载药微球在肝细胞肝癌动脉化疗栓塞治疗中的研究进展

目的就近年来国内外4种主流载药微球在肝细胞肝癌(HCC)动脉化疗栓塞(TACE)治疗中的研究进展进行总结。方法对国内外有关4种主流载药微球的理化性质和药代动力学、临床治疗的有效性与安全性进行研究的相关文献进行综述。结果目前市场上主流的载药微球具有药物装载速率高、可持续释放药物的特性,能在一定程度上降低栓塞后不良反应,接受载药微球-TACE治疗的患者比接受传统TACE治疗的患者安全性和耐受性略高,术后未见严重并发症,但两者的近远期疗效差异并不明显。结论目前大多数研究认为载药微球的安全性和耐受性均略高于传统TACE,但是前者的有效性是否优于后者国内外仍存在较大争议,仍需更多高质量多中心随机对照试验来研究证实。     

载药微球经导管动脉化疗栓塞治疗肝细胞癌研究进展

载药微球经导管动脉化疗栓塞(DEB-TACE)利用微球在靶病灶内释放化学治疗(简称化疗)药物,使靶肿瘤内药物浓度更高,而全身化疗药物浓度及不良反应降低;且微球可较完全栓塞肿瘤毛细血管网,闭塞肿瘤邻近血管,致癌细胞缺血、缺氧而坏死。本文对DEB-TACE治疗肝细胞癌(HCC)研究进展进行综述。     

载平阳霉素的离子交换型微球栓塞兔颈外动脉的初步实验研究

目的初步研究载平阳霉素的离子交换型微球（PYM-MS）在实验动物体内的栓塞效果。方法将18只健康成年新西兰大白兔随机分为3组,每组6只。以兔右颈外动脉为栓塞模型,分别予PYM-MS、空白离子交换型微球（MS）及平阳霉素（PYM）水剂进行栓塞,于栓塞后2天、2周及4周时于每组各随机抽取2只复查造影及进行组织学检查。结果栓塞2天、2周及4周后PYM-MS组复查造影均未见血管再通,组织学检查可见微动脉血管内膜从2天～2周、4周进行性增生,甚至管腔闭塞,并可见毛细血管闭塞;MS组复查造影可见少量血管再通,组织学检查见微动脉栓塞;PYM组造影见血管通畅,组织学仅见血管内皮细胞肿胀。结论 PYM-MS栓塞后可使微动脉内膜增生、管腔闭塞,栓塞效果优于MS及PYM。     

三氧化二砷联合载药微球经导管肝动脉化疗栓塞对中晚期肝癌的疗效分析

目的探讨三氧化二砷联合载药微球经导管肝动脉化疗栓塞对中晚期肝癌的疗效。方法选取郑州大学第一附属医院2017-03—2018-01间收治的90例中晚期肝癌患者作为研究对象。根据随机数表法分为2组,每组45例。2组患者均接受奥沙利铂经肝动脉灌注化疗。研究组使用三氧化二砷与载药微球混悬液栓塞肿瘤供血动脉,对照组使用表柔比星与载药微球混悬液栓塞肿瘤供血动脉。比较2组治疗前及治疗后1个月的肝肾功能、AFP、疾病缓解率(CR+PR)、疾病控制率(CR+PR+SD)。结果 2组患者术前、术后1个月的肝肾功能指标及术前的AFP水平等指标比较,差异均无统计学意义(P0.05)。研究组术后AFP水平明显低于对照组,术后1个月CR+PR和CR+PR+SD均高于对照组,差异均有统计学意义(P0.05)。结论三氧化二砷联合载药微球经导管肝动脉化疗栓塞,是治疗中晚期肝癌效果较好的方案。     

肝癌患者行载药微球栓塞治疗不良反应的观察及护理

目的 探讨肝癌患者行载药微球经导管动脉化疗栓塞治疗不良反应的护理方法。 方法 选取行载药微球经导管动脉化疗栓塞术的原发性肝癌患者172例,观察记录不良反应,并及时进行预防护理。 结果 患者术后发生肝区疼痛137例,发热51例,便秘74例,恶心呕吐114例,溶瘤综合征2例。1例溶瘤综合征经治疗无效死亡,其余171例经处理均顺利恢复出院。 结论 载药微球经导管动脉化疗栓塞治疗肝癌术后常见不良反应有肝区疼痛、发热、便秘、恶心呕吐等。应提前采取有效措施,及时观察和处理,降低并发症发生率。     

载药微球在肿瘤与非肿瘤疾病治疗中的应用

近年来,载药微球(Drug-eluting beads,DEB)因其对血管的栓塞作用和释放药物的靶向性而在介入治疗领域广受关注。大量研究证明,载药微球可以延长药物的活性,提高稳定性,维持一定的血药浓度,从而使药物的释放效果更为理想。载药微球发展至今,其种类、性能正不断地丰富并优化。在肿瘤治疗中,载药微球的栓塞化疗已应用于治疗肝、肾、胃肠、乳腺等部位的肿瘤;在非肿瘤疾病的治疗中,载药微球亦具有很大的应用潜力。我们相信,载药微球是一个极具前景的研究领域,利用其结合分子靶向药物可能会实现多种疾病的治疗突破。     

DR5mAb-载替加氟高分子材料微球的构建及体外靶向肝癌能力

目的构建一种DR5mAb-载替加氟主动靶向载药高分子微球,并鉴定其理化性质和体外寻靶能力。方法采用双乳化法制备替加氟载药微球,以碳二亚胺法和生物素-亲和素法将DR5mAb与载药微球连接,构建DR5mAb-载替加氟主动靶向载药高分子微球。检测载药微球的一般性质;用流式细胞仪检测抗体连接率,并对比碳二亚胺法和生物素-亲和素法的连接率;以人肝癌细胞株SMMC-7721和正常肝细胞株L02为实验对象验证其体外细胞靶向性。结果生物素亲和素法的载药微球抗体连接率高于碳二亚胺法(P0.05);靶向载药微球-7721组的细胞表面及周围有大量微球聚集,非靶向载药微球-7721组和靶向载药微球-L02组的细胞表面及周围均无明显微球聚集。结论 DR5mAb-载替加氟主动靶向载药高分子微球可与肝癌细胞SMCC-7721主动靶向结合,有望为肝癌靶向治疗提供一种新的手段和思路。     

CalliSpheres载药微球栓塞治疗原发性肝细胞癌自发性破裂出血的有效性及安全性

目的 观察CalliSpheres载药微球治疗原发性肝细胞癌(PHC)自发性破裂出血的有效性及安全性。方法 对23例PHC自发性破裂出血患者以CalliSpheres载药微球(加载表柔比星)予以栓塞,之后酌情行TACE或靶向治疗等;监测心率、血压及血红蛋白,以判断止血效果;统计术中及术后不良反应及并发症发生率;于栓塞前及栓塞后3天、1个月检测肝功能。随访12个月,绘制K-M生存曲线,统计术后1、3、6、12个月生存率。结果 23例均顺利完成治疗,未见相关不良反应。栓塞后6 h心率较术前下降(P=0.001),血压及血红蛋白保持稳定未再下降,表明有效止血。栓塞后1~2天,17例出现轻微发热、恶心、呕吐、腹痛等栓塞综合征,经对症处理后均缓解;未见肝、肾衰竭及肝性脑病、胆道感染等严重并发症。栓塞后3天谷丙转氨酶(GPT)、谷草转氨酶(GOT)及总胆红素(TBil)均高于栓塞前及栓塞后1个月(P均<0.05),栓塞后1个月与栓塞前差异均无统计学意义(P均>0.05);各时间点白蛋白(ALB)差异无统计学意义(P>0.05)。栓塞后随访1~12个月,未见再次出血。栓塞后1、3、6及12个月,患者生存率为分别100%、82.61%、69.57%及56.52%。结论 CalliSpheres载药微球栓塞治疗PHC自发性破裂出血的有效性及安全性均较好。     

CalliSpheres载药栓塞微球治疗中晚期肝癌的短期效果与安全性

目的 探讨CalliSpheres载药栓塞微球治疗中晚期肝癌的短期疗效和安全性。方法 回顾性分析2017年8月至2021年4月中国医科大学附属盛京医院放射科行CalliSpheres载药微球栓塞（DEB-TACE组,37例）和碘化油栓塞（cTACE组,40例）治疗的中晚期肝癌患者的临床资料。依据改良实体瘤疗效评价标准（mRECISET）评估两组患者疗效,比较两组患者治疗后不良反应发生率以及术后肝功能指标。结果DEB-TACE组与cTACE组治疗后1个月客观缓解率（ORR）[54.1%(20/37) vs 40.0%(16/40)]、疾病控制率（DCR）[97.3%(36/37) vs 92.5%(37/40)]以及治疗后3个月ORR[41.7%(15/36) vs 32.5%(13/40)]、DCR[83.3%(30/36) vs 77.5%(31/40)]均无统计学差异（P> 0.05）;治疗后6个月DEB-TACE组ORR高于cTACE组[46.9%(15/32) vs 21.6%(8/37),P<0.05],但两组DCR[81.2%(26/32) vs 67.6%(2...     

32 磷玻璃微球内放射栓塞治疗肝癌

目的 :探讨3 2 磷玻璃微球内放射栓塞治疗中晚期肝癌的效果。方法 :应用3 2 磷玻璃微球通过介入方法治疗肝癌 2 1例。结果 :治疗后用彩色多谱勒超声和SPECT肝扫描显示肝动脉灌注3 2 磷玻璃微球后肿瘤动脉血供明显减少或消失 ,肿瘤体积缩小 ,3 2 磷玻璃微球聚集于肿瘤区内 ,治疗后 6、12、18个月生存率分别为 85 .7%、6 1.9%、5 7.1% ,无明显毒副反应。结论 :3 2 磷玻璃微球内放射栓塞治疗中晚期肝癌是一种有效的治疗手段     

Studies in pharmacokinetics and tolerance of substances temporarily retained in the liver by microsphere embolization.

Earlier investigation has shown that a temporary arrest of arterial blood flow can be achieved by embolization with degradable microspheres. This study was made to investigate the change in pharmacokinetics, and drug tolerance which takes place when a substance is retained in the liver by a microsphere embolization. 14C-labelled inulin and 5-fluorouracil were studied. The administration of these substances with microspheres led to a delay in their systemic distribution. Furthermore there was an increased tolerance to 5-fluoro-uracil, probably due to a prolonged first pass effect when the substance was temporarily retained in the liver by a microsphere embolization.     

Preoperative embolization of intracranial meningiomas with Embosphere microspheres.

BACKGROUND: To reduce intraoperative bleeding and to facilitate surgery by inducing tumor softening, a preoperative embolization of meningiomas is commonly recommended. PATIENTS AND METHODS: We report on our experience with non-resorbable microspheres (Embosphere) in the preoperative endovascular embolization of 17 intracranial meningiomas. After adding contrast media to the particles sized 40-500 micron, the embolization process was followed under fluoroscopy. There was a good passage of microcatheters if high concentrations of particles were avoided. RESULTS: The obstruction of the tumor feeders by particles was accompanied by a regression of tumor blush in DSA. CT controls showed a diminished contrast accumulation of the tumors already 1-2 days after embolization. Histologically, Embosphere microspheres were easy detectable with all commonly used staining methods. Embolization triggered, microscopically detectable necrosis was found in 77 % of the tumors. The mean interval between embolization and tumor extirpation was 2.5 days. The average time required for tumor extirpation was 244 minutes, while the average blood loss was 749 ml. CONCLUSIONS: Our experiences show that Embosphere microspheres are effective embolic agents in obstructing meningeal feeders of preoperatively treated meningiomas.     

An experimental study of the basic properties of drug microspheres and target treatment of rats with liver tumor

This experimental hepatic artery embolization with Camptothecin (CPT) albumin microspheres was performed in normal rats and rats with liver tumor. The basic properties of the CPT albumin microspheres and the effects of target treatment on rats with liver tumor were studied. The results showed that the concentration of the drug released into hepatic vein was almost stable for over 3 hours after hepatic arterial infusion of CPT albumin microspheres, the partial and complete recovery of hepatic artery inflow occurred within 50-70 days after embolization. Pathological examination revealed many irreversible damages of the liver, and the tumor vessels and stains disappeared after hepatic arterial embolization, some of the tumor were decreased in size and had complete necrosis. Therefore, CPT albumin microspheres are peripheral biodegradable embolizatic substances with the property of slowly drug-releasing. It can exert the effect of chemoembolization in treating the hepatic malignant tumor, alleviating the toxic reaction of CPT and increasing the patient's tolerance to CPT.     

Relationship between cardiopulmonary bypass flow rate and cerebral embolization in dogs.

BACKGROUND: Cerebral embolization is a primary cause of cardiac surgical neurologic morbidity. During cardiopulmonary bypass (CPB), there are well-defined periods of embolic risk. In theory, cerebral embolization might be reduced by an increase in pump flow during these periods. The purpose of this study was to determine the CPB flow-embolization relation in a canine model. METHODS: Twenty mongrel dogs underwent CPB at 35 degrees C with alpha-stat management and a fentanyl-midazolam anesthetic. In each animal, CPB flow was adjusted to achieve a mean arterial pressure of 65-75 mmHg. During CPB, an embolic load of 1.2 x 10(5) 67 microm fluorescent microspheres was injected into the arterial inflow line. Before and after embolization, cerebral blood flow was determined using 15-microm microspheres. Tissue was taken from 12 brain regions and microspheres were recovered. The relation between pump flow and embolization/g of brain was determined. RESULTS: The mean arterial pressure at embolization was 67 +/-4 mmHg, and the range of pump flow was 0.9-3.5 l x min(-1)x m(-2). Cerebral blood flow was independent of pump flow. At lower pump flow, the percentage of that flow delivered to the brain increased. There was a strong inverse relation between pump flow and cerebral embolization (r = -0.708, P < 0.000 by Spearman rank order correlation). CONCLUSIONS: Cerebral embolization is determined by the CPB flow. At an unchanged mean arterial pressure, as pump flow is reduced, a progressively greater proportion of that flow is delivered to the brain.     

Relationship between Cardiopulmonary Bypass Flow Rate and Cerebral Embolization in Dogs

Background: Cerebral embolization is a primary cause of cardiac surgical neurologic morbidity. During cardiopulmonary bypass (CPB), there are well-defined periods of embolic risk. In theory, cerebral embolization might be reduced by an increase in pump flow during these periods. The purpose of this study was to determine the CPB flow-embolization relation in a canine model.

Methods: Twenty mongrel dogs underwent CPB at 35[degrees]C with [alpha]-stat management and a fentanyl-midazolam anesthetic. In each animal, CPB flow was adjusted to achieve a mean arterial pressure of 65-75 mmHg. During CPB, an embolic load of 1.2 x 105 67 [mu]m fluorescent microspheres was injected into the arterial inflow line. Before and after embolization, cerebral blood flow was determined using 15-[mu]m microspheres. Tissue was taken from 12 brain regions and microspheres were recovered. The relation between pump flow and embolization/g of brain was determined.

Results: The mean arterial pressure at embolization was 67 +/- 4 mmHg, and the range of pump flow was 0.9-3.5 l [middle dot] min-1 [middle dot] m-2. Cerebral blood flow was independent of pump flow. At lower pump flow, the percentage of that flow delivered to the brain increased. There was a strong inverse relation between pump flow and cerebral embolization (r = -0.708, P < 0.000 by Spearman rank order correlation).     

Quantification and Distribution of Cerebral Emboli during Cardiopulmonary Bypass in the Swine: The Impact of PaCO(2)

Background: Patients undergoing cardiac surgery have a substantial incidence of neurologic complications related to cerebral embolization during cardiopulmonary bypass. The purpose of this study was to determine if adjustments in the arterial carbon dioxide (PaCO(2)) level can reduce cerebral and ocular embolization.

Methods: Twenty pigs underwent cardiopulmonary bypass at 38 [degree sign]C. At either hypercarbia (PaCO(2) = 50-55 mmHg, group H, n = 10) or hypocarbia (PaCO(2) = 25-30 mmHg, group L, n = 10), an embolic load of 1.2 x 105 67-[micro sign]M orange fluorescent microspheres was injected into the aortic cannula. Before and after embolization, cerebral and ocular blood flows were determined at norcocapnia using 15-[micro sign]m fluorescent microspheres. After cardiopulmonary bypass was completed, the eyes were enucleated and brain tissue samples were collected. Microspheres were isolated and the fluorescence was measured.

Results: In groups H and L, the mean PaCO(2) values at embolization were 52 +/- 3 mmHg and 27 +/- 2 mmHg, respectively (P < 0.0001). Total and regional embolization were significantly less in hypocapnia than in hypercapnic animals: 142% more emboli were detected in the brain in group H than in group L (P < 0.0001). Cerebral blood flow after embolization was unchanged in both groups. Similarly, fewer ocular emboli occurred in hypocapnic animals than in hypercapnic animals (P = 0.044), but in contrast to the brain, ocular blood flow decreased significantly in both groups after embolization.     

Experimental modeling of the blood vessels magnetic embolization

The embolization of blood vessels is used on a large scale: the method is applied in different diseases, in the ablation of organs, but especially in tumor necrosis. The embolization can be also magnetic, if the embolus is obtained through the deposit in the vessel of magnetic nano or microparticles in the presence of an external magnetic field. The objective of our study was the modeling of the magnetic embolization using amorphous magnetic microspheres that have strong magnetic properties and are biocompatible. Experimental tests were made in order to observe the building of the magnetic embolus inside a thin spiral tube and to determine the influence of some parameters on the efficiency of occlusions: the dimensions of magnetic microspheres (1-300 mm), the debit of the liquid (4.66 - 16.5 ml/min), the viscosity of the carrier liquid (1.007 - 7.34 cSt), the direction and the intensity of the external magnetic field (340 - 600 Gs), the shape of the tube and the linear length of the deposit (5 - 50 mm). Under pre-established experimental conditions the efficiencies of occlusions were between 67% and 100%.     

肾动脉栓塞术作为姑息疗法在中晚期肾癌治疗中的应用:附28例临床分析

目的评价肾动脉栓塞术作为姑息疗法治疗中晚期肾癌的效果。方法 2009年2月—2011年12月共28例中晚期肾癌患者在我院接受经皮肾动脉栓塞治疗,栓塞剂选用明胶海绵颗粒、弹簧圈和（或）聚乙烯醇微粒球。对其临床资料进行回顾性分析,观察肾动脉栓塞的疗效。结果对28例患者进行超选择性肾动脉栓塞,其中22例采用栓塞剂及抗癌药物栓塞,6例仅用栓塞剂进行栓塞。术后所有患者症状消失或显著减轻,无明显并发症。结论作为姑息疗法,经皮肾动脉栓塞疗法治疗中晚期肾癌安全有效。     

Effect of cerebral embolization on regional autoregulation during cardiopulmonary bypass in dogs

BACKGROUND: Embolization during cardiopulmonary bypass probably alters cerebral autoregulation. Therefore, using laser Doppler flowmetry we investigated the cerebral blood flow velocity changes in response to changes in arterial pressure, before and after embolization in a canine bypass model. METHODS: After Institutional Animal Care and Use Committee approval, 8 anesthetized dogs had a laser Doppler flow probe positioned over the temporoparietal dura. During 37 degrees C cardiopulmonary bypass, the cerebral blood flow velocity response to changing mean arterial pressure (40 to 85 mm Hg in random order) was assessed before and after systemic embolization of 100 mg of 97-microm latex microspheres. RESULTS: Before embolization, cerebral blood flow velocity increased 39% as mean arterial pressure increased from 40 to 85 mm Hg. Following embolization, a 94% increase in cerebral blood flow velocity was demonstrated over the same mean arterial pressure range. The slopes of the curves relating cerebral blood flow velocity to mean arterial pressure were 0.21+/-0.74 and 1.31+/-0.87, before and after embolization (p = 0.016) respectively. CONCLUSIONS: Regional cerebral blood flow autoregulation may be impaired by microembolization known to occur during cardiopulmonary bypass, increasing the dependence of cerebral blood flow on mean arterial pressure.