosis, apoptosis, and proliferation after transcatheter arterial embolization or chemoembolization in a standardized rabbit model

Purpose

To evaluate the effect of transcatheter arterial chemoembolization versus transcatheter arterial embolization on hepatocellular damage, apoptosis, proliferation, and proinflammatory response in a rabbit VX2 tumor model.

Materials and Methods

Rabbits implanted with VX2 tumors in left liver lobes were randomly divided into three groups: a control group (n = 9) that underwent infusion of distilled water into the left hepatic artery, an embolization group (n = 15) that underwent left hepatic artery embolization with polyvinyl alcohol (PVA) particles, and a chemoembolization group (n = 15) that underwent left hepatic artery infusion of a mixture of 10-hydroxycamptothecin and iodized oil followed by PVA embolization. Serum and liver samples were collected at 6 hours, 3 days, and 7 days postoperatively. Liver damage was measured by liver function tests and histologic analysis. Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling were performed to quantify proliferating and apoptotic cells. Serum tumor necrosis factor (TNF)–α levels were measured to assess proinflammatory response.

Results

Compared with embolization, chemoembolization caused liver injury with a greater increase in serum alanine aminotransferase and aspartate aminotransferase levels on days 3 and 7; histologic analysis showed increased hepatic necrosis in adjacent liver tissue beginning at day 3 and increased serum levels of TNF-α at 6 hours. By contrast, chemoembolization resulted in a slower increase in hepatocyte proliferation. Additionally, increased apoptotic hepatocytes were observed after embolization and chemoembolization.

Conclusions

In contrast to embolization, nonsuperselective transcatheter arterial chemoembolization increased hepatocellular damage and stimulated systemic proinflammatory cytokine release, but inhibited hepatocyte proliferation.     

Use of Double-Occlusion Balloon Catheter: Preoperative Portal Vein Embolization for Induction of Future Remnant Liver Hypertrophy

Purpose: To evaluate the efficacy and safety of using double-occlusion balloon catheters in preoperative portal vein embolization (PVE) to induce future remnant liver hypertrophy. Materials and Methods: PVE was achieved with gelatin sponges by using double-occlusion balloon catheter in seventeen patients with hepatobiliary malignant tumors. The ipsilateral approach was used in thirteen patients and the contralateral approach in four patients due to large size of tumor in the right hepatic lobe. Surgery was performed in 15 patients, 14–27 days (mean, 21.9 days) after PVE. Computed tomographic liver volumetric studies were performed before embolization and before surgery. The changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), prothrombin time (PT), and total bilirubin levels before and after the PVE were evaluated. Complications were evaluated after PVE. Results: PVE using double-occlusion balloon catheter was successful in all cases, irrespective of approach technique. The future remnant liver (FRL) volumes were 251–920 cm³ (mean, 437 cm³) before PVE and 281–1042 cm³ (mean, 555 cm³) after PVE. The mean increase in the volume of the FRL was 28.6%; this represented 37% of the preresection volume of the liver. Clinical and biologic tolerance of PVE was mandatory. There were no complications. Conclusions: PVE using the double-occlusion balloon catheter is safe and well-tolerated and can be performed technically with ease. This hypertrophy allows hepatectomy to be performed safely when the FRL volume is initially insufficient in patients with hepatobiliary tumors.     

经皮门静脉栓塞治疗肝癌的临床应用

目的探讨经皮选择性门静脉右支栓塞(PVE)在肝癌治疗中的应用价值。方法12例无手术切除指征的中晚期肝癌患者,在电视透视引导下经导管行经皮穿肝或穿脾行PVE。栓塞前、后用CT测量左侧肝叶的体积,并测量栓塞前后的门静脉压力、肝功能。结果12例患者均成功行经皮PVE,栓塞术后左肝叶代偿增生明显,其中3例PVE后顺利实行右肝切除术。PVE后未出现门静脉高压,肝功能损害轻,均未发现并发症。结论经皮选择性PVE能诱导非栓塞侧肝叶代偿性增生及栓塞侧肝叶萎缩,增加肿瘤手术切除机会,提高手术切除的安全性,对于无法手术切除的肝癌患者重新获得手术切除的机会,具有潜在的临床应用价值。     

经肝动脉化疗栓塞术联合重组人血管内皮抑制素对兔VX_2肝移植瘤生长及转移的影响

目的 观察重组人血管内皮抑制素(rh-Endostatin)联合经肝动脉化疗栓塞术(TACE)对兔VX_2肝移植瘤生长及转移的影响. 方法 30只家兔肝内肿瘤种植后2周,随机分为3组,每组10只:生理盐水灌注组(对照组)、TACE组及rh-Endostatin联合TACE组.治疗后5周,所有动物均处死,取出肝脏及双肺标本观察.测量动物体重、肝脏的重量、计算肝脏指数(HI),计算肝移植瘤的体积、坏死面积,观察肝内、双肺肿瘤转移的发生率.结果 肿瘤植入后5周,各处理组动物体重均有明显的下降,肝脏重量增加,计算的肝指数各组分别为10.2±2.8、8.5±6.1、6.2±4.4;肿瘤体积各组分别为(36.2±3.4) cm~3、(23.6±4.5) cm~3、(10.9±5.1) cm~3,各组间差异有统计学意义.平均坏死率分别为(52.0±2.3)%、(63.6±3.5)%、(78.6±4.8)%,各组间差异有统计学意义.双肺转移结节的数目各组分别为50.3±31.3、53.6±35.1、16.8±18.4;转移结节的直径各组分别为(3.6±1.4) mm、(3.8±0.6) mm、(1.2±0.6) mm.rh-Endostatin联合TACE组与其它各组相比差异有统计学意义(P <0.01).肝内转移率、转移结节数目、rh-Endostatin联合TACE组与其它各组相比差异有明显的统计学意义( P<0.01). 结论 rh-Endostatin联合TACE治疗抑制肝移植瘤的生长,并对其肺转移也有抑制作用.     

Ipsilateral percutaneous transhepatic portal vein embolization with gelatin sponge particles and coils in preparation for extended right hepatectomy for hilar cholangiocarcinoma

PURPOSE: To evaluate the effectiveness and safety of ipsilateral percutaneous transhepatic portal vein embolization (PTPVE) with gelatin sponge particles and coils to induce lobar hypertrophy in patients with hilar cholangiocarcinoma in preparation for extended right hepatectomy. MATERIALS AND METHODS: Between 1999 and 2004, PTPVE was performed in 22 patients with hilar cholangiocarcinoma (mean age, 67 years; range, 57-77 y; 16 men and six women). Percutaneous puncture of the right portal vein was performed under ultrasound guidance. A reverse-curve catheter was used for right portal vein embolization. Coils were used to occlude second-order branches. The future liver remnant volume was assessed by comparing computed tomographic scans before and 14-24 days after PTPVE. RESULTS: PTPVE was technically successful in all cases. The average increase in ratio of future liver remnant volume to total liver volume was 8.6%. Liver function tests after PTPVE but before surgery showed no significant changes. Nineteen patients underwent hepatic resection without liver failure. In three patients, tumors could not be removed because of detection of extrahepatic disease. One patient who underwent successful hepatic resection had an abscess in the removed right lobe. CONCLUSION: Ipsilateral PTPVE with gelatin sponge and coils appears to be effective and safe for extended right hepatectomy for hilar cholangiocarcinoma.     

低浓度α-氰基丙烯酸正丁酯栓塞兔VX2肝脏肿瘤的实验研究

目的 观察低浓度α-氰基丙烯酸正丁酯(NBCA)经肝动脉栓塞兔肝脏肿瘤的可行性、安全性和有效性.方法 24只实验兔,开腹在肝脏左叶种植瘤细胞建立VX2肝脏肿瘤模型,建模后14 d CT扫描测量肿瘤大小,并用数字表法随机等分为3组,后通过肝动脉对肿瘤进行栓塞.A组为空白对照组,B组为超液化碘油组,C组为2.5% NBCA组.肝脏损害通过检测血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)评价.栓塞术后第7天再次通过CT扫描测量肿瘤体积,肿瘤生长比率(术后7 d肿瘤体积与术前肿瘤体积之比);并于栓塞治疗后记录各组实验兔的生存时间.对ALT和AST采用重复测量方差分析,肿瘤生长比率和生存时间采用单因素方差分析比较.结果 所有动物模型均成功建立并插管治疗.A、B、C各组实验兔在栓塞前后不同时间ALT和AST均值的差异有统计学意义(ALT的 F值分别为10.508、16.443、19.828,AST 的F值分别为23.696、23.334、15.594,P值均＜0.05).栓塞治疗后第4天A、B、C组ALT水平分别为(49.4±13.5)、(115.2±48.8)、(124.7±49.4)U/L,AST水平分别为(52.3±12.0)、(128.3±50.1)、(137.0±66.9)U/L,B组和C组血清ALT和AST水平均较A组高(P值均＜0.05).B、C组术后第4天ALT、AST均较术前明显升高(P值均＜0.05).各组ALT和AST术后第7天和术前相比,差异均无统计学意义.术后第7天肝脏肿瘤生长比率在3组之间差异有统计学意义(F=110.865,P=0.000);C 组的肿瘤生长比率为(0.839±0.144)%,显著低于A 组的(2.978±0.547)%(P=0.000),与B组的(0.871±0.073)%相比差异无统计学意义(P=0.845).栓塞治疗后C组生存期为(38.9±4.0) d,明显长于A组的(32.1±3.1) d(P=0.006);与B组的(36.9±4.8)d相比差异无统计学意义(P=0.366).结论 经肝动脉栓塞低浓度NBCA治疗兔VX2肝脏肿瘤是一种可行的、安全的治疗方法,为治疗肝脏肿瘤提供一种新的选择,可能有潜在的临床推广价值.

Abstract：

Objective To investigate the feasibility, safety and efficacy of transarterial embolization with low concentration of n-butyl cyanoacrylate(NBCA) in rabbit VX2 liver tumor models. MethodsTwenty-four rabbits were implanted with VX2 hepatic tumors into the left hepatic lobes, and were scanned with CT to measure the volume of the tumor after 14 days. They were randomly divided into three groups with 8 rabbits assigned to each group. Transarterial embolization was conducted with physiological saline in control group A, with pure Lipiodol in group B, with 2.5% NBCA in group C. Hepatic toxicity was evaluated by blood biochemical analysis of the plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). One week later, the volumes of the tumors were measured by CT again. Tumor growth rate was the ratio of tumor's volume at 7th day after embolization to the tumors' volume before embolization. The survival periods of the rabbits of the three groups after treatment were also recorded. The data of ALT and AST mean values from each group were analyzed with repeated measurement analysis of variance (ANOVA). Tumor growth rates and survival periods were analyzed by using one-way ANOVA. Results All animal models were successfully established and underwent interventional catheterization. Both ALT and AST mean values of the rabbits in group A, B and C at each time point before and after embolization were significantly different (ALT F=10.508, 16.443, 19.828, respectively; AST F=23.696, 23.334, 15.594, respectively)(P＜0.05). ALT in group A, B, C were (49.4±13.5), (115.2±48.8), (124.7±49.4)U/L, while AST in group A, B, C were (52.3±12.0), (128.3±50.1), (137.0±66.9)U/L 4 days after embolization. The ALT and AST mean values were significantly elevated 4 days after embolization in group B and group C compared with those before embolization and those of group A 4 days after treatment(P＜0.05). However, the ALT and AST mean values showed no statistically significant difference in all the groups before embolization and 7 days after embolization. On the other hand, the growth rates of the tumors differed significantly among the three groups(F=110.865, P=0.000). The group C showed significantly lower tumor growth rate (0.839±0.144)% than the group A(2.978±0.547)%(P=0.000), but no significantly different tumor growth rate compared with group B(0.871±0.0725)%( P=0.845). Consequently, the survival period of the animals in group C(38.9±4.0) days was significantly longer than that in group A(32.1±3.1)days (P=0.006), while it was not significantly different from that in group B(36.9±4.8)days(P=0.366). ConclusionsTransarterial embolization with low concentration of NBCA was feasible and safe. It could be a new option of treatment for HCC and might have potential further clinical value.     

Response to percutaneous transhepatic portal embolization: new proposed parameters by 99mTc-GSA SPECT and their usefulness in prognostic estimation after hepatectomy.

Accumulation of 99mTc-galactosyl human serum albumin (GSA) in the liver correlates well with the parameters of hepatic function tests. We performed 99mTC-GSA SPECT before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe before extensive hepatic resection and analyzed the responses of new proposed parameters in the future remnant lobe that showed hypertrophy. The aim of this study was to evaluate the usefulness of these parameters in prognostic estimation after hepatectomy. METHODS: We studied 10 patients with cholangiocarcinoma and 1 patient with metastatic liver tumor from sigmoid colon cancer. 99mTc-GSA SPECT was performed immediately before and 2 wk after PTPE. We analyzed the responses of the liver uptake ratio (LUR), functional volume (FV), and liver uptake density (LUD) in the future remnant lobe and evaluated their relationship with the prognosis after subsequent hepatic resection. RESULTS: LUR and FV increased slightly but were not associated with the prognosis after hepatic resection. LUD increased significantly after PTPE in the group showing a good outcome after hepatic resection but decreased after PTPE in the group showing a poor outcome (post-PTPE LUD, 0.064+/-0.017%/cm3 versus 0.035+/-0.006%/ cm3, P<0.05; response rate, 22.2%+/-11.9% versus -8.9%+/-17.6%, P<0.01). CONCLUSION: Responses of LUD to PTPE before hepatic resection in the future remnant lobe represent changes in asialoglycoprotein receptor activity per hepatocyte and predict responses to subsequent hepatic resection. LUD may be an important parameter for determining the outcome after hepatic resection.     

Portal vein ligation is as effective as sequential portal vein and hepatic artery ligation in inducing contralateral liver hypertrophy in a rat model

PURPOSE: Dual embolization of the hepatic artery and portal vein (PV) has been proposed to enhance contralateral liver regeneration before resection. The aim of this study was to evaluate the effect of PV ligation compared with simultaneous or sequential dual ligation on regeneration, proinflammatory response, and liver damage. MATERIALS AND METHODS: Single hepatic artery ligation (HAL), PV ligation (70%), or dual ligation of the hepatic artery and PV (70%) simultaneously or sequentially within a 48-hour interval was performed in a rat model. Liver regeneration, proinflammatory mediators, hepatocellular synthetic function and injury, histopathology, and apoptosis were assessed at a maximum of 14 days after surgery. RESULTS: Sequential dual ligation resulted in a faster increase in hepatocyte proliferation at 24 hours without additional increase in liver mass compared with PV ligation after 14 days. Both dual ligations significantly increased proinflammatory response in plasma and in the regenerating liver compared with PV ligation alone. Fourteen days after PV ligation, the hepatic parenchyma was completely restored, whereas fibronecrosis was seen in the sequentially dual-ligated groups and complete necrosis was seen in simultaneously ligated groups. Increased apoptosis in the regenerating liver and prolonged hepatic dysfunction were observed after both dual ligations. CONCLUSIONS: PV ligation is as effective as dual ligation in inducing liver regeneration. No additional benefit of arterial ligation was observed.     

肝动脉栓塞后肝功能改变及病理基础

目的：探讨单纯全肝动脉末梢栓塞对正常肝组织的影响。方法：用５０～１００ｕｍ明胶海棉微球末梢栓塞１０条犬的全肝动脉，栓后１、３、７、１４和２８ｄ，分别处死１或２条犬，观察组织病理改变，处死前抽血化验肝功能，动态观察肝功能的变化及相应的病理改变。结果：栓后１ｄＧＰＴ、ＧＯＴ及ＡＫＰ升高，超过正常值范围，肝细胞变性、坏死。栓后３ｄＧＰＴ、ＧＯＴ升至高峰，肝细胞变性严重，坏死明显。然后下降，２周后恢复。结论：肝动脉栓塞对肝细胞的急性损害是暂时的