羟基喜树碱明胶微球肝动脉化疗栓塞治疗肝肿瘤的实验研究

目的：对羟基喜树碱明胶微球（ＯＰＴ－ｍｓ）进行栓塞特性的实验研究。方法：以草犬为实验对象，比较了肝动脉注射常规型ＯＰＴ，空白明胶微球和ＯＰＴ－ｍｓ对大鼠肝癌的作用，并以肝动脉注射生理盐水作对照。结果：发现微球栓塞后血管造影可见末梢动脉有不同程度的减少，３０ｄ复查未见侧支循环形成。ＡＫＰ，ＧＰＴ在肝动脉灌注后３ｄ可达到最大值，７ｄ后明显下降，１４ｄ恢复正常，肝功能指标与微球的剂量呈正相关。病理检查有局限性或小灶性坏死，其程度与范围与剂量的大小有关，其它主要脏器无明显改变。结论：ＯＰＴ－ｍｓ对于肝肿瘤治疗是理想的。     

肝动脉注入羟基喜树碱明胶微球对大鼠移植性肝癌的疗效研究

目的：为了观察羟基喜树碱明胶微球（ＯＰＴ－ｍｓ）的疗效，我们建立了大鼠移植性肝癌模型。材料与方法：以肝动脉注射生理盐水作对照，比较了肝动脉注射常规型ＯＰＴ（１ｍｇ／ｋｇ），空白明胶微球（１０ｍｇ／ｋｇ）和ＯＰＴ－ｍｓ［１０ｍｇ（含药１ｍｇ）／ｋｇ］治疗大鼠肝癌的作用。结果：接受常规ＯＰＴ、空白明胶微球治疗的大鼠，其肿瘤生长受到显著抑制（Ｐ＜０．０５），肿瘤组织发生不同程度的坏死，但与对照组相比动物的生存期未显著延长（Ｐ＞０．０５），而接受ＯＰＴ－ｍｓ治疗的大鼠，其肿瘤的坏死更彻底、更广泛，且动物的生存期明显延长（Ｐ＜０．０１）。结论：ＯＰＴ－ｍｓ疗效明显优于常规型ＯＰＴ单纯肝动脉化疗和空白明胶微球的单纯肝动脉栓塞。     

TACE并IL—2／LAK肝动脉灌注治疗晚期肝癌的初步报告

本文采用ＴＡＣＥ并ＩＬ－２／ＬＡＫ肝动脉灌注治疗晚期肝癌１０例。结果为ＰＲ２例，ＭＲ４例，ＳＤ２例和ＰＤ２例。１０例病人生存期３－１０个月，平均７．８个月。ＩＬ－２／ＡＬＫ灌注后６例ＡＦＰ值明显下降；Ｔ细胞亚群中Ｔｈ数量明显增多，Ｔｓ数量明显显减少，与灌注前比较有显著性差异。ＩＬ２／ＬＡＫ肝动脉灌注未见严重副反应。结果提示ＴＡＣＥ并ＩＬ－２／ＬＡＫ肝动脉灌注为晚期肝癌较好的一种综合治疗方法。     

^125—BMIPP检测缺血和再灌注区存活心肌及其与局部血流的关系

目的 通过犬心肌梗死及缺血再灌注模型，观察碘标β－甲基碘苯酯十五烷酸（ＢＭＩＰＰ）检测缺血区存活与坏死心肌的作用及其与局部血流的关系。方法 １２条实验犬结扎左回旋支冠状动脉后分成２组，即单纯缺血组与缺血再灌注组。静脉注射＾１２５Ｉ－ＢＭＩＰＰ和＾９９Ｔｃ＾ｍ－右旋糖酐微球（ＴＭ），３０ｍｉｎ后处死实验犬，摘除心脏，分别进行ＥＶＡＮＳ蓝和ＮＢＴ染色，确定正常，缺血和坏死心肌范围，并分别测定同一组织块     

羟基喜树碱明胶微球肝动脉化疗栓塞治疗原发性肝癌

目的：在动物实验的基础上,我们将ＯＰＴ－ｍｓ进行临床研究。材料和方法：选择２６例原发性肝癌采用粒径为１５４μｍ－２００μｍ,用量１５０ｍｇ－４００ｍｇ：如微球加ＭＭＣ（２０ｍｇ）进行肝动脉灌注,平均２．６次。通过观察血清中ＡＦＰ的下降和肿瘤在ＣＴ上最大层面的两相互垂直的最大径的乘积的改变判定其临床效果,可进行了粗略地随访。结果：９３．３％的病人（１４／１５）ＡＦＰ下降在５０％以下。治疗后肿瘤缩小大于５０％者１２例占４６．６％;缩小在２５％－５０％（ＭＲ）７例占２６．９％;缩小（ＰＲ）小于２５％（ＮＣ）５例占２０％;２例增大（ＰＤ）占７．７％。所有治疗的病人临床症状得以好转和生活质量提高,生存期明显延长,全身副作用仅是一过性的。结论：初步临床应用表明：ＯＰＴ－ｍｓ对于ＰＬＣ肝动脉栓塞化疗效果是明显的,是一种良好未梢栓塞剂。     

柔红霉素－白蛋白药物微球制备、特性及对小鼠实验肿瘤的疗效

为了提高化疗药物的治疗指数和降低其毒性，制备了柔红霉素－人血清白蛋白微球（Ｄａｕ－ＨＡ－ＭＳ），绝大多数为单分散相微球，平均直径５６±１６μｍ，范围为２９─１９４μｍ，适用于导管动脉栓塞治疗。Ｄａｕ－ＨＡ～ＭＳ在生理盐水中能有效释放Ｄａｕ，但无爆发释放的缺点。释放的Ｄａｕ的光谱特性和体外细胞毒效应与原药相比无变化，表明Ｄａｕ通过微球制备仍保留原有的理化及生物学特性。实验表明经腹腔注射Ｄａｕ－ＨＡ－ＭＳ使３０％的Ｓ１８０腹水癌小鼠活存超过６个月，而肿瘤对照组及Ｄａｕ治疗肿瘤组均分别在２１ｄ和１４ｄ全部死亡，说明Ｄａｕ－ＨＡ－ＭＳ有较好的疗效及较低的毒性，提示Ｄａｕ－ＨＡ－ＭＳ有可能用于人肝癌的导管动脉栓塞治疗，有进一步研究的价值。     

外磁场控制磁性明胶微球肝动脉栓塞的实验研究

本实验随机使用杂种犬１７只。磁性明胶微球（ＭＧ－ｍｓ）粒径１０～３０μｍ。含ｘ－Ｆｅ＿２Ｏ＿３３０％（Ｗ／Ｗ）。血管造影、放射性核素扫描、ＣＴ扫描以及病理组织学检查，均显示出磁性明胶微球通过外磁场导向控制，在肝动脉内具有明显的靶向栓塞作用。栓塞术后，血清ＡＬＴ、ＡＳＴ、ＡＬＰ短时间内升高，２～３天达高峰，尔后下降，于３～４周内恢复到术前水平。末发现不良反应及异位栓塞。     

肝动脉栓塞化疗对肝损害的观察（附100例分析）

肝动脉栓塞化疗对肝损害的观察（附１００例分析）肖承江郑丽吟蒋晓红笔者从我院６００例接受肝动脉碘油化疗（ＨＡＩ－Ｌｐ）或碘油化疗加明胶海绵栓塞（ＨＡＩ－Ｌｐ－Ｇｓ）治疗的病例中，采用抽签法随机抽取１００例，依丙氨酸转氨酶（ＡＬＴ）、胆红素（ＢＩＬ）及血...     

肝肿瘤经动脉植入式导管药盒系统的灌注和栓塞化疗

目的：探讨介入放射学方法留置导管药盒治疗肝肿瘤的方法和效果。材料与方法：采用Ｓｅｌｄｉｎｇｅｒ技术经左锁骨下动脉穿刺将导管插入肝动脉，然后与植入式药盒连接并埋置于皮下，对３１例原发性和转移性肝肿瘤患者经导管药盒系统进行了多次动脉灌注和栓塞化疗，灌注抗癌药物有ＡＤＭ和ＣＤＤＰ，栓塞采用ＭＭＣ－碘油乳剂。结果：有３０例病人导管超选择置入肝左右动脉、肝固有动脉或肝总动脉，１例导管留置在腹腔动脉。患者术后     

肝动脉化疗栓塞及注射无水乙醇,^32P—玻璃微球治疗原发性？…

目的 评价肝动脉化疗栓塞（ＴＡＥ）结合Ｂ超引导下注射无水乙醇（ＰＥＩ）、＾３２Ｐ－玻璃微球（＾３２Ｐ－ＧＭＳ）治疗原发性肝癌的临床价值。方法 ８３例中、晚期肝癌分为２组，４３例综合应用ＴＡＥ＋ＰＥＩ＋＾３２Ｐ－ＧＭＳ治疗，４０例单纯应用ＴＡＥ治疗。结果 综合治疗组手术切除１４例（３３％），有９例肿瘤组织完全坏死，５例有残存的肿瘤细胞，单纯ＴＡＥ组手术切除４例（１０％），肿块及周边有肿瘤细胞，血清Ａ     

Concordant F-18 FDG PET and Y-90 Bremsstrahlung scans depict selective delivery of Y-90-microspheres to liver tumors: confirmation with histopathology

Selective Internal Radiation Therapy using yttrium-90 (Y-90) microspheres is a novel method for the treatment of advanced liver cancer. The procedure involves intrahepatic arterial delivery of the Y-90 microspheres. Since hepatic tumors derive their blood supply mainly from the hepatic arteries, it is assumed that the microspheres will be preferentially delivered to tumor cells. However, this has not been confirmed at histology. We report a case of hepatic metastasis from an unknown primary, where treatment with Y-90 microspheres was the only available option due to inoperability and low tolerance to chemotherapy. Pretherapy F-18 FDG-PET scan defined the distribution of the active tumor within the liver. Following the injection of Y-90 microspheres, Bremsstrahlung imaging showed uptake only in the F-18 FDG-PET-defined tumor area. Post therapy debulking surgery was performed and histopathology of tumor samples confirmed the preferential distribution of the injected microspheres in the hepatic tumor circulation with very little in the healthy liver tissue. The case confirms the preferential blood flow to hepatic tumors as depicted by the distribution of Y-90 microspheres injected directly in the hepatic arteries. It also demonstrates that concordance between F-18 FDG-PET and Y-90 Bremsstrahlung scans can be a useful clue to the in vivo distribution of microspheres.     

经动脉导管四氧化三铁微粒栓塞临床应用价值

目的　探讨四氧化三铁 (Fe3 O4)微粒栓塞肿瘤及血管性疾病临床应用价值。方法　临床 10 6例患者 ,采用Seldinger技术插管 ,置导管端于靶血管内 ,在X线电视监测下 ,用Fe3 O4微粒或Fe3 O4化疗药物混悬液栓塞。结果　恶性肿瘤 94例 ,良性血管性病变 12例 ,多数患者栓后 1月CT、USG或DSA复查 ,肿瘤明显缩小。 18例肿瘤栓塞后手术切除 ,病理检查 :肿瘤组织坏死 10 0 %。血生化检查 :肝肾功能有轻度变化 ,经一般临床处理可接近栓塞前正常水平或优于术前水平。原发性肝癌栓塞后血清AFP多数有明显下降 ,血清铁浓度栓塞前后变化显示 :Fe3 O4微粒栓塞治疗有助于血清铁浓度指标正常值的维持。栓塞前后DSA对照显示 ,1月后Fe3 O4微粒由栓塞动脉血管近端移向远端末梢 ,临床观察栓后综合征明显下降。结论　通过 10 6例患者临床栓塞治疗 ,Fe3 O4微粒是一种理想的永久性颗粒栓塞剂。     

国产PVA微球肝动脉栓塞的实验研究

Polyvinyl alcohol microsphere impregnated with barium sulfate was found to be a good embolizing agent in regard to shape, suspension and distribution in the arteries. Different-phase hepatic artery embolization with microspheres (50 approximately 100 microns, 100 approximately 300 microns) was performed in 20 dogs to evaluate the angiographic and histopathologic changes and hepatic function alterations. Permanent occlusion of the peripheral arterioles was observed on follow-up angiograms one week to six months after embolization. Shrinkage of the embolized segment and focal infarct of the liver were noticed in nearly half of the specimens both grossly and microscopically. The shape and structure of the microspheres were seen unchanged on different-phase specimens, and microspheres as small as 50 microns could reach the corresponding small peripheral arterioles. The liver function alterations were comparable with gelfoam embolization. This study suggested that permanent embolization of small arterioles was possible with such microspheres.     

Biocompatibility,Inflammatory Response,and Recannalization Characteristics of Nonradioactive Resin Microspheres: Histological Findings

Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10–30 microspheres (15–30 μm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15–30 μm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.     

肝动脉栓塞微球对移植型肝癌大鼠疗效的实验研究

肝动脉栓塞微球是80年代国外少数国家开始研究用于治疗中晚期肝癌的新剂型。采用超选导管将微球注入肝动脉末梢,起阻断肝癌血供和在局部缓释药物等双重功能。本综述着重介绍笔者实验室研究的羟基喜树碱,甲氨蝶呤明胶微球和顺铂乙基纤维素微球的大鼠栓塞药效学试验,结果证明该剂型对移植性肝癌的治疗是有显著作用的。     

Therapieresponse von Lebertumoren nach selektiver interner Radiotherapie

Selective internal radiation therapy (SIRT) is used for the treatment of patients with liver tumors, especially for those with hepatocellular carcinoma (HCC) or liver metastases from various primary tumors. Currently this innovative treatment concept is recommended when established state-of-the-art treatment regimes have failed and tumor progression is noted or if the treatment has to be abandoned because of intolerable toxic effects. For SIRT small biocompatible microspheres (SIR-Spheres(R)) are labelled with the radioactive isotope 90Yttrium, a pure beta emitter, and are superselectively infused into the hepatic arteries. The microspheres are collected in the precapillary vessels in and surrounding the tumor. The beta radiation of 90Yttrium has an average penetration in tissue of approximately 2.5 mm and results in very high doses of radiation being selectively targeted to metastases providing protection to the surrounding healthy liver tissue. In this paper we review the results of SIRT in patients with hepatic metastases from colorectal cancer, breast cancer, neuroendocrine tumors and primary liver cancer (HCC).     

去甲斑蝥素微球对兔肝动脉栓塞作用的研究

目的观察去甲斑蝥素鄄海藻酸/聚酸酐微球(NAPMS)对兔肝动脉的栓塞作用。方法新西兰兔18只,在DSA下,行肝动脉造影后,以8mg/kg的剂量经肝动脉注入NAPMS,注入后10min、1,7、14、21和30d各取3只再次造影,观察肝动脉栓塞情况,并处死,取心、肝、肾、脾、肺、胰、胃等组织,观察病理变化,同时作肝、肾功能、血常规检查。结果兔肝动脉栓塞前,肝脏血管造影清晰,栓塞后10min造影,远端微血管消逝,肝动脉增粗、迂曲。介入栓塞后第1、7、14、21和30天造影远端血管均未显影。肝脏病理结果显示微球栓塞于肝窦前小动脉。栓塞后出现一过性肝功能损害,AST,ALT均在栓塞后1d达最高值,以后逐渐下降,7d左右恢复正常水平(P>0.05)。栓塞后白细胞出现一过性升高,第3天达最高值,第7天接近正常水平(P>0.05)。结论去甲斑蝥素微球具有良好的肝动脉末梢栓塞作用,栓塞时间在1个月以上,是较理想的介入栓塞剂。     

Effects of the type of embolization particles on carboplatin concentration in liver tumors after transcatheter arterial chemoembolization in a rabbit model of liver cancer

PURPOSE: To study the effect of particle type used during transarterial hepatic chemoembolization (TACE) on carboplatin concentration after TACE in an animal model of liver cancer (VX2) and to determine the concentration of carboplatin within tumor, liver, and plasma. MATERIALS AND METHODS: The VX2 tumors were grown in the livers of 23 rabbits. Carboplatin (5 mg/kg) was selected because of its known potency against VX2 tumor. Group 1 was treated with TACE with tris-acryl gelatin microspheres (100-300 microm), group 2 was treated with TACE with polyvinyl alcohol (PVA; 150-250 microm), group 3 (control) was treated with intraarterial saline solution, and group 4 (pharmacokinetic) was treated with intraarterial carboplatin. Animals were killed after 48 hours, and concentrations of carboplatin were measured by atomic absorption spectroscopy from samples of blood and liver (central and peripheral zones of tumor and nontumorous liver tissue). RESULTS: In group 1 (tris-acryl gelatin microspheres) and group 2 (PVA), the mean carboplatin concentrations were 117 microg/g and 31.8 microg/g, respectively, within the central zone of the tumor and 38.5 mug/g versus 7.9 microg/g, respectively, in the peripheral zone. No carboplatin was detected in nontumorous liver tissue and plasma concentrations were low in both treated groups (<0.079 microg/mL). CONCLUSIONS: Carboplatin concentration was significantly greater (by a factor of two to four) within the central zone of the tumor compared with the peripheral zone in both treated groups. The overall tumor carboplatin concentrations were significantly greater in the tris-acryl gelatin microsphere group than in the PVA group (P < .001), which could translate into greater potency and tumor kill. Administration of tris-acryl gelatin microspheres may be clinically advantageous during TACE, as it contributed to greater delivery of chemotherapy to tumor in the present study.     

Transarterial Chemoembolization in a Woodchuck Model of Hepatocellular Carcinoma

PurposeTo assess the feasibility of transarterial chemoembolization with drug-eluting embolic (DEE) microspheres in a woodchuck model of hepatocellular carcinoma (HCC).Materials and MethodsNine woodchucks were studied: 4 normal animals and 5 animals infected with woodchuck hepatitis virus in which HCC had developed. Three animals with HCC underwent multidetector CT. A 3-F sheath was introduced into the femoral artery, and the hepatic arteries were selectively catheterized with 2.0–2.4-F microcatheters. Normal animals underwent diagnostic angiography and bland embolization. Animals with HCC underwent DEE transarterial chemoembolization with 70–150-μm radiopaque microspheres loaded with 37.5 mg doxorubicin per milliliter. Cone-beam CT and multidetector CT were performed. Following euthanasia, explanted livers underwent micro-CT, histopathologic examination, and fluorescence imaging of doxorubicin.ResultsThe tumors were hypervascular and supplied by large-caliber tortuous vessels, with arteriovenous shunts present in 2 animals. There was heterogeneous enhancement on multidetector CT with areas of necrosis. Six tumors were identified. The most common location was the right medial lobe (n = 3). Mean tumor volume was 30.7 cm³ ± 12.3. DEE chemoembolization of tumors was achieved. Excluding the 2 animals with arteriovenous shunts, the mean volume of DEE microspheres injected was 0.49 mL ± 0.17. Fluorescence imaging showed diffusion of doxorubicin from the DEE microspheres into the tumor.ConclusionsWoodchuck HCC shares imaging appearances and biologic characteristics with human HCC. Selective catheterization and DEE chemoembolization may similarly be performed. Woodchucks may be used to model interventional therapies and possibly characterize radiologic–pathologic correlations.     

去甲斑蝥素明胶微球肝节段性栓塞的犬实验研究

目的:研究去甲斑蝥素明胶微球肝节段性栓塞术后肝脏的病理变化过程,及此过程中肝肾功能的改变,为临床推广应用提供依据。方法:以健康杂种犬为实验对象(n=8),去甲斑蝥素(NCTD)明胶微球(直径约200μm)与60％泛影葡胺混和液作为栓塞剂,行肝节段性栓塞,术前术后监测血常规、淀粉酶、肝肾功能,术后定期复查肝动脉造影、CT,术后1d及1、2、4周分批处死实验犬进行肝肺组织学检查。结果:术后定期复查肝动脉造影示靶动脉均有不同程度的闭塞,术后病理检查发现肝栓塞区小动脉血栓形成,1周后血栓机化,栓塞肝组织以灶性坏死为主,坏死肝细胞完全崩解,代之以纤维组织增生。术后1d白细胞出现-过性升高,术后2周恢复至术前水平。肝功能呈-过性损害,术后2-3周恢复,主要表现为ALT和ALP的升高。结论:直径为200μm的NCTD明胶微球为一种有效的新型动脉栓塞剂。