兔肝癌模型的改良接种及其DSA影像分析

目的建立可供实验研究稳定的兔Vx2移植性肝癌模型,探讨不同植瘤方式的成功率,并分析该肿瘤的DSA影像特征。方法60只新西兰白兔随机分3组,每组20只。将Vx2瘤细胞(5×107个)经肝动脉或经肝包膜分别接种于2组兔的肝左叶,建立对照肝癌模型。第3组经肝包膜植入瘤组织块(约含106～108个瘤细胞)建立改良肝癌模型。观察:①不同组植瘤的成活率。②改良Vx2移植性肝癌的DSA影像特征。结果3组植瘤成活率分别为7/20、10/20、19/20,改良组植瘤成活率最高,差异有统计学意义(P<0.05)。DSA影像示该移植性肝癌具有丰富的血供。结论成功建立了兔Vx2移植性肝癌改良模型,瘤组织块种植方式成功率明显高于动脉途径和细胞液注射方式,为肝癌介入治疗的基础及临床研究提供了成熟的大型实验动物模型。     

兔Vx-2移植性肝癌模型的建立及其影像学表现

目的　用 3种不同植瘤方式建立稳定的兔Vx 2移植性肝癌模型 ,分析移植性肝肿瘤的DSA影像特征。方法　 6 0只新西兰白兔随机分成 3组 ,每组 2 0只。第 1组 ,将Vx 2瘤细胞 (约 5× 10 7个 )经肝动脉灌注入兔的肝脏 ;第 2组 ,将Vx 2瘤细胞 (约 5× 10 7个 )经剖腹途径接种于兔的肝左叶 ;第3组 ,将瘤组织块 (约含 10 6～ 10 8个瘤细胞 )经剖腹途径植入兔肝左叶。之后 ,对 3组兔比较观察 :1.不同方式植瘤的成活率 ;2 .肝内肿瘤体积变化和肿瘤生长率 ;3.大体及镜下 (光镜和电镜 )瘤组织形态特征 ;4 .成熟模型的DSA表现。结果　 1.3组植瘤成活率分别为 7/ 2 0、10 / 2 0、19/ 2 0 ,第 3组植瘤成活率最高 (P <0 .0 5 ) ,其瘤体呈指数性生长 ;2 .病理学及CT表明该瘤在肝组织中呈浸润式生长 ,其性状与移植于兔其它部位的Vx 2鳞状细胞癌特征相似 ;3.DSA影像示移植性肝肿瘤具有丰富的血供。结论　成功建立了兔Vx 2移植性肝癌模型 ,瘤组织块种植方式成功率明显高于其他两种方法 ,为肝癌介入治疗的实验研究提供了可靠的大型动物模型     

兔肝VX2移植癌模型的病理学和影像学表现

目的　采用三种不同植瘤方式建立稳定的介入实验研究兔VX2 移植性肝癌模型。方法　 6 0只新西兰白兔随机分 3组 ,每组 2 0只。第一组 ,将VX2 瘤细胞 (约 5× 10 7个 )经肝动脉灌注入兔的肝脏 ;第二组 ,将VX2 瘤细胞 (约 5× 10 7个 )经剖腹途径接种于兔的肝左叶 ;第 3组 ,将瘤组织块 (约含 10 6～ 10 8个瘤细胞 )经剖腹途径植入兔肝左叶。对三组进行比较观察 :①不同方式植瘤的成活率 ;②肝内肿瘤体积变化和肿瘤生长率 ;③大体及镜下 (光镜和电镜 )瘤组织形态特征 ;④成熟模型的DSA表现。结果　①三组植瘤成活率分别为 7/ 2 0、10 / 2 0、19/ 2 0 ,第三组植瘤成活率最高 (Ρ <0 .0 5 ) ,其瘤体呈指数性生长 ;②病理学及CT表明该瘤在肝组织中呈浸润式生长 ,其性状与移植于兔其它部位的VX2 鳞状细胞癌特征相似 ;③DSA影像示移植性肝肿瘤具有丰富的血供。结论　成功建立了兔VX2 移植性肝癌模型 ,瘤组织块种植方式成功率明显高于其他两种方法 ,为肝癌介入治疗的实验研究提供了可靠的大型动物模型     

兔VX2肝癌模型的移植方式及生长特性的研究

目的　探讨不同植瘤方式建立兔VX2 肝癌模型的成功率 ,并分析该肿瘤的生长特性。方法　 60只新西兰白兔随机分 3组 ,每组 2 0只。将VX2 瘤细胞 (5× 10 7个 )经肝动脉或经肝包膜分别接种于 2组兔的肝左叶 ,第 3组经肝包膜植入瘤组织块 (约含 10 6 ～ 10 8个瘤细胞 )建立肝癌模型。观察 :①不同组植瘤的成活率。②肿瘤 7d、10d、14d、17d、2 1d时的体积 (B超测 ) ,并计算肿瘤生长率。③大体及镜下 (光镜和电镜 )瘤组织形态特征。④VX2 移植性肝癌的DSA影像特征。结果　 3组植瘤成活率分别为 7/ 2 0、10 / 2 0、19/ 2 0 ,第 3组瘤块植瘤成活率最高 (Ρ <0 .0 5 ) ,瘤体呈指数性生长 ,组织病理及电镜表明该瘤在肝组织中浸润式生长 ,其性状与VX2 鳞状细胞癌特征相似。DSA影像示该移植性肝癌具有丰富的血供。结论　瘤块种植是建立兔肝癌模型的首选方式 ,该模型是肝癌的基础及临床的理想动物模型     

改良的经大鼠胃十二指肠动脉逆行肝动脉插管实验研究

目的 探讨改良的经大鼠胃十二指肠动脉逆行肝动脉插管方法的可行性及价值.方法 Wistar大鼠120只随机分为4组,每组30只.A组、B组为预实验组,分别采用改良法与传统法作肝动脉插管.C组、D组以穿刺种植法构建大鼠肝癌模型,分别以改良法与传统法插管作肝动脉造影及经导管动脉化疗栓塞(TACE)治疗,比较两种插管法成功率、大鼠肝癌建模成功率,TACE治疗前后肿瘤体积变化、死亡率、死亡原因.结果 A、B组肝动脉插管成功率分别为90.0％(27/30)、63.3％(19/30),差异有统计学意义(x2=4.565,P=0.033).C、D组大鼠肝癌模型均成功构建,肿瘤种植率为100％;插管成功率分别为93.3％(28/30)、70.0％(21/30),差异有统计学意义(x2=4.007,P=0.045);C、D组TACE治疗前后平均肿瘤体积差异无统计学意义(P＞0.05),但D组大鼠术后10 d死亡率较C组高(42.86％对10.71％,x2=5.079,P=0.024),死亡原因可能为血管受损、肝脏损伤及麻醉意外等.结论 改良的经胃十二指肠动脉逆行肝动脉插管方法简单易掌握、成功率高,TACE术后死亡率低、并发症少,值得继续深入研究和在相关实验中尝试.     

实验兔VX2肝肿瘤模型制作及动脉插管技术探讨

目的介绍应用VX2细胞株制作兔移植性肝癌模型,并探讨插管技术的应用。方法实验对象为新西兰大白兔(n=80),VX2瘤块组织接种于肝脏,接种后2~3周实验组(n=51)行剖腹直视下肝动脉直接楔入插管,并作DSA造影。对照组1和2(各10只)分别采取经股动脉-肝动脉插管和开腹经胃十二指肠动脉逆行插管方法对比研究。结果实验组插管成功率为98%(50/51),其中88%(45/51)完成超选择栓塞;对照组1和2的插管成功率分别为30%和40%,只有0/10和4/10完成超选择栓塞。结论移植性兔VX2肝癌是介入治疗实验研究较为理想的动物模型,综合影像评价有利于实验动物的筛选。采用肝动脉细针直接穿刺楔入法插管成功率高,可完成超选择栓塞,是值得推广的实验方法。     

暂时阻断肝静脉行动脉化疗栓塞治疗栓塞治疗大鼠移植性肝肿瘤

目的　观察暂时阻断肝静脉行肝动脉化疗栓塞术 (TACE -THVO)的疗效 ,对比阿霉素碘油 ,无水乙醇碘油化疗栓塞剂对移植瘤的作用。方法　建立 75只肝内移植性肝癌大鼠模型 ,随机将其分为 5组 ,设立对照 ,暂时阻断肝静脉后 ,用 2种不同的化疗药物碘油栓塞剂行肝动脉化疗栓塞术。 1周后 ,处死实验大鼠 ,观察大体标本与光镜下苏木素 -伊红染色病理切片的移植瘤缩小和坏死状况 ;苏丹Ⅲ染色切片光镜及扫描电镜观察药物碘油栓塞剂沉积部位与瘤细胞超微结构改变。结果　经肝动脉化疗栓塞治疗各组瘤灶体积均缩小。TACE -THVO试验组的肿瘤生长率小于未阻断肝静脉行肝动脉化疗栓塞的对照组 ;试验组肿瘤坏死范围和门静脉碘油沉积例数高于对照组 ;应用阿霉素碘油栓塞剂行肝动脉化疗栓塞术组的肿瘤坏死范围小于用无水乙醇碘油栓塞剂组 ;试验组中肿瘤细胞粗面内质网出现空泡变性 ,瘤细胞核内出现脂滴样物质 ,细胞核崩解。结论　用无水乙醇碘油做化疗栓塞剂经肝动脉栓塞移植性肝癌 ,其肿瘤的坏死范围高于用阿霉素碘油栓塞剂 ,TACE -THVO有可能成为治疗肝癌的一种有效方法。     

兔VX2肝癌模型建立与经兔股动脉微导管超选择性肝左动脉插管技术的探讨

目的 探讨开腹肝穿刺法建立兔VX2肝癌模型以及经兔股动脉微导管肝左动脉超选择性插管的可行性及技术特点.方法 健康新西兰大白兔40只,开腹以16G腰椎穿刺针将VX2瘤组织块种植到兔肝左内叶.2周后行螺旋CT扫描,然后在兔一侧腹股沟区行股动脉鞘管置入,在DSA引导下应用微导管行腹腔动脉造影,分析兔腹腔动脉主要分支走行及肝脏...     

阿霉素毫微粒肝动脉灌注后在荷肝肿瘤鼠体内的分布研究

目的 检测阿霉素毫微粒（ＮＡＤＭ）与游离阿霉素（ＦＡＤＭ）经肝动脉灌注后荷肝肿瘤鼠体内的药物分布，并比较其差异。方法 ＳＤ纯系大鼠３０只，建立Ｗ２５６移植性肝癌模型并随机分为两组，每组各１５只动物，经肝动脉以２ｍｇ／ｋｇ药物剂量分别注入ＮＡＤＭ与ＦＡＤＭ，每组于给药后１小时，５小时，１５小时各处死５只大鼠，分别提取血浆，肝，心，脾，肺，肾，肝肿瘤样品，采用反相高效液相色谱荧光检测法（ＲＰ－ＨＰＬＣ     

供影像学诊断实验的大鼠移植肝癌模型的可行性研究

研究大鼠移植性肝癌的血供情况，以此来确定该模型能否作为影像诊断技术进行微小肝癌检出敏感性研究的理想实验动物。大鼠移植性肝癌模型的仲瘤由肝动脉供血为主，门静脉几乎不参与肿瘤供血或仅在肿瘤边缘部分参与肿瘤营养，其类似于人肝细胞癌血供情况。故作者认为该模型可作为影像诊断技术进行微小肝癌检出敏感性研究的理想实验动物模型。     

Transarterial ethanol ablation of cirrhotic liver with lipiodol-ethanol mixture: safety and efficacy study in rats

PURPOSE: The intra-arterial administration of lipiodol-ethanol mixture (LEM, mixed in 4:1 by volume) through the hepatic artery is known to produce dual hepatic-arterial and portal-venous embolization that could be a potent treatment of hepatocellular carcinoma. The aim of this animal experiment was to study the effectiveness and safety of such transarterial ethanol ablation in cirrhotic livers. METHODS: The study model consisted of a control group of 6 normal rats and a study group of 6 cirrhotic rats. LEM was infused intra-arterially into the right lobe of all 12 rats after selective catheterization under microscopic observation. LEM distribution within the hepatic vasculature, liver function tests, change in liver volume, and histology of the embolized lobe were studied. RESULTS: The radiographs showed peripheral distribution of LEM within the portal venule in the right lobe of all rats. There was a marked reduction in the volume of right lobe 14 days after LEM, with an average reduction of 63.4 +/- 16.9% and 59.4 +/- 20.6% observed in the control group and study group, respectively. The difference between the 2 groups was not statistically significant. Before LEM treatment, there was a difference between the 2 groups (P = 0.002) regarding the plasma level of albumin and bilirubin, indicating that the blood test was sensitive enough to differentiate the liver function status between the normal rats and cirrhotic rats. On day 14, there was no difference between the 2 groups in plasma albumin, bilirubin, and ALT levels (P = 0.065, 0.818, 0.589), indicating almost equal extent of hepatic reaction towards LEM administration in normal and cirrhotic rats. On day 14, histologic study showed complete vascular infarction in 90% to 100% of the right lobe in both groups. CONCLUSION: Intraarterial ethanol ablation with LEM is equally effective in causing infarction of hepatic tissue in both normal and cirrhotic liver; it can be tolerated with equal safety by both normal and cirrhotic rats in this animal experiment.     

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。     

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。     

移植性大鼠肝癌模型肝动脉栓塞前后的影像学特征与病理分析

目的 探讨大鼠Walker-256肝癌模型肝动脉造影表现及介入栓塞前后MRI、CT的影像学特征与病理征象。材料与方法 采用移植法建立Wistar大鼠Walker-256肝癌模型，于接种后第14天行肝动脉造影并栓塞，于第8、11、14、21天分别行MRI检查，部分行CT检查，并与病理结果对照。结果 40只肝癌模型大鼠经MRI、CT检查证实均种植成功。经血管造影显示为肝动脉供血，且为富血供。病理检查提示该模型生长方式与人肝癌生长方式相近。结论 大鼠Walker-256肝癌模型适合于进行肝癌介入实验研究，MRI及CT检查有助于筛选实验动物，评估实验结果。     

Compensatory hypertrophy of the liver after external beam radiotherapy for primary liver cancer

Purpose

We investigated whether external beam radiotherapy (EBRT) could induce compensatory liver hypertrophy in liver cancers and assessed related clinical factors.

Methods

A total of 82 consecutive patients receiving EBRT for hepatocellular carcinoma (n?=?77) or cholangiocarcinoma (n?=?5) from April 2012 to June 2014 were recruited and divided into two subgroups according to tumor location in the right or left lobe. The left lateral and right lobes were considered as unirradiated volumes accordingly. Total liver volume (TLV), nontumor liver volume (NLV), left and right lobe whole volume (LLWV and RLWV, respectively), volume of liver irradiated?<?30?Gy (V_<?₃₀?_Gy), Child–Pugh (CPS) score, future liver remnant (FLR) ratio, and percentage of FLR hypertrophy from baseline (%FLR) were assessed.

Results

In the right lobe group, %FLR hypertrophy and LLWV increased significantly at all follow-ups (p?<?0.001). %FLR hypertrophy steadily increased until the fourth follow-up. Multivariate analysis showed that the factor associated with maximum %FLR hypertrophy was tumor extent (upper or lower lobe vs. both lobes; p?=?0.022). Post-RT treatments including transarterial chemoembolization or hepatic arterial infusion chemotherapy were associated with a CPS increase?≥?2 (p?=?0.002). Analysis of the RT only subgroup also showed a significant increase of %FLR until the fourth follow-up (p?<?0.001). In the left lobe group, %FLR hypertrophy and RLWV showed no significant changes during follow-up.

Conclusion

Significant compensatory hypertrophy of the liver was observed, with a steady increase of %FLR hypertrophy until the fourth follow-up (median: 396 days). Locally advanced tumors extending across the upper and lower right lobe were a significant factor for compensating hypertrophy after EBRT.

     

连续CT检查对病毒性慢性肝病的诊断价值

目的:评价连续CT检查对病毒性慢性肝病的临床应用价值。方法:回顾性分析42例病毒性慢肝患者连续螺旋CT检查>2年的系列图像,测量肝(左、右叶)及脾体积,以及侧支循环的范围及程度。所有病例的CT表现与肝功能(按Child-Phgh分级)和肝组织学结果进行对照。结果:13例Child分级积分增加(积分增加组),其余积分无改变(积分不变组)。在积分增加组初次检查与末次检查相比肝体积比率明显变小(P<0.05),右叶体积比率也明显变小(P<0.01)。左叶及脾体积比率在初末次检查均无明显变化(P>0.05)。积分不变组中有6例初末次检查示侧支循环的范围及程度均有发展。结论:连续CT检查对评价病毒性慢性肝病十分有用。肝体积变小,尤其是右叶体积变小提示病情进展。     

Hepatic volume changes induced by radioembolization with 90Y resin microspheres. A single-centre study

Purpose

Lobar radioembolization (RE) of the liver can result in reduction in volume of the ipsilateral lobe as well as hypertrophy of the contralateral lobe. Theoretically, hypertrophy of the contralateral liver lobe after RE could increase the chance of a successful liver resection, especially in patients with limited liver function reserve. The aim of this preliminary study was to evaluate the early effects of RE with resin microspheres on the volumes of the liver lobes and spleen.

Methods

We retrospectively investigated 24 patients (12 women, 44?C78?years old) with different types of cancer and liver-dominant metastatic disease who had undergone RE of the liver with resin microspheres. Changes in the volumes of the liver lobes and spleen were quantified by CT before and about 4 to 8?weeks after treatment.

Results

Of the 24 patients, 17 suffered from metastases in both liver lobes (group A) and 7 had metastases only in the right liver lobe (group B). The patients in the group A underwent sequential treatment starting with the right liver lobe. The median administered dose was 1.75?GBq. RE was associated with a median increase in volume of the left liver lobe of 34?% (P?<?0.001) and a median decrease in volume of the right liver lobe of 11?% (P?=?0.03). The volume of the spleen showed a median increase of 17?% (P?=?0.01). Separate analysis of the two groups showed a median increases in volume of the left liver lobe of 30?% (P?=?0.001) in group A and 70?% (P?=?0.01) in group B. There was no correlation between the injected dose and the volume alteration (r?=?0.1?C0.3).

Conclusion

RE of the right liver lobe with resin microspheres caused a significant increase in the volume of the left liver lobe. This may allow liver resection in patients with metastases in the right liver lobe and a small left liver lobe.     

Chronic hepatic disease: usefulness of serial CT examinations

PURPOSE: Our purpose was to confirm whether the progression of chronic liver disease could be determined by serial CT examinations. METHOD: We calculated the liver (right and left lobes) and spleen volumes of 34 patients with chronic liver disease, who were examined serially for >2 years using a helical CT scanner. Progression of collateral formations was also checked during follow-up. These CT findings were compared with the liver function tests by Child-Pugh score. RESULTS: The Child-Pugh score got worse in eight patients ("score-worse group") and did not change in the other patients ("score-static group"). The liver volume ratio between the first and last CT examinations was significantly smaller in the score-worse group than in the score-static group (p = 0.015). The right lobe volume ratio was also significantly smaller in the score-worse group (p = 0.009); however, the left lobe volume ratio and spleen volume ratio were not significantly different between the two groups (p = 0.656 and p = 0.365). In four patients of the score-static group, collateral formations progressed. CONCLUSION: Serial CT examinations are useful to evaluate patients with chronic liver disease. The left lobe does not become hypertrophied but tends to be preserved, in contrast to the right lobe, with the progression of the disease.     

白芨在经肝动脉化疗栓塞术治疗大鼠肝细胞癌实验中的应用

目的评价白芨在经肝动脉化疗栓塞术(transarterialchemoembolization,TACE)治疗ACI大鼠肝细胞癌实验中的应用价值。方法在30只ACI大鼠肝包膜下植入MorrisHepatom3924A肝癌瘤块(2mm3),移植术后13d进行MR检查,测量肿瘤体积(V1),第14天时,经大鼠胃十二指肠动脉逆行插管至肝动脉,采取以下治疗方案A组01mg丝裂霉素+01ml碘油+10mg白芨(10只);B组01mg丝裂霉素+01ml碘油+10mg白芨+肝动脉结扎(10只);C组01mg丝裂霉素+01ml碘油(对照组,10只)。13d后再次进行MR检查以测量肿瘤体积(V2),比较肝肿瘤体积生长率(V2/V1)。结果介入治疗后与治疗前肿瘤体积之比(V2/V1)分别为A组628,B组153,C组914。与对照组C相比,采取A、B组的治疗方案均能抑制肝肿瘤的生长(P<005和P<001),A组与B组之间的肿瘤生长率差异亦有统计学意义(P<001)。结论白芨作为肝动脉栓塞剂,结合局部化疗术和肝动脉结扎术能明显抑制大鼠肝细胞癌的生长。     

骨髓间充质干细胞对大鼠急性放射性肝损伤修复的研究

目的 探讨骨髓间充质干细胞(BMSCs)对大鼠急性放射性肝损伤的修复作用。方法 雌性SD大鼠12只,肝右叶接受单次6MVX射线20Gy照射,建立急性放射性肝损伤模型;随机分成2组,干预组注射雄性大鼠BMSCs悬液,对照组注射等量生理盐水。4周后观察大鼠肝组织的病理形态学改变,采用原位杂交技术检测肝脏中性别决定基因Y(SRY)及免疫组织化学技术检测ɑ-平滑肌肌动蛋白(ɑ-SMA)的阳性表达。结果 两组大鼠肝右叶组织中均可见汇管区炎性反应及肝实质细胞的损伤,但干预组的损伤程度比对照组轻。干预组大鼠肝右叶中检测到的SRY阳性细胞多于肝左叶(t=3.77,P＜0.05),ɑ-SMA的阳性表达率低于对照组(t=2.25,P＜0.05)。结论 单次20Gy照射可以造成大鼠肝右叶急性放射性损伤;SRY阳性细胞可以被征募到大鼠的放射性肝损伤部位,在一定程度上可能减轻放射性肝纤维化的发生。